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Boletín Médico del ISSN-1665-1146 Boletín Médico del Hospital Infantil de México PUBLICACIÓN BIMESTRAL Vol. 69 Noviembre-Diciembre, 2012 No. 6 CONTENTS In memóriam Gustavo Gordillo Paniagua Felipe Mota Hernández, Luis Velásquez Jones EDITORIAL 513 Food insecurity and abdominal obesity in adolescents Samuel Flores Huerta REVIEW ARTICLE 516 Current role of—and new evidence for—continuous positive airway pressure in respiratory distress syndrome Lorenzo Osorno-Covarrubias RESEARCH ARTICLES 524 534 541 553 Obesity, eating behavior, and food insecurity among adolescents in Mexico City Luis Ortiz-Hernández, Magdalena Rodríguez-Magallanes, Hugo Melgar-Quiñónez Niches of opportunity for improving health care of children covered by “Medical Insurance for a New Generation” Luis Jasso-Gutiérrez, Luis Durán-Arenas, Samuel Flores-Huerta, Gabriel Cortés-Gallo, Onofre Muñoz-Hernández Global neurodevelopmental screening tests for children <5 years of age in the United States and Latin America: a systematic review and comparative analysis Beatriz Romo-Pardo, Silvia Liendo-Vallejos, Guillermo Vargas-López, Antonio Rizzoli-Córdoba, Guillermo Buenrostro-Márquez Risk factors and consequences of cyberbullying in teenagers: association with bullying Gerardo García-Maldonado, Gerardo Jesús Martínez-Salazar, Atenógenes Saldívar-González, Rafael Sánchez-Nuncio, Gerardo Manuel Martínez-Perales, María del Carmen Barrientos-Gómez CLINICAL CASES 564 570 Acrodermatitis enteropathica Marco A. Toxtle-Román, Ana Elena Hernández-Arroyo Erratic migration of Ascaris lumbricoides to the scrotum Rubén Martín Álvarez-Solís, Marcela Vargas-Vallejo, Griselda Orozco-Barrientos, Armando Quero-Hernández, Gabriel GarcíaHernández, David Bulnes-Mendizábal CLINICOPATHOLOGICAL CASE 575 Acute respiratory failure secondary to Bordetella pertussis infection in a 4-month-old infant Sarbelio Moreno Espinosa, Bárbara Inés Morales Mérida, Carlos Alberto Serrano Bello, Orlando Domínguez Pacheco, Olga Camaño Andrade, Rubí Rojas Padilla, Ernesto Calderón Jaimes PEDIATRIC THEME 589 Renal tubular acidosis Luis Velázquez Jones VITAL STATISTICS 595 Mortality due to exposure to smoke, fire and flames in children under 15 years of age during the period 19982010 Sonia B. Fernández-Cantón, Ana Ma. Hernández-Martínez, Ricardo Viguri Uribe Boletín Médico del Hospital Infantil de México Indexado en/Indexed in Scopus, Elsevier Embase/Excerpta Medica Current Awareness in Biological Sciences (CABS) Index Medicus Latinoamericano (IMLA) Literatura Latinoamericana en Ciencias de la Salud (LILACS) Scientific Electronic Library Online (SciELO) Biblioteca Virtual en Salud (BVS)Periódica-Índice de Revistas Latinoamericanas en Ciencias, UNAM Latindex EBSCO/MedicLatina Artemisa Versión completa (español e inglés): www.himfg.edu.mx www.nietoeditores.com.mx La revista Boletín Médico del Hospital Infantil de México es una publicación del Hospital Infantil de México Federico Gómez. Revista bimestral. Editor responsable Gonzalo Gutiérrez. Reserva de Título de la Dirección General del derecho de Autor (SEP): 04-1985-000000000361-102. Certificado de Licitud de Título 11924 y Certificado de Licitud de Contenido de la Comisión Calificadora de Publicaciones y Revistas Periódicas (SeGob) 8328. Publicación realizada por Edición y Farmacia SA de CV. José Martí 55, colonia Escandón, 11800 Ciudad de México. El contenido de los artículos firmados es responsabilidad de sus autores. Todos los Derechos Reservados. Boletín Médico del Hospital Infantil de México La revista pediátrica con mayor difusión en México Más de 65 años de publicación ininterrumpida. Seis números al año con más de 70 artículos de investigadores nacionales y extranjeros con los temas más actuales en Pediatría. Suscripciones 2012 En México: $500 pesos En el extranjero: $60 USD Departamento de Ediciones Médicas Edificio Mundet, tercer piso Dr. Márquez 162, Col. Doctores 06720 Cuauhtémoc, Ciudad de México Formas de pago Condiciones Efectivo Directo en la caja del Hospital Infantil de México Federico Gómez Trámite en el Departamento de Ediciones Médicas Edificio Mundet, tercer piso Dr. Márquez 162, Col. 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Campos Lara Editora Ejecutiva Ricardo Viguri Uribe Editor Asociado y Administrativo Sharon Morey Editora Asociada Julia Segura Uribe Editora Adjunta COMITÉ EDITORIAL BIOMÉDICO Jesús Kumate Rodríguez1 Pedro Valencia Mayoral2 SALUD PÚBLICA Sonia Fernández Cantón5 Hortensia Reyes Morales4 TEMAS PEDIÁTRICOS Luis Jasso Gutiérrez2 Luis Velásquez Jones2 EDUCACIÓN EN SALUD Y ÉTICA CLÍNICA Jaime Nieto Zermeño2 Juan José Luis Sienra Monge2 CLÍNICO Blanca Estela del Río Navarro2 Fortino Solórzano Santos3 EPIDEMIOLOGÍA CLÍNICA Juan Garduño Espinosa2 Miguel Ángel Villasis3 CASOS CLÍNICOS Salvador Villalpando Carrión2 CASOS CLÍNICO PATOLÓGICOS Stanislaw Sadowinski Pine2 1 Fundación IMSS Hospital Infantil de México Federico Gómez 3 Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social 4 Instituto Nacional de Salud Pública, Secretaría de Salud 5 Dirección de Información Epidemiológica, Dirección General de Epidemiología, Secretaría de Salud 2 Boletín Médico del Hospital Infantil de México CONSEJO EDITORIAL José Luis Arredondo GarcíaInstituto Nacional de PediatríaMéxico D.F., México Manuel Baeza BacabCentro Médico de las AméricasMérida, Yucatán, México Eduardo Bancaleri Holtz Children´s HospitalMiami, Florida, EUA Alessandra Carnevale CantoniInstituto Nacional de Medicina GenómicaMéxico D.F., México Aldo CastañedaUnidad de Cirugía Cardiovascular de Guatemala Guatemala, Guatemala Leticia CastilloChildren´s Medical Center, Dallas, Texas, EUA University of Texas Southwestern Francisco CigarroaUniversity Hospital San Antonio, Texas, EUA Alejandro Cravioto QuintanaOrespes S.A. de C.V.México D.F., México Blanca Estela Del Río Navarro Hospital Infantil de México Federico GómezMéxico D.F., México Alfonso Delgado Rubio Hospital Universitario Madrid SanchinarroMadrid, España Arturo Fajardo GutiérrezCentro Médico Nacional S. XXI, IMSSMéxico D.F., México Samuel Flores Huerta Hospital Infantil de México Federico GómezMéxico D.F., México Carlos Franco ParedesEmory University HospitalAtlanta, Georgia, EUA Sara Huerta Yepez Hospital Infantil de México Federico GómezMéxico D.F., México Fima LifshitzCottage Children´s Hospital Sta. Barbara, California, EUA Gabriel ManjarrezCentro Médico Nacional S. XXI, IMSSMéxico D.F., México Homero Martínez Salgado Hospital Infantil de México Federico GómezMéxico D.F., México Mara Medeiros Hospital Infantil de México Federico GómezMéxico D.F., México Juan Pablo Méndez BlancoInstituto Nacional de Ciencias Médicas y NutriciónMéxico D.F., México Salvador Zubirán Guadalupe Miranda NovalesCentro Médico Nacional S. XXI, IMSSMéxico D.F., México Verónica Morán Barroso Hospital Infantil de México Federico GómezMéxico D.F., México Ángel Nogales Espert Hospital Universitario Reina SofíaCórdoba, España Samuel NurkoChildren’s Hospital BostonBoston, Massachusetts, EUA Miguel O’ryanUniversidad de Chile Santiago de Chile, Chile Alberto PeñaCincinnati Children´s HospitalCincinnati, Ohio, EUA Francisco J. Puga MuñuzuriMayo ClinicRochester, Minnesota, EUA Guillermo Ramón Hospital Infantil de México Federico GómezMéxico D.F., México Vesta Richardson López ColladaCentro Nacional de Salud para la Infancia yMéxico D.F., México la Adolescencia Fabio Salamanca GómezCentro Médico Nacional S. XXI, IMSSMéxico D.F., México Eduardo Salazar LindoDS-CONSULT S.A.C.Lima, Perú Norberto Sotelo CruzEscuela de Medicina, Universidad de Sonora Hermosillo, Sonora, México Alejandro Sweet Cordero Stanford University School of Medicine Stanford, California, EUA Gustavo Varela Fascinetto Hospital Infantil de México Federico GómezMéxico D.F., México Arturo Vargas Origel Facultad de Medicina, Universidad de GuanajuatoLeón, Guanajuato, México Edgar Vásquez GaribayInstituto de Nutrición Humana Guadalajara, Jalisco, México Federico Raúl VelázquezCentro Médico Nacional S. XXI, IMSSMéxico D.F., México Alberto Villaseñor SierraCentro de Investigaciones Biomédicas de Occidente Guadalajara, Jalisco, México In memóriam Dr. Gustavo Gordillo Paniagua (1923-2012) (Died on September 12, 2012) P rofessor Gustavo Gordillo was born in Comitán, Chiapas on May 20, 1923. He completed his professional studies at the Military Medical School (1941-1946), postgraduate studies at the Hospital Infantil de México (HIM) (1948-1950) and the Division of Metabolism of the Children’s Medical Center in Boston, MA (1952-1954). Upon completion of graduate school he was named “Full-time Investigator” of the Department of Hematology and Nephrology at Children’s Hospital of Mexico by Dr. Rafael Soto Allende. In 1961 he founded and was the first director of the Research Department of Nephrology, newly created in the same hospital institution. Professor Gordillo was a pioneer in both national and international professional circles. He continued in that position, carrying out prolific activities both in research and teaching until his retirement in 1990. In 1990 he was commissioned by La Salle University to create and direct the Graduate Division of the Medical School (1990-2000) and remained a member of the Academic Council of the Faculty of Medicine until 2005. The first line of research developed by Professor Gordillo in the Hospital Infantil de México Federico Gómez (HIMFG) was in relation to electrolyte disturbances in the malnourished child with acute diarrhea. This area of research led to the decline of the lethality of this condition, which was mainly due to inadequate correction of these changes and are simply part of the same characteristics of chronic malnutrition. Along this line of research, studies in severely malnourished children allowed the definition of a new problem: severe kaliopenic nephropathy due to severe potassium deficiency. Another line of research was the histopathological study of childhood kidney diseases using percutaneous renal biopsy, a procedure introduced in the Department of Nephrology at the HIMFG in 1967. With this resource it was possible to contribute to the prognosis of glomerulonephritis and to some tubulointerstitial nephropathies by performing renal immunohistopathological studies at disease onset and to establish clinicopathological correlations in children with nephritic syndrome, acute nephritic syndrome and nephropathies due to analgesics, among others. These patients were able to be maintained under surveillance on an outpatient basis for several years. These pioneering studies at the international level led to the invitation of the Nephrology Department of HIMFG to participate in the International Study of Kidney Disease in Children. Professor Gordillo had an impressive and outstanding role in this study. The development of the Department of Nephrology in its first 20 years culminated in the publication of five books: • Pediatric Nephrology • Epidemiology and Prevention of Renal Disease • Acute Dehydration in Children • Diagnostic and Therapeutic Procedures in Kidney Diseases of Children • Electrolytes in Pediatrics: Physiology and Clinical These publications marked a milestone in the knowledge of nephrology during his career and had a great impact on the pediatric community and pediatric nephrology in Mexico and Latin America. These publications were the product of more than 150 investigations conducted and published by Professor Gordillo and colleagues: 17 publi- cations in international journals, 126 in national journals, nine collaborations in international books and 15 national book collaborations. Likewise, during this time, the first kidney transplant in children in Mexico was done. In addition to founding the first pediatric nephrology service worldwide and certainly with this endorsement, Professor Gordillo was able to organize and “chair” the First International Symposium of Pediatric Nephrology in Guadalajara, Jalisco in December 1968, which launched the presence of Mexico into the international arena. The foundation of the International Pediatric Nephrology Association and the Latin American Association of Pediatric Nephrology were derived from these activities, and Professor Gordillo was president of these associations. He was also president and founder of the Mexican Society of Nephrology, the Mexican Institute of Nephrology Research and an honorary member of 40 research partnerships, both national and international. To commemorate his 30 years of professional activities, Professor Gordillo was honored with the publication of a book “Select Topics in Nephrology” written by several of the “academic heavyweights” of the international arena of pediatric nephrology 36 years ago. It was a universal tribute to his work, which is still valid, in which 60 distinguished pediatric nephrologists of various countries of the American continent and Europe participated. Professor Gordillo received other major awards, among which are the following: • Member of the National Academy of Medicine of Mexico • “Federico Gomez” Award from the Physicians Association of HIM • Medical Excellence Award granted by the Ministry of Health of Mexico • “Golden Kidney” medal of the European Society of Pediatric Nephrology • “Ira Greifer” Recognition Award (the highest award of the International Pediatric Nephrology, New York, July 2010) We are convinced that the most important and permanent recognition that Professor Gustavo Gordillo has received (and will receive) is that which is given with admiration and respect from his students and from pediatric nephrologists trained under his tutelage from all areas of the country and from many countries of Latin America and the Caribbean. Many of his students were, in turn, pioneers in their countries of origin in the creation and development of pediatric nephrology services. These professionals keep alive and in force his thought and his tireless struggle in the development of pediatric nephrology for the benefit of thousands of children who in the Americas suffer from illnesses that affect renal structure and function and, above all, his willingness to always be present to teach, educate and guide along the correct pathways by his example. His decisive influence paved the way of life for his students. Our highest tribute to his memory will be to keep the tradition of a high level of medical care alive in the field of kidney disease, and to conduct an ongoing search for answers to many questions already posed and those that continue to be posed in pediatric nephrology. Dr. Felipe Mota Hernández Ex-Jefe, Departamento de Nefrología y Decano Hospital Dr. Luis Velásquez Jones Jefe del Departamento de Nefrología Hospital Infantil de México Federico Gómez Mexico, D.F., Mexico E-mail: Bol Med Hosp Infant Mex 2012;69(6):513-515 Editorial Food insecurity and abdominal obesity in adolescents Samuel Flores Huerta W ith regard to the worldwide overweight and obesity epidemic and given the serious consequences on the health of the population due to the strong relationship with metabolic and cardiovascular diseases, there is interest in understanding the mechanisms conducive to obesity as well as the mechanisms that triggers its consequences. Genetic and environmental factors deserve the most attention. With respect to genetic factors, >400 genes associated with this problem have been described in both adults and children.1 In certain populations, some of these factors partially explain this problem, but not necessarily in other populations. However, the genetic factor has remained stable since the advent of mankind and does not explain the emergence of the problem of overweight and obesity dating back to the last three or four decades. Regarding environmental factors, the focus is on changing lifestyles that are increasing becoming "civilized ways of living." Technological changes and economic interests have left behind thousands of years in which a large investment in energy was required for both obtaining Departamento de Investigación en Salud Comunitaria, Hospital Infantil de México Federico Gómez, México, D.F., México Correspondence: Dr. Samuel Flores Huerta Departamento de Investigación en Salud Comunitaria Hospital Infantil de México Federico Gómez México, D.F., México E-mail: [email protected] Received for publication: 11-5-12 Accepted for publication: 11-5-12 Vol. 69, November-December 2012 food and for the occupational way of life. Specifically, the availability of food followed the seasonal cycles, balancing the periods of abundance and scarcity. Not long ago, more natural and fresh foods were consumed than those currently commercialized. However, in recent decades there has been a reversal in the ratio of its consumption.2 To consume a higher proportion of processed foods equals the consumption of foods that are densely energetic, high in sodium and high in saturated fat. Meanwhile, high-caloric commercial beverages that use fructose as a sweetener have displaced plain water.3 This means that humans consume nutrients that cannot be metabolized appropriately.4 Commercialized foods and drinks have been made available to all populations even in remote areas, competing in price with natural healthy foods. The imbalance between consumption/energy expenditure has been associated with the occurrence of changes in nutritional status and health that start with obesity. Recently, as part of the complexity of the overweight and obesity problem, the paradox has emerged that involves not only the abundance of food as a factor for developing obesity but also its shortage. This issue is addressed by Ortiz Hernandez et al. in this issue of Boletín Médico del Hospital Infantil de México. This article explores the role of food insecurity as a factor in the development of obesity and particularly abdominal obesity in adolescents in Mexico City schools.5 Whatever the limitations of the study—whether related to the set of instruments used to gather information about the presence of food insecurity, not having questioned in homes those persons connected with the processes for food access, failing to investigate food consumption on weekends, using skin folds to establish a criterion of obesity6—the issue is 513 Samuel Flores Huerta relevant for the growing number of persons living in food poverty, a situation not exclusive to rural areas. Food insecurity is an indicator with which the Food and Agriculture Organization (FAO) systematically monitors world hunger, for which it continually updates its instruments. To date, the main interest of the FAO is to monitor chronic hunger (acute or cyclical) to avoid or reduce forms of malnutrition related to lack of or food insufficiency.7,8 The agency assumes that under conditions of food safety, proper food availability should be available to 100% of the members of a family or community. However, in virtually all populations, there are periods when nutritionally appropriate foods may not be available, initiating the first link in the chain of food insecurity. If, due to the lack or insufficiency of food for socioeconomic reasons, one adds the fact of not having access to purchase food, the gap further widens. In order to compensate for food shortages that are not culturally accepted, acceptability and consumption are further limited. Additionally, the availability of foods and access to their consumption are not a guarantee of good nutritional status because food bioavailability is affected by many other factors. Thus, it is advisable to determine the concepts of security/food insecurity and food poverty. Food security is when all people have, at all times, physical and economic access to satisfy their need for food and their preferences with regard to food in order to have an active and healthy life. On the other hand, food insecurity is when there is a limited or uncertain capability of acquiring nutritionally appropriately and adequate foods in a socially acceptable manner.7,8 The National Council for Evaluation of the Policy of Social Development in Mexico (CONEVAL) establishes that food poverty is the inability to obtain a basic food basket, even when use is made of all available family economic resources for its purchase.9 In this publication, CONEVAL shows the co-existence in the same home of problems of malnutrition, overweight and obesity, but not stipulated as proposed by Ortíz-Hernández et al., that food insecurity also plays a role in the development of the problem of overweight and obesity. It has recently been reported that in a North American population of children of Mexican descent who live on the U.S. border with Mexico and are subjected to conditions of very low food security, foods more densely energetic are consumed than by children who do not find themselves in the same condition, being positively associated with a greater prevalence 514 of obesity.10 Food insecurity and its association with the consumption of unhealthy foods that carry a cardiovascular risk have also been mentioned in reviews about this topic.11 When one lives with food insecurity, the first alteration observed is the change in eating habits. When there are food shortages, households with limited economic resources increase their reliance on processed foods, which are less expensive than fresh natural foods but at the same time are more energy dense. Moreover, chronic dissatisfaction or prolonged fasting predisposes to food gorging when it is available, a phenomenon different from what was proposed by Ortiz-Hernandez et al. According to the definition proposed by Hernandez et al., eating without inhibition is associated with eating without being hungry, caused by emotional factors or stress.5 In adults, it was found that skipping breakfast is associated with obesity. 11 Recent studies found that the proportion of school children, in a manner similar to their parents, who do not eat breakfast reached 23.5% (20% in eutrophic children vs. 26% in obese children).12 When the child has access to food, he/ she does so greedily. The metabolic response between a child who ate breakfast and another child who did not is different, although both consume the same amount of energy. Abdominal fat is higher in those who regularly skip breakfast vs. those who have breakfast.13 Eating breakfast, therefore, appears to be a healthy habit for school-age children, whether they do so at home or as part of school programs to address food insecurity. These programs have shown that children, who participate in breakfast, increase their school performance and reduce malnutrition without evidence of increasing obesity. Conversely, breakfast would be a way to reduce this problem.14 Moreover, faced with the problem of obesity (particularly of abdominal obesity), it is relevant that the formation of healthy habits such as eating breakfast daily is promoted by both the home and the schools. On the other hand, we must pay attention to the work of OrtizHernandez et al., whose results suggest the possibility that food insecurity participates in increasing this health problem in children.5,15 REFERENCES 1. Snyder EE, Walts B, Pérusse L, Chagnon YC, Weisnagel SJ, Rankinen T, Bouchard C. The human obesity gene map: the 2003 update. Obesity Res 2004;12:369-439. Bol Med Hosp Infant Mex Food insecurity and abdominal obesity in adolescents 2. 3. 4. 5. 6. 7. 8. 9. Rivera JA, Barquera S, Campirano F, Campos I, Safdie M, Tovar V. Epidemiological and nutritional transition in Mexico: rapid increase of non-communicable chronic diseases and obesity. Public Health Nutr 2002;5(1A):113-122. Barquera S, Campirano F, Bonvecchio A, Hernández-Barrera L, Rivera JA, Popkin BM: Caloric beverage consumption patterns in Mexican children. Nutrition J 2010;9:47. Bremer AA, Mietus-Snyder M, Lustig RH. Toward a unifying hypothesis of metabolic syndrome. Pediatrics 2012;129:557570. Ortiz-Hernández L, Magallanes MR, Melgar-Quiñónez H. Obesidad, conducta alimentaria e inseguridad alimentaria en adolescentes de la ciudad de México. Bol Med Hosp Infant Mex 2012 (include pages on final proofs) WHO Expert Committee (Ed.). Physical status: the use and interpretation of anthropometry. Geneva; 1995. FAO. El estado de la inseguridad alimentaria en el mundo. Rome: FAO; 2012. FAO and UN. Handbook for defining and setting up a food security information and early warning systema (FSIEWS). Rome: FAO; 2000. Consejo Nacional de Evaluación de la Política de Desarrollo Social: Dimensiones de la seguridad alimentaria: evaluación estratégica de nutrición y abasto. México: CONEVAL; 2010. Vol. 69, November-December 2012 10. Sharkey JR, Nalty C, Johnson CM, Dean WR: Children's very low food security is associated with increased dietary intakes in energy, fat, and added sugar among Mexican-origin children (6-11 y) in Texas border colonias. BMC Pediatr 2012, 12:16. 11. Ma Y, Bertone ER, Stanek EJ III, Reed GW, Hebert JR, Cohen NL, et al. Association between eating patterns and obesity in a free-living US adult population. Am J Epidemiol 2003;158:385392. 12. Vilchis-Gil J, Galván-Portillo M, Klünder-Klünder M, Cruz M, Flores-Huerta S. Healthy eating, increased exercise and less sedentary are protective factors against obesity in school age children, despite high caloric intake. 2012 (in press). 13. Alexander KE, Ventura EE, Spruijt-Metz D, Weigensberg MJ, Goran MI, Davis JN: Association of breakfast skipping with visceral fat and insulin indices in overweight Latino Youth. Obesity 2009;17:1528-1533 14. Ramírez-López E, Grijalva-Haro MI, Valencia ME, Ponce JA, Artalejo E: Impacto de un programa de desayunos escolares en la prevalencia de obesidad y factores de riesgo cardiovascular en niños sonorenses. Salud Publica Mex 2005;47:126-133. 15. Ortíz-Hernández L, Acosta-Gutiérrez MN, Núñez-Pérez AE, Peralta-Fonseca N, Ruiz-Gómez Y. En escolares de la ciudad de México la inseguridad alimentaria se asoció positivamente con el sobrepeso. Rev Invest Clín 2007;59:32-41. 515 Bol Med Hosp Infant Mex 2012;69(6):516-523 Review article Current role of—and new evidence for—continuous positive airway pressure in respiratory distress syndrome Lorenzo Osorno Covarrubias ABSTRACT Mechanical ventilation and early or prophylactic surfactant has been the standard of care for many years in neonates with respiratory distress syndrome (RDS). Evidence for this practice is supported in meta-analyses of well-controlled clinical trials. Observational studies shown at the end of the 1980s in perinatal centers that used continuous positive airway pressure (CPAP) as the primary method of ventilatory support had a lower rate of bronchopulmonary dysplasia and used less ventilation for their neonates. Lack of more solid evidence has been one of the reasons for which this method of care of RDS has remained restricted to a few perinatal centers worldwide. Randomized multicenter clinical trials carried out during the last decade in very low birth weight neonates, which compare prophylactic or early nasal CPAP vs. mechanical ventilation with prophylactic or selective surfactant with early or programmed extubation, were reviewed. Recent clinical trials enable us to assert that early nasal CPAP is an alternative to intubation, and surfactant in the delivery room, decreases the need for mechanical ventilation, use of surfactant and steroids for bronchopulmonary dysplasia. A low threshold for surfactant in neonates supported early with CPAP diminishes the need for mechanical ventilation. Key words: continuous positive airway pressure, respiratory distress syndrome, surfactant. INTRODUCTION In this study we review the evidence of the efficacy and safety of nasal continuous positive airway pressure (CPAP) in infants with respiratory distress syndrome (RDS) from initial clinical trials in the 1970s to the present. We reviewed all clinical trials written in English that appear in PubMed, 1995 to date, with the following keywords: continuous positive airway pressure, newborn infant, respiratory distress syndrome. We analyzed the reasons why this method fell into disuse and the subsequent renewed interest in this treatment. In light of the studies published in the last decade, the author attempts to answer several clinical dilemmas: What Pediatra Neonatólogo, Hospital Star Médica Mérida, Mérida, Yucatán, México Correspondence to: Dr. Lorenzo Osorno Covarrubias Pediatra Neonatólogo, Hospital Star Médica Mérida Mérida, Yucatán, México E-mail: [email protected] Received for publication: 5-17-12 Accepted for publication: 10-5-12 516 to choose—initial nasal CPAP support or intubation and surfactant? When to use surfactant in infants assisted early with CPAP? When to start CPAP? Are there advantages to early extubation vs. conventional post surfactant? At the end of the text the information presented regarding the use of nasal CPAP in preterm infants with RDS is summarized. Evidence of the Efficacy and Safety of Nasal CPAP in the 1970s The application of continuous distending pressure in the airway in neonates with RDS in the 1970s from the work of Gregory et al.1 had a huge impact on neonatal morbidity and mortality, with a 50% decrease in overall mortality from RDS [relative risk, RR 0.52 (95% CI 0.32-0.87)] and 76% in infants with birth weight >1500 g [RR 0.24 (95% CI 0.07-0.84)], with a 40% decrease in the need for mechanical ventilation (MV).2 This effect is comparable to that obtained 20 years later with the use of the alveolar surfactant. This simple therapeutic method has spread rapidly worldwide. However, its use declined thereafter for several reasons, among which are the availability of mechanical ventilators specifically designed for infants, the high Bol Med Hosp Infant Mex Current role of—and new evidence for—continuous positive airway pressure in respiratory distress syndrome rate of failure in infants <1500 g, and increased risk of pneumothorax.2 Other factors that had a later influence were 1) availability of exogenous surfactant and 2) staff perceptions that infants on CPAP require more medical and nursing care. Impact of Exogenous Surfactant Therapy on Morbidity and Mortality from RDS Use of exogenous surfactant in the treatment of RDS has been a breakthrough in the treatment of RDS. It was quickly established as the standard of care. Seger and Soll, in a meta-analysis, reported a 32% decrease in neonatal morbidity and mortality, 53% decrease of air leaks, 17% decrease in the risk of bronchopulmonary dysplasia (BPD) or death at 28 days.3 The benefits are greater for early (within 2 h) vs. late (RDS established) application: lower mortality [RR 0.87 (0.77, 0.99)]; less pneumothorax [RR 0.70 (0.59, 0.82)], and less BPD [RR 0.70 (0.55, 0.88)].4 Furthermore, in neonates <32 weeks gestational age, prophylactic use (in the first 15-30 min) has more benefits than rescue treatment (after 2 h), lower mortality [RR 0.61 (0.48, 0.77)], less pneumothorax [RR 0.62 (0.42, 0.89)], and less BPD or death [RR 0.85 (0.76, 0.95)].5 Reasons for CPAP Resurgence of CPAP from the Late 1980s to Date In the late 1980s there was a resurgence of interest in CPAP beginning with the work of Avery et al.6 who compared the rate of BPD in eight perinatal centers in the U.S. The center with the lowest rate of BPD was at Columbia University Hospital in New York that used nasal CPAP (NCPAP) as the primary method of care in preterm infants with RDS and had a lower proportion of infants assisted with MV, with a similar rate of mortality. The beneficial effect of NCPAP in preventing BPD has been supported by other observational studies. In a multivariate logistic regression analysis it was found that onset of MV (vs. NCPAP) explains the difference between the prevalence of BPD in two hospitals (Babies and Children’s Hospital in New York, 4% and Children’s Hospital in Boston 22%).7 The association between MV and BPD and the protective role of CPAP in this disease has been fairly consistent in several observational studies with historical controls, before and after implementing the CPAP as the primary Vol. 69, November-December 2012 method of ventilation.8-15 However, until now, there was a lack of clinical trials to support those observations. Role of MV in the Generation of BPD Various experiments in preterm animals have demonstrated an association of MV with BPD. Brief MV with high tidal volume initiated pulmonary damage in preterm lambs.16 Preterm lambs assisted with CPAP had lower levels of inflammatory markers compared with those that had been subjected to MV.17 Preterm baboons managed early with surfactant and CPAP compared with those who received only surfactant and gentle MV at 28 postnatal days had higher respiratory efficiency (greater a/A ratio of O2, less ventilatory resistance, increased dynamic compliance, normal volume pressure curve), favoring the formation of pulmonary alveoli and preventing changes compatible with BPD.18 Bohrer et al. demonstrated that even a short period of MV induces elevation of proinflammatory cytokine levels up to 10 times the baseline level in late preterm and term neonates.19 The mechanisms of lung damage induced by MV include high pressure in the airway (barotrauma), excessive lung volume (volutrauma), alveolar collapse and alveolar re-expansion (atelectotrauma) and exaggerated inflammation (biotrauma).20 BPD Pathogenesis Is Complex and Multifactorial Pulmonary inflammation plays a central role in the complex multifactorial pathogenesis of BPD. The most susceptible population is that representing low gestational age, low birth weight, male gender, Caucasian, genetic factors, intrauterine growth retardation, among others. Also, pre- and postnatal factors such as chorioamnionitis, oxygen toxicity, MV, patent ductus arteriosus and postnatal infections can induce and perpetuate a harmful and complex inflammatory response in the airways, epithelium and pulmonary endothelium of very immature neonates.21 The protective effect of CPAP may be obscured by the multiplicity of involved factors.22 CPAP or MV and Surfactant: Clash of Cultures For many years, use of CPAP as the primary method of ventilatory support in infants with RDS has been restricted to a few perinatal centers in Scandinavia and to the Columbia University Hospital in New York. The reasons 517 Lorenzo Osorno Covarrubias are basically two: 1) lack of evidence of safety and efficacy of NCPAP in controlled clinical trials in extremely preterm neonates, 2) difficulty in CPAP implementation because of the characteristics of the system as well as to the acceptance of the health care personnel. This has led to an apparent dilemma—whether to intubate a neonate for prophylactic application of a surfactant (but with increased risk of BPD due to being subjected to MV) or temporarily assist the neonate with NCPAP and early administration of rescue surfactant, with greater risk of morbidity and mortality on deferring administration of the surfactant.23 In Scandinavian countries, since the 1980s, a combination of strategies has been used: early NCPAP, surfactant, brief MV, NCPAP postextubation NCPAP called INSURE (intubation, surfactant, extubation) or ISX (intubation, surfactant, extubation) that seems to have overcome the dilemma.13,24,25 In the past decade, results of multicenter controlled clinical trials have been published that allow us to answer several questions regarding the efficacy and safety of CPAP. These studies have added to the publications on perinatal experiences of several centers in the implementation of CPAP. Recent Evidence on Efficacy and Safety of CPAP in Mild to Moderate RDS in Preterm Infants Weighing <1500 g This new evidence from several multicenter clinical trials answered several questions about the role of CPAP in the management of RDS. Initial CPAP support or intubation and surfactant? The SUPPORT study group showed that early CPAP (in the delivery room) + rescue surfactant (FiO2 >50%) is an alternative to intubation and surfactant in the delivery room in neonates of 24-27 weeks.26 There was no difference in oxygen requirement or death at 36 weeks 47.8%. vs. 51.0% [RR 0.95, 95% CI (0.85-1.05)]. Infants in the CPAP group required fewer days of MV 24.8 vs 27.1 (p = 0.03), less steroids for BPD 7.2% vs. 13.1% (p = 0.001) and less use of surfactant 67.1% vs. 98.9% (p <0.001). The results are similar to those obtained in the study group COIN (Cpap Or INtubation) with the same initial management scheme, although the following criteria (surfactant application, mechanical ventilation, and extubation) were not controlled and were left to the judgment of 518 the participating institutions.27 There were no differences observed between BPD or death at 36 weeks adjusted age: CPAP 33.9% vs. intubation 38% [RR 0.80 (0.58-1.12)]. There was a lower risk of death or oxygen requirement at 28 days in the CPAP group [RR 0.63 (0.16 to 0.88)], less use of surfactant CPAP 38% vs. 77% (p <0.001), and higher incidence of pneumothorax in the CPAP group 9% vs. 3% (p = 0.001). It should be noted that in this protocol a CPAP pressure of 8 cm H2O or greater was used. Prophylactic application of surfactant vs. the selective method has advantages in reducing morbidity and mortality as previously discussed.5 The recent review (March 2012) of the meta-analysis, in light of new published clinical trials, shows that infants in whom NCPAP was used early there was no advantage in the use of prophylactic surfactant in mortality [RR 1.24 (0.97, 1.58)], in BPD or death [RR 1.12 (0.96, 1.31)]. In fact, the data show a trend of less morbidity and mortality in favor of selective use of surfactant in neonates assisted early with NCPAP.28 When should surfactant be used in infants assisted early with CPAP? Verder et al. demonstrated that using a low threshold for early surfactant therapy (a/A PaO2 ratio 0.35-0.22) vs. (a/A PaO2 ratio 0.21-0.15) with immediate extubation (10 min) reduces the need of MV (63-21% p <0.05) in neonates of 25-29 weeks.25 The previous findings were confirmed in a stratified meta-analysis, where a low threshold (FiO2 <45%) for treatment with surfactant and extubation to NCPAP resulted in fewer air leak syndromes (RR 0.52, 95% CI 0.28-0.96) and BPD (RR 0.51, 95% CI 0.26-0.99).29 The CURPAP study group showed that prophylactic surfactant (INSURE prophylactic) was not superior to INSURE early surfactant (FiO2> 40%) in infants of 25-28 weeks gestational age with early assisted NCPAP.30 There was no significant difference in mortality or morbidity or in the need for MV [31.4 vs. 33.0%, RR 0.95 (95% CI 0.64-1.41)]. With this strategy, 50% of infants needed only NCPAP, 48% required intubation and surfactant and about a third of the infants required MV during the first 5 days of life. The recently published study developed by the Vermont Oxford Neonatal Network supports the findings identified in the previous paragraphs.31 It compared three strategies of assistance to infants 26-29 weeks gestational age and Bol Med Hosp Infant Mex Current role of—and new evidence for—continuous positive airway pressure in respiratory distress syndrome showed that early NCPAP with early rescue surfactant or prophylactic surfactant with rapid extubation to NCPAP has similar results to those treated with prophylactic surfactant followed by MV. Early CPAP may obviate the need for MV and/or surfactant. When to initiate CPAP? Some meta-analyses of clinical trials developed in the 1970s demonstrate the advantage of early initiation of CPAP (FiO2 requirements <60%): lower mortality [RR 0.68 (0.34-1.38)] and lower need for MV [RR 0.55 (0.32-0.96)].32 Currently, the word “early” CPAP means at birth or upon presentation of any signs of respiratory distress. The European consensus guidelines for management of RDS recommend initiating CPAP from birth in all infants at risk for RDS, such as those <30 weeks who do not require MV until their status is evaluated.33 International consensus on neonatal resuscitation in its 2010 update of the Neonatal Resuscitation Program included CPAP as an option for initial management in infants who had spontaneous respirations with heart rate >100/min with respiratory difficulty.34 The evidence that supported this recommendation is based on the results of the following studies: SUPPORT,26 COIN,27 CURPAP,30 and that of Dunn et al.31—commented upon previously—that showed that infants managed early with CPAP have the same mortality rate as infants managed with prophylactic surfactant and MV, with the benefits of reducing the use of surfactant, time on MV, and use of steroids for BPD. Levesque et al. observed that the sooner the application of NCPAP (from birth) the more likely the success.15 The median NCPAP startup time, when successful, was 4.3 min (range 3-19 min) vs. 29 min (range 13-33 min) those in which NCPAP failed (p = 0.007) in an infant cohort of 26-32 weeks gestational age. Use of prophylactic NCPAP (regardless of respiratory condition) in more mature infants than shown in previous studies (28-31 weeks) does not decrease the need for MV or surfactant or the incidence of air leaks. The percentages were as follows: the need for surfactant 22.6% vs. 21.7% (p >0.05), the need for MV 2.12 vs. 12.2% (p >0.05), pulmonary air leaks 2.6 vs. 2.6% (p >0.05). More than 80% of subjects received antenatal steroids.35 Vol. 69, November-December 2012 Are there advantages for early extubation vs conventional post surfactant? Dani et al. demonstrated that immediate extubation (<5 min) vs. the conventional method has advantages in neonates <30 weeks gestational age, less hours of NCPAP therapy (3.2 vs. 6.2 days, p = 0.009), shorter duration of MV (2.0 vs. 5.6, p <0.001), and less need for a second dose of surfactant (0 vs. 50%, p = 0.06).36 Immediate reinstitution of NCPAP after surfactant administration is safe and effective. Bohlin et al. found improved oxygenation as measured by a/A oxygen ratio in infants extubated immediately vs. those maintained on MV. This difference is evident within minutes and lasts for >48 h. 37 The most optimal clinical and blood gases results of NCPAP vs. MV appear to be related to a lower amount of alveolar protein, inactivation of alveolar surfactant, inflammation indicators, gas exchange and pulmonary mechanics observed with NCPAP.17,19,38 What pressure to use with NCPAP? There is consensus among Scandinavian39 and American40 authors about using minimum pressure of 5 cm. There is still no consensus on whether to raise the pressure to 6, 7 or 8 cm H2O or to remain at only 5 cm H2O and increase the FiO2 only if necessary. No clinical trials have compared these strategies. The use of 5 cm H2O or more of NCPAP postextubation is supported not only by the opinion of experts, but in the meta-analysis by Davis and Henderson-Smart41 where morbidity decreases postextubation [RR 0.40 (95% CI 0.37-0.66)]. There was no difference when using <5 cm H2O [RR 1.00 (95% CI 0.60-1.73)]. Progressive decrease in pressure or only of FiO2 while there is improvement in respiratory distress? Evidence in favor of maintaining pressure at 5 cm H2O and only decreasing the FiO2 is strong and is based on a previously discussed meta-analysis.41 Experts suggest decreasing FiO2 up to 21% and removing NCAP if there is no respiratory distress and apnea and blood gases are aceptable.15 In extremely low-birth-weight infants who required MV at birth for >7 days, it is recommended to use NCPAP for longer periods, up to 32 weeks postconceptional age. 519 Lorenzo Osorno Covarrubias Does the use of early CPAP improve pulmonary function tests in the mid term vs. MV? A subgroup of infants included in the COIN study was studied at 8 weeks post-term. CPAP group had lower respiratory rates (41 vs. 48/min; p = 0.007), lower minute ventilation (223 vs. 265 ml/min/kg; p = 0.009), better pulmonary distention (0.99 vs. 0.82 ml/cm H2O/kg; p = 0.008) and better lung elasticity (p = 0.004).42 Does the surfactant used influence on the rate of success of the INSURE strategy? The INSURE strategy implies prompt extubation to continue with assistance with NCPAP, after the application of a surfactant. The definition of prompt varies according to different authors and may be from 5 min to 1 h. The poractant has several advantages on the beractant, a more rapid effect manifested with less requirements of FiO2, increase in the a/A O2 ratio, and less time of MV. These effects begin in a few minutes and persist for >48 h.43-45 The preceding would facilitate a more rapid extubation. The 200 mg/kg dose of a poractant decreases the need for reintubation and additional doses of surfactant.45 However, clinical implications of these differences have not yet been fully elucidated. Currently, there is only one clinical trial comparing the percentage of infants extubated at 48 h of the poractant vs. beractant in neonates of 24-27 weeks managed with MV.46 The extubation criteria was somewhat conservative for it to be really INSURE (FiO2 <25%, PMVA <5 cm H2O). The percentage of infants extubated at 48 h was higher with poractant (52 vs. 22%, p = 0.027) and at 72 h (60 vs. 27%, p = 0.029). What impact do antenatal steroids have in the effectiveness of CPAP? Antenatal steroids are an indispensable part in the management of infants at risk of preterm birth. The effects are clearly beneficial with decreased mortality [RR 0.69 (0.58 to 0.81)], RDS [RR 0.66 (0.59 to 0.73)], severity of RDS (moderate and severe) [RR 0.55 (0.43 to 0.71)], need for MV [0.51 (0.26, 0.99)], duration of MV (days) [weighted mean difference (WMD) -3.47 (-5.08 to -1.86)], and days of supplemental oxygen [WMD -2.86 (-5.51 to -0.21)].47 The American Academy of Pediatrics (AAP) and American College of Obstetricians and Gynecologists (ACOG) recommend the administration of a course of corticoste- 520 roids in all women at 24-34 weeks of pregnancy who are at risk of preterm delivery in the following 7 days.48 What is the probability of success with CPAP at a lower gestational age and weight? Is there a weight or gestational age limit to provide the option of CPAP? The probability of success in extremely preterm neonates increases as gestational age and birth weight increase. Ammari et al. observed that CPAP was successful in 76% of neonates with weighing <1250 g and in 50% weighing <750 g.49 Of the group of 26-28 weeks, 95% received initial support with CPAP in the delivery room and in 78% of these neonates CPAP was successful as sole ventilatory support. Of the neonates with birth weight <700 g, 73% received initial CPAP support, with a success rate of 33%. In the group weighing 800-899 g, 91% began CPAP and it was successful in 84%. The initial severity of respiratory distress (alveolar gradient/arterial O2) is an adverse factor in the success of CPAP. However, the authors noted that several indicators of severity were poor predictors of CPAP failure. Does the experience of the health care personnel on the use of CPAP have an influence on success rate? Aly et al. observed from the time of CPAP implementation in their hospital as the primary method of respiratory assistance that the greater the rate of CPAP utilization in an extremely premature neonate cohort, the greater the success rate.50 In the three time periods studied, the use of nasal CPAP increased from 17.6-61.8 and 66.7%, respectively (p <0.001). Failure of CPAP on infants initiated early with nasal CPAP and who were intubated decreased from 38.5-13.8 and 7.4%, respectively. The use of surfactant decreased from 48% to 13.3 and 33.3%, the incidence of BPD decreased from 46.2% to 25.9 and 11.1%. The authors concluded that there is a learning curve for the staff. What implementation strategies increase acceptance of CPAP by health care personnel as the primary method of care in preterm infants? The use of nasal CPAP has been confined to a few centers of perinatal care, largely because of staff resistance to adopt the method. Over the last decade there have been several successful experiences published in implementing NCPAP that used similar strategies to improve the quality of care. We can summarized these as follows: a) review Bol Med Hosp Infant Mex Current role of—and new evidence for—continuous positive airway pressure in respiratory distress syndrome of the evidence for the use of early NCPAP, b) review of “best care” practices in hospitals with the lowest neonatal mortality and BPD rates, c) clear guidelines for indications of CPAP, MV, surfactant, extubation, d) full and adequate equipment to provide NCPAP (blender, humidifier with heater, system of interface fixation, nasal prongs, pressure generator), e) training for all medical and paramedical staff on the use of CPAP, f) assessing staff adherence to the new standards with a focus on technical aspects and focus on changing attitudes of care providers, g) discussion of clinical cases of infants managed using CPAP, and h) evaluation of the results so as to improve over time. Among the best care practices adopted in these studies are the antenatal administration of steroids in pregnancies at risk for preterm delivery, saturation goal of 88-92%, alarm limits of saturation 85-96%, selective intubation ≤29 weeks, to not intubate if there is good respiratory automatism, heart rate, and positive response after ventilation with bag and mask, reevaluation in the nursery for intubation, introduction of CPAP in the delivery room (ventilation with resuscitation with T piece, ventilation with positive pressure at end expiration, application of CPAP with mask, CPAP bubble for transfer), prolonged use of CPAP (avoid oxygen without pressure), avoid endotracheal intubation routinely in the delivery room without a careful assessment of respiratory effort of the infant or response to facial CPAP before intubation and avoid unnecessary intubations while receiving NCPAP without proper assessment of the patient and CPAP circuit.14,15 Nasal CPAP, MV and surfactant are integral to the current management of RDS. Antenatal steroids play a central role in the prevention of RDS in reducing its severity and increasing the success rate of CPAP as the primary method of ventilatory support. In preterm infants with respiratory automatism and cardiac frequency (CF) >100/min, early installation of CPAP (in the delivery room or when breathing difficulties begin) with selective application of surfactant (with low threshold) is an alternative to intubation and prophylactic application of surfactant because there is no difference in morbidity and mortality. The current trend is to use MV only when necessary and for the shortest time possible to prevent complications. Reviewed research confirms that early CPAP reduces the need for mechanical ventilation and surfactant. Early extubation (INSURE) after application of surfactant has Vol. 69, November-December 2012 advantages (higher ventilation efficiency and reduced exposure to oxygen). At least 5 cm H2O of CPAP should be used to prevent extubation failure. For additional information on the level of evidence and grade of recommendation of the current role of CPAP in the management of RDS, a review of the Management Guidelines of RDS in preterm neonates from the European33 consensus and that published by Mexican authors is recommended.51 REFERENCES 1. Gregory GA, Kitterman JA, Phibbs RH, Tooley WH, Hamilton WK. Treatment of the idiopathic respiratory-distress syndrome with continuous positive airway pressure. N Engl J Med 1971;284:1333-1340. 2. Ho JJ, Subramaniam P, Henderson-Smart DJ, Davis PG. Presión de distensión continua de las vías respiratorias para el síndrome de dificultad respiratoria en recién nacidos prematuros (Revisión Cochrane traducida). Available at: http://www.update-software.com/BCP/BCPGetDocument. asp?DocumentID=CD002271 3. Seger N, Soll R. Animal derived surfactant extract for treatment of respiratory distress syndrome. Cochrane Database Syst Rev 2009;2:CD007836. doi: 10.1002/14651858.CD007836.pub2 4. Soll R. 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Comparison of three treatment regimens of natural surfactant preparations in neonatal respiratory distress syndrome. Eur J Pediatr 2003;162:476-480. Speer CP, Gefeller O, Groneck P, Laufkötter E, Roll C, Hanssler L, et al. Randomised clinical trial of two treatment regimens of natural surfactant preparations in neonatal respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed 1995;72:F8-F13. Ramanathan R, Rasmussen MR, Gerstmann D, Finer N, Sekar K; North American Study Group. A randomized, multicenter masked comparison trial of poractant alfa (Curosurf) versus beractant (Survanta) in the treatment of respiratory distress syndrome in preterm infants. Am J Perinatol 2004;21:109-119. Fujii AM, Patel SM, Allen R, Doros G, Guo CY, Testa S. Poractant alfa and beractant treatment of very premature infants with respiratory distress syndrome. J Perinatol 2010;30:665-670. Vol. 69, November-December 2012 47. Roberts D, Dalziel S. Corticosteroides prenatales para la aceleración de la maduración del pulmón fetal en mujeres con riesgo de parto prematuro (revisión). Available at: http:// www.update-software.com. 48. Committee on Obstetric Practice. ACOG committee opinion. Antenatal corticosteroid therapy for fetal maturation. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2002;78:95-97. 49. Ammari A, Suri M, Milisavljevic V, Sahni R, Bateman D, Sanocka U, et al. Variables associated with the early failure of nasal CPAP in very low birth weight infants. J Pediatr 2005;147:341-347. 50. Aly H, Milner JD, Patel K, El-Mohandes AA. Does the experience with the use of nasal continuous positive airway pressure improve over time in extremely low birth weight infants? Pediatrics 2004;114:697-702. 51. Ballesteros del Olmo JC, Udaeta Mora E, Villegas Silva R, Cardiel Marmolejo L, Fernández Carrocera LA, Flores Nava G, et al. Guía de práctica clínica. Tratamiento del síndrome de dificultad respiratoria neonatal. Rev Mex Pediatr 2011;78(suppl 1):S3-S25. 523 Bol Med Hosp Infant Mex 2012;69(6):524-533 Research article Obesity, eating behavior, and food insecurity among adolescents in Mexico City Luis Ortiz-Hernández,1 Magdalena Rodríguez-Magallanes,2 Hugo Melgar-Quiñónez3 ABSTRACT Background. Food insecurity is presented when there is a limited availability of nutritionally adequate food. Food disinhibition refers to excessive eating in the absence of hunger. We analyzed the relationships among food insecurity, food disinhibition, food consumption and obesity in Mexico City adolescents. Methods. A cross-sectional survey was carried out with a convenience sample (n = 543) of adolescents in Mexico City. Food insecurity was the independent variable and was assessed through the U.S. Household Food-Security/Hunger Survey Module. Food consumption, food disinhibition (assessed through an ad hoc inventory), and nutritional status (overweight using body mass index, obesity through triceps and subscapular skinfolds, and abdominal obesity using waist circumference) were the dependent variables. Logistic regression models were estimated to assess the existence of associations. Results. Adolescents who experienced food insecurity had a higher probability of reporting an indicator of food disinhibition (hunger in the presence of stimuli), higher intake of animal-origin food and higher rate of abdominal obesity. According to the logistic regression models it was observed that the higher probability of abdominal obesity among adolescents with food insecurity without hunger was partially due to another indicator of dietary disinhibition (eating rapidly). Conclusions. In this sample of adolescents, food insecurity was related to higher probability of abdominal obesity. More studies are necessary to explore this problem in depth and to confirm the possible mediating role of dietary disinhibition. Key words: food insecurity, hunger, obesity, overweight, food consumption, disinhibition. INTRODUCTION Obesity is a public health problem in Mexico with a rapidly increasing prevalence. From the National Health Survey of 2000 it was estimated that among adolescents aged 10-17 years, according to the criteria of the U.S. Centers for Disease Control and Prevention (CDC), the prevalence of overweight was 24.7% nationally and 28.5% in the metropolitan area of Mexico City.1 By 2006, according 1 2 3 Departamento de Atención a la Salud, Licenciatura en Nutrición Humana, Universidad Autónoma Metropolitana Xochimilco, México, D.F., México Departamento de Nutrición Humana, Ohio State University, Columbus, Ohio Correspondence: Dr. Luis Ortiz-Hernández Departamento de Atención a la Salud Universidad Autónoma Metropolitana Xochimilco México, D.F., México E-mail: [email protected] Received for publication: 4-24-12 Accepted for publication: 9-20-12 524 to the National Health and Nutrition Survey2 it was found that in males aged 12–19 years the prevalence of being overweight and obese (evaluated using the tables from The International Obesity Task Force) was 31.2%, whereas for females it was 32.6%. Between 1999 and 2006 there was an increase in both overweight (21.6% –23.3%) and obesity (6.9%–9.2%) in females of that age. Food insecurity occurs when an individual experiences limited or uncertain availability of nutritionally adequate and safe foods or limited ability to access food in socially acceptable ways.3 Since the 1990s, studies have been carried out that have postulated that food insecurity can increase the risk of obesity.4 Most studies that have scrutinized the relationship between food insecurity and obesity have been conducted in countries with a high socioeconomic status.5,6 It has mainly been in the U.S. where such links have been explored in adult women7-13 and in children.14-20 However, there are few studies that have been carried out in school-age children21-23 or adults24,25 of low or medium socioeconomic status. Studies have not been identified that have been carried out in adolescents in Bol Med Hosp Infant Mex Obesity, eating behavior, and food insecurity among adolescents in Mexico City these countries. In these countries, this relationship with food may be more relevant because of the rapid increase in the prevalence of obesity. In these societies a greater proportion of the population lives in poverty. Three mechanisms have been proposed to explain the relationship between food insecurity and increased risk of obesity, which are as follows. First, in households that experienced this phenomenon, consumption of purchased foods are related to low-cost energy-dense foods with a greater capacity to generate satiety.15,22 Second, subjects who experience food insecurity have cycles of loss (at times when they do not have access to food) and weight gain (when there is access), which causes changes in their body composition and metabolism, making it more efficient for accumulation of body fat.4,12 Third, subjects who frequently suffer food insecurity experience a cognitive restriction, which causes them to focus their attention on food. This is expressed in binge eating when food is available.4,12,13 However, there is little empirical evidence to support the latter two explanations.26 The term “food disinhibition” is used to refer to overeating in the absence of hunger and when certain stimuli are present such as emotional stress or situations of social interaction.27,28 Only one study has been identified that explored the relationship between food insecurity and changes in eating behavior.29 Considering the above, the main objective of our study was to analyze the relationship between food insecurity, food disinhibition, food intake and obesity in adolescents in Mexico City. SUBJECTS AND METHODS An analytical, cross-sectional study was done. Sample size was estimated with the EPIDAT program.30 Using a previous study as a basis21 along with the results of the ENSANUT,2 the sample size was estimated according to two scenarios: (1) the prevalence of being overweight— defined as +1 standard deviation of the body mass index (BMI) for age, of at least 35% less in the group studied, with a prevalence ratio of 1.70 and accuracy of 25%, and (2) the prevalence of obesity—defined as >90 percentile of skinfold or waist circumference, <13% in the group studied, with a prevalence ratio of 1.70 and an accuracy of 40%. Sample size, obtained with a 95% level of confidence and proportion of those not studied of 1.5, were 515 and Vol. 69, November-December 2012 545, respectively. Inclusion criteria were subjects 11–16 years of age, without endocrinological disease, and without any extremity with a cast. Written informed consent obtained from students and their guardian was required for study participation. The ethical aspects of the study were approved by the Research Committee of the Division of Biological Sciences and Health, Metropolitan Autonomous University–Xochimilco campus. In order to obtain a heterogeneous sample in terms of socioeconomic status, we chose five secondary public schools located in different areas of Mexico City. Three were located in delegations or municipalities with a low socioeconomic status (Xochimilco, Iztapalapa and Ecatepec), whereas two other schools were located in a delegation with higher socioeconomic conditions (Miguel Hidalgo). All students were invited to participate (taking into consideration that in the five schools there were 1205 students), but informed consent and data were obtained from only 534 adolescents, implying a response rate of 44.3%. Fieldwork was conducted during October and November 2006 in the following schools: Secondary School No. 56 Juan Rodríguez Puebla (n = 124), Secondary School No. 291 Javier Barros Sierra (n = 185), Secondary School Constitution 1857 (n = 43), Secondary School No. 30 Don Benito Juarez (n = 107) and Secondary School Xochimilco No. 107 (n = 84). Areas of study interest were included in a questionnaire. The socioeconomic status was evaluated using the number of assets in the child’s home. Questions included if the household has six assets (refrigerator, washer, water heater, telephone line, automobile or pick-up truck, and computer). According to the General Census of Population and Housing 2010, those are the assets available in few households. The number of assets was totaled and the children were classified accordingly in three levels of socioeconomic status: high (6 assets), medium (5 or 4) and low (≤3). To determine the existence of food insecurity the six-question version of the U.S. Household Survey Food-Security/Hunger Module was used.3 Questions and answers adapted for Mexico were used.31 Initially it was planned to apply the 18-question version of the scale. However, upon application of the pilot questionnaire it was observed that for adolescents the questions were repetitive and, therefore, it was decided to use the short version. It has been shown that the six-question scale is reasonably 525 Luis Ortiz-Hernández, Magdalena Rodríguez-Magallanes, Hugo Melgar-Quiñónez sensitive and specific when compared to the 18-question scale.3 In order to score the questions of scale 3 (Table 1), the procedures suggested by Bickel were followed.3 The answers to questions 1 and 2 were dichotomized to give them values of zero (options “never” and “do not know”) or one (option “sometimes” and “very often”). For questions 3, 4 and 5, response options were “no” (zero) and “yes” (one). Question 4 refers to the frequency of the occurrence of the situation described in the previous item. Responses were also dichotomized into “almost every month of the year” and “a few months, but not all” (one) and “only one or two months” or omitted responses (zero). To determine the internal validity of the food insecurity scale, the procedure described by Melgar-Quiñonez et al. was followed, recommending the use of the scaling analysis based on the Rasch model.32 Attributed to this model is the underlying premise that the phenomenon of interest is one-dimensional and that it varies according to the degree of severity with which it is present. In the case of the food insecurity scale, the questions in the scale were designed to explore the different intensity levels of insecurity; therefore, it was expected that as the questions inquire about the most severe situations, they will be answered by fewer subjects. This analysis yields two summary statistics: (1) a severity score for each question, which is an expression of the probability that a question is answered affirmatively, and (2) a statistical model fit (infit-internal adjustment), which provides information on the relationship between the item and the underlying construct. Low values of the statistics indicate that the relationship is stronger. The infit statistical values of 0.80–1.20 are considered acceptable. Table 1 presents the results of the analysis of the validity of the scale of food insecurity. The infit values (0.85–1.13) are within the satisfactory range. However, one noticed problem was that question 4 had the highest severity score in addition to having had the lowest percentage of affirmative responses (3.1%) when conceptually it should have a lower severity to questions 5 and 6. Because of this, and because it was a question related to the frequency of occurrence of the condition established in the previous question and not of a condition by itself, it was decided to eliminate it. With this, the fit of the model was maintained (infit statistics of 0.81–1.11). Only questions that referred to underlying conditions of the construct were included. Questions that reflected a situation of more intense insecurity have higher severity values than those with milder underlying conditions of food insecurity. Answers to the questions in the scale of insecurity (excluding question 4) were added to the results of the scaling analysis. The authors of the scale of insecurity suggested that food insecurity be identified with two or more positive responses.3 It was decided to lower the cutoff point to a positive response because of the question that was eliminated. This procedure has been proposed by authors who have implemented this type of scale in other Latin American countries.33, 34 Thus, the groups that were formed are food security (zero positive responses), insecurity without hunger or with moderate hunger (one or two positive responses) and insecurity with severe hunger (three to five positive responses). Considering that obese subjects tend to eat faster than those who are thin,35 adolescents were asked about the Table 1. Analysis of the internal validity of the scale of food insecurity Questions %* Including question 4 Severity Infit Excluding question 4 Severity Infit 1. Foods that your family bought met the needs and there was no money to buy additional food? 25.6 -2.12 1.07 -1.83 1.06 2. You did not eat a varied diet because your family had no more money? 3. Food portions were small or you did not eat because there was no more money? 19.7 11.0 -1.43 0.40 1.13 0.85 -1.14 0.70 1.11 0.90 4. How frequent did this situation occur? 5. You ate less at home because there was no more money to buy food? 3.1 9.2 1.50 0.72 1.01 0.85 1.03 0.81 6. You were hungry but you did not eat because there was not enough food in your house? 8.1 0.93 1.10 1.25 0.81 Infit, internal adjustment. *Positive responses, n = 543. Omitted responses or “I do not know” were considered as missing. 526 Bol Med Hosp Infant Mex Obesity, eating behavior, and food insecurity among adolescents in Mexico City time they took for eating. This variable was used as an indicator of food disinhibition. Also, on a scale of 13 items, the presence of food disinhibition was evaluated (Table 2). The items consisted of phrases that described situations in which one eats without being hungry or in the presence of external stimuli. After all phrases were read, the adolescents had to respond with what happened to them in the mentioned situations for which they had three options: no, sometimes, and yes. The responses were dichotomized for the analysis (“sometimes” and “yes” = 1 and “no” = 0). Table 2 shows the results of the exploratory factor analysis with varimax rotation that was carried out with the items on the scale of food disinhibition. From this analysis, five food disinhibition scales were formed corresponding to the five factors identified in the factorial analysis. To consider that an item was part of a factor, the criteria used was that it had a weight of at least 0.40. In the first subscale seven items were included (explaining 18% of the variance) and this was called “hunger in the presence of stimulus.” From this, two groups were formed, with (4–7 positive items) and without disinhibition (0 or 3 positive items). In subscale 4 (called “emotional eating”) and 5 (eating without being hungry), 2 items were included in each (explaining ~8% of the variance). It was defined that there was disinhibition when the adolescents responded positively to the two phrases. The factors 2 (“eats fast”) and 3 (“eats foods they like”) were each comprised of a question. To evaluate food consumption, a questionnaire of the frequency of consumption was designed, which inquired about the number of days of the last week in which the adolescents had eaten 25 foods. The questionnaire was developed to identify differences in the diversity of the adolescent’s diet. For this reason, serving size was not included in the questionnaire. Also, a week was defined as a period of reference to reduce the memory effect. Considering the manner in which it has been suggested that dietary diversity be measured,36 data were dichotomized as follows: if each food had been eaten (1) or not (0) during the prior week. Foods were classified into five groups: fruits (apple, mandarin, papaya, melon, orange, banana and guava), vegetables (spinach, swiss chard or purslane; cucumber or lettuce; corn; pumpkin and cactus), high energy-dense foods (bakery sweet bread or packaged pastries, chips, tamales, quesadillas or tacos, candy, lollipops or chocolates, and sodas), animal products or foods high Table 2. Factorial analysis of the scale regarding food disinhibition Eigen value % variance Hunger with stimulus 1. If you are at a party, are you hungrier than usual or do you crave more food? 3. When you have money, do you buy foods that you like? 6. You are hungry almost every day? 8. You are very hungry between meals? 9. Do you consider that you eat a lot of food? 12. If you are happy, are you hungrier than usual or do you crave more food? 13. If you are with your friends, are you hungrier than usual or do you crave more food? Eating rapidly 5. Do you think you eat quickly? Eating foods that you like 4. If someone invites you to eat foods that you like, do you eat a lot of these foods? Emotional eating 10. If you see tasty food advertised on TV, do you crave them and want to eat? 11. If you are sad, are you hungrier than usual or do you crave more food? Eating without being hungry 2. You're eating and you feel full and yet you still eat? 7. Sometimes when you finish eating, you feel very full? F1 F2 F3 F4 F5 2.35 18.19 1.25 9.63 1.22 9.36 1.11 8.56 1.03 7.93 0.55 0.42 0.56 0.62 0.45 0.52 0.56 -0.20 -0.26 0.28 0.00 0.33 0.04 -0.13 0.15 0.34 -0.13 0.08 -0.13 -0.06 -0.04 -0.38 0.38 0.13 -0.08 -0.30 -0.13 -0.11 -0.13 -0.19 -0.07 -0.01 -0.20 -0.30 0.19 0.10 0.59 0.57 -0.12 0.03 0.25 -0.49 -0.50 -0.20 0.05 0.33 0.28 -0.39 0.23 0.40 -0.36 0.52 0.48 -0.01 0.19 0.37 0.13 0.33 -0.18 -0.28 0.32 0.33 -0.33 0.44 0.76 Questions recoded: no = 0; yes = 1 and sometimes = 1. Numbers of the items corresponded to the order of the questions in the questionnaire. Vol. 69, November-December 2012 527 Luis Ortiz-Hernández, Magdalena Rodríguez-Magallanes, Hugo Melgar-Quiñónez in protein [beans, chicken wings (or chicken breast, thigh or leg), ham or sausage, and milk] and cereals (breads, tortilla and noodle soup). For each group the number of foods consumed for each food group was added. Following standardized measurement techniques,37,38 four observers performed the following measurements on the adolescents: weight, height, waist circumference, and triceps or subscapular folds. Before beginning the fieldwork, observers were trained according to the procedures described by Habicht.39 Using tables of the WHO,40 the Z score for the BMI was estimated for age and two groups were formed: with (Z score ≥1.0) and without (≤0.99) overweight. From tables published by a group of WHO experts,41 adolescents were diagnosed with obesity when they were placed in a ≥90 percentile of triceps and subscapular skinfolds. Abdominal obesity was assessed by waist circumference using the reference tables published by Fernandez et al.37 Two categories were formed with (≥90 percentile) and without abdominal obesity (<90 percentile). Statistical analysis was done with the program SPSS v.10. First, a descriptive analysis of each variable was obtained (simple and relative frequency). Food disinhibition was then compared, food consumption and nutritional status by gender, socioeconomic status (Table 3) and food insecurity (Table 4). Also analyzed were differences in food consumption and nutritional status according to food disinhibition (Table 5). For comparing averages, Student t-test was used for independent samples (comparisons according to gender and food disinhibition) or analysis of variance (to compare according to the socioeconomic level and food insecurity). χ2 test was used for comparison of ratios. Using logistic regression analysis (Table 6), effect of possible confounders was adjusted (gender and socioeconomic status) in regard to the relationship between food insecurity and nutritional status. To assess the impact of food disinhibition in the association of food insecurity with nutritional status, we estimated models that incorporated indicators for food insecurity.42 RESULTS Table 3 shows the characteristics of the study population. The percentage of females was higher than for males. The majority of adolescents were 13 years of age and 50% were classified as middle class. Nearly 4/10 teens experienced 528 food insecurity. The frequency of food disinhibition ranged between 16% and 56%, according to the indicator used. The frequency of overweight was 30%, whereas the frequency of obesity did not exceed 15%. Students in the lower socioeconomic status experienced food insecurity more often and ate faster but had lower rates of obesity. Regarding gender, it was more common in males to eat foods they liked, but emotional eating was less frequent, unlike for females. Also, it was more likely for males to present obesity. Compared with adolescents with food security, those with food insecurity ate in less time (p = 0.025) and the frequency of hunger due to stimuli was higher (<0.000) (Table 4). In males, the same difference was observed for hunger due to stimuli (p = 0.003). Hunger due to stimuli (p = 0.020) and consumption of animal foods (p = 0.013) were more common in female students who had food insecurity than for those with food security. Adolescents who were hungry due to stimuli more frequently consumed energy-dense foods, foods from animal products and cereals, but they had lower rates of obesity and abdominal obesity (Table 5). Children who ate fast had a lower consumption of fruits and foods from animal products, but higher prevalence of overweight, obesity and abdominal obesity. Those who ate foods they more frequently liked energy-dense foods, foods from animal products and cereals. Those who experienced emotional eating more frequently consumed high-energy dense foods and cereals, but had a lower rate of obesity. The consumption of high energy-dense foods was higher in those who reported eating without being hungry. After adjusting for gender and socioeconomic status, food insecurity was not associated with overweight and obesity (Table 5). With regard to adolescents presenting food security, those with food insecurity without hunger had a higher risk of abdominal obesity (OR = 1.76, p = 0.056). The difference became clear when adjusting for gender and socioeconomic status (OR = 1.80, p = 0.049). The relationship was attenuated by incorporating into the food disinhibition model the indicator of eating rapidly (OR = 1.72, p = 0.073). DISCUSSION In the Mexico City adolescents we studied, it was observed that in relation to those who had food insecurity, Bol Med Hosp Infant Mex Obesity, eating behavior, and food insecurity among adolescents in Mexico City Table 3. Descriptive characteristics of the adolescents Total Socioeconomic status Middle High % % n % Low % 225 318 41 59 45 55 40 60 41 59 0.572 172 190 181 32 35 33 32 43 25 30 32 38 34 33 33 0.090 135 267 141 25 49 26 p Male % Gender Female % 29 36 35 34 34 32 0.502 27 47 26 23 51 26 0.572 p Gender Male Female Age (years) 11–12 13 14–16 Socioeconomic level Low Middle High Insecurity food Security Insecurity without hunger Insecurity with hunger Food disinhibition Hungry in the presence of stimulus Eating rapdly Eating food that you like Emotional eating Eating without hunger 300 203 40 55 37 7 48 38 14 54 40 6 65 31 4 0.001 54 37 9 56 38 6 0.334 196 304 283 89 123 26 56 52 16 23 36 62 53 18 21 36 55 52 15 23 56 53 52 17 23 0.983 0.294 0.948 0.803 0.828 39 56 60 9 20 34 56 47 21 25 0.218 0.995 0.004 0.000 0.147 Time to eat (h) M 0.7 D.E. 0.4 M 0.6 M 0.7 M 0.7 0.053 M 0.7 M 0.7 0.267 Consumtion of foods (#of foods) Fruits Vegetables High energy-dense Animal origin Cereals All 4.3 2.4 3.7 3.7 2.5 16.6 1.9 1.5 1.1 1.1 0.7 4.2 4.3 2.3 3.7 3.7 2.5 16.4 4.3 2.4 3.7 3.8 2.5 16.7 4.1 2.4 3.8 3.7 2.4 16.4 0.588 0.844 0.559 0.280 0.851 0.700 4.5 2.3 3.8 3.8 2.5 17.0 4.1 2.4 3.7 3.7 2.4 16.3 0.006 0.448 0.105 0.137 0.136 0.041 Nutritional status Overweight Obesity (subscapular skinfold) Obesity (tríceps skinfold) Abdominal obesity (WC) N 214 75 35 56 % 39 14 6 10 % 41 15 6 10 % 36 13 5 10 % 45 15 11 11 0.146 0.774 0.053 0.878 37 23 11 11 41 8 4 10 0.405 0.000 0.001 0.820 M, medium; SD, standard deviation; WC, waist circumference. those who experienced insecurity without hunger had the greater risk of presenting abdominal obesity; the difference was independent of the socioeconomic status and gender. This finding is similar to that observed in other Mexican pediatric populations21 and in countries with Vol. 69, November-December 2012 high socioeconomic status.19,22 For example, according to data from the U.S. Continuing Survey of Food Intakes by Individuals (CSFII), it was found that in subjects 0–17 years of age, the prevalence of overweight was higher in subjects from low-income households and there was 529 Luis Ortiz-Hernández, Magdalena Rodríguez-Magallanes, Hugo Melgar-Quiñónez Table 4. Association of food insecurity, food consumption, and indicators of obesity Total population IWOH ISWH % % S % Food dishinibition Hunger due to stimulus Eating rapidly Eating foods that you like Emotional eating Eating without hunger Time for eating (h) Food consumption (# of foods) Fruits Vegetables High energy-dense Animal origin Cereals All Nutricitional status Overweight Obesity (subscapular skinfold) Obesity (tricep skinfold) Abdominal obesity (WC) p S % Males ISWOH ISWH % % p S % Female ISWOH ISWH % % p 29 52 52 14 21 42 60 52 17 25 60 65 53 28 28 0.000 0.134 0.998 0.098 0.435 31 53 61 6 17 45 59 60 12 24 67 62 48 19 14 0.003 0.582 0.500 0.088 0.400 28 52 46 20 23 40 60 47 21 25 53 68 58 37 42 0.020 0.206 0.603 0.235 0.183 M 0.7 M 0.6 M 0.6 0.015 M 0.7 M 0.6 M 0.6 0.025 M 0.7 M 0.6 M 0.7 0.302 4.2 2.4 3.7 3.7 2.5 16.4 % 38 13 6 8 4.2 2.3 3.8 3.8 2.5 16.6 % 42 14 6 13 4.8 2.6 3.7 4.0 2.5 17.6 % 35 20 10 13 4.5 2.3 3.8 3.8 2.5 16.8 % 36 21 11 8 4.5 2.4 3.8 3.9 2.6 17.2 % 36 23 8 12 5.0 2.3 4.0 3.7 2.4 17.3 % 48 33 19 19 4.1 2.5 3.6 3.6 2.4 16.2 % 40 8 3 8 3.9 2.3 3.7 3.8 2.4 16.1 % 46 8 4 14 4.6 3.0 3.4 4.3 2.7 18.0 % 21 5 0 5 0.146 0.469 0.653 0.074 0.853 0.228 0.611 0.484 0.625 0.142 0.550 0.831 0.737 0.639 0.490 0.753 0.592 0.440 0.371 0.294 0.297 0.082 0.475 0.013 0.232 0.136 0.110 0.922 0.648 0.156 S, security; ISWOH, insecurity without hunger; ISWH, insecurity with hunger; M, medium; WC, waist circumference. Table 5. Association of food inhibition with food consumption and indicators of obesity Hunger with estimulus Total Food consumption (# of foods) No M Fruits 4.2 Vegetables 2.3 High energy-dense 3.5 Animal origin 3.7 Cereals 2.4 All 16.1 Nutritional status % Overweight 42 Obesity (subscapular 16 skinfold) Obesity (triceps skinfold) Abdominal obesity (WC) 8 13 Yes M 4.3 2.5 4.0 3.9 2.6 17.3 % 35 9 3 6 Eating rapidly p No M 0.829 4.4 0.196 2.5 0.000 3.7 0.004 3.9 0.000 2.5 0.001 17.0 % 0.132 34 0.019 10 0.016 0.016 3 6 Yes M 4.1 2.3 3.8 3.7 2.4 16.6 % 44 17 9 14 p Eating foods that you like No M 0.049 4.2 0.190 2.3 0.345 3.6 0.010 3.6 0.124 2.4 0.045 16.1 % 0.012 39 0.024 14 0.009 0.002 7 12 Yes M 4.3 2.4 3.8 3.9 2.6 17.0 % 40 14 6 9 Emotional eating p No M 0.260 4.3 0.354 2.4 0.008 3.7 0.011 3.7 0.003 2.4 0.007 16.5 % 0.664 40 0.820 15 0.664 0.368 7 11 Yes M 4.0 2.5 3.8 3.8 2.6 16.8 % 38 7 5 9 Eating without being hungry p No M 0.116 4.3 0.531 2.4 0.074 3.6 0.569 3.7 0.037 2.5 0.630 16.5 % 0.799 40 0.034 13 0.412 0.653 7 11 Yes M p 4.1 2.3 4.0 3.8 2.5 16.7 % 37 15 0.412 0.493 0.006 0.717 0.505 0.742 6 7 0.698 0.214 0.604 0.550 M, medium. 530 Bol Med Hosp Infant Mex Obesity, eating behavior, and food insecurity among adolescents in Mexico City food insufficiency (i.e., not having an adequate amount of food) (46.7%) compared with children from high-income households with sufficient food (31.5%).15 However, other studies have found inconsistent patterns in the relationship between obesity and food insecurity. Some authors have reported that this association is negative in certain age groups, but in other groups the relationship is positive.14,43 In school-age children in Bogota, Colombia, there were no differences in the prevalence of overweight according to the level of food insecurity.23 In studies on food insecurity and obesity, gender differences have been observed such that initially a positive relationship was reported in females, whereas in males no such association was observed or even that the relationship was negative.14,43 Nevertheless, in more recent studies the association was also observed among adult males, although less than in females.44 In the case of Mexico City adolescents, upon stratifying the relationship of food insecurity with the nutritional status according to gender, no differences were seen between males and females (Table 4). Similarly, when adjusting for gender in the regression models, the relationship between insecurity and overweight was maintained (Table 6). A possible explanation for why food insecurity can increase the risk of obesity is that in homes where it is experienced, there is a greater availability of inexpensive, high energy-dense foods that are perceived as more satisfying such as refined cereals, fatty meats, etc.15,22 At the same time, in homes with food insecurity there is less access to healthier but more costly foods such as fruits, vegetables, whole cereals and lean meats. In our study, partial support was found for this explanation as the students with food insecurity had a higher consumption of animal products. It should be pointed out that in Mexico, in recent years, meats have become less expensive.45 Persons in the lower socioeconomic strata have increased their expenditure for these products, especially for inexpensive, high-fat meats.46 However, in some studies in the pediatric population, it has been reported that food insecurity is accompanied by a reduction of calorie consumption20,47,48 and foods such as meats.19,20,23 Table 6. Logistic regression models using obesity as the dependent variable and food insecurity and food disinhibition as independent variables Overweight1 Overweight2 Obesity (subscapular skinfold)1 Obesity (subscapular skinfold)2 Obesity (triceps skinfold)1 Obesity (triceps skinfold)2 Abdominal obesity (WC) 1 Abdominal obesity (WC) 2 Abdominal obesity (WC) 3 Abdominal obesity (WC) 4 Abdominal obesity (WC) 5 Abdominal obesity (WC) 6 Abdominal obesity (WC) 7 Abdominal obesity (WC) 8 OR ISWOH 95% CI p OR ISWH 95% CI p 1.16 1.20 1.07 1.08 0.93 1.00 1.76 1.80 2.03 1.72 1.81 1.81 1.84 1.77 0.81-1.67 0.83-1.73 0.64-1.80 0.63-1.85 0.44-1.96 0.46-2.13 0.99-3.16 1.00-3.24 1.12-3.68 0.95-3.10 1.00-3.24 1.00-3.25 1.02-3.31 0.98-3.20 0.426 0.336 0.797 0.779 0.847 0.989 0.056 0.049 0.020 0.073 0.048 0.047 0.042 0.057 0.87 0.90 1.67 1.50 1.64 1.74 1.64 1.69 2.29 1.55 1.69 1.74 1.76 1.67 0.43-1.73 0.44-1.81 0.72-3.89 0.62-3.62 0.53-5.10 0.54-5.66 0.59-4.58 0.60-4.81 0.78-6.74 0.54-4.44 0.59-4.82 0.61-4.98 0.62-5.02 0.59-1.72 0.683 0.759 0.232 0.365 0.390 0.355 0.343 0.324 0.133 0.416 0.326 0.299 0.292 0.334 Reference group: food security; WC, waist circumference. 1 Crude estimates. 2 Adjusted estimates according to gender and socioeconomic status. 3 Adjusted estimates according to gender, socioeconomic status and indicator of food disinhibition in the presence of stimulus. 4 Adjusted estimates according to gender, socioeconomic status and indicator of food disinhibition of eating rapidly. 5 Adjusted estimates according to gender, socioeconomic status and indicator of food disinhibition of eating foods that are liked. 6 Adjusted estimates according to gender, socioeconomic status and indicator of food disinhibition of emotional eating. 7 Adjusted estimates according to gender, socioeconomic status and indicator of food inhibition of eating without being hungry. 8 Adjusted estimates according to gender, socioeconomic status and indicator of food disinhibition of time for eating. Vol. 69, November-December 2012 531 Luis Ortiz-Hernández, Magdalena Rodríguez-Magallanes, Hugo Melgar-Quiñónez It has also been postulated that persons who experience chronic food insecurity develop food disinhibition, i.e., they learn to ignore the signs of hunger and satiety and guide their consumption in terms of food availability.12,26 One study documented that females with food insecurity have more problems with feeding habits such as having food binges.29 In Mexican adolescents, food insecurity was related to a greater probability of having two forms of food disinhibition: hunger in the presence of stimulus and eating in a shorter time. Although two other indicators were more frequent between students with food insecurity (eating fast and eating due to emotional state), the differences were not statistically significant (p >0.050). Moreover, the greatest risk of abdominal obesity among adolescents with insecurity without hunger was due in part to the disinhibition indicator of eating fast. A limitation of the study is its cross-sectional design in addition to the fact that the rate of response was relatively low, which prevents making categorical conclusions. Until recently, the majority of studies that explored the relationship between insecurity and obesity were cross-sectional in design. Recently analyses with longitudinal data have been carried out confirming the relationship between food insecurity and weight gain.44 Another limitation of our study is that we did not use a representative sample of adolescents, which reduces the possibility of extrapolating the results. The concept of food disinhibition is just beginning to be used, and for the Mexican population there is no valid tool available for its measurement. Therefore, a scale that allowed a primary approximation of the phenomenon had to be developed. Measurement of food disinhibition can be performed through controlled procedures under laboratory conditions; however, its use is not possible in epidemiological research. A further limitation of the study is that there is selection bias: having conducted the study in educational institutions implied that those adolescents not enrolled in any educational institution would not be included, and they have the greatest risk of having food insecurity. In conclusion, in our sample of adolescents, food insecurity was related with a greater risk of accumulation of excessive abdominal fat, which can be attributed in part to eating behaviors related to the loss of capacity of regulating food consumption. However, more studies are needed to strengthen and confirm the mediating role 532 of food disinhibition. 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Diet and food insufficiency among Hispanic youths: acculturation and socioeconomic factors in the third National Health and Nutrition Examination Survey. Am J Clin Nutr 2003;78:1120-1127. Rose D, Oliveira V. Nutrient intakes of individuals from foodinsufficient households in the United States. Am J Public Health 1997;87:1956-1961. 533 Bol Med Hosp Infant Mex 2012;69(6):534-540 Research article Niches of opportunity for improving health care of children covered by “Medical Insurance for a New Generation” Luis Jasso-Gutiérrez,1 Luis Duran-Arenas,2 Samuel Flores-Huerta,3 Gabriel Cortes-Gallo,4 Onofre Muñoz-Hernández5 ABSTRACT Background.The focus of the program “Medical Insurance for a New Generation” (SMNG) is to offer social and economic protection and to eliminate costs for those families who lack medical insurance coverage. The objective of this study was to identify niches of opportunity in the program to improve health care for children funded by the SMNG. Methods. With information provided by the SMNG, nine “performance indicators” were calculated and described in the rules of operation of the SMNG and a “documentary review” was carried out in accordance with the National Council of Social Development Policy Evaluation. Results. Three of the “performance indicators” were poor. The “documentary review” revealed some faults in the quality of completing the database of 6,440 children and 128 accredited hospitals. Of these, only 51.9% were admitted during the first 24 h of birth. Overall mortality was 4.43%, with differences according to federal entities from 0.0% to 18.8%. There was a predominance of intrauterine hypoxia, necrotizing enterocolitis and diaphragmatic hernia. From 108 diseases, 41 represented 90.9% of all children admitted. Conclusions. It is necessary to improve the efficiency of three of the “performance indicators.” In regard to the “documentary review” it will be required to expand information and the quality of the clinical information contained in the database, promote more timely admission of children to the hospital, and analyze mortality differences among the federal entities. Key words: performance indicators, documentary review, Medical Insurance for a New Generation, newborn morbidity, newborn mortality. INTRODUCTION With the goal of continuing to decrease neonatal and infant mortality in Mexico, as of December 2006 the Federal government implemented the program Medical Insurance for a New Generation (SMNG) with well-defined rules of operation.1,2 The focus of this program is to provide costfree social and financial protection to those families who 1 2 3 4 5 Departamento de Evaluación y Análisis de Medicamentos, Centro de Estudios Económicos y Sociales en Salud, Departamento de Investigación en Salud Comunitaria, Dirección del Seguro Médico para una Nueva Generación, Dirección de Investigación, Hospital Infantil de México Federico Gómez, México, D.F., México Correspondence: Dr. Luis Jasso-Gutiérrez Departamento de Evaluación y Análisis de Medicamentos Hospital Infantil de México Federico Gómez México, D.F., México E-mail: [email protected] Received for publication: 4-25-12 Accepted for publication: 10-15-12 534 lack a system of medical insurance and whose newborn children require generally high-cost medical care. SMNG included for the year 2008 a total of 108 diseases which, in general, present themselves during the neonatal age and require hospital care. The listing is recorded in the rules of operation of the SMNG itself.1 With the goal of reducing the variability in clinical practice and to improve as much as possible the quality of medical care,3 a Medical Care Protocol was developed for each disease. These protocols describe the basic elements of the etiology, diagnosis and treatment, which also serve as a guideline for the National Commission of Social Health Protection as an orientation for estimating the costs of care of each illness. SMNG also finances other specific neonatal diseases (e.g., prematurity, respiratory insufficiency and certain types of congenital malformations that will be discussed in this study) at a much higher cost and that tax medical care in the newborn intensive care unit (NICU) through the program called Fund for Protection Against Catastrophic Costs (FPCGC).4,5 Social programs of the federal government, such as the SMNG, need to periodically evaluated after beginBol Med Hosp Infant Mex Niches of opportunity for improving health care of children covered by “Medical Insurance for a New Generation” ning their operations, by external organizations that are not part of their management directors, for which reason the Hospital Infantil de México (HIMFG) was chosen to perform this evaluation. The evaluation must adhere to the guidelines that are described and set forth in the regulations issued by the National Council for Evaluation of Social Development Policy(CONEVAL)6 in which is indicated to verify the degree of compliance with the “performance indicators” that were previously designed in the Rules of Operation of the SMNG1,2—in which aspects of financial coverage for the population are determined and the “document review”, which consists of analyzing achievements and deficiencies present in the document review that justifies medical care for those neonates covered under the SMNG. Therefore, the goal of this study was to verify the level of compliance with the performance indicators of the program and document review. Based on the results, there were niches of opportunity for improvement identified to upgrade the processes of care of infants treated in 2008. MATERIALS AND METHODS Pursuant to the terms and conditions outlined in the Rules of Operation of the SMNG1 and in accordance with regulations issued by the CONEVAL,6 two components were evaluated. The first corresponding to the nine performance indicators whose numerators and denominators were already preset in the above operating rules and where the ideal result of the calculation of each indicators should be 100% or greater. Calculations and their analysis were carried out with the information that was provided by the General Directorate of the SMNG (GD-SMNG) to the HIMFG. The second component, corresponding to the document review, is supported according to the guidelines, revising and analyzing the corresponding document information which, in this case was included on the basis of data of children hospitalized in 2008. On this basis along with what is indicated in the Protocols for Medical Care for each disease, degree of compliance was verified. The database was provided by the GD-SMNG and included a total of 128 medical centers that were accredited by the Department of Health to provide medical care to children of the 108 diseases authorized by the SMNG. The process of accreditation of the medical centers was carried out by health authorities of each federal entity, supported by the Manual of Accreditation published for this purpose.7 Vol. 69, November-December 2012 The database contained the following information: name of the child’s parents, date of report, state, hospital name, membership number, child’s name, date of birth, gender, age in days, months or years, medical record number, date of confirmation of diagnosis, treatment start date, reason for discharge (improvement, death or transfer to another hospital), principal diagnosis with its corresponding International Classification of Disease (ICD-10) code, type of treatment (medical or surgical), authorized cost of care for each condition and number of the report with which the information that was sent to the appropriate federal entity to the GD-SMNG. With this database provided in Excel (Microsoft, Redmond, WA), diverse runs were done that would allow for different components to be analyzed such as behaviors of federal entities, medical centers, number of patients, diseases, age at birth, age at admission to the hospital, gender, discharge condition, cause of death, among other variables. The protocol was approved by the HIMFG Research and Ethics Committee. When necessary, simple linear correlations were used as statistical method. RESULTS Performance Indicators The indicators identified with performance numbers 1, 2, 5, 7, 8 and 9 were 100% efficient or higher, whereas those related to numbers 3, 4, and 6 showed percentages of 1.8, 5.5 and 64%, respectively, and were classified as poor (Table 1). Document Review The first type of data verified was which medical centers were accredited in 2008. It was identified that the accreditation process began in that year and was done progressively by states. Therefore, in the first 7 months there were medical centers accredited in 14 states, by October there were 14 more and between November and December another three, with the last state being Nayarit. The only federal entity without an accredited medical center in 2008 was Baja California Sur. Accreditation is an indispensable condition for receiving funds for the care of children protected by SMNG.7 The total number of medical centers accredited was 28, the majority of which were concentrated in the Federal District, Guanajuato, Jalisco, Morelos and Veracruz. The states of Sinaloa, 535 Luis Jasso-Gutiérrez, Luis Duran-Arenas, Samuel Flores-Huerta, Gabriel Cortes-Gallo, Onofre Muñoz-Hernández Table 1. Percentage of results of indicators of performance corresponding to SMNG in 2008 Indicator 1. % of children with access to the system of social protection in health under the SMNG 2. % of children affiliated with SMNG vs. the previous year* Method of calculation Data N° of children affiliated with SMNG 1,852,891 Children born from December 1, 2006 without health insurance 1,748,000 No. of children affiliated in 2008 with SMNG 1,033,481 No. of children affiliated in 2007 with SMNG 3. Care of children by SMNG as Cases treated of children by SMNG a percentage of those incorpoChildren affiliated with SMNG rated with the SMNG Cases treated of children affiliated with SMNG paid with FPCGC with 4. % follow-up of cases of follow-up appointment children treated* Cases treated of children incorporated into SMNG paid from the FPCGC Budgetary exercise of SMNG in MDP 5. Percentage of budgetary exercise of SMNG Modified budget of SMNG in MDP 6. Efficiency of budgetary exercise of SMNG* 7. Advance in transfer of capital* 8. Advances in the transfer of reimbursements* Observations 106 The denominator was estimated according to CONAPO projections, assuming that 54% of children were born unprotected by any social security system 126 819,410 18,505* 1,033,507 1.8 Reported by hospital care* 5.5 Most of the interventions in the NICU in medical care are resolved without the need for follow-up 646 11,739 1,697.8 100 1,697.8 Budgetary exercise of SMNG in MDP 1,697.8 Budget of SMNG authorized in MDP 2,641.2 Funds transferred per capita in MDP 67.8 Total funds budgeted per capita MDP 67.8 Funds transferred for reimbursement in MDP 154.5 Total budgetary resources reimbursed in MDP 154.5 Funds transferred for vaccines in 9.Advances in funds transfer for MDP vaccines* Total budgetary resources for vaccines in MDP Value (%) 64 Returned to TESOFE 943.4 MDP for budgetary savings 100 100 1,428.7 1,428.7 100 Financing of pneumococcal and heptavalent vaccines (2008 and 2009) *The first rules of operation of the health program, Seguro Médico para una Nueva Generación, were published 3/31/08. Indicators refer to the 2008 exercise. SMNG, Seguro Médico para una Nueva Generación (Medical Insurance for a New Generation); FPCGC, Fondo de Protección Contra Gastos Catastróficos (Fund for the Protection Against Catastrophic Expenses); NICU, neonatal intensive care unit; MDP, millions of pesos; CONAPO, Consejo Nacional de Población (National Population Council); TESOFE, Tesorería de la Federación (Federal Treasury). Chiapas, Chihuahua, Mexico, Nuevo Leon, and Aguascalientes, despite having numerous accredited medical centers, had a proportionately less demand for medical care for children. It can be noted that the total financing of the 6440 children treated was $201,644,884 (Mexican pesos). This represented an average cost per patient of 536 $31,311.31. The greatest numbers of patients treated and financed by the federal entities were in the states of Guanajuato, Federal District, Jalisco, Tamaulipas, Veracruz and Puebla, and the lowest number of patients was in Yucatán, Campeche and Michoacán (Table 2). No significant linear correlation was found depending on the Bol Med Hosp Infant Mex Niches of opportunity for improving health care of children covered by “Medical Insurance for a New Generation” Table 2. Number of patients, financing, number of deaths and percentage of mortality according to federal entity of children protected by SMNG Federal entity Aguascalientes Baja California Baja California Sur Campeche Chiapas Chihuahua Coahuila Colima México Distrito Federal Durango Guerrero Guanajuato Hidalgo Jalisco México Michoacán Morelos Nayarit Nuevo leon Oaxaca Puebla Quintana Roo Querétaro Sinaloa San Luis Potosi Sonora Tabasco Tampico Tlaxcala Veracruz Yucatán Zacatecas Total Patients Financing Death Mortality (n) ($) (n) (%) 89 135 SD 11 119 81 31 132 614 130 220 1307 152 485 244 7 274 37 159 322 298 63 117 116 248 187 105 365 103 341 6 166 6440 3,408,312 3.946.606 SD 415,800 3,834,312 2,480,978 943,597 4,650,973 21,692,756 2,956,923 7,281,595 42,193,132 4,948,310 16,725,638 8,473,358 271,779 6,679,646 927,351 5,027,565 9,138,640 9,556,795 1,747,750 2,749,535 3,311,827 7,779,485 5,375,986 3,428,151 8,730,118 4,992,032 11,186,079 210,232 3,934,541 201,644,884 2 1 SD 2 5 3 0 13 25 2 17 86 11 23 4 0 4 3 3 7 21 4 0 8 9 5 4 7 6 12 0 6 290 2.25 0.74 SD 18.18 4.20 3.70 0.00 9.85 4.07 1.54 7.73 6.58 7.24 4.74 1.64 0.00 1.46 8.11 1.89 2.17 7.05 6.35 0.00 6.90 3.63 2.67 3.81 1.92 5.83 3.52 0.00 3.61 4.43 ND, no data; SMNG, Seguro Médico para una Nueva Generación (Medical Insurance for a New Generation). number of months in which medical centers were added to the number of patients seen. There were a total of 290 deaths, representing a mortality rate of 4.43%. Linear correlation coefficient showed no statistical significance(r = 0.038) between the number of cases managed by state and percentage of mortality, so that the reasons for the Vol. 69, November-December 2012 variations from 18.8% in Campeche to 0% in the states of Coahuila, Querétaro and Yucatán could not be identified with the information contained in the database. Of the 108 authorized diseases in the Operating Rules, 41 accounted for 90.9% of the children cared for. There are 12 diseases listed that accounted for 57.32% of the total 6440 admissions which, in turn, represented 67.7% of the total budget provided by the SMNG. Moreover, of the total revenue, 51.94% of children were admitted within 24 h of postnatal age, 28.9% between 2 and 28 days and 24.8% after 28 days (Table 3). Several children who were admitted after 24 h of postnatal age had the following diagnoses: child of a hypertensive mother, intrauterine malnutrition, acute renal failure, neonatal intracranial hemorrhage, necrotizing enterocolitis, seizures and congenital diaphragmatic hernia. In contrast, there were diagnoses of children with bilateral hearing loss, congenital lacrimal duct stenosis, polydactyly, syndactyly, hydrocele, and spermatocele and who exceeded their hospital stay for 100, 55, 55 and 45 days, respectively. It should be noted that a statistical linear correlation was not identified between the increase in the length of stay and the amount in pesos disbursed by GD-SMNG. In the analysis of the database there were several omissions found on the health status at discharge, type of treatment (medical or surgical) and identification of the principal disease diagnosis and secondary diagnosis including ICD-10 coding, as well as data capture of errors and inconsistencies. For example, some children, in addition to receiving medical treatment, required a surgical resolution as with cases of pyogenic arthritis or intestinal obstruction, but it was not mentioned in the database if they had undergone surgery or may have been referred to another hospital. In contrast, children who should have undergone medical treatment such as in the case of bronchopulmonary dysplasia or lactose intolerance and who were classified as cases requiring surgical intervention only. It can be appreciated that the five principal causes of death in the population examined were intrauterine hypoxia (14.9%), necrotizing enterocolitis (10.1%), congenital diaphragmatic hernia (6.4%), hypovolemic shock (6.1%) and atraumatic intracranial hemorrhage (5.4%) (Table 4). 537 Luis Jasso-Gutiérrez, Luis Duran-Arenas, Samuel Flores-Huerta, Gabriel Cortes-Gallo, Onofre Muñoz-Hernández Table 3. Selection by number of patients and total cost or both of the top 12 diseases of the total for children cared for in medical units funded by SMNG in the year 2008 Age at admission Discharge condition Treatment Code ICD-10 Description No. of cases Total cost ≤24 h 2-28 days >28 days Imp (n) P20, P21 P05 Intrauterine hypoxia 1206 34,610,707 893 236 77 1155 3.8 1202 4 Delayed fetal development and fetal malnutrition Necrotizing enterocolitis Hemolytic disease of fetus and NB, other excessive hemolysis 548 27,534,649 378 150 20 532 1.4 548 0 302 562 21,895,912 13,863,740 101 257 132 272 69 33 269 556 2.6 0.5 273 554 29 2 256 13,094,416 68 60 128 241 1.3 256 0 150 151 4,616,113 4,118,414 8 57 27 57 115 37 144 137 0.4 1.2 47 149 103 2 69 3,698,534 14 33 22 53 1.4 61 8 52 67 3,323,783 3,297,438 21 12 19 4 12 51 33 66 1.6 0.0 6 8 46 59 88 59 3,295,738 3,277,187 8 6 8 20 72 33 69 55 1.5 0.2 87 9 1 50 3510 6440 136,626,632 201,644,844 1823 1018 671 3315 5.5 3200 304 P77 P55, P58 P00.0 Q79.0 Q69; Q70 R57.1 Q43 Fetus and NB affected by maternal hypertension Other intestinal obstruct-ions Convulsions of NB Cerebral depression Hypoxic ischemic encephalopathy Nontraumatic intracranial hemorrhage of the NB CDH Polydactyly Syndactyly Hypovolemic shock Other intestinal mal-formations Subtotal Total K56.4 P90,X; P91.4; P91.6 P52 Death Medical Surgical (%) (n) (n) NB, newborn; CDH, congenital diaphragmatic hernia; SMNG, Seguro Médico para una Nueva Generación (Medical Insurance for a New Generation); Imp, improved. DISCUSSION Performance Evaluation of Indicators Indicator 1, related to access to SMNG-funded public health services, presented a percentage of 106%, which was considered satisfactory based on the number of members as of December 1, 2006, which was slightly higher than the number of births. With this result there are no recommendations for improvement opportunity for the program. Regarding indicator 2 that refers to the number of SMNG members compared to the previous year, this was 126%, exceeding the proposed target of 100%, which was shown to have been met and exceeded the policy of the Popular Insurance of a progressive expansion of the coverage. 538 Indicator 3, which assesses the number of children served by the SMNG as a percentage of program affiliates, had a poor performance (1.8%) because the GD-SMNG only had available statistics of hospitalized children, but not for children seen as outpatients. This result represents a niche of opportunity that must be addressed and, in the following evaluation, must be corrected, and include outpatients in the database. Regarding indicator 4, which refers to follow-up of children, this showed an efficiency of 5.5% because the GDSMNG database did not have that information for 2008. For this reason, the time to do it did not run in parallel with the time that the Operating Rules were issued in March 2008. In addition, the GD-SMNG considered these children to be discharged, and generally there was no follow-up required. Bol Med Hosp Infant Mex Niches of opportunity for improving health care of children covered by “Medical Insurance for a New Generation” Table 4. Most relevant causes of mortality of 290 patient deaths presented by children protected by SMNG Disease Mortality (%) Intrauterine hypoxia NEC CDH Hypovolemic shock Newborn nontraumatic IC Developmental delay and intrauterine malnutrition Newbornwith maternal hypertension Superficial scalp trauma Convulsions and ischemic hypoxic encephalopathy DIC ARI Pneumothorax, aspiration of meconium, pulmonary hemorrhage Cardiac insufficiency Alterations of Na and K equilibrium of newborn 14.9 10.1 6.4 6.1 5.4 5.4 5.1 4.7 4.7 Bronchopulmonarydyplasia 2.0 Hemolytic disease of the newborn and other hemolysis Pneumothorax, pleural effusion Intestinal obstruction 2.0 4.1 3.7 2.7 2.4 2.0 1.7 1.7 NEC, necrotizing enterocolitis; CDH, congenital diaphragmatic hernia; IC, intracranial hemorrhage; DIC, disseminated intravascular coagulopathy; ARI, acute renal insufficiency. Despite the above, this is an area of opportunity for improvement in that, necessarily, there should be a follow-up program to ensure the complete recovery of the children and minimize the risks posed by the precarious socioeconomic conditions of their families. Follow-up should be incorporated not only for neonates who require hospitalization but also those who, having been born healthy, need to be examined periodically in the outpatient primary care clinic to check the progress of their growth and development, administer vaccines, offer dietary guidelines, and treat intercurrent infections, among others. This will certainly result in a decrease in childhood morbidity and mortality. An issue of great concern in the management of the budget in the public sector is to assure that the programmed budget is equal to that spent, which was not the case in 2008 as demonstrated in indicator 6 (64%). The explanation for this was that the GD-SMNG, because of a requirement from theFederal Treasury, had to return part of the budget. Another area for improvement is ensuring that Vol. 69, November-December 2012 from 2009 its complete cost is guaranteed. With respect to progress indicators, the transfer of capital (indicator 7), the progress in the transfer of funds (indicator 8), the progress in the transfer of funds for vaccines (indicator 9), which reached 100%, these were considered as accomplished targets with efficient results. Document Evaluation We identified deficiencies in completing the database, producing variations in the results. This situation occurred with the number of deaths by state, with the emission of different diagnoses for the same disease or prolonged duration of hospital days based on the child’s condition. For these examples and many others, opportunities for improvement reside in making adjustments to the contents of the existing database in the following order: first and last name of the child, complete address of the insured, date of report, federal entity and name of the hospital where the child was born, name of the accredited hospital and federal entity to which the child was referred, affiliation number, date of birth, gender, age in days, months and year on admission, date of confirmation of diagnosis, date of start of treatment, cause for discharge (improvement, death, transfer to another hospital, or voluntary discharge), principal diagnosis and two secondary diagnoses (when they exist), precise coding of death based on the ICD-10, type of treatment used (medical, surgical, or both), cost authorized for financing of the principal illness, number of the report with which the information was sent to the GD-SMNG, date of release, days of hospital stay and date of confirmation of the diagnosis. The existence of different diagnoses for the same disease within the same medical center and among other centers required that training be carried out for those responsible for management in the SMNG of each state. Once trained, there should be no errors in completing the data bases until they have been corrected by the physicians responsible for the care of each infant. Special emphasis should be placed on making the diagnosis according to the strict adherence to the description of the disease and its respective ICD-10 code. All this must be done in accordance with the existing medical protocols issued by the GD-SMNG.3 It is shown that the ideal time to hospitalize an infant with a condition requiring hospitalization is within the first 24 h of postnatal age. However, this occurred in only 55% of the children evaluated. Therefore, another area of oppor- 539 Luis Jasso-Gutiérrez, Luis Duran-Arenas, Samuel Flores-Huerta, Gabriel Cortes-Gallo, Onofre Muñoz-Hernández tunity recommended is that if the mother is affiliated with Seguro Popular during pregnancy and before or during labor and the child is born with any of the conditions listed, the child will be timely transferred to an accredited hospital in the care of diseases covered by the SMNG in case the center where the child was born does not have the capacity to treat the child. The mortality rate of 4.43% shown when analysis is carried out by federal entity showed a great variability, which did not permit a precise analysis to be carried out of the results based only on the information present in the database. This is relevant because the primordial objective, in addition to social protection and decrease in costs to the family, is the decrease in neonatal mortality. To place these findings in context, it is important to note that in the year 2008 there were 8,795,000 children <5 years of age who died worldwide. Of these, 45% (3,575,000) were neonates whose principal causes of death were prematurity in 12% (1,033,000), asphyxia 9% (814,000), septicemia 6% (521,000) and pneumonia 4% (366,000).8 With the exception of the latter, this is similar to what occurs in Mexico and other countries.9,10 However, the results found in the present evaluation indicate that intrauterine hypoxia was the principal cause of death followed by necrotizing enterocolitis, congenital diaphragmatic hernia and atraumatic intracranial hemorrhage. These results do not coincide in that order with the statistics from Mexico.9 This is noteworthy, which makes it indispensable that the database be reviewed in depth by those responsible for the 128 medical centers evaluated. Having found a low mortality rate (4.43%) and taking into account the diseases identified, it is possible that it may be due to a deficiency in completing the database. This is inferred by the large differences found between the different states ranging from 0% to18.8%. In practice, this does not correspond to reality, even though respiratory failure, prematurity, sepsis and congenital cardiac malformations were not included among the 108 diseases evaluated that are covered by the FPCGC. Taking into consideration that the international goal No. 4 of Millenium of the WHO has as its goal to reduce mortality by two thirds between the years 1990 and 2015 in children <5 years of age and because neonatal mortality represents 50% of deaths, it is indispensable that 540 the SMNG continues to improve and develop different quality strategies at the federal level to achieve reduction in mortality in the years after 2008.8,11 REFERENCES 1. ACUERDO por el que se emiten las Reglas de Operación del Programa Seguro Médico para una Nueva Generación, para el ejercicio fiscal 2008. México; 2008. Available at: http://www. ropsa.net/ropsa/ 2. Secretaría de Salud. Seguro Popular. México. Seguro Médico para una Nueva Generación. Available at: http://www.seguropopular.salud.gob.mx/index.php?option=com_content&view= article&id=280&Itemid=295 3. Secretaría de Salud. Seguro Popular. México. Protocolos de Atención Médica. Available at: http://www.seguro-popular. gob.mx/images/contenidos/SeguroNuevaGeneración/protocolos_smng.pdf 4. Jasso-Gutiérrez L, Duran-Arenas L, Flores-Huerta S, CortésGallo G. Recommendations to improve health care of neonates with respiratory insufficiency beneficiaries of Seguro Popular. Salud Pub Mex 2012;54(suppl 1):S57-S65. 5. Secretaría de Salud. Seguro Popular. México. Intervenciones médicas cubiertas por el Programa Seguro Médico para una Nueva Generación(SMNG). Available at: http://www. seguro-popular.gob.mx/images/contenidos/FPGC/IntervencionesFPGC.pdf 6. CONEVAL. México. Lineamientos Generales para la Evaluación de los Programas Federales de la Administración Pública Federal. Diario Oficial de la Federación. México. Viernes 30 de marzo de 2007. Available at: http//www.coneval.gob.mx/ contenido/eva_mon/361pdf 7. Secretaría de Salud. México. Sí Calidad. Manual para la acreditación y garantía de calidad en establecimientos para la prestación de servicios de salud. Available at: http://www. calidad.salud.gob.mx/calidad/acred.html. 8. Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 2010;375:1969-1987. doi:10.1016/S0140-6736(10)60549-1. 9. Jasso GL. Mortalidad perinatal y neonatal. In: Neonatología Práctica. Mexico: Manual Moderno; 2008. pp.1-5. 10. Subspecialty Group of Neonatology, Pediatric Society, Chinese Medical Association. Epidemiologic survey for hospitalized neonates in China. Zhongguo Dang Dai ErKeZaZhi 2009;11:15-20. 11. Rajaratnam JK, Marcus JR, Flaxman AD, Wang H, LevinRector A, Dwyer L, et al. Neonatal, postneonatal, childhood, and under-5 mortality for 187 countries, 1970–2010: a systematic analysis of progress towards Millennium Development Goal 4. Lancet 2010;375:1998-2008. doi:10.1016/S01406736(10)60703-9. Bol Med Hosp Infant Mex Bol Med Hosp Infant Mex 2012;69(6):541-552 Research article Global neurodevelopmental screening tests for children <5 years of age in the United States and Latin America: a systematic review and comparative analysis Beatriz Romo-Pardo, Silvia Liendo-Vallejos, Guillermo Vargas-López, Antonio Rizzoli-Córdoba, Guillermo Buenrostro-Márquez ABSTRACT Background. The American Academy of Pediatrics recommends the application of neurodevelopmental screening tests for early intervention of neurodevelopmental disorders. In order to refer these tests appropriately, it is important to have well-founded information in regard to these tools. Methods. A systematic literature search targeted on validation studies of neurodevelopmental screening tests in children <5 years of age in the U.S. and Latin America from 1980 to 2012 was conducted. Results. We found 19 validation studies of 13 screening tests. Battelle Developmental Screening Inventory (2nd edition) reported the best sensitivity and specificity (0.93/0.88) and PRUNAPE, with predictive positive and negative values (0.94/0.97) Conclusions. From 1980-2012 we found 13 neurodevelopmental screening tests in the U.S. and Latin America for children <5 years of age. The best criterion and predictive validity was for the Battelle Developmental Inventory Screening and PRUNAPE, respectively. No validation studies were found in Mexico; therefore, we consider it important to have a validated tool in our country. Key words: neurodevelopment, screening tests, validation. INTRODUCTION Early detection of neurodevelopmental problems is critical to the welfare of children and their families because it allows access to timely diagnosis and treatment.1 In developing countries, a large number of children <5 years of age are exposed to multiple risk factors such as poverty, malnutrition, health problems and an environment with poor stimulation, which affects their cognitive, motor and socioemotional development.2 It has been observed that children who receive early long-term intervention had improvement in IQ, better school performance, lower crime Dirección de Investigación, Hospital Infantil de México Federico Gómez, México, D.F., México Correspondence: Dra. Beatriz Romo Pardo Dirección de Investigación Hospital Infantil de México Federico Gómez México, D.F., México E-mail: [email protected] Received for publication: 10-3-12 Accepted for publication: 10-26-12 Vol. 69, November-December 2012 rate and, during adulthood, a greater chance of obtaining employment and higher incomes compared to those who did not receive early intervention.3 To identify alterations in neurodevelopment, the American Academy of Pediatrics (AAP) suggests continuous surveillance and monitoring of development, taking into account risk factors, both biological and environmental, as well as the concerns of parents about their child’s development at each follow-up visit. Another recommendation is the systematic application of screening tests in key moments of development, i.e., at 9, 18 and 30 months of age.1 Several studies have shown that the pediatrician’s clinical judgment is not sufficient to identify neurodevelopmental delays. From this time, the importance of using standardized screening tools to detect these patients was emphasized.4,5 A screening test identifies individuals suspected to be ill in an apparently healthy population, establishes the risk or suspicion of a developmental problem but does not define a diagnosis. It should be easy and quick to implement, economically viable, reliable and valid (sensitivity and specificity >0.70).4 The usefulness of a 541 Beatriz Romo-Pardo, Silvia Liendo-Vallejos, Guillermo Vargas-López, Antonio Rizzoli-Córdoba, Guillermo Buenrostro-Márquez test must be preceded by a concurrent validation process, which seeks to understand the extent to which the test results coincide with diagnostic evaluations commonly used (gold standard).6,7 Having solid evidence on the neurodevelopmental screening tests is to facilitate understanding of their advantages and disadvantages as an assessment tool. In order to have a better knowledge about the effectiveness and accuracy of screening tests in children as well as to provide useful information about these tools based on wellfounded evidence, we conducted a systematic review of the literature on the validation of the screening tests in the U.S. and Latin America designed to detect developmental problems in children <5 years of age. SUBJECTS AND METHODS For inclusion and exclusion criteria, we conducted a systematic search and review of the literature on validation studies of screening tests of global neurodevelopment of children <5 years of age in the U.S. and Latin America, from 1980 until February 14, 2012, in English and Spanish. Editorials and conference papers were excluded from the review articles. Studies were identified by a search of electronic databases and bibliographies of the articles retrieved. This search was conducted in MEDLINE/PubMed, LILACS and Artemisa. The search was limited to studies in English or Spanish that were conducted in humans, in children <5 years of age, in the U.S. and Latin America, and classified according to the category of validation studies. The following sets of terms were combined in the search: 1. For illness: developmental delay 2. For study types: screening 3. For outcome: psychometric properties, sensitivity, specificity 4. For personnel administering screening in primary care: general practitioner. Below are examples of the search strategies of the different combinations of terms in PubMed/MEDLINE: • Strategy 1: 184 articles ("diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "screening"[All Fields] OR "mass screening"[MeSH Terms] OR ("mass"[All Fields] AND "screening"[All Fields]) OR "mass screening"[All 542 Fields] OR "screening"[All Fields] AND ("sensitivity and specificity"[MeSH Terms] OR ("sensitivity"[All Fields] AND "specificity"[All Fields]) OR "sensitivity and specificity"[All Fields] OR "sensitivity"[All Fields]) AND (developmental[All Fields] AND delay[All Fields]) • Strategy 2: 154 items, 143 items + 11 included in strategy 1 ("diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "screening"[All Fields] OR "mass screening"[MeSH Terms] OR ("mass"[All Fields] AND "screening"[All Fields]) OR "mass screening"[All Fields] OR "screening"[All Fields] AND ("sensitivity and specificity"[MeSH Terms] OR ("sensitivity"[All Fields] AND "specificity"[All Fields]) OR "sensitivity and specificity"[All Fields] OR "sensitivity"[All Fields]) AND (developmental[All Fields] AND delay[All Fields]) • Strategy 3: 74 articles; 53 articles + 21 included in strategies 1 and 2 ("diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "screening"[All Fields] OR "mass screening"[MeSH Terms] OR ("mass"[All Fields] AND "screening"[All Fields]) OR "mass screening"[All Fields] OR "screening"[All Fields] AND ("primary health care"[MeSH Terms] OR ("primary"[All Fields] AND "health"[All Fields] AND "care"[All Fields]) OR "primary health care"[All Fields] OR ("primary"[All Fields] AND "care"[All Fields]) OR "primary care"[All Fields]) AND (developmental[All Fields] AND delay[All Fields]) • Strategy 4: 47 articles; 36 articles + 11 included in strategies 1, 2 and 3 ("diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "screening"[All Fields] OR "mass screening"[MeSH Terms] OR ("mass"[All Fields] AND "screening"[All Fields]) OR "mass screening"[All Fields] OR "screening"[All Fields] AND ("psychometrics"[MeSH Terms] OR "psychometrics"[All Fields] OR "psychometric"[All Fields]) AND (developmental[All Fields] AND delay[All Fields]) AND ((English[lang] OR Spanish[lang]) AND ("infant"[MeSH Terms] OR "child, preschool"[MeSH Terms])) • Strategy 5: 12 articles; 9 articles + 3 included in strategy 3 ("diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "screening"[All Fields] OR "mass screening"[MeSH Terms] Bol Med Hosp Infant Mex Global neurodevelopmental screening tests for children <5 years of age in the United States and Latin America: a systematic review and comparative analysis OR ("mass"[All Fields] AND "screening"[All Fields]) OR "mass screening"[All Fields] OR "screening"[All Fields] AND ("general practitioners"[MeSH Terms] OR ("general"[All Fields] AND "practitioners"[All Fields]) OR "general practitioners"[All Fields] OR ("general"[All Fields] AND "physician"[All Fields]) OR "general physician"[All Fields]) AND (developmental) [All Fields] AND delay[All Fields]). Evaluation of the choice of included articles was done openly and independently by two reviewers. Disagreements were resolved by consensus. We developed a data uptake sheet based on data extraction template user group communication and Cochrane reviews. Evidence of global neurodevelopmental screening was based on those articles that assessed multiple domains of development (e.g., motor, cognitive, adaptive, communication, etc.). We excluded those tests that focused on a single area of development or those directed at the diagnosis of a disease or to evaluate academic areas. Information obtained from each test was as follows: 1) test characteristics (name, country of origin, authors, mode of evaluation, domain of development, age range in which it is applied, rating system, criteria of normality and abnormality and evaluation time), 2) diagnostic test used for its validation, and 3) validation of results. RESULTS With regard to the results of the systematic review in the different search strategies we found a total of 454 articles; 19 articles were included that described 13 neurodevelopmental screening tests (Figure 1). These 19 articles selected were diverse studies (validation as well as systematic reviews) of the neurodevelopment screening tests published on the American continent. We used those written in English or Spanish. Of the 13 tests found, those that had the greatest number of publications were Ages and Stages Questionnaires (five articles) and CAT/CLAMS (three articles). The oldest study included was from 1986 of the screening test CAT/ CLAMS. A total of 9217 children <8 years of age were included in the different validation test studies carried out in Argentina, Canada, Chile, Costa Rica, Cuba and the U.S. It is interesting to mention that in the systematic review only one article was found on the psychometric Vol. 69, November-December 2012 characteristics of a screening test in a Mexican population. This was a standardization study of the Denver I test in 288 children from 2–54 weeks of age where the motor scale of the Bayley test was also used. The Denver I scale failed to identify as suspicious 16/17 children identified by the Bayley test. The study was considered to be unsatisfactory and in practice the results were not used as Mexican standards. At present we use the second Denver version, so it was decided to not include this article in the systematic review. According to their method of administration, the selected screening tests can be categorized into two major groups: direct observation or evaluation (done by the physician to the child) and parent questionnaires (which can be applied by any members of the health care team). There are tests that utilize both resources in which questions are asked of the parents and the child is also observed. The items that evaluate each test are distributed in different areas of development. Although there is considerable homogeneity in the grouping of motor or language milestones, in the domains of adaptive and social behavior they are distributed differently in the various tests. The different screening tests found are described, with mention of their authors, country of origin, mode of administration, domains of development for evaluation, time of administration and available languages (Table 1). Rating systems vary among the different tests. The total score is generally obtained from the individual scores of the items. These, in turn, are derived from the parental responses to the survey questions (i.e., Ages & Stages Questionnaires) or the score given by the physician to the child’s performance (Battelle Developmental Inventory). In general, screening tests qualify the child as normal—or as suspicious for—or at risk for developing problems. Table 2 shows the rating method and criteria of normality and abnormality for each test. The efficiency of detection measurements are reported in the validation studies. The concept of validity refers to how well a tool measures what it purports to measure. For concurrent validation of the screening tests, different diagnostic tools have been used such as the Battelle Developmental Inventory, Bayley Scales of Infant Development, preschool and primary Wechsler Scale (Wechsler Preschool and Primary Scale or Intelligence), among others. We examined both the criterion and predictive validity. 543 Beatriz Romo-Pardo, Silvia Liendo-Vallejos, Guillermo Vargas-López, Antonio Rizzoli-Córdoba, Guillermo Buenrostro-Márquez Citations found in the search of PubMED/Medline Citations found in the search of LILACS Citations found in the Artemisa search n=425 n=19 n=0 Citations found in the bibliographic search of citations of PubMED/Medline and LILACS n=10 Total de Artículos n=454 Articles excluded during the title/abstract stage n=435 Specific pathology Specific group Review Specific area of development Prognostic No validation Other type of study Experimental Epidemiological Other type of study Animal model Clinical guidelines Case report 167 50 48 39 33 31 23 14 13 8 6 2 1 Articles revised in extenso included n=19 Figure 1. Flow chart of the results of the systematic review Criterion Validity Criterion validity is a type of concurrent validity that establishes the validity of a measuring instrument by comparing it with some external criterion. The sensitivity shows how well a test correctly identifies children with delays, whereas specificity indicates the degree to which a test detects those without delay. Some tests resulted to be a poor screening tool for identifying children with neurodevelopmental delay because they showed a sensitivity of 0.50, such as the test of Child Development Inventory (CDI) or were unable to differentiate those with normal neurodevelopment compared with those that are abnormal, with a specificity of 0.43 to 0.80, such as the Denver test. In contrast, other studies proved to be useful tools in assessing neurodevelopment after maintaining a high sensitivity and specificity such as the Battelle Developmental Inventory 544 Screening (2nd edition) with a sensitivity of 0.93 and specificity of 0.88. Predictive Validity Predictive validity is a type of concurrent validity referring to the ability of a test to predict or correlate with another of the same construct. We found eight predictive validity studies. The predictive value was poorer for Ages & Stages Questionnaires with positive predictive value 0.34 (PPV) and negative predictive value (NPV) 0.71, whereas the best predictive validity test was PRUNAPE with PPV of 0.94 and NPV of 0.97 (Table 3). Each neurodevelopmental screening test selected for this review has advantages and disadvantages in terms of method and time of application, materials and features of the validation study. We have summarized the strengths and weaknesses of each of the Bol Med Hosp Infant Mex Global neurodevelopmental screening tests for children <5 years of age in the United States and Latin America: a systematic review and comparative analysis Table 1. General description of the screening tests according to the method of administration, age range, time of administration and available languages Test name Country of origin Authors Age range (months) Time Language Ages & Stages Questionnaires Parent questionnaires Communication, fine and 3th ed. gross motor skills, pro(EUA) blem resolution, language, Squires, et al, 19958 personal- social Squires, et al, 20099 4-60 10-15 min English, Spanish, French and Korean Battelle Developmental Inventory (BDI) Screening Test 2nd ed. (EUA) Newborg J, 200512 0-95 10-30 min English and Spanish Method of evaluation Developmental areas evaluated Direct observation of Personal-social, adaptive, the child and parent motor, communication and questionnaires cognition Bayley Scales of Infant and Toddler Development (BSID) Neurodevelopment Screening Test 3rd ed. (EUA) Aylward G, 201013 Direct observation of the child Cognition, language and motor 1-42 15-25 min English Brigance Early Childhood Screen (EUA) Glascoe F, 200214 CAT/CLAMS Clinical Adaptative Test/Clinical Linguistic and Auditory Milestone Scale (EUA) Capute, et al, 198615 Direct observation of the child and parent questionnaires Cognition, language, motor, adaptive and socioemotional 0-35 36-60 10-15 min English and Spanish Direct observation of child Language, problem resolution and motor skills 1-36 10-15 min English and Spanish Child Development Inventory (EUA) Doig, et al, 199916 Direct observation of child Social, language, motor, adaptive, reading and arithmetic skills 15-72 30-50 min English Denver Development Screening Test (EUA) Glascoe, et al, 199217 Direct evaluation of child and parent questionnaires Gross and fine motor skills, language, adaptive, personal-social 0-72 10-20 min English and Spanish Escala de Evaluación del Direct evaluation of Desarrollo Psicomotor (EEDP) child (Chile) Schapira, 200718 Bedregal, 200819 Vericat Ay Orden, 201020 Social, language, coordination and motor skills 0-24 20 min Spanish Escala de Desarrollo Integral del Niño (EDIN) (Costa Rica) Schapira, 200718 Vericat Orden, 201020 Neurodesarrollo Pediátrico (NPED) (Cuba) Guadarrama-Celaya, et al, 201121 Direct evaluation of child Fine and gross motor skills, reflexes, socioemotional and cognition 0-72 NR Spanish Direct evaluation of the child Language/communication, psychomotor and sensory maturation (hearing/ vision) 1-60 15 min Spanish Vol. 69, November-December 2012 545 Beatriz Romo-Pardo, Silvia Liendo-Vallejos, Guillermo Vargas-López, Antonio Rizzoli-Córdoba, Guillermo Buenrostro-Márquez Table 1. General description of the screening tests according to the method of administration, age range, time of administration and available languages Test name Country of origin Authors Method of evaluation Developmental areas evaluated Age range (months) Time Language PEDS Parents Evaluation of Developmental Status (EUA) Glascoe, 1998 Parent questionnaires that ask about concerns Global development/cognitive, expressive language, receptive language, behavior, socioemotional, schooling, self-help, fine and gross motor skills and others (sensory and medical concerns) 0-96 2-5 min English and Spanish PRUNAPE (Argentina) Pascucci, et al, 200222; 200623 Direct evaluation of the child and some questions for the parents Fine and gross motor skills, personal-social and language 0-60 10-15 min Spanish Test de desarrollo Psicomotor TEPSI (Chile) Haeussler, Marchant, 1980 Direct evaluation of the child Coordination, motor skills and language 24-60 15-20 min Spanish tests as well as offering some comments on the validation process (Table 4). DISCUSSION Recommendations on the systematic application of neurodevelopmental screening tests suggested by the AAP have led to an increasing demand for tests with solid evidence, reliability, usefulness, validity, specificity and sensitivity. Awareness of the available evidence on these tools leads to well-founded decision-making by physicians. It is useful to know how an investigation on a research instrument was carried out and if it has the ability to support its use. Although some tests have a large number of investigations, it does not necessarily mean that these are optimal or more stringent for detecting developmental delays. No evidence was found to justify using one application method over another (direct observation, parental questionnaire or mixed) because what matters in a screening test is its scientific basis and methodology of the validation study. For example, in the study of Rydz et al., it was found that the Child Development Inventory has a low sensitivity compared to other studies. Only 5/31 children failed the Battelle Developmental Inventory (comparison) and it would be necessary to analyze a larger sample. 546 Regarding the rating scales, there are quantitative scoring systems (with a scoring system per item) or qualitative scoring systems (with a categorical classification as failed/ passed, present/absent, yes/no, etc.). No tendency was found for increased reliability with respect to a scoring method in different screening tests included in this study because, for example, PRUNAPE and the Battelle have different rating systems. However, they were the two tests found with better sensitivity and specificity. With regard to studies included in this review, it was found that very few meet the optimal conditions to support its reliability, validity and usefulness because some are limited in terms of design. Few studies use a quasi-experimental design or randomized assignment, resulting in being one of the main problems for its reliability. Furthermore, accuracy in the administration of the test is crucial, although there are limitations in both test knowledge and experience of the person who administers it, as well as the time and place where it is administered. This causes a variability in the results as important as having a sensitivity of 0.67–0.90 and specificity of 0.39–0.95, as in the case of Ages & Stages Questionnaires studies where, in some cases, the questionnaire was administered to parents in the waiting room, with a time of 15 min, and others were sent home, allowing time for greater trust in the results. Bol Med Hosp Infant Mex Global neurodevelopmental screening tests for children <5 years of age in the United States and Latin America: a systematic review and comparative analysis Table 2. Qualification method and criteria of normality and abnormality of the screening tests included in the systematic review Screening test Qualification system Criteria of normality and abnormality Ages & Stages Questionnaires (EUA) Questions for parents with option of responses: yes, sometimes, or no Giving a score of 0 for no, 5 for sometimes and 10 for yes Evaluating the concerns of parents with yes or no answers Divided into three categories (higher than cut-off point, close to cut-off point and below the cut-off point) Battelle Developmental Inventory Screening 2nd ed (EUA) There are 100 items (20 of each area of develop- Abnormality: ment: motor, communication, cognition, adaptive and social behavior). Scores of 0, 1 and 2 in each < -1 SD and > -1.5 SD: borderline. Refer child for one reflect the level of acquisition of skills further evaluation with BDI-2 Cut-off point is between 1.5 and 2 SD With this, determination of the possibility of a subsequent value < -1.5 SD and > -2.0 SD: clear indication for referral. Administer BDI-2 to determine specific areas of deficiency < -2.0 SD: clear indication of serious developmental problems. Administer BDI-2 and determine the origin and extent of deficit Bayley Scale of Infant and Toddler Development Screening Test (EUA) Qualification of four areas (basic/intact neuroTwo cut-off points divided into three risk categories: logical function, receptive functions, expressive mild, moderate and severe functions and cognitive process) with qualification options 1 (optimal) and 2 (not optimal) No total development score, only for each of the four areas evaluated Brigance Screens-II (EUA) Results based on the criteria of the examiner Without established criteria for classification CAT/CLAMS (EUA) Two domains: communication and problem resolution Items organized according to age group with scores (0.3-1.5) Total score according to area tested and general test score Establishes baseline age, ceiling equivalent age and developmental quotient Child Development Inventory (EUA) Eight areas quantified by parents with options of yes or no for response Classification according to three groups: Normal limits, borderline <1.5 SD and with developmental delay <2 SD DENVER-II (EUA) Items administered to child or according to information obtained by parents in accordance with age line Each item was quantified using success, failure or rejection Normal: skills appropriate for age (1 failure by area) Suspicion: failure to perform skills carried out by 7590% of children their age (>2 failures in two areas Delay: failure to carry out activities compared to >90% of children their age EEDP Escala de Evaluación Items administered to child. del Desarrollo Psicomotor Score 0 = failure, 1 or 2 = passing (Chile) NPED Neurodesarrollo Pediátrico (Cuba) Cut-off point, development quotient <70: developmental delay Sum and cut-off point. Establishment of categories: normal, risk, delay Computerized evaluation instrument for nurses to Reported as: normal, overall failure or by areas answer Parents Evaluation of Deve- The parent responds: yes, no and somewhat lopmental Status Answer questions in regard to concerns about (EUA) overall development, expressive and receptive language, fine and gross motor skills, behavior and social interests Vol. 69, November-December 2012 Classification according to three risk categories of developmental delay: slight, moderate and severe 547 Beatriz Romo-Pardo, Silvia Liendo-Vallejos, Guillermo Vargas-López, Antonio Rizzoli-Córdoba, Guillermo Buenrostro-Márquez Table 2. Qualification method and criteria of normality and abnormality of the screening tests included in the systematic review Screening test Screening test Criteria of normality and abnormality PRUNAPE (Argentina) Guidelines are given to the child and questions to parents are according to child’s age line. Each pattern is described as pass (if criteria are met) or failure (if not met) Type A patterns are completely to the left of the age. Type B patterns cross the age line at the 7590% percentile Passes the test if meets all type A patterns and fails when not meeting one type B pattern The child is described as suspect or at risk with failure on one type A pattern or two type B patterns TEPSI Test de evaluación del desarrollo psicomotriz Evaluation of the child with items that can be quali- Sum and cut-off point. Establish categories: normal, fied with scores 0, 1 and 2 risk, delay Table 3. Comparison of screening tests designed and validated according to the results of the systematic literature review Diagnostic test used for comparison Validation results Ages & Stages Questionnaires (EUA) Squires & Bricker, 1997 BSID SBIS MSCA S=0.70-0.90 Sp=0.76-0.91 PPV=0.45 Ages & Stages Questionnaires (EUA) BSID WPPSI-III VABS PLS-IV S = 0.82 Sp = 0.78 PPV = 0.30 (>1 domain) and 0.48 (>2 domains) NPV = 0.97 (>1 domain) and 0.94 (>2 domains) BDI-2 S=0.67 Sp=0.39 PPV=0.34 NPV=0.71 BDI Battelle Developmental Inventory Screening 2nd edition (EUA) Newborg J, 2005 BDI-2 S=0.72-0.93 Sp=0.79-0.88 BSID Bayley Infant Neurodevelopmental Screen (EUA) Aylward GP, 2005 BSID S=0.61-0.80 Sp=0.81-0.90 Multidisciplinary panel of specialists: pediatricians, nurses, teachers and developmental psychologists Parental report BSID S=0.76-0.77 Sp=0.85-0.86 Validation test Limbos MM, Joyce DP; 2011 Ages & Stages Questionnaires (Canada) Rydz, 2006 Brigance Screens-II Glascoe FP, 2002 CAT/CLAMS Capute, 1986 CDI Child Development Inventory (EUA) Doig, et al, 1999 CDI Child Development Inventory Rydz, et al, 2006 548 CAT/CLAMS and BSID BDI S=0.21- 0.66 Sp=0.79-0.95 PPV=0.80 NPV=0.65 S=0.70-0.80 Sp=0.70-0.80 S=0.50 Sp=0.86 Bol Med Hosp Infant Mex Global neurodevelopmental screening tests for children <5 years of age in the United States and Latin America: a systematic review and comparative analysis Table 3. Comparison of screening tests designed and validated according to the results of the systematic literature review Validation test DENVER-II (EUA) Glascoe, et al, 1992 EDIN Integral Child Evaluation Scale (Costa Rica) Schapira, 2007 Vericat, 2010 EEDP Evaluation Scale of Psychomotor Development (Chile) Schapira, 2007 Bedregal, 2008 Vericat A, 2010 NPED Pediatric Neurodevelopment (Cuba) Guadarrama-Celaya et al., 2011 PEDS Parents Evaluation of Developmental Status (EUA) Glascoe, et al, 2003 Glascoe , 2001 PEDS Parents Evaluation of Development Status (EUA) Limbos MM, 2011 PRUNAPE (Argentina) Pascucci MC, 2002 and 2004 TEPSI Psychomotor Development Test (Chile) Schapira, 2007 Bedregal P, 2008 Vericat A, 2010 Diagnostic test used for comparison Validation results BSID KABC SBIS VABS No validation data available S=0.56-0.83 Sp=0.43- 0.80 PPV=0.37 Low S and Sp in children of 4 months PPV in children >4 months: 97-100% No validation data found No detailed validation data found S=0.95 Sp=0.86 Development of the child was measured using a standard test package by psychology graduate psychologists blindly, either with regard to the concerns of the parents or to their relevance S=0.74-0.79 Sp=0.70-0.80 BSID WPPSI-III VABS PLS-IV S = 0.74 Sp = 0.64 PPV = 0.19 (>1 concern) and 0.30 (>2 concerns) NPV = 0.96 (>1 concern) and 0.93 (>2 concerns) BSID WISC Terman VABS Gardner test EN Psychiatric clinical evaluation EA Tonal audiometry BAEP S=0.80 Sp=0.93 PPV=0.94 NPV=0.97 No published validation studies found BSID, Bayley Scales of Infant Development; SBIS, Stanford Binet Intelligence Scales; MSCA, McCarthy Scales of Children’s Abilities; BDI-2, Battelle Development Inventory-2; WPPSI-III, Wechsler Preschool and Primary Scale of Intelligence; KABC, Kaufman Assessment Battery for Children; VABS, Vineland Adaptive Behavior Scale; PLS-IV, Preschool Language Scale–Fourth Edition; WISC, Wechsler Intelligence Scale for Children; OE, otoacoustic emissions; BAEP, brainstem auditory-evoked potentials; NE, neurological examination; S, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value. Vol. 69, November-December 2012 549 Beatriz Romo-Pardo, Silvia Liendo-Vallejos, Guillermo Vargas-López, Antonio Rizzoli-Córdoba, Guillermo Buenrostro-Márquez Table 4. Advantages and disadvantages of screening tests according to the literature Screening test Advantages Ages & Stages Questionnaires (USA) Squires & Bricker, 1997 Limbos MM, 2011 Rydz, 2006 Can be resolved by the parents No direct observation of the at home or in the waiting room child by experienced health (recommended to be sent home) personnel Application is short and quickly quantified Material support for parents Battelle Developmental Inventory Screening 2nd ed. (EUA) Newborg J, 2005 Requires minimal training Low sensitivity (0.64-0.67) Three cut-off points used with a wide Training materials and specificity (0.74- 0.76) for sample of children High sensitivity and specificity for motor skills the area of communication Can be modified for children with disabilities Bayley Scale of Infant and Helpful materials Toddler Development Scree- Is short term ning Test (EUA) Aylward GP, 2005 Disadvantages Observations Sensitivity and specificity show much variation between one study and another. Sensitivity is from 0.67-0.82 and a specificity as low as 0.39. Personnel required who can Validation study was carried out with evaluate muscle tone and basic a significant sample of 600 cases, neurological functions correcting the age and with three cut-off points Brigance Screens-II Glascoe FP, 2005 Short term Cannot account for material In the study, cut-off points cannot be Can be answered by parents, help explained by direct observation or by both methods In waiting rooms or schools CAT/CLAMS Capute, 1986 Short duration Good material help Is quantitative, establishes developmental age Child Development Inventory (EUA) Doig, et al, 1999 Rydz, et al, 2006 Short time of application No helpful materials Sensitivity and specificity are not Total of 300 questions and can changed depending on the so- last 30 min cioeconomic level of the parents Validation study carried out for open and at-risk population Is the unique study evaluating 36 patients comparing them with the “gold standard” (Battelle) DENVER-II Glascoe, et al, 1992 Ease of application Low sensitivity and specificity Does not require intensive training Evaluation time of 30 min The study sample was subject to only 104 children, of whom very few were <24 months of age Despite re-standardization and using different combinations of scoring methods, lacks adequate sensitivity and specificity Integral Developmental Child Adequate psychometric properties Scale (Costa Rica) Observations at different socioecoVericat A, 2010 nomic levels EEDP Escala de Evaluación Ease of application del Desarrollo Psicomotor Can be carried out by (Chile) nonspecialized personnel Bedregal P, 2008 Vericat A, 2010 550 Considers only two developmental areas (communication and problem resolution) No published validation data found for this test Does not encompass all areas Validation studies not available in the of development literature Bol Med Hosp Infant Mex Global neurodevelopmental screening tests for children <5 years of age in the United States and Latin America: a systematic review and comparative analysis Table 4. Advantages and disadvantages of screening tests according to the literature Screening test Advantages Disadvantages Pediatric Neuroevelopment (Cuba) Guadarrama-Celaya, 2011 High sensitivity and specificity Can be carried out by nurses without requirement of extensive complicated training Short duration Necessary to have a computer No reports of psychometric characteand training may be necessary ristics of the test to manage software with difficult application Parents Evaluation of Developmental Status (EUA) Glascoe, et al, 2003 Glascoe, 2001 Limbos MM, Joyce DP; 2011 Based on discussions with parents Requires an experienced evaabout their concerns of child de- luator to obtain adequate invelopment formation With an experienced evaluator, highly valid information can be obtained Requires short time of administration In the study by Limbos MM and Joyce DP, it was determined that very low specificity leads to over-referrals (1/3 children did not require evaluation) PRUNAPE (Argentina) Pascucci MC, 2002 y 2004 Design similar to Denver that allows quick organization of the evaluator about guidelines to be administered Helpful materials Brief time of administration Test is validated with 78 guidelines The “father/mother-specific pattern was incorporated after the validation process For validation, the study is significant with 839 children Uses diagnostic tests for validation, and evaluations by hearing and vision specialists Test de desarrollo Psicomotor (Chile) Bedregal P, 2008 Vericat A, 2010 Well-designed Can be used by pre-school teachers Has a version for the blind Does not evaluate all develop- No published validation data available mental areas Sample size in some studies is not sufficient. It is particularly problematic when calculating the specificity and sensitivity of the test because the number of patients with a developmental alteration may be limited. In other cases, the problem is that it does not include a similar number of patients by age group, as in the Denver case where, in addition to a small sample (104 subjects), very few were <24 months of age. It is critical to determine suitable cut-off points to calibrate the tool in order to obtain accurate results. Those tests that have low specificity produce large numbers of false positives that may result in diagnostic over-reporting. The opposite problem leads to not refer and to not detect those children with a developmental problem and, therefore, to not intervene early. On the basis of the results observed, it is concluded that between the period of 1980 and 2012, which includes the systematic review, we found 13 neurodevelopmental screening tests in the U.S. and Latin America for use in children <5 years of age. Battelle Development Inventory Screening and PRUNAPE were the two screening tests that had the greatest sensitivity and specificity in the validity criteria. It should be noted that the evidence of its validation offered by the Vol. 69, November-December 2012 Observations publications is of high methodological quality, which confirms that they are reliable tools for detection of neurodevelopmental alterations. Although there are different methods of administration, scoring and criteria of normality and abnormality, there was no scientific evidence to support either of the test systems because what matters is the scientific basis on which the validation test is performed. Of the screening tests included, we found no validation study in Mexico. Therefore, we believe it to be of utmost importance to have a valid tool, preferable for our own country, in order to be applied to our own population and to use it to implement early interventions in a directed, systematic manner with a scientific foundation. This is in order to achieve the maximum potential of developing—and avoiding—the causal factors of intergenerational poverty. REFERENCES 1. Council on Children With Disabilities; Section on Developmental Behavioral Pediatrics; Bright Futures Steering Committee; Medical Home Initiatives for Children With Special Needs 551 Beatriz Romo-Pardo, Silvia Liendo-Vallejos, Guillermo Vargas-López, Antonio Rizzoli-Córdoba, Guillermo Buenrostro-Márquez Project Advisory Committee. Identifying infants and young children with developmental disorders in the medical home: an algorithm for developmental surveillance and screening. Pediatrics 2006;118:405-420. 2. Grantham-McGregor S, Cheung YB, Cueto S, Glewwe P, Ritcher L, Strupp B, et al. Developmental potential in the first 5 years for children in developing countries. Lancet 2007;369:60-70. 3. Hamilton S. Screening for developmental delay: reliable, easyto-use tools. J Fam Pract 2006;55:415-422. 4. Rydz D, Srour M, Oskoui M, Marget N, Shiller M, Birnbaum R, et al. Screening for developmental delay in the setting of a community pediatric clinic: a prospective assessment of parent-report questionnaires. Pediatrics 2006;118:e1178-e1186. 5. Mackrides PS, Ryherd SJ. Screening for developmental delay. Am Fam Physician 2011;84:544-5499. 6. Rydz D, Shevell MI, Majnemer A, Oskoui M. Developmental screening. J Child Neurol 2005;20:4-21. 7. Glen P Aylward, T. S. Measurement and psychometric considerations. In: Wolraich ML, Drotar DD, Dworkin PH, Perrin EC, eds. Developmental-Behavioral Pediatrics: Evidence and Practice. Philladelphia: Mosby Elsevier; 2008. pp. 123-201. 8. Squires J, Bricker D, Potter L. Revision of a parent-completed developmental screening tool: Ages and Stages Questionnaires. J Pediatr Psychol 1997;22:313-328. 9. Squires J, Twombly E, Bricker D, Potter L. ASQ-3™ User’s Guide. Baltimore, MD: Paul H. Brookes Publishing Co.; 2009. 10. Schonhaut BL, Salinas AP, Armijo RI, Schönstedt GM, Álvarez LJ, Manríquez OM. Validación de un cuestionario autoadministrado para la evaluación del desarrollo psicomotor. Rev Chil Pediatr 2009;80:513-519. 11. Limbos MM, Joyce DP. Comparison of the ASQ and PEDS in screening for developmental delay in children presenting for primary care. J Dev Behav Pediatr 2011;32:499-511. 12. Newborg J. Development and standardization. In: Newborg J, ed. Battelle Developmental Inventory. Itaska, IL: Riverside Publishing; 2004. pp. 95-148. 552 13. Aylward GP. The Bayley Infant Neurodevelopmental Screener (BINS): different test and different purpose. In: Weiss LG, Oakland T, Aylward G, eds. Bayley III Clinical Use and Interpretation. New York: Academic Press; 2010. pp. 201-233. 14. Glascoe FP. The Brigance Infant and Toddler Screen: standardization and validation. J Dev Behav Pediatr 2002;23:145-150. 15. Capute AJ, Shapiro BK, Watchel RC, Gunther VA, Palmer FB. The Clinical Linguistic and Auditory Milestone Scale (CLAMS). Identification of cognitive defects in motor-delayed children. Am J Dis Child 1986;140:694-698. 16. Doig KB, Macias MM, Saylor CF, Craver JR, Ingram PE. The Child Development Inventory: a developmental outcome measure for follow-up of the high-risk infant. J Pediatr 1999;135:358-362. 17. Glascoe FP, Byrne KE, Ashford LG, Johnson KL, Chang B, Strickland B. Accuracy of the Denver-II in developmental screening. Pediatrics 1992;89:1221-1225. 18. Schapira IT. Comentarios y aportes sobre desarrollo e inteligencia sensorio-motriz en lactantes. Análisis de herramientas de evaluación de uso frecuente. Actualización bibliográfica. Rev Hosp Mat Infant Ramón Sardá 2007;26:21-27. 19. Bedregal P. Instrumentos de medición del desarrollo en Chile. Rev Chil Pediatr 2008;79(suppl 1):32-36. 20. Vericat A, Orden AB. Herramientas de screening del desarrollo psicomotor en América. Rev Chil Pediatr 2010;81:391-401. 21. Guadarrama-Celaya F, Otero-Ojeda GA, Pliego-Rivero B, Porcayo-Mercado MR, Garcell JR, Pérez-Ábalo MC. Screening of neurodevelopmental delays in four communities of Mexico and Cuba. Public Health Nurs 2012;29:105-115. 22. Pascucci MC, Lejarraga H, Kelmansky D, Álvarez M, Boullón M, Breiter P, et al. Validación de la prueba nacional de pesquisa de trastornos de desarrollo psicomotor en niños menores de 6 años. Arch Argen Pediatr 2002;100:374-384. 23. Pascucci MC, Lejarraga H, Kelmansky D, Álvarez M, Boullón M, Breiter P, et al. Validación de la prueba nacional de pesquisa de trastornos de desarrollo psicomotor en niños menores de 6 años. Arch Pediatr Urug 2004;75:79-90. Bol Med Hosp Infant Mex Bol Med Hosp Infant Mex 2012;69(6):553-563 Research article Risk factors and consequences of cyberbullying in teenagers: association with bullying Gerardo García-Maldonado,1,2 Gerardo Jesús Martínez-Salazar,2 Atenógenes H. Saldívar-González,2 Rafael Sánchez-Nuncio,2 Gerardo Manuel Martínez-Perales,1 María del Carmen Barrientos-Gómez2 ABSTRACT Background. Cyberbullying (CB) uses electronic tools to intimidate. We undertook this study to determine the prevalence of CB and to identify its characteristics. We explored the association with bullying and analyzed consequences and risk factors. Methods. Junior-high-school students were included. CB was used as exposure and outcome variable. Nonparametric statistics and logistic regression were applied. Results. Six hundred three students with a mean age of 13.4 years (±0.98 years) were included. Cybervictims were more prevalent. The cell phone was the most common tool used to intimidate. The most important risk factor for cybervictims was “feeling unsafe at school” (c2 = 6.485, p = 0.011, OR = 4.1, 95% CI 1.30-11.2); for cyberaggressors it was “to use the computer hidden from parents and late at night” (c2 = 14.584, p <0.05, OR = 4.2, 95% CI 2.10-16.30); for cybervictims–cyberaggressors it was “to be female” (c2 = 2.891, p >0.05, OR = 3.50, 95% CI 1.70-16.80). The strongest association with bullying was shown for males and between traditional victim–aggressor and cyberaggressor roles (c2 = 28.821, p <0.05, OR = 7.37, 95% CI 3.78-14.3). When CB was considered as the exposure variable, the most relevant outcome measure was “to have headaches” for cyberaggressors (c2 = 15.125, p <0.05, OR = 7.91, 95% CI 2.28-29.6). Conclusions. The prevalence of CB was less than demonstrated in other studies, but the risk factors and consequences are relevant. Key words: cyberbullying, risk factors, consequences, bullying. INTRODUCTION Cyberbullying (CB)1-3 is defined as continuous intimidation or harassment used by one person (cyberaggressor) against another (cybervictim) through electronic means (internet or text messages via cell phone).4 Some cases have been documented where subjects can simultaneously 1 2 Departamento de Enseñanza e Investigación, Hospital Psiquiátrico de Tampico, Secretaría de Salud, Tampico, Tamaulipas, Mexico Departamento de Investigación, Facultad de Medicina de Tampico Dr. Alberto Romo Caballero, Universidad Autónoma de Tamaulipas, Tampico, Tamaulipas, Mexico Correspondence: Dr. Gerardo García Maldonado Departamento de Enseñanza e Investigación Hospital Psiquiátrico de Tampico Secretaría de Salud Tampico, Tamaulipas, Mexico E-mail: [email protected] Received for publication: 6-26-12 Accepted for publication: 10-23-12 Vol. 69, November-December 2012 be cybervictims and cyberaggressors or be concurrently engaged in traditional bullying.5,6 Unlike the latter, CB invades the privacy of the home of abused subjects at any time of day or night.6,7 Although it is more common for high school students to be involved in this practice,8,9 various reports have shown the participation of students from other grade levels.9-12 For children at high risk of being cyberintimidated, the factors involved are using computers for prolonged periods,13-15 having a profile on a social electronic network,16 and being in the age range of 14 to 17 years.13,16,17 Fear of CB6,13,18 as well as low self-esteem,19-23 depression14,16,17 and loneliness13 are risk factors. For cyberbullies, the fact that they are frustrated, angry and anxious,24 that their parents underestimate their aggressive behavior,9.25 or use of the computer for long periods17,26,27 are important elements. Gender also appears to have a direct and significant effect. It has been noted that there is a greater prevalence of females who are cyberbullied and males who are cyberaggressors.13,14,16 The literature points out some 553 Gerardo García-Maldonado, Gerardo Jesús Martínez-Salazar, Atenógenes H. Saldívar-González, Rafael Sánchez-Nuncio, Gerardo Manuel Martínez-Perales, María del Carmen Barrientos-Gómez consequences surrounding this phenomenon: in the case of cybervictims the presence of low self-esteem, insomnia, enuresis, anxiety, headache and abdominal pain,21,22 emotional alterations (unhappiness and loss of self confidence)28 and academic difficulties have been noted. In the case of cyberaggressors, behavior disorders and, in extreme cases, criminal behavior are notable,29,30 although the presence of insomnia, headache, anxiety, lack of empathy, absenteeism and school suspension are also present.21,22 Another problem at present is the association between CB and traditional bullying, such that in some countries this co-occurrence has been studied.29,31-33 Regarding the use of alcohol and tobacco among those involved in CB, there are reports that victims of CB do not consume more alcohol than cyberaggressors.30 As far as tobacco, the unlikelihood that cybervictims smoke as a consequence of the event has been documented.32,34,35 With regard to CB and ADHD disorder, there are no studies at this time where the latter has been analyzed as a risk factor. The objectives of this study were as follows: 1) to describe the prevalence of CB and traditional bullying in our study sample; 2) to identify the methods and tools most frequently used for CB and to clarify if there are differences in terms of gender, document if there are differences between males and females who are cyberaggressors related to the gender they preferentially cyberintimidate and also if there were differences among the victims (males and females) regarding gender identification of their aggressors, and finally to establish the presence or absence of fear of cyberintimidation, 3) to explore if in those involved in CB there is the presence of psychopathological or psychosomatic manifestations, sleep difficulties and use of alcohol and tobacco; 4) to explore the relationship of each of the roles in the CB phenomenon with different variables, adding traditional bullying which, according to the literature, are likely associated circumstances and to explore also if CB is a risk variable for development of some of these; and 5) to determine the index or magnitude of risk. SUBJECTS AND METHODS Study Sample We included students from a morning shift of a high school located in the town of Tampico, Tamaulipas, Mexico, enrolled in the school year 2010-2011 and with an age range of 11-15 years. 554 The total official campus population during that period was 625 students but because some students were absent during the study period, the sample was comprised of only 603 adolescents. Included in this study were all students present during the day of the field work. With regard to gender, the distribution was 53.4% males and 46.6% females; with respect to school grade 35.7% were in the first year of high school, 31.3% in the second year and 33% in the third year. The campus has six groups for each school year. The project was reviewed and approved by the Ethics Committee of the institutions that were headquarters for the researchers after certifying that the facility complied with the guidelines of the General Health Law regarding human research for human health in Mexico and with the principles as published in the Declaration of Helsinki. All students voluntarily signed an informed consent and their participation was kept confidential. Instruments CB measurement and other variables At the time of study development, there was no identification of a specific instrument designed and validated in Mexico for evaluation of CB. In a consensus it was decided that two direct and concrete questions be posed in a manner similar to those formulated by Sourander et al. in their study on CB27 where a similar questionnaire was used. The goal was to establish the presence or absence of each of the three roles that may be present in CB (cybervictimcyberaggressor, cybervictim, and cyberaggressor). Each of the questions posed with this purposed constituted an individual variable that required an individual and specific response.33 Participating students were asked that they consider their responses within their personal context, ranging from 6 months prior to the time of study in the school. CB was defined as a situation where someone repeatedly intimidates another through e-mail or telephone text messages and/or disseminates private information of others or embarrasses someone via the internet.36 The questions to establish CB were: 1) During the last 6 months, how often have you been assaulted or intimidated by others through the internet or cell phone text messages? 2) During the last 6 months, how often have you attacked or bullied others via the internet or cell phone text messages? Bol Med Hosp Infant Mex Risk factors and consequences of cyberbullying in teenagers: association with bullying Response options for these questions were: a) never b) once a week c) more than once a week; d) almost every day. Choices b, c and d are considered together as “sometimes.” Thus, the response was dichotomized for operational purposes as “never” or “sometimes” in the two items. Based on the two questions, the sample was divided into four groups also for operational purposes: 1) never cybervictim or cyberaggressor, 2) only cybervíctim (at least “sometimes” cybervictim, but “never” cyberaggressor), 3) only cyberaggressor (at least “sometimes” cyberaggressor, but never “cybervictim”), 4) cybervictim–cyberaggressor (at least “sometimes” and cybervictim and cyberaggressor simultaneously). The questions listed below, including those of traditional bullying, were raised in consensus and were also incorporated and considered to be individual variables under the same premise as the previous two: 3) How often have you been assaulted or intimidated via the internet or cell phone text messages in the form of 1) being ignored, 2) offended by profanity, 3) nicknames, 4) who speak ill of you (rumors), 5) threats; 6) criticisms or 7) made fun of? For each of these seven options, the participant had the following response alternatives: a) never b) once a week c) more than once a week; d) almost every day. 4) In what ways are you intimidated or attacked? 5) In what ways do you intimidate or bully? Response options were the same for these two questions: 1) cell phone messaging, 2) IM, 3) e-mail, 4) social networking page. For each of these options, the participant had the following alternatives: a) never b) once a week c) more than once a week; d) almost every day. In questions 4 and 5, the students were able to select more than half if that was the case. 6) By whom have you been intimidated or attacked through internet or mobile messaging? 7) Who do you assault or bully via internet or mobile messaging? The options for these questions were as follows: 1) girls, 2) boys, 3) boys and girls at the same time, 4) indifferent to gender. The response alternatives for each of these four options as for the previous questions were these: a) never b) once a week c) more than once a week; d) almost every day. 8) Have you felt fear from the intimidation or aggression to which you were subjected through the interVol. 69, November-December 2012 net or text messages? The response alternatives were a) never, b) once a week, c) more than once a week, d) almost every day. Responses b, c and d of questions 3–8 were considered together as “sometimes” for operational purposes, in the same manner as questions 1 and 2, which allowed for dichotomize the responses. We collected sociodemographic information (age, gender, education and parent with whom the child lives) with a format (yes/present-no/absent) and screened for the presence or absence of psychopathology, psychosomatic manifestations, sleep problems, alcohol use, smoking and traditional bullying, as variables of interest. Psychopathological manifestations For evaluation and measurement of psychopathological problems, we used the strengths and weaknesses questionnaire (SDQ) in its self-reporting version for children and adolescents 11–16 years of age.37,38 This questionnaire is comprised of 25 items divided into five scales [hyperactivity-inattention, emotional symptoms (unhappiness, loss of confidence and fear), behavior problems (oppositional defiant), peer problems and prosocial behavior]. For the first two scales, a score >7 was considered positive; positivity with the instrument in the case of behavior problems and with peers was >5. Three response options are available on a Likert-type scale that are answered directly by the participant and coded as 0 (not true), 1 (sometimes true) or 2 (absolutely true), except for 5 “inverse” items that are rated in the opposite direction. Translation and validation of the self-reporting version used in this study was carried out to add more reliability to the results obtained. To ensure greater equivalency of the translation, WHO guidelines were followed.39 For study purposes we only used the hypersensitivity–inattention scale and emotional symptoms (unhappiness, loss of self-confidence and fear) of the SDQ questionnaire. We conducted an analysis of internal consistency of these two scales to determine its internal consistency and coherence of the items in their intercorrelation with each other, for which the Cronbach’s alpha statistic was applied. For the scale of hyperactivity– inattention, emotional symptoms, and the questionnaire as a whole, Cronbach’s alpha was 0.78, 0.78 and 0.76, respectively, which are acceptable values according to Nunnally.40 For exploring the variables of psychosomatic manifestations, sleep problems, use of alcohol, tobacco and 555 Gerardo García-Maldonado, Gerardo Jesús Martínez-Salazar, Atenógenes H. Saldívar-González, Rafael Sánchez-Nuncio, Gerardo Manuel Martínez-Perales, María del Carmen Barrientos-Gómez school environment, questions were raised in consensus and formulated as direct and concrete questions, also similar to those formulated by Sourander et al.27 Each of the questions constituted individual variables that required individual and specific responses.33 Psychosomatic manifestations There were basically two common and known symptoms explored: headache and abdominal pain. The first was addressed with the question “During the last 6 months, have you experienced headaches that distract you from what you are doing at the time?”, with the following response options: a) at least once a week b) at least once a month, c) never. Abdominal pain was approached with the question “During the last 6 months have you experienced recurrent abdominal pain?” Response options were as follows: a) at least once a week, b) at least once a month, c) never. For operational purposes, responses “a” and “b” were considered together as “yes/present” for both manifestations. Sleep problems This situation was addressed with two questions. The first was “During the last 6 months, have you experienced trouble falling asleep at night?” Response options were as follows: a) at least once a week, b) <1 time per month, c) never. The other question was “During the last 6 months, have you experienced waking up during the night and then having difficulty going back to sleep?” Response options were these: a) almost every night; b) one or two times a week, c) never. Similarly, for operational purposes the responses and b were considered yes/present for both questions. Alcohol Use Drinking alcohol to the point of intoxication was documented with the following question: “When you drink alcohol, do you become drunk?” Response options were as follows: a) never b) once a month; c) once a week; d) daily. Responses b, c, and d were considered together as “yes/present.” Tobacco use The use of tobacco was explored with the question: “Do you smoke?” Response options were as follows: a) never, 556 b) rarely, c) some weekdays, d) daily. Responses b, c, and d were considered together as “yes/present.” School environment To this end, two assertions were raised expressed in the first person: 1) I feel insecure in my school or 2) the teachers at my school care about me. Response options were as follows: a) never b) sometimes c) frequently d) forever. Responses b, c, and d were considered together as “yes/present.” Determination of traditional bullying There were four questions raised, following the same principles and considerations as those adopted for the CB. The conceptual definition was used by Olweus.41 1) How often have you been bullied or harassed in your school during the past 6 months? 2) How often have you been bullied or harassed outside your school during the past 6 months? 3) How often have you bullied or harassed others in your school during the past 6 months? 4) How often have you bullied or harassed others outside your school during the past 6 months? According to the literature, the bullying phenomenon can occur within or outside a school campus.42,43 To prevent participants from considering this problem exclusive within the campus, it was decided to ask the question including adverbs “within” and “outside.” The response was considered positive with any of the four questions, or with all, if that was the case. Response options for these four questions were as follows: a) never b) once a week c) more than once a week; d) almost every day. Responses b, c and d are considered together as “at least sometimes.” For operational purposes the sample was categorized into four groups: 1) never aggressor or victim, 2) only victims (at least sometimes victim, but never aggressor), 3) only aggressors (at least sometimes aggressor. but never victim), 4) victim–aggressor (sometimes both victim and aggressor). Procedures An informational meeting was conducted days before with the school authorities. All information was handled confidentially. Staff members who administered the questionnaires presented directly to the classrooms with the students to explain the goal of the study. Teacher support Bol Med Hosp Infant Mex Risk factors and consequences of cyberbullying in teenagers: association with bullying was available at all times. The participating students answered the questionnaires in a voluntary and anonymous manner with an average time of 50 min. Statistical Analysis This was a cross-sectional, open, observational and analytical study composed of two groups of participants: one group was involved in the CB phenomenon and another group was not involved. Those involved comprised the group of cybervictims, cyberaggressors and cybervictims–cyberaggressors. These three groups were analyzed separately from the group not involved. The decision to use the uninvolved group as a control group allowed representation of the population that had not experienced CB. It was felt that this group corresponded to the subpopulation of individuals at risk of developing this and, if it should present itself, they would be included in the population involved. The same strategy was applied to traditional bullying, which allowed integration of the groups of victims, perpetrators and victims–aggressors involved in this phenomenon. Once selected, the presence or absence of significant associations of this phenomenon with the variables of interest was explored (including traditional bullying), and the relative exposure of each role in the CB with each of these variables was compared, which were formed as independent variables. According to the literature, these have relevance as risk factors for CB. In the analysis that specifically included variables of psychosomatic manifestations, sleep problems and alcohol and tobacco use, analyses were performed on the same principles, but CB was integrated as an exposure factor for the development of these variables. For data analysis, descriptive statistics and Pearson 2 χ test for correlation of categorical qualitative variables was done. To test the hypotheses regarding risk factors and the correlation among the groups involved in CB, logistic regression analysis calculating the odds ratio (OR) was carried out. To accurately quantify the association, calculation of the 95% confidence interval was done; α ≤0.05 was considered statistically significant. For the analysis, the three groups involved in the CB with values (0-1) were dichotomized as were all study variables. Vol. 69, November-December 2012 RESULTS Sociodemographic Variables Among the participating students, the average age was 13.4 years (±0.98). According to high-school year, it was 12.5 years (±0.50) for first year, 13.4 years (±0.53) for the second year and 14.4 (SD 0.54) for the third year. According to gender, the figures were 13.4 years (±1.01) for boys and 13.3 years (±0.96) for girls. Prevalence of CB in 6 Months Of the total sample, 3.5% of students were cybervictims, 2.8% cyberaggressors and 1.3% cybervictims–cyberaggressors. Although more females participated in the mixed role, in general males predominate in this phenomenon. Prevalence of Traditional Bullying in 6 Months Regarding bullying, it was reported that 19.2% of the sample corresponds to the aggressors, 24.4% to victims and 32.9% to victims–aggressors. Methods and Tools in CB The manner in which victims are stalked and electronic media through which participants cyberintimidate or are cyberintimidated are listed in Table 1. A distinction based on gender is also made. False rumors and criticisms as a way of CB were the most commonly used. These and cell phones as tools of harassment had higher significant differences between males and females (p <0.05). Who Has Cyberintimidated You? Who Do You Cyberintimidate? The largest proportion of females are predominantly cyberintimidated by persons of the same gender (p <0.05). In the case of cyberaggressors, it shows that males abuse persons of their own gender with greater frequency (p >0.05) (Table 1). Fear of CB Thirteen percent of the cybervictims stated they have been afraid of the CB to which they are subjected, corresponding to 4.3% of males and 8.7% female. One youngster expressed fear that at some point he could be a victim of CB. It is noteworthy in this context that >80% of children 557 Gerardo García-Maldonado, Gerardo Jesús Martínez-Salazar, Atenógenes H. Saldívar-González, Rafael Sánchez-Nuncio, Gerardo Manuel Martínez-Perales, María del Carmen Barrientos-Gómez Table 1. Factors inherent to cyberbullying Males Table 2. Distribution of the study variables according to gender Females (p) Methods and tools used in cyberbullying How often and in what manner have you been cyberintimidated? - Being ignored 21% 21% 0.24 - Offended 37% 19% 0.15 - Name calling 43% 24% 0.17 - False rumors 34% 58% <0.05 - Embarrassment 20% 10% 0.36 - Criticism 40% 60% <0.05 - Teasing 28% 19% 0.68 What method has been used to cyberbully you? - Cell phone messages 5% 6% <0.05 - Text messages 35% 34% 0.64 - E-mail 10% 6% 0.58 - Social network page 28% 34% 0.11 What methods have you used to cyberbully? - Cell phone messages 2% - Text messages 18% - E-mail 4% - Social network page 21% By whom have you been cyberbullied? - Girls 14% - Boys 42% - Girls and Boys at the same 6% time - Gender unknow 26% Who have you cyberintimidated? - Girls 8% - Boys 22% - Girls and boys at the same 6% time 4% 22% 0% 25% 0.23 0.37 0.31 0.13 46% 21% 16% <0.05 0.13 <0.05 29% 0.08 20% 10% 5% <0.05 0.33 0.58 Variables Psychopathological manifestations Emotional symptoms Hyperactivity-inattention Psychosomatic manifestations Recurrent headaches Recurrent abdominal pain Problems sleeping Beginning Afterwards Tobacco and alcohol use Tobacco Alcohol Gender Male Female Total 1.0% 4.6% 2.3% 3.2% 3.3% 7.8% 14.9% 12.3% 20.4% 35.3% 13.2% 25.5% 20.6% 9.5% 21.4% 42.0% 7.9% 17.4% 3.5% 8.0% 0.8% 2.0% 4.3% 10.0% computer hidden from parents and use of the computer late at night is a more representative risk [c2 = 14,584, p <0.05, OR = 4.2, 95% CI (2.10-16.30)] (Table 3). Finally, for development of the cyberaggressor–cybervictim role, being female is a salient factor for developing this condition [c2 = 2891, p >0.05, OR = 3.5, 95% CI (1.70-16.80)]. Traditional Bullying As a Risk Factor for CB spend much time at the computer, not necessarily for homework, and many of them do this even late at night, unknown by their parents. It is notable that for males there is a much greater risk association between traditional victim–aggressor and cyberaggressor [c2 = 28.821, p <0.05, OR = 7.3, 95% CI (3.7-14.3)]. In females, the cybervictim–cyberaggressor condition and traditional victim–aggressor [c2 = 5.603, p <0.05, OR = 7.3, 95% CI (1.7-21.3)], p <0.05 OR = 7.3 95% CI (1.7-21.3)] showed the most significant association (Table 4). Presence and Distribution of the Study Variables CB As a Risk Factor The results of the following variables—psychopathological, psychosomatic, sleep problems manifestations and use of alcohol and tobacco—with regard to gender are shown in Table 2. Interestingly, a significant proportion of sleep problems are noted. Risk Factors Associated with CB Fear of CB and, therefore, feeling unsafe at school has a significant risk of impacting on the condition of the cybervictim [c2 = 6.485, p = 0.011, OR = 4.1, 95% CI (1.30-11.2)]. For the role of cyberaggressor, the use of the 558 It is noteworthy that the condition of cyberaggressor had a major impact on all variables considered, with headaches being the most prominent [c2 = 15.125, p <0.05, OR = 7.9, 95% CI (2.2-29.6)] (Table 5). DISCUSSION To our knowledge, this study is the first to explore the theme of CB, some consequences, characteristics and various risk factors associated with traditional bullying, including a group of teenagers in Tampico, Tamaulipas, Bol Med Hosp Infant Mex Risk factors and consequences of cyberbullying in teenagers: association with bullying Table 3. Risk factors for cyberbullying Cybervíctim (n=23) Risk factors Age Older than 13 years Younger than 13 years Gender Male Female SDQ scale Hyperactivity Emotional problems High school year First year Second year Third year Live with one parent Yes No Time spent using the computer Less than an hour More than an hour Use computer hidden from parents or at late night hours Yes No Fear of cyberintimidation No Yes (*) p ≤0.05 Cyberaggressor (n=16) Cybervíctim-Cyberaggressor (n=10) X2 CI OR (p) 95% OR CI 95% X2 (p) OR CI 95% 0.020 (0.887) 0.020 (0.887) 1.9 1 1.3-24.6 1.4-12.8 0.654 (0.419) 0.654 (0.419) 1.8 0.5 0.4-7.8 0.1-2.3 0.695 (0.405) 0.695 (0.405) 2.3 0.4 1.2-18.2 0.0-3.3 0.094 (0.760) 0.094 (0.760) 1 2.9 0.7-1.5 1.5-14.9 3.556 (0.04)* 1.556 (0.212) 2.2 0.6 2.9-13.2 2.891 (0.089) 0.3-1.3 2.891 (0.089) 3.4 3.5 1.7-16.3 1.7-16.8 3.064 (0.080) 0.4 0.1-1.1 2.2 1.1-14.9 0.079 (0.778) 2.7 1.1-15.3 9.355 (0.031)* 0.564 (0.453) 0 0.280 (0.594) 0.674 (0.412) 0.71 (0.790) 2.7 1.4 0.8 1.3-19.3 0.6-3.3 0.3-2.1 0.813 (0.367) 1.176 (0.278) 0.023 (0.880) 0.939 (0.333) 0.939 (0.333) 1.4 0.9 0.7-2.9 0.7-1.1 0.158 (0.691) 0.158 (0.691) 1.1 0.5-2.6 3.9 2.7-11.2 1.634 (0.201) 1.8 0.7-4.6 1.634 (0.201) 0.9 4.586 (0.112) 6.485 (0.011)* 0.8 4.1 X2 (p) 3.1 1.3-14.3 0 14.675 (0.000)* 8.826 (0.003)* 2.1 1.2-16.2 0.5 1.7 0.9 0.1-1.8 0.6-4.7 0.3-2.6 0.142 (0.707) 0.354 (0.552) 0.041 (0.839) 0.7 1.4 2.8 0.1-3.1 0.4-5.2 1.2-33.6 0.001 (0.971) 0.001 (0.971) 1 0.9 0.3-2.8 0.7-1.2 0.910 (0.340) 0.910 (0.340) 1.6 0.8 0.6-4.3 0.5-1.2 0.401 (0.527) 0.401 (0.527) 0.6 0.1-2.4 0.494 (0.482) 0.5 0.8-3.4 1 1.8-13.7 0.494 (0.482) 1.1 0.8-1.3 4.2 2.1-16.3 1.244 (0.265) 2.9 1.5-7.4 0.7-1.1 14.584 (0.000)* 1.789 (0.321) 0.6 0.4-1.0 1.244 (0.265) 0.8 0.6-1.2 0.7-1.0 1.3-11.2 0.372 (0.542) 0.372 (0.542) 0.9 1.8 0.8-1.1 0.368 (0.544) 0.2-12.8 0 1.03 0 1.2-3.5 0 OR: Odds Ratio; IC: confidence interval. Mexico. We believe that this is relevant if we consider that bullying43 and CB44 currently constitute forms of violence with their own characteristics. Although CB is less prevalent than traditional bullying, this does not make its presence any less alarming, especially in children. The prevalence of this phenomenon in our study was lower than that reported by Smith et al.6 and Sourander et al.27 However, it is important to consider that the sample in this study was comparatively lower. However, this phenomenon was able to be identified. Vol. 69, November-December 2012 We note that false rumors and criticism as forms of CB are more often used by females, whereas in males the use of name calling was most often used. This was similar to that reported in other studies.45 We were also able to document that females participate less frequently in CB, and this was in agreement with several other reports.15,17 However, it is important to point out that there are other reports that note the opposite results.22,45 The differences may be explained by the sociocultural heterogeneity of the participants and the discrepancy in sample sizes. 559 Gerardo García-Maldonado, Gerardo Jesús Martínez-Salazar, Atenógenes H. Saldívar-González, Rafael Sánchez-Nuncio, Gerardo Manuel Martínez-Perales, María del Carmen Barrientos-Gómez Table 4. Traditional bullying as a risk factor for cyberbullying Cybervíctim (n=23) Bullying groups Cyberaggressor (n=16) X2 (p) OR CI 95% Victim Aggressor Victim-Aggressor 16.005 (0.000)* 0.030 (0.861) 0.029 (0.866) 4.6 1.1 0.8 2.3-9.04 0.17-8.1 0.12-5.7 Victim Aggressor Victim-Aggressor 7.589 (0.006)* 0.358 (0.550) 2.603 (0.107) 3.6 1.8 3.01 1.5-8.2 0.26-12.3 0.80-11.2 X2 (p) Boys 1.479 (0.224) 16.637 (0.000)* 28.821 (0.000)* Girls 0.701 (0.403) 1.940 (0.164) 8.326 (0.004)* Cybervíctim-Cyberaggressor (n=10) OR CI 95% X2 (p) OR CI 95% 0 6.6 7.3 0 2.6-16.4 3.7-14.3 1.065 (0.302) 0.572 (0.449) 16.823 (0.000)* 0 0 6.2 0 0 2.8-13.8 0 3.6 6.1 0 0.59-22.7 1.9-19.6 0.277 (0.598) 0.122 (0.727) 5.603 (0.018)* 0 0 7.3 0 0 1.7-21.3 *p ≤0.05; X2: Ji cudadrada; OR: Odds Ratio; CI: Confidence interval. Table 5. Cyberbullying as a risk factor Headaches (n=23) X2 (p) OR CI 95% Recurrent abdominal pains (n=16) X2 CI (p) OR 95% Sleep problems Alcohol use (n=10) X2 (p) OR Tobacco use (n=16) CI 95% X2 (p) OR (n=10) CI 95% X2 (p) OR CI 95% Cybervictim 0.256 0.79 0.33-1.9 0.439 1.3 0.55-3.2 0.008 1.06 0.33-3.3 0.838 0.41 0.05-2.9 0.000 1.01 0.14-7.1 (0.613) (0.507) (0.927) (0.360) (0.993) Cyberaggressor 15.125 7.9 2.2-29.6 7.997 3.7 1.40-9.7 4.299 4.4 0.94-20.8 13.923 5.4 2.04-14.4 8.304 5.1 1.55-16.8 (0.000)* (0.005)* (0.038)* (0.000)* (0.004)* Cybervíctim- 0.950 1.8 0.53-6.2 1.080 1.9 0.55-6.7 0.627 2.5 0.23-27.5 1.146 2.2 0.49-10.4 0.797 2.4 0.32-18.7 Cyberaggressor (0.330) (0.299) (0.429) (0.284) (0.372) * p≤0.05; X2: Ji cudadrada; OR: Odds Ratio; CI: confidence interval. As for the tools used for harassment, as established by other researchers,5,16 it was found that a high proportion of participants used cell phones as a primary means of CB. The cell phone, a universal communication tool that is versatile and affordable (in many cases given to the child by his/her parents) becomes an important tool of harassment. As in other studies,42,43 we were able to establish that the persons who were cyberintimidated were able to identify that those who intimidated them were of the same gender and, on the other hand, cyberaggressors also preferred to intimidate subjects of the same gender. In this sense, there are no studies identifying the reasons for this behavior. Because of the anonymity, which is characteristic of CB, we initially thought that the attackers would choose males and females alike to carry out the harassment. However, according to our observed results, this dynamic is not ne- 560 cessarily what is done. Future studies will be worthwhile to explore this situation further. As reported by other experts,29 only 13% of the identified cybervictims expressed fear from the harassment they encounter. This is probably because the cyberaggressions, at least in this study sample, did not show serious repercussions. We must not forget, however, that fear of aggression by itself promotes problems of adjustment, academic achievement, dropouts and, of course, psychopathology. It was possible to identify that >80% of youngsters spend much time at the computer. This is relevant if we consider that it has been reported that the longer students surf the net, most face the likelihood of being targeted for anonymous intimidation. We may also note that excessive internet use can foster the intention of harassing others.10,16 Bol Med Hosp Infant Mex Risk factors and consequences of cyberbullying in teenagers: association with bullying The posture that the parents take with regard to how much time their children spend in front of a computer as an entertainment tool is concerning. It was relevant to observe that more than half of the children stated that their parents do not comment about the excessive use of this tool. Either way, it would be important to explore the opinion of the parents directly, above all if we take into account that the involvement in CB most frequently begins in the computer at the home and that the observations made by the parents to the children may not be taken as a disciplinary measure. It is fundamental, nevertheless, that children be constantly supervised and informed of the risks implied in the excessive and inappropriate use of the internet. In this study we addressed the previously unreported risk variables for the development of CB as in the case of emotional symptoms (unhappiness, loss of confidence and fear) and of hyperactivity–inattention. This was all documented by the SDQ scale. Validation of this instrument that was done in the study sample allowed more certainty in regard to the results. For the role of cybervictim–cyberaggressor, hyperactivity is a significant risk factor and, for the role of cybervictims, emotional problems constituted an important risk factor. However, in both cases, confidence intervals showed a very wide and, hence, imprecise range, which may be due to lack of power of the study for these particular variables. It will be appropriate in future studies with a larger sample of participants, to once again review these elements, which obviously play an important role. The other factors considered (age, school grade and living with a single parent) should not be minimized because, as we know, these have multifactorial implications for CB. Another objective of this study was to determine whether there was an association between CB and bullying, and the implication of the latter as a risk factor. The results were positive, depending on the role played in these problems. These findings should compel teachers and parents to provide solutions not only to traditional bullying but also to the possible presence of CB, which can go unnoticed and result in severe implications for adolescents. It has been hypothesized that victims of traditional bullying will eventually become aggressors using the internet, apparently within a context of personal revenge.5,6,26 Based on the results of this study, it would be precipitious to take this circumstance into consideration—first, because the study design is not focused on approaching causality Vol. 69, November-December 2012 and because the number of participants was not larger. In a future study it would be pertinent to increase the sample size through the collaboration of several campuses and to further explore this particular relationship. Any of the CB roles can lead to the presence of psychosomatic manifestations, sleep problems and tobacco and alcohol use. Our results were consistent with the findings from other authors.30,31 The repercussions generated by this phenomenon, in varying degrees, are undeniable. Therefore, it is important to consider these eventualities, especially considering that they may become the reason for consultation in child psychiatry services. The results observed in this sample of high school students showed the prevalence of CB and the significant presence of various factors involved. If it is true that the results are not able to be generalized or are conclusive, they demonstrate, in this preliminary study, a complicated and risky reality, which unfortunately is becoming increasingly common in school populations. Early identification of CB and structuring of programs aimed at the eradication of the cases already present should be an urgent priority for parents and school authorities. Within the limitations of this study, we can cite, of course, that the sample size was not sufficient so that the results may have a higher statistical power. In fact, we observed that virtually all confidence intervals were very wide. But we reiterate that this is a preliminary study. Also, an element that may lend itself to discussion is not having had a self-administered and standardized CB instrument. However, its approach was serious, reliable, structured and similar to other previous studies.27 Due to the cross-sectional design of this study, it was not feasible to address causality. However, the results obtained are relevant and may be a guide to structure other methodological designs. We should also note that it is likely that use of the same sample to check for risk factors and consequences may have overstated the associations observed. Finally, it is always advisable to document information through other sources. Although it was not the subject of this paper, risks and consequences of CB generated by adults on minors should not be ignored. This phenomenon is unfortunately becoming more frequent and alarming. The research is still in early stages and, although there are difficulties in its approach, efforts need to be redirected to provide scientific, not only anecdotal, information. 561 Gerardo García-Maldonado, Gerardo Jesús Martínez-Salazar, Atenógenes H. Saldívar-González, Rafael Sánchez-Nuncio, Gerardo Manuel Martínez-Perales, María del Carmen Barrientos-Gómez On behalf of our team, the next project will be to expand the study to other basic secondary schools, both private and public, in the southern suburbs of Tamaulipas in order to generalize the results. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 562 Aricak T, Siyahhan S, Uzunhasanoglu A, Saribeyoglu S, Ciplak S, Yilmaz N, et al. Cyberbullying among Turkish adolescents. Cyberpsychol Behav 2008;11:253-261. 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Bullying en alumnos de secundaria. Características generales y factores asociados al riesgo. Bol Med Hosp Infant Mex 2011;68:193-202. Li Q. Cyberbullying in schools: a research of gender differences. School Psychol Int 2006;27:157-170. Ortega R, Calmaestra J, Mora-Merchán JA. Cyberbullying. Int J Psych Psychol Ther 2008;8:183-192. Ybarra M, Mitchell KJ, Wolak J, Finkelhor D. Examining characteristics and associated distress related to internet harassment: findings from the Second Youth Internet Safety Survey. Pediatrics 2006;118:e1169-e1177. Slonje R, Smith PK. Cyberbullying: another main type of bullying? Scand J Psychol 2008;49:147-154. Mesch GS. Parental mediation, online activities, and cyberbullying. Cyberpsychol Behav 2009;12:387-393. Williams KR, Guerra NG. Prevalence and predictors of internet bullying. J Adolesc Health 2007;41(6 suppl 1):S14-S21. Ang RP, Goh DH. Cyberbullying among adolescents: the role of affective and cognitive empathy, and gender. Child Psychiatry Hum Dev 2010;41:387-397. Ybarra ML. Linkages between depressive symptomatology and internet harassment among young regular internet users. Cyberpsychol Behav 2004;7:247-257. Kaltiala-Heino R, Fröjd S, Marttunen M. Involvement in bullying and depression in 2-year follow-up in middle adolescence. Eur Child Adolesc Psychiatry 2010;19:45-55. Frisén A, Jonsson AK, Persson C. Adolescents’ perception of bullying: who is the victim? Who is the bully? What can be done to stop bullying? Adolescence 2007;42:749-761. 19. Jankauskiene R, Kardelis K, Sukys S, Kardeliene L. Associations between school bullying and psychosocial factors. Soc Behav Personal 2008;36:145-162. 20. Cava MJ, Musitu G, Murgui S. Individual and social risk factors related to overt victimization in a sample of Spanish adolescents. Psychol Rep 2007;101:275-290. 21. Patchin J, Hinduja S. Traditional and nontraditional bullying among youth: a test of General Strain Theory. Youth Society; 2010. Available at: www.cyberbullying.us 22. Dehue F, Bolman C, Völlink T. Cyberbullying: youngsters’ experiences and parental perception. Cyberpsychol Behav 2008;11:217-223. 23. Ybarra ML, Mitchell KJ. Online aggressor/targets, aggressors, and targets: a comparison of associated youth characteristics. J Child Psychol Psychiatry 2004;45:1308-1316. 24. Topçu C, Erdur-Baker O, Capa-Aydin Y. Examination of cyberbullying experiences among Turkish students from different school types. Cyberpsychol Behav 2008;11:643-648. 25. Garaigordobil M. Prevalencia y consecuencias del cyberbullying: una revisión. Int J Psychol Psychol Ther 2011;11:233254. 26. Hinduja S, Patchin JW. Offline consequences of online victimization, school violence and delinquency. J School Viol 2007;6:89-112. 27. Sourander A, Brunstein Klomek AB, Ikonen M, Lindroos J, Luntamo T, Koskelainen M, et al. Psychosocial risk factors associated with cyberbullying among adolescents, a populationbased study. Arch Gen Psychiatry 2010;67:720-728. 28. Comisión Nacional de Derechos Humanos en México (CNDH). Comunicado 121. Acciones para proteger a los menores. México; 2011. Available at: http://www.cndh.org.mx/node/37. 29. Gradinger P, Strohmeier D, Spiel C. Traditional bullying and cyberbullying: identification of risk groups for adjustment problems. J Psychol 2009;217:205-213. 30. Vieno A, Gini G, Santinello M. Different forms of bullying and their association to smoking and drinking behavior in Italian adolescents. J School Health 2011;81:393-399. 31. Forero R, McLellan L, Rissel C, Bauman A. Bullying behavior and psychosocial health among school students in New South Wales, Australia: cross sectional survey. BMJ 1999;319:344348. 32. Garcia X, Pérez A, Nebot M. Factores relacionados con el acoso escolar (bullying) en los adolescentes de Barcelona. Gac Sanit 2010;24:103-108. 33. Asociación Psiquiátrica Mexicana. Programa de Actualización Continua en Psiquiatría. México: Evaluación Clínica en Psiquiatría; 2003. 34. Hinduja S, Patchin JW. Bullying Beyond the Schoolyard. Preventing and Responding to Cyberbullying. Thousand Oaks, CA: Corwin Press, A Sage Company; 2009. 35. Hinduja S, Patchin JW. Bullying, cyberbullying, and suicide. Arch Suicide Res 2010;14:206-221. 36. Patchin JW, Hinduja S. Bullies move beyond the schoolyard. A preliminary look at cyberbullying. Youth Viol Juv Justice 2006;4:148-169. 37. Woerner W, Fleitlich-Bilyk B, Martinussen R, Fletcher J, Cucchiaro G, Dalgalarrondo P, et al. The Strengths and Difficulties Questionnaire overseas: evaluations and applications of the SDQ beyond Europe. Eur Child Adolesc Psychiatry 2004;13(suppl 2):ii47-ii54. Bol Med Hosp Infant Mex Risk factors and consequences of cyberbullying in teenagers: association with bullying 38. Marzocchi GM, Capron C, Di-Pietro M, Duran Tauleria E, Duyme M, Frigerio A, et al. The use of the Strengths and Difficulties Questionnaire (SDQ) in Southern European countries. Eur Child Adolesc Psychiatry 2004;13(suppl 2):ii40-ii46. 39. Sartorius N, Janca A. Psychiatric assessment instruments developed by the World Health Organization. Soc Psychiatry Psychiatr Epidemiol 1996;31:55-69. 40. Nunnally JC. La Teoría Psicométrica. Nueva York: McGrawHill; 1978. 41. Olweus D. Bullying at School. Malden, MA: Blackwell Publishers; 1993. Vol. 69, November-December 2012 42. Raskauskas J, Stoltz AD. Involvement in traditional and electronic bullying among adolescents. Dev Psychol 2007;43:564575. 43. Vanderbilt D, Augustyn M. The effects of bullying. Pediatr Child Health 2010;20:315-320. 44. Spears B, Slee P, Owens L, Johnson B. Behind the scenes and screens: insights into the human dimension of covert and cyberbullying. J Psychol 2009;217:189-196. 45. Wang J, Iannotti RJ, Nansel TR. School bullying among adolescents in the United States: physical, verbal, relational, and cyber. J Adolesc Health 2009;45:368-375. 563 Bol Med Hosp Infant Mex 2012;69(6):564-569 Clinical case Acrodermatitis enteropathica Marco Antonio Toxtle Román,1 Ana Elena Hernández Arroyo2 ABSTRACT Background. Acrodermatitis enteropathica is a rare but easy to manage condition but with great clinical relevance. The condition must be diagnosed properly and timely. We present an infant with the following clinical triad: acral dermatitis, diarrhea and alopecia. Zinc treatment should be initiated, even from a primary care level. Clinical response is immediate and without sequelae. Case report. We present the case of an infant with chronic malnutrition, short stature, psychomotor retardation and large symmetrical scaly skin lesions with disseminated alopecia totalis. The patient was admitted to the Hospital Regional de la Huasteca, Huejutla, Hidalgo. Acrodermatitis enteropathica was suspected in the clinic and serum zinc and skin biopsy were carried out. Clinical improvement was obtained after the first 2 weeks of treatment. Conclusions. Treatment initiation with zinc sulfate at a dose of 2-5 mg/kg/day has immediate clinical implications with complete symptom remission. Key words: acrodermatitis enteropathica, zinc. “What is not considered is not diagnosed and what is not known is not thought about.” INTRODUCTION Acrodermatitis enteropathica (AE) is a rare autosomal recessive disease caused by an impairment of zinc absorption at the level of the duodenum and jejunum. It responds quickly to adequate dietary zinc supplementation.1 The genetic defect has been mapped to human chromosome 8q24.3 locus in the Slc39a4 gene identified as that encoding the zinc transporter (zip4).1-4 Diagnosis is accomplished clinically together with histopathology and laboratory studies.3 Its presentation is characterized by the clinical triad: acral dermatitis, alopecia and diarrhea (Figure 1).5 1 2 Servicio de Pediatría, Hospital Regional de la Huasteca, Secretaria de Salud, Huejutla, Hidalgo, Mexico Residente de Pediatría, Hospital General de Pachuca, Hidalgo, México Correspondencia: Dr. Marco A. Toxtle Román Servicio de Pediatría Hospital Regional de la Huasteca Secretaria de Salud Huejutla, Hidalgo, Mexico E-mail: [email protected] Received for publication: 2-17-12 Accepted for publication: 6-18-12 564 In this paper we present the case of an older infant, an AE carrier who presented a characteristic clinical picture and with favorable progress and prognosis. CLINICAL CASE We present the case of an older male infant who at the time of admission was 2 years and 10 months of age. The patient was from a low socioeconomic background. He was the third child of a 39-year-old mother who admitted to an unwanted pregnancy. The mother received regular prenatal care and there was no report of intake of iron and folic acid. The infant was born after 40 weeks of gestation through vaginal delivery in a primary care center. Birth weight was 2500 g and length was 48 cm. Apgar is unknown. Regarding psychomotor development, the infant presented head support (2 months), social smile (5 months), sitting (8 months), standing (9 months), and walking (1 year 6 months) with assistance only. The patient had poor language development (disyllabic). He was breastfed for 1 year. Weaning was accomplished on the basis of fruits and vegetables from 4 months of age. The patient became integrated to the family diet at 1 year of age. When breastfeeding was stopped at 1 year of age, the patient began Bol Med Hosp Infant Mex Acrodermatitis enteropática to have angular cheilitis and erythematous, symmetrical, well-defined lesions associated with erosions, crusts and exudate on the face, neck, lower back and limbs (Figure 2) between 5 and 10 cm diameter and covering areas of flexion (Figure 3). Paronychia and onychodystrophy were also present (Figure 4). Subsequently, total alopecia of the scalp, eyebrows and eyelashes appeared (Figure 1). There were intermittent periods of diarrhea from 1½ years of age with clinical data of malnutrition and failure to thrive. Neurologically, the patient alternated with episodes of irritability and apathy. He received multiple treatments at a primary care hospital with amoxicillin, hydrocortisone and colloidal baths, without improvement. At the time of his admission to the Hospital Regional de la Huasteca, he was evaluated by the emergency department with the following diagnoses: febrile syndrome of 1 week evolution (38–39°C), generalized dermatosis, and acute diarrhea manifested by five to six bowel movements diminished in consistency and accompanied by non-bloody mucus. The infant suffered from chronic malnutrition from 1 year of age. An evaluation was requested by our Department of Pediatrics due to suspicion of AE with the clinical triad of alopecia, chronic diarrhea and periorificial acral dermatitis, along with changes in mood, alternating with periods of apathy and irritability. younger than his chronological age. He was irritable and frightened, seeking his mother’s protection. The skull was without exostosis or depressions and there was total alopecia including eyebrows and eyelashes. Eyes were symmetrical with isochoric and normoreflexic pupils, photophobia, conjunctivitis and blepharitis, well-set ears, and choanal permeability. Oral cavity was normal with intact palate. There were erythematous, symmetrical, oozing, scaly lesions on the face, neck, periorbital and perioral regions, and covering the cheeks. The patient had characteristic angular cheilitis (perlèche). The patient’s lips were dry and the mucous membranes were poorly hydrated (Figure1). Chest demonstrated normal dimensions with a large, ~12 cm erythematous and weeping lesion in the lumbosacral region (Figure 2). The lesions covered the diaper area and inguinal and gluteal regions as well as hyperkeratotic zones in the areas of flexion of the lower Physical Examination Physical examination revealed weight 7500 g, height 80 cm, and head circumference 49 cm. The patient appeared Figure 1. Alopecia of the scalp, eyebrows and eyelashes. Vol. 69, November-December 2012 Figure 2. Large weeping lesions in the lumbosacral and gluteus regions. 565 Marco Antonio Toxtle Román, Ana Elena Hernández Arroyo Figure 3. Erythematous lesions in the genital and perineal regions. Figure 5. Lesions on the face 5 days after treatment. and upper extremities (Figure 3) along with paronychia and onychodystrophy (Figure 4). There were impetiginous lesions in the face and diaper area. No cardiovascular alterations were reported. The abdomen was soft without organomegaly or lesions. Extremeties were hypotrophic. There were clinical data of third-degree malnutrition with 45% weight deficit. Laboratory Analysis Figure 4. Paronychia and onychodystrophy. 566 The following laboratory results were reported: hemoglobin 12.3 g/dl, hematocrit 38.5%, WBC 32,800, platelets 219,000; glucose 70.5 mg/dl; urea 18.2 mg/dl; creatinine 0.5 mg/dl. There were 38-40 leucocytes/high power field (hpf), bact+, erythrocytes 0/2 hpf, Na 134.7 mEq/L, K 5.6 mEq/L, and Cl 108 mEq/L, albumin 3.36 g/dl, total protein 5.55 g/dl, TGO 23 U, TGP 26 U, and ALP 348 U. Bol Med Hosp Infant Mex Acrodermatitis enteropática to cover impetiginized lesions with marked improvement (Figures 5 and 6). As for recovery of nutritional status, the patient was managed with a high-protein and high-calorie diet (800 kcal). Diet was supplemented with Pediasure for 2 weeks and the patient was started on parenteral trace elements. For urinary tract infection and diarrheal syndrome, the patient was administered amikacin (21 mg/ kg/day) and metronidazole (30 mg/kg/day). Skin lesions were managed with topical zinc sulfate in the form of a poultice three times daily and sweet almond oil. Around the diaper area, topical myconazole was added empirically for clinical suspicion of likely cutaneous candidiasis. For correction of zinc deficiency, oral zinc sulfate was initiated (5 mg/kg/day). Improvement was observed from the first 2 weeks of treatment initiation (Figure 7). Outpatient follow-up was continued monthly for 6 months with administration of zinc sulfate (5 mg/kg/day). The patient showed hair growth and recovery from the alopecia of the eyebrows and eyelashes 1½ months after Figure 6. Skin lesions of the extremities 7 days after treatment. Fecal cytology reported positive for sugar reducers; gram stain, gram-positive cocci (+), gram negative bacilli (+); PMN 69%, positive for fresh ameba and E. histolytica cysts (+). Serum levels of zinc were 41 mg/dl (normal values 50–120 mg/dl). Skin Biopsy (Left Hip) We observed loss of epidermal epithelial lining. The baseline showed melanin deposits with substitution of countless erythrocytes and polymorphonuclear leukocytes infiltrating the wall. In the lamina propria there were lymphocytic nodules and plasma cells. Severe chronic nonspecific dermatosis was reported associated with melanin incontinence. Treatment For correction of the patient’s hydration status, a crystalloid bolus was administered at 20 ml/kg/dose and i.v. fluids at 150 ml/kg/day were administered. Antibiotic coverage was initiated with dicloxacillin (50 mg/kg/day) Vol. 69, November-December 2012 Figure 7. Disappearance of the lesions of the head and lumbosacral regions after 1½ months. 567 Marco Antonio Toxtle Román, Ana Elena Hernández Arroyo treatment initiation (Figure 8). The patient had a significant weight gain with a weight of 12,600 g (10th percentile) and height of 85 cm (3rd percentile) recorded. DISCUSSION Primary AE is a rare autosomal recessive disorder due to deficiency or absence of a zinc ligand at the intestinal level.7,8 Its presentation is 1:500,000 cases in infants with a 1:4 risk of transmission from parents to children without predilection for race or gender.3,9 The most common age of symptom onset is during the first months of life immediately after the replacement of breast milk by dairy milk.6 Clinical presentation is striking with characteristic skin lesions. Treatment is fairly simple and based on zinc sulfate. Full recovery of skin lesions and nutritional status is achieved (Figure 9).10 Because breast milk has a better zinc bioavailability in relation to cow’s milk, breastfeeding has a protective function, which justifies the clinical presentation after its interruption.6,11,12 The functions of zinc have been organized into three categories: catalytic, structural and regulatory. Zinc deficiency can cause growth retardation, immune system dysfunction, male hypogonadism, skin lesions and neurological disorders in humans.2,13 Figure 9. Complete recovery of the alopecia, of the skin lesions and nutritional status 3 months after treatment. Figure 8. Hair growth of the scalp and eyebrows after 1½ months of treatment. We must consider this disease each time we are presented with a patient with features of alopecia, diarrhea and acral and periorificial dermatitis. Within the differential clinical diagnoses that must be considered are the following: pellagra, seborrheic dermatitis, disseminated candidiasis, hypovitaminosis, fatty acid deficiency and isoleucine deficiency. Histopathological examination of the skin can be useful in ruling out pathologies such as contact dermatitis and seborrheic dermatitis. However, the diagnosis is essentially clinical.6 There may also be secondary or acquired zinc deficiency from various causes such as prematurity, parenteral nutrition, kidney disease, pancreatic insufficiency, diuretic use, infections, malabsorption syndromes, intestinal surgery, diets high in phytates and calcium, and neoplasms.6 The importance of clinical diagnosis, corroborated with serum zinc and timely treatment, even from a primary care level should be emphasized because serum zinc levels rapidly 568 Bol Med Hosp Infant Mex Acrodermatitis enteropática normalize once supplement are initiated. Treatment duration is prolonged and frequently must continue for life.14,15 This case is notable because of the striking chronic skin lesions presented by the patient, the time of evolution and the age of the patient, which was even confused with immunodeficiencies or neoplastic process. The patient also presented angular cheilitis and characteristic paronychias, which comprise early manifestations of primary AE, as well as lesions in the extremity folds, which are not seen in acquired AE.6 Our patient evolved rapidly with a complete recovery of nutritional status, skin lesions with hair growth and clinical improvement in psychomotor development. It coincides with the cases reported in the literature, which note an evident clinical improvement immediately after zinc supplementation is begun. However, there are a limited number of cases reported of older infants, such as is the case in our patient, probably because the diagnosis is not suspected or is delayed. Finally, it should be mentioned that major diagnostic and therapeutic resources are not required, only suspicion of the existence of the disease and timely initiation of management at any level of care. 2. Acknowledgments 11. We appreciate the collaboration of Drs. Jazibe Sahira Moreno Castillo (Departamento de Enseñanza), Jorge Luis Ortuño Miranda (Servicio de Cirugía) and Erasmo García Juárez (Servicio de Laboratorio). 3. 4. 5. 6. 7. 8. 9. 10. 12. 13. 14. REFERENCES 15. 1. Wang K, Zhou B, Kuo YM, Zemansky J, Gitschier J. A novel member of a zinc transporter family is defective in acrodermatitis enteropathica. Am J Hum Genet 2002;71:66-73. Vol. 69, November-December 2012 Dufner-Beattie J, Weaver BP, Geiser J, Bilgen M, Larson M, Xu W, et al. The mouse acrodermatitis enteropathica gene Slc39a4 (Zip4) is essential for early development and heterozygosity causes hypersensitivity to zinc deficiency. Hum Mol Genet 2007;16:1391-1399. Maverakis E, Fung MA, Lynch PJ, Draznin M, Michael DJ, Ruben B, et al. Acrodermatitis enteropathica and an overview of zinc metabolism. J Am Acad Dermatol 2007;56:116-124. Küry S, Dréno B, Bézieau S, Giraudet S, Kharfi M, Kamoun R, et al. Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet 2002;31:239-240. Rubio I, Ascione I, Glaussiuss G, Salmentón M. Acrodermatitis enteropática. Arch Pediatr Urug 2001;72:298-302. Bressan G, Oliveira V, Parolin L, Taniguchi K, Giraldi S. Acrodermatitis enteropática: descripción de siete casos y revisión de la literatura. Dermatol Pediatr Lat 2006;4:211-216. Moynahan EJ. Letter: Acrodermatitis enteropathica: a lethal inherited human zinc-deficiency disorder. Lancet 1974;2:399400. Avellaneda CF, Cruz CM, Palacio CA. Acrodermatitis enteropática, un reto diagnóstico. Reporte de un caso y revisión de la literatura. Rev Fac Med 2009;17:150-154. Van Wouwe JP. Clinical and laboratory assessment of zinc deficiency in Dutch children. A review. Biol Trace Elem Res 1995;49:211-225. Sandström B, Cederblad A, Lindblad BS, Lönnerdal B. Acrodermatitis enteropathica, zinc metabolism, copper status, and immune function. Arch Pediatr Adolesc Med 1994;148:980-985. Coelho S, Fernandes B, Rodrigues F, Reis JP, Moreno A, Figueiredo A. Transient zinc deficiency in a breast fed, premature infant. Eur J Dermatol 2006;16:193-195. Prasad AS. Zinc: an overview. Nutrition 1995;11(suppl 1):9399. Prasad AS. Zinc deficiency. BMJ 2003;326:409-410. Álvarez P, Pais ME, Hernández M, Soliani A, GarcíaDíaz R. Acrodermatitis enteropática. Arch Argent Pediatr 2007;105:536-538. Radja N, Charles-Holmes R. Acrodermatitis enteropathica— lifelong follow-up and zinc monitoring. Clin Exp Dermatol 2002;27:62-63. 569 Bol Med Hosp Infant Mex 2012;69(6):570-574 Clinical case Erratic migration of Ascaris lumbricoides to the scrotum Rubén Martín Álvarez-Solís,1 Marcela Vargas-Vallejo,1 Griselda Orozco-Barrientos,2 Armando QueroHernández,2 Gabriel García-Hernández,3 David Bulnes-Mendizábal4 ABSTRACT Background. Ascaridiasis is one of the main parasitoses affecting children. The main objective is to demonstrate the case of a child with erratic migration of Ascaris lumbricoides found next to the testis in the vaginalis tunic, secondary to a perforation of Meckel diverticulum. Case report. We present the case of a school-age male patient who was treated at our clinic due to acute abdomen. Laparotomy was carried out, revealing a perforation of Meckel diverticulum with Ascaris lumbricoides free in the abdominal cavity and with migration to scrotum of female adult Ascaris lumbricoides by way of an inguinal hernia. Conclusions. We discuss the epidemiology and clinical presentation of acute abdomen of Ascaridiasis and intraoperative study. Key words: Ascaris lumbricoides, complications, erratic migration, Meckel diverticulum, acute scrotum. INTRODUCTION Acute abdomen (AA) in children is usually accompanied by the triad of vomiting, abdominal distension, and lack of bowel movements. Diagnosis is clinical and imaging techniques are used to confirm and to locate the area of the obstruction.1 The main cause of AA in children is acute appendicitis.2 However, there are other conditions that can produce symptoms and signs of AA such as intussusception, Meckel’s diverticulum or intestinal obstruction by Ascaris lumbricoides (AL).3,4 Ascariasis may cause AA when there is an intestinal obstruction due to inadequate management of AL. Sometimes it may be accompanied by bowel “volvulus.” Among the most common surgical complications is infestation due 1 2 3 División de Cirugía Pediátrica, Sevicio de Pediatría, 4Servicio de Patología, Hospital del Niño Dr. Rodolfo Nieto Padrón, Villahermosa, Tabasco, Mexico Servicio de Gineco-Obstetricia, Hospital de Alta Especialidad de la Mujer, Tabasco, Mexico Correspondence: Dr. Rubén Martín Álvarez Solís División de Cirugía Pediátrica Hospital del Niño Dr. Rodolfo Nieto Padrón Villahermosa, Tabasco, Mexico E-mail: [email protected] Received for publication: 2-17-12 Accepted for publication: 2-14-12 570 to AL. The following have been described: partial bowel obstruction, intestinal obstruction, volvulus,5,6 appendicitis7,8 and intestinal perforation.9 However, other less reported complications are cases of erratic migration to other organs and tissues, most notably to the gallbladder,10 pancreas,11 lacrimal sac12 and chest.13 The objective of this study was to present an unusual case of a school-aged child with erratic migration of AL revealed within the vaginalis tunica attached to the testis in the scrotum, whose migration was facilitated by the peritoneum vaginal ductus or indirect right-side inguinal hernia secondary to AA from a perforated Meckel’s diverticulum caused by AL. CLINICAL CASE We present the case of a 6-year-old male native to Pichucalco, Chiapas who presented a clinical picture of 24 h onset characterized by abdominal pain, fever, vomiting and no bowel movements. During physical examination, the patient appeared thin and with generalized pain. Cardiopulmonary exam was normal. The abdomen showed data of AA characterized by the presence of diffuse abdominal pain, positive rebound and abdominal irritation. McBurney, Rovsing and Blumberg signs were positive, and there was mild abdominal distension and absence of peristalsis. The patient presented with mild edema and erythema of Bol Med Hosp Infant Mex Erratic migration of Ascaris lumbricoides to the scrotum the right scrotum (Figure 1). CBC reported mild anemia, hemoglobin 9.5, leukocytosis 15,000, segments 80% with 5% bands and 5% eosinophils. Simple abdominal x-ray while standing was done, which revealed poor air distribution, air-fluid levels, absence of air in the pelvic cavity, and diffuse core opacity. There was no calcification, no antalgic column, or fecaliths (Figure 2). With this data along with the data of AA, we decided to perform an exploratory laparotomy with a preoperative diagnosis of a probable complicated appendicitis vs. AA secondary to incarcerated hernia. For this reason, a Rocky-Davis type, transverse infra-umbilical incision was made on the right side. The appendix was found to be “normal” with hyperemia. Subsequently, we looked at the terminal ileum and a Meckel’s diverticulum was located 75 cm from the valve. We found the tip to be perforated (Figure 3) with mild peritonitis; therefore, resection and ileo-ileal enteroanastomosis were performed. When conducting a thorough saline lavage of the abdominal cavity, surprisingly we found two 25-cm AL, free between bowel loops. For this reason, we decided to perform “taxis” of the jejunal ileal intestinal content (Ascaris skein) that had gone unnoticed into the colon. We cleaned the cavity with an intense washing with 2 L of saline and, prior to closure of the abdominal wall, we palpated and explored the right hemiscrotum. Due to feeling swollen and crackly, we decided to explore the right inguinal canal. We found a 25-cm adult female curled in the vaginalis tunica of the right testicle (Figure 4). It was extracted and the patient underwent inguinal hernia repair, extensively washing the area. Intravenous antibiotics were prescribed along with fasting for 7 days. Oral feeding was begun on the seventh day. The patient had a satisfactory outcome and was discharged without complications, with regular follow-ups for 2 years postsurgery. Figure 1. Abdomen and genitalia of the patient before surgery. DISCUSSION In the approach of AA in children, clinical history and physical examination are essential for the diagnosis of acute appendicitis. Laboratory tests and medical imaging tests such as abdominal x-ray usually confirm the diagnosis of acute appendicitis. However, in some cases, ranging from 5 to 10%, the clinical picture can be modified when there is prior use of painkillers or antibiotics; therefore, there may be diagnostic doubt and, subsequently, the need for differential diagnosis.14,15 Vol. 69, November-December 2012 Figure 2. Simple x-ray of the abdomen. Intestinal invagination, one of the differential diagnoses of AA, is presented most frequently in children <1 year of age. The main symptoms are vomiting, intermittent 571 Rubén Martín Álvarez-Solís, Marcela Vargas-Vallejo, Griselda Orozco-Barrientos, Armando Quero-Hernández, Gabriel García-Hernández, David Bulnes-Mendizábal Figure 3. Perforated Meckel’s diverticulum. Figure 4. Female Ascaris lumbricoides adjacent to the testicle during hernioplasty. “colic-like” pain and bowel movements characterized as “currant jelly.”16 Another differential diagnosis is Meckel’s diverticulum, which is the most common congenital malformation of the small intestine. It is present in 2% of the population and occurs as a result of incomplete obliteration of the vitelline or omphalomesenteric duct, which can occur at any age, but is most frequently reported at 2 years of age.3 Failure of involution of this duct gives rise to various residual structures. This solitary diverticulum is found on the edge of the antimesenteric bowel, usually in the terminal 60 cm of the ileum before the ileocecal valve. It is a true diverticulum because it has all three layers of the normal 572 intestinal wall. In half the cases, there were remains of heterotopic gastric mucosa or pancreatic tissue.3,17 The clinical presentation may be due to bleeding or intestinal obstruction. In pediatrics, clinical presentation that occurs most often is due to bleeding.3,17,18 Due to the characteristics of this patient, the clinical picture of AA suggests, in the first place, complicated acute appendicitis for being the most common abdominal emergency in children.8 However, the patient’s clinical picture suggested differential diagnoses with other diseases such as intestinal perforation caused by Salmonella, strangulated right inguinal hernia, volvulus or possible obstruction by Meckel’s diverticulum, among others.3 Preoperatively, there was no suspicion of any surgical complications due to ascariasis because there was no history of expulsion of Ascaris though the digestive duct and abdominal x-ray did not show the classic “bread crumb” appearance of ascariasis.5,6 AL is the second most commonly seen parasite in outpatient pediatric coproparasitoscopy at the Hospital del Niño in Tabasco.8 It is always associated with different clinical presentations ranging from chronic abdominal pain and diarrhea to more serious scenarios requiring hospitalization such as subocclusion Ascaris. On other occasions, surgical intervention is required when there is a small bowel volvulus or acute appendicitis.8 Ascariasis is a widely disseminated helminth worldwide and it has been estimated that ~25% of the population suffers from it. In Mexico, intestinal parasites are endemic with a high incidence in pediatric patients. It is found in >50% of preschoolers in the suburban areas of Mexico City and close to 100% in some of the states of the Mexican Republic such as Tabasco, Veracruz and Yucatan.6,8 It is estimated that 33% of the population suffers from it and 5% suffer from massive ascariasis.6 Ascariasis is an asymptomatic infestation. Most of the complications are caused by the rapid reproduction in the GI tract causing mechanical obstruction. Clinical presentation depends on the mechanism of the obstruction and can be acute or subacute, requiring medical or surgical treatment.5,6 Female AL parasites measure between 20 and 49 cm in length and produce 200,000 eggs/day. The fertilized eggs are excreted in the feces and must mature in the ground for 10 to 14 days before the development of the first stage larvae, which are infectious.19 The adult worms live in the Bol Med Hosp Infant Mex Erratic migration of Ascaris lumbricoides to the scrotum jejunum and ileum. Mechanical obstruction occurs when their population increases and reaches 100 to 200 worms, forming a solid mass causing obstruction, inflammation, ischemia, necrosis and even intestinal perforation.7 The adult AL may have erratic migration, i.e., the parasite may travel to other organs and ducts and is favored by many factors such as fever, diarrhea, consumption of spicy foods, prolonged fasting, anesthesia, stress and even pesticides.4,6 In the case described here, the clinical scenario of AA was secondary to perforation of Meckel’s diverticulum caused by AL. In other cases, erratic migration can occur in the bile duct, gallbladder, pancreas and mouth.6,10 Ascaris can pass through the stomach and be expelled through vomiting, or enter the bronchi and the lungs by the same motility. Through the pharynx it may enter the eustachian tube, nose, external ear by eardrum perforation, tear ducts and trachea.12,13,20 The parasite can also enter the appendix and cause acute appendicitis or transient pain that disappears when the adult parasite leaves. It can also penetrate the common bile duct and the duct of Wirsung.8 Through the formation of abscesses or fistulas, the Ascarids can move to the peritoneal cavity, pleura, lung, vagina, bladder, urethra and superficial lymph nodes.21 Recently, Diago-Caballero et al. published a case of the erratic migration to the heart of a pregnant woman.22 In this particular case it is thought that the adult female heartworms possibly migrated to the peritoneal cavity after perforating the Meckel’s diverticulum, later finding the peritoneovaginal duct or inguinal hernia that is indirectly on the right, introducing itself and placing itself and ending near the testicle in the scrotum. They also found AL in the abdominal cavity, supporting the diagnosis of massive or chronic untreated ascariasis. Cases have been reported in which eggs are deposited in the lamina appendiceal serosa of the uterine tube and the mesosalpinx, causing tissue parasitism and inflammation suggestive of chronicity.21 Migration to the biliary tract is the most frequently reported. It is produced by the canalicular duct, blood or lymphatics, and possibly by the peritoneal route.10,23,24 However, to date there are no case reports of erratic migration of Ascaris into the scrotum of children. Patients affected by erratic ascariasis to the appendix and female genitals may present with abdominal pain localized in the right lower quadrant, with positive McBurney point, Vol. 69, November-December 2012 Rovsing and Blumberg sign. If the inflammatory process progresses, we may find defensive or abdominal rigidity, which suggests AA as interpreted in the initial clinical scenario when the patient was referred to our facility.6,8 In literature, hematologic biometry of patients with ascariasis observed eosinophilic leukocytosis. It is usually noticeable during larval migration and erratic migration of the adult heartworms but tends to decrease and, at times, disappear during the chronic intestinal phase of the infection.19 In this case, the patient was admitted to the emergency department with abdominal pain and was diagnosed with acute appendicitis, the reason for which he was taken to surgery. Abnormal eosinophilic values were observed at the time of the patient’s hospital admission, suggesting geo-helminth infection. This may have originated, from the beginning, as the diagnosis of intestinal parasites as a cause of abdominal pain.5-7 The pathological findings of the patients with erratic ascariasis are directly related with the inflammatory process during the erratic migration. Macroscopically, multiple yellow nodular masses were observed of welldefined fibrous tissue in the affected organs, as in other granulomatous lesions, measuring between 0.1 and 3 cm. They can be observed in the mesentery, in the visceral peritoneum and in the parietal, resembling tuberculosis.20,21 Histopathological findings consist of a granulomatous inflammatory process with fibroblastic reaction. Granulomas are composed of epithelioid cells, lymphocytes, giant cells to foreign body that sometimes engulfs eggs, abundant eosinophils and, occasionally, Charcot-Leyden crystals.25 Macrophages recognize the presence of the parasite and try to destroy it before giving a cellular and humoral immunological response. Macrophages as well as granulocytes generate reactive O2 intermediaries that lead to the destruction of the parasite. Eosinophilic response is triggered when the parasite is too large to be phagocytized, although its phagocytosis capacity is lower than by neutrophils.26-28 Ascaris was found in liver lesions during different stages of their life cycle.21 For patient diagnosis of Ascariasis, the presence of the parasite, in any form, in tissue, fecal matter or other samples is required. In Mexico, Vargas et al. described the perforation of Meckel’s diverticulum by AL as a rare complication and, if not timely diagnosed, usually has fatal consequences.25 573 Rubén Martín Álvarez-Solís, Marcela Vargas-Vallejo, Griselda Orozco-Barrientos, Armando Quero-Hernández, Gabriel García-Hernández, David Bulnes-Mendizábal In the current case we described how we managed the patient according to the findings and in a manner most appropriate at that time. Although it would cause some controversy to first explore the inguinal canal and then perform exploratory laparotomy, which we are fully in agreement with, we felt that the resolution of both situations were important: first, the AA of the patient and second, the extraction of Ascaris in the scrotum, secondary to indirect inguinal hernia. A rare case of erratic migration of AL has been presented, characterized by the scenario of an AA secondary to perforation of Meckel’s diverticulum by Ascaris and migration of it towards the vaginalis tunica of the right testicle through a permeable vaginal duct, peritoneum or indirect inguinal hernia. Although in our case the eosinophilia was not as significant, it is necessary to regard it as a cause of helminthiasis in endemic areas. AL is a worm capable of migrating erratically to almost any organ and may have very different symptoms, including migration to the peritoneum and scrotum. The clinical scenario of AA in children living in ascariasis endemic areas can be a complication when considering the cause due to AL. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 574 Rebollar GR, García AJ, Trejo TR. Apendicitis aguda: revisión de la literatura. Rev Hosp Jua Mex 2009;76:210-216. Barahona JL, Wildt RD. Apendicitis aguda ¿ser o no ser? Revisión bibliográfica pediátrica. Rev Med Hondur 2009;77:99-152. Álvarez-Solís RM, Reyes-Magaña JG, Vargas-Vallejo MP, Ulloa-Patiño P, Bulnes-Mendizábal D. Divertículo de Meckel. Salud Tabasco 2002;8:51-57. Erdener A, Ozok G, Herek O, Arikan A. Abdominal complications of Ascaris lumbricoides in children. J Pak Med Assoc 1992;42:73-74. Rodríguez GA, Belmares TJ, Hernández SJ. Factores de riesgo para oclusión y suboclusión intestinal por Áscaris lumbricoides. Cir Ciruj 2004;72:37-40. Álvarez-Solís RM, Gutiérrez-Lucatero S, Vargas-Vallejo MP, Quero-Hernández A, Bulnes-Mendizábal D, Hernández SJ. Diferencias clínicas entre oclusión y suboclusión intestinal por Áscaris que puedan sugerir cirugía. Pediatr Mex 2010;12:1117. Wani I, Maqbool M, Amin A, Shah F, Keema A, Singh J, et al. Appendiceal ascariasis in children. Ann Saudi Med 2010;30:63-66. Álvarez-Solís RM, Graham-Zapata LF, Montalvo-Marín A, Ulloa-Patiño P, Vargas-Vallejo MP. Apendicitis aguda asociada a parásitos en el apéndice. Bol Med Hosp Infant Mex 1999;56:10-17. 21. 22. 23. 24. 25. 26. 27. 28. Chawla A, Patwardhan V, Maheshwari M, Wasnik A. Primary ascaridial perforation of the small intestine: sonographic diagnosis. J Clin Ultrasound 2003;31:211-213. De la Fuente-Lira M, Molotla-Xolalpa C, Rocha-Guevara ER. Biliary ascariasis. Case report and review of the literature. Cir Cir 2006;74:195-198. Kenamond CA, Warshauer DM, Grimm IS. Ascaris pancreatitis. Radiographics 2006;26:1567-1570. Kumar V. Parasitic invasion of the lacrimal sac. Vestn Oftalmol 2003;119:45-46. Zamora-Almeida O. Localization of Ascaris lumbricoides in the thoracic cavity. Report of a case. Rev Cubana Med Trop 1976;28:71-75. Nadler EP, Reblock KK, Vaughan KG, Meza MP, Ford HR, Gaines BA. Predictors of outcome for children with perforated appendicitis initially treated with non-operative management. Surg Infect (Larchmt) 2004;5:349-356. Newman K, Ponsky T, Kittle K, Dyk L, Throop C, Geiseker K, et al. Appendicitis 2000: variability in practice, outcomes, and resource utilization at thirty pediatric hospitals. J Pediatr Surg 2003;38:372-379. Ibrahim-Ibrahim A. Prolapsed ileocolic intussuception. Ann Pediatr Surg 2011;7:76-78. Vane DW, West KW, Grosfeld JL. Vitelline duct anomalies. Experience with 217 childhood cases. Arch Surg 1987;122:542547. Park JJ, Wolff BG, Tollefson MK, Walsh EE, Larson DR. Meckel diverticulum: the Mayo Clinic experience with 1476 patients (1950-2002). Ann Surg 2005;241:529-533. Holland CV. Predisposition to ascariasis: patterns, mechanisms and implications. Parasitology 2009;136:1537-1547. Goyal A, Vishwakarma SK, Kumar R. Abnormal migration of ascaris to the middle ear. Indian J Pediatr 1998;65:147148. Baeza HC, Godoy EA, Sánchez FL, García CL, Nájera GH. Coledocoascariasis. Bol Med Hosp Infant Mex 2002;59:786-791. Diago-Caballero D, García-Valdés R, Salabarria-Fernández M. Áscaris lumbricoides en el corazón de una gestante. Rev Cubana Obstet Ginecol 2011;37:243-250. Cáceres Z, Arredondo C, González I, Landaeta N, Moreno E, López C, et al. Absceso hepático ascardiano en la migración errática de Áscaris lumbricoides en niños. Rev GEN 2007;61:262-265. González AH, Regalado VC, Van den Ende. Non-invasive management of Ascaris lumbricoides biliary tract migration: a prospective study in 69 patients from Ecuador. Trop Med Int Health 2001;6:146-150. Vargas-González R, Camacho-González C, García-Galicia A. Clinical images in gastroenterology. Perforation of Meckel’s diverticulum by Ascaris lumbricoides. Rev Gastroenterol Mex 2005;70:324. Hopkin J. Immune and genetic aspects of asthma, allergy and parasitic worm infections: evolutionary links. Parasite Immunol 2009;31:267-273. Keiser J, Utzinger J. Efficacy of current drugs against soiltransmitted helminth infections: systematic review and metaanalysis. JAMA 2008;299:1937-1948. Llop-Hernández A, Valdéz-Dapena VM, Zuazo-Silva JL. Ascaris. Microbiología y Parasitología Médicas. La Habana: Editorial Ciencias Médicas; 2001. Bol Med Hosp Infant Mex Bol Med Hosp Infant Mex 2012;69(6):575-588 Clinicopathological case Acute respiratory failure secondary to Bordetella pertussis infection in a 4-month-old infant Sarbelio Moreno Espinosa,1 Bárbara Inés Morales Mérida,2 Carlos Alberto Serrano Bello,3 Orlando Domínguez Pacheco,4 Olga Camaño Andrade,5 Rubí Rojas Padilla,5 Ernesto Calderón Jaimes6 SUMMARY OF THE CLINICAL HISTORY (A-11-10) We report the case of a 4-month-old infant who presented to the Emergency Service due to a clinical picture of cough and rhinorrhea. The patient was fed exclusively with maternal breast milk. She followed eye movements from 1 month of age, social smile was noted and she was able to hold her head up at 2 months of age. She received immunization with bacilli Calmette-Guerin (BCG) and hepatitis B at birth but did not receive the remainder of the vaccines. Family History The patient’s mother is a 32-year-old healthy, married housewife with a primary education. The father is a healthy, 32-year-old male with a primary education and works as a driver. Four siblings aged 8 to 15 years were reported as healthy. Both maternal and paternal grandparents have diabetes mellitus. Nonpathological History The family has a low socioeconomic status. They are originally from and reside in Iguala, Guerrero. They live in their own home with four rooms to accommodate six people. There is no potable water or drainage. There are adequate hygiene facilities. The home is shared with a dog. 1 2 3 4 5 6 Departamento de Infectología, Departamento de Terapia Intensiva, Departamento de Imagenología, Departamento de Patología, Departamento de Pediatría, Subdirección de Servicios Auxiliares de Diagnóstico, Hospital Infantil de México Federico Gómez, México D.F., México Correspondence: Dr. Sarbelio Moreno Espinosa Departamento de Infectología Hospital Infantil de México Federico Gómez México, D.F., México E-mail: [email protected] Received for publication: 10-23-12 Accepted for publication: 10-30-12 Vol. 69, November-December 2012 Perinatal and Pathological History The patient was the product of a fifth pregnancy. The mother received prenatal care from the second month of gestation with folic acid and iron intake and tetanus toxoid was given. Two obstetrical ultrasounds were done and reported as normal. Term delivery took place at the hospital and the newborn had a birth weight of 3500 g. The mother was discharged at 24 h without complications. The mother denied any history of allergies, surgeries, trauma, transfusions or exanthems. Present Illness The patient’s current condition began 27 days prior to her hospital admission with sudden nonprogressive, watery rhinorrhea along with sneezing. Seven days later she presented with long bouts of coughing 20 days before admission, which began suddenly, becoming progressive and with respiratory pause at the end. No time schedule was noted or cyanosis, dyspnea or hemoptysis. February 12, 2011 The patient was seen at a second-level care hospital with progressive cough, cyanosis, and without hemoptysis. Blood test was performed and showed leukocytes of 40,000, increasing to 78,000 at 48 h. Chest x-ray was done and showed bilateral perihilar infiltrate and air trapping. Antibiotic treatment was administered with erythromycin 575 Sarbelio Moreno Espinosa, Bárbara Inés Morales Mérida, Carlos Alberto Serrano Bello, Orlando Domínguez Pacheco, Olga Camaño Andrade, Rubí Rojas Padilla, Ernesto Calderón Jaimes for 1 day as well as ambroxol and micronebulizations. The patient was referred to Hospital Infantil de México Federico Gómez (HIMFG) with the diagnosis of coqueluchoide syndrome. There were three similar cases reported in the referral hospital during the same time period with two deaths. February 14, 2011 The patient was admitted to HIMFG. Physical Examination Physical examination demonstrated a well-hydrated female whose appearance matched her chronological age, normocephalic without depressions or exostosis. Eyes and pupils were reactive and symmetrical. Nostrils were permeable and ears were properly placed with intact tympanic membranes. Pharynx was hyperemic without exudate, posterior discharge or lesions of the oral cavity. Neck was cylindrical without adenopathy. Thorax was in alignment, respiratory movements were preserved and with thoracoabdominal dissociation. Lung fields demonstrated fine crepitant basal rales. Wheezing was absent, expiration was prolonged and lung fields were clear to percussion. There was normodynamic precordium without murmurs or added sounds. Abdomen was soft, depressible, and nontender with peristalsis. Liver was at 2-0-0 cm of the costal border. Extremities were symmetrical with redundant folds. There was preserved capillary refill and peripheral pulses. The patient was alert and reactive without neurological deterioration (Table 1). Laboratory Analysis Table 2 shows the results of the laboratory analysis. Chest X-ray There was horizontalization of the costal arches in the eighth intercostal space and bilateral perihilar infiltrate with image of “hairy heart.” Management The patient was managed with fasting, base solutions (150 ml/kg/day), glucose (6 g/kg/min), sodium and potassium (3 mEq/kg/day), calcium (100 mg/kg/day), magnesium (50 mg/kg/day), erythromycin (50 mg/kg/day), benzonatate (8 mg/kg/day), and oxygen with face mask (9 l/min). 576 February 15, 2011 The patient was evaluated by the Infectious Disease Service. Heart rate was 147/min. Respiratory frequency was 48/min. Blood pressure was 90/60 mmHg. Temperature was 36.2°C. The patient was admitted with face mask at 9 l/min, epidemiology was notified and serology for B. pertussis was requested. Patient continued with tachypnea, tachycardia, prolonged bouts of coughing, dyspnea, cyanosis and hemoptysis, with thoracoabdominal dissociation and intercostal retraction. The same management was continued with face mask at 10 l/min. February 16, 2011 At 00:16 h the patient experienced prolonged coughing with respiratory difficulty, perioral cyanosis, tachycardia (40/min) and 20% O2 saturation. Cardiac rhythm was recovered with basic resuscitation maneuvers. Rapid intubation was done on the second attempt and there were abundant secretions and edema of the vocal cords. Mechanical assisted ventilation was begun with fentanyl and midazolam and the patient was admitted to the intensive care unit. At 03:00 h, in the intensive therapy unit, a central venous catheter was placed: PVC (1 cm H2O). Due to low output, the patient was managed with crystalloids (20 mL/kg/dose) (2), PVC 7 H2O but without clinical improvement. Dobutamine was given with discrete improvement, adding norepinephrine and milrirone. The antibiotic was changed to clarithromycin (Table 3). Chest X-ray Right basal opacity suggestive of consolidation was demonstrated on chest x-ray (Figure 1). At 1600 h the patient was reported to be in critical condition. Department of Infectious Diseases suggested broadening empiric coverage against S. pneumoniae, H. influenzae type B and S. aureus, with cefotaxime (150 mg/kg/day) and dicloxacillin (100 mg/kg/day) (Figure 2). February 17, 2011 At 1100 h the patient’s vital signs were blood pressure (average 47 mmHg) with 4-sec capillary refill. The patient had tachycardia, which did not improve with the administration of crystalloids and albumin. Dobutamine, milrinone and norepinephrine were continued at the maximum dose without improvement. Hydrocortisone, vasopressin at a dose for physiological restitution with gradual increase up Bol Med Hosp Infant Mex Acute respiratory failure secondary to Bordetella pertussis infection in a 4-month-old infant Table 1. Antropometry and vital signs Weight Length CF RF SAP Temperature CP Glasgow 5,500 g 55 cm 168/min 60/min 85/55 mmHg 37.4°C 39 cm 15 CF, cardiac frequency; RF, respiratory frequency; SAP, systemic arterial pressure; CP, cephalic perimeter. Table 2. Laboratory results (2-14-11) Hemoglobin Hematocrit Leukocytes Lymphocytes Bands Neutrophils Platelets Monocytes Eosinophils 11.2 g/dL Sodium 33.3% Potassium 86,900/mm3 Chloride 42% Calcium 16% Phosphorus 32% Viral panel 563,000 Bun 6% Creatinine 4% Uric acid 136 mEq/L 4.6 mEq/L 104 mEq/L 9.1 mg/dL 5 mg/dL Negativo 4 mg/dL 0.3 mg/dL 3.3 mg/dL Table 3. Laboratory results (2-16-11) Hemoglobin Hematocrit Leukocytes Lymphocytes 10.8 g/dL IB 32.6% TB 0.21 mg/dL 0.21 mg/dL BUN Sangre Orina Bands Neutrophils Platelets PT 107,900/mm3 ALT 48% AST 14% Albumin 32% T protein 498,000 pH 14.8” PaO2 33 U Creat 36 U Na 2 g/dL K 3.7 g/dL Cl 7.3 Ca 120 P 2 mg/dL 0.4 mg/dL 121 mg/dL 18.1 mg/dL PTT INR Uric acid DB 76.8” 1.15” 1.3 mg/dL 0.06 mg/dL PaCO2 HCO3 LDH 48.8 23.7 1.7 127 mEq/L 4.1 mEq/L 99 mEq/L 9.3 mg/dL 3.9 mg/dL 69 mEq/L 33.1 mEq/L 74 mEq/L 61.8 mg/dL DB, direct bilirubin; IB, indirect bilirubin; TB, total bilirubin; PT, prothrombin time; PTT, partial thromboplastin time; ALT, alanine aminotrans ferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; INR, international normalized ratio. to 0.0012 U/kg/h and norepinephrine (2 U/kg/min) were begun. There was positive fluid balance and urine output decreased from 5.1 to 1.5 mL/kg/h during the previous night. With hyponatremia and elevated sodium/urea, a correction was made to delta 10. For hyperglycemia, glucose was reduced in the solutions. The patient presented an increase in creatinine (from 0.4-0.7 mg/dL), oliguria and metabolic acidosis and bicarbonate was administered. Mechanical assisted ventilation was continued with high parameters. Due to hemoglobin of 7 g/dL, the patient was transfused with red blood cells at 10 ml/kg/dose (Figure 3). February 18, 2011 At 1350 h, the patient had anuria during the previous 4 h without dialysis. At 1600 h, in intensive therapy department, the patient had bradycardia, hypotension and sudden desaturation with a decrease in central and periVol. 69, November-December 2012 pheral pulses. Adrenalin was administered and PVC 1-5 cm H2O was continued due to probable right heart failure. Levosimendan was begun. There was frank pulmonary edema, increase in ventilatory parameters, high index of oxygenation and decreased Kirby index, and episodes of bronchospasm that improved with salbutamol. The patient continued with anuria and metabolic acidosis and a catheter was placed for initiating peritoneal dialysis (Table 4). At 1800 h, a rigid catheter was placed and abundant clear fluid was obtained. Peritoneal dialysis was performed with standard solution at 18.8 ml/kg/dose for 2 h in the cavity, alternating with hypertonic solution for 1 h in the cavity, with some neutral and negative balance. February 19, 2011 At 2:45 h, the patient had cardiorespiratory arrest without response to 15-min resuscitation maneuvers. 577 Sarbelio Moreno Espinosa, Bárbara Inés Morales Mérida, Carlos Alberto Serrano Bello, Orlando Domínguez Pacheco, Olga Camaño Andrade, Rubí Rojas Padilla, Ernesto Calderón Jaimes A B Figure 2. (A) Follow-up projections of the same day. There is an increase in interstitial as well as reticulonodular infiltrate. (B) At the right apical level there is a zone of condensation. There is a decrease in intestinal gas. Department of Radiology (Dr. Orlando Dominguez Pacheco) Figure 1. Thoraco-abdominal projection (2-6-11). Patchy, bilateral diffuse interstitial infiltrate is observed. At the level of the abdomen, abundant intestinal gas is observed. Case Report Coordinator (Dr. Sarbelio Moreno Espinosa) We report the case of a patient from the state of Guerrero with a 4-day hospitalization at the HIMFG. During this period the patient presented multiple complications secondary to her basic condition, requiring evaluation by several of our hospital services. This was a multidisciplinary case with a great deal to learn from the events of her illness. At the same time, this case is reminiscent of a condition that is sometimes forgotten but which has become very timely. 578 Classic findings of Bordetella pertussis infection demonstrated on chest x-rays consist of diffuse bilateral reticular opacities that can coalesce into ground-glass opacities with air bronchogram, complicated by atelectasis.1 Radiographically, these findings are indistinguishable from those observed in patients with various viral respiratory tract infections or other pathogens that cause disease, primarily bronchial and peribronchial disease as observed in mycoplasma infections, Chlamydia and viral infections.2,3 Chief of the Department of Evaluation and Drug Analysis (Dr. Luis Jasso Gutiérrez) The patient’s clinical history mentioned the presence of “hairy heart.” Our colleagues who recall whooping cough are accustomed to seeing this image. In this patient, was this image there? Department of Radiology (Dr. Orlando Dominguez Pacheco) Reference is made to the ill-defined heart border due to perihilar and peribronchial infiltrate. Discussion (Dr. Barbara Ines Morales Merida) The patient was a 4-month-old female whose condition evolved during a 27-day period of her and 4 days of hosBol Med Hosp Infant Mex Acute respiratory failure secondary to Bordetella pertussis infection in a 4-month-old infant Figure 3. Thoraco-abdominal projections (2-17-11). Increased infiltrate effacing cardiac borers and hemidiaphragms. Minimal intestinal gas. Increase in volume of soft tissue. Table 4. Laboratory results (2/18/11) Hemoglobin Hematocrit Leukocytes Lymphocytes 7.3 g/dL Glucose 21.6% BUN 103,300/mm3 Creatinine 25% DB 170 mg/dL DB 4 mg/dL IB 0.7 mg/dl TB 125 mEq/L ALT 0.14 mg/dL 0.02 mg/dL 0.16 mg/dL 18 U Bands Neutrophils Platelets PT PTT INR Fibrin 28% IB 36% TB 351,000 Mg 40.5” >120” 3.42” 113 mg/dL 1.6 mg/dL Cl Mg pH PaO2 PaCO2 HCO3 2.5 g/dL 3.1 g/dL 7.04 227 45.1 11.7 3.5 mEq/L 97 mEq/L Na K 16 U 40 U CPK, creatinine phosphokinase (see Table 3 for other abbreviations). pitalization in this institution. The following syndromatic diagnoses were integrated: 1. Coqueluchoide syndrome—characterized by sudden onset of cough that was progressive, productive, cyanotic, dyspneic and with hemoptysis. There were long bouts of coughing with respiratory pause at the end. 2. Respiratory distress syndrome (RDS)—characterized by tachypnea, thoracoabdominal dissociation, fine basal rales and intercostal retractions. 3. Systemic inflammatory response (SIR) syndrome— characterized by tachycardia, tachypnea and elevated leukocytes. Based on these syndromatic diagnoses as well as the findings and results evidenced during its evolution, the following nosological diagnoses were integrated: 1. Pertussis— presence of coqueluchoide syndrome, RDS, hyperleukocytosis, and x-rays with evidence of Vol. 69, November-December 2012 air trapping, bilateral perihilar infiltrates and image of “hairy heart” as well as a history of three similar cases in the referral hospital with the death of two children. 2. Lobar pneumonia—respiratory distress without improvement after initial treatment, evolving to respiratory failure, in addition to the SIR and hypoperfusion and x-rays suggestive of consolidation. 3. Septic shock refractive to catecholamines—shown by data of sepsis with cardiovascular dysfunction and hypotension, without relief after i.v. fluid administration, vasoactive drugs, or steroids. 4. Multiple organ failure—based on the history of refractory septic shock and data of cardiovascular, hematological, renal and lung dysfunction. Important Points in the Evolution and Treatment of the Patient during Hospitalization The patient had a history of living at home with her parents and siblings, some of whom were adolescents. The 579 Sarbelio Moreno Espinosa, Bárbara Inés Morales Mérida, Carlos Alberto Serrano Bello, Orlando Domínguez Pacheco, Olga Camaño Andrade, Rubí Rojas Padilla, Ernesto Calderón Jaimes latter are risk factors for disease transmission because even though they may have had whooping cough or were immunized during infancy, immunity is not conferred for a lifetime, resulting in a risk of contagion to certain age groups. Overcrowding was observed, lack of potable water and no drainage, increasing the risk of transmission of infectious diseases. The vaccination scheme was incomplete as the patient had only BCG and one dose of hepatitis B. At her age, this patient should have had BCG, two doses of hepatitis B, two doses of acellular pentavalent including diphtheria, pertussis and tetanus (Tdap), polio (IPV) and H. influenzae type B (HiB), two doses of rotavirus and two doses of conjugated pneumococcus. Furthermore, although the patient was breastfed, this does not provide immunoprotection for pertussis. Given this background and the patient’s clinical history, notification should have been made to epidemiology and serology for B. pertussis from the time of admission to the emergency room. The patient’s clinical history noting that 20 days prior to her admission she presented with a 7-day evolution of watery rhinorrhea should have been taken into consideration from the time of admission to the emergency room—which corresponds to the catarrhal period described in whooping cough and later begins with cough, the characteristics of which are previously described and are typical of this disease and that already have an evolution of 20 days (corresponding to the paroxysmal period). Also, the absence of fever during the course of the illness is notable and is another important piece of information that may lead one to think of this diagnosis and to rule out other etiologies such as viral. Finally, I will mention the findings of hyperleukocytosis with lymphocytosis that were seen in the disease due to the pertussis toxin that increases sensitivity to histamine and promotes leukocyte dysfunction, recruiting lymphocytes that remain in the circulation; thus, the typical, previously described radiological findings of air trapping, perihilar infiltrate and image of “hairy heart.” However, it was evident that upon the patient’s admission, she had fever, respiratory difficulty and fine crepitant basal rales atypical of whooping cough. Also, younger patients may usually develop complications such as pneumonia and cultures should be taken. Empiric antibiotic treatment should be initiated for the most common bacteria seen at the age of this patient. Treatment should be initiated with nebulization to decrease 580 bronchospasm, air trapping and, as a consequence, the frequency of bouts of coughing, emesis and hypoxia. Above all, consideration should have been given that the high risk factors in this infection are that they be <6 months (because it is in this age group that 90% of the fatalities due to B. pertussis present themselves and is common for complications to develop, such as pneumonia of viral or bacterial origin, as pertussis generally does not affect the lower respiratory tracts) and that leukocyte counts are >50,000. Association between pneumonia due to B. pertussis and magnitude of the leukocytosis is described, which represents a poor prognosis. Another consideration is that at no time was there a pulse oximetry done to assess the peripheral saturation despite the degree of respiratory distress, in spite of it being a practical, accessible, inexpensive and noninvasive measure for adequate monitoring and to evaluate the response to treatment with oxygen. Because the patient was at high risk for the previously mentioned reasons, in addition to respiratory distress that did not improve with oxygen therapy and that among the most frequent complications for admission to intensive care was pulmonary hypertension (which occurs due to leukostasis and hypoxemia), she should have been admitted to intensive care from that time for strict monitoring, assessment of endotracheal intubation and blood transfusion or leukopheresis, as the number of white blood cells continued to rise. It is noteworthy that despite the increase in the flow of O2, the patient continued with increased respiratory distress and no other intervention was performed. I believe that an arterial blood gas should have been performed to again evaluate respiratory function because there was absence of clinical improvement or of PaO2. Whether or not there was hemodynamic stability, a new intervention should have been carried out which, in this case, would have been through programmed orotracheal intubation so as to limit tissue damage due to hypoxia and prevent development of pulmonary hypertension. It is dangerous to assume that the administration of supplemental oxygen is sufficient to correct a picture of hypoxemia without taking into consideration additional causes of hypoxia, as the availability of O2 depends as much on the administration of O2 as ventilation, of the O2 concentration, O2 saturation and cardiac output. Each cause should be corrected at once, but all need to be corrected. Bol Med Hosp Infant Mex Acute respiratory failure secondary to Bordetella pertussis infection in a 4-month-old infant As is expected due to the natural history of the disease, there was respiratory insufficiency precipitated by a picture of coughing bouts, which led to severe desaturation and bradycardia, and then led to laryngospasm or vagal stimuli, making it necessary to perform an urgent intubation in an untimely manner. Shock presented itself, which may have been of septic origin or secondary to a cardiac lesion due to hypoxia. Nevertheless, antibiotics should have been administered because it has been shown that in cases of septic shock there is a direct impact on the decrease in mortality with the use of antibiotics during the first hour. Once in intensive care, being intubated and in a state of shock, it was decided to change the antibiotic from erythromycin to clarithromycin, which is proven to be effective in whooping cough. It is assumed that the change was to go from oral antibiotics to i.v. because of the low absorption of the mucosa during shock. However, one must remember that the aim of early administration is to decrease transmission. The infectious period is usually in the catarrhal stage and the first 3 weeks when live bacteria still exist; however, in our patient the administration was delayed. Therefore, clinical improvement or decrease in transmission was not expected. Initial blood gas analysis showed mild respiratory acidosis with acidemia and a Kirby index of 120, which is in relation to the amount of pulmonary short circuits that do not permit adequate oxygenation. This translates as acute respiratory distress syndrome (ARDS), indicated from the outset that there was a high degree of lung injury with a predisposing factor for the development of pulmonary hypertension and, therefore, a determining factor in the evolution and outcome of the patient. In severe infections due to B. pertussis, it is reported that patients presenting with treatment-refractory pulmonary hypertension, especially those with WBC counts >60,000, experience a severe disease course with a poor outcome. Echocardiogram should have been requested to assist with diagnosis and to guide disease management. Hemodynamically, the patient showed little response to bolus administration of crystalloid solutions and presented data of heart failure due to elevation of preventricular contractions without clinical improvement. Vasoactive amines were begun (inotropic and vasopressor) as described in the guidelines for management of septic shock (2005), with a slight recovery. However, the patient presented with hypotension. This is an indication that the compenVol. 69, November-December 2012 satory mechanisms are exhausted and that the approach to the shock was probably delayed, or that the patient has pulmonary hypertension manifested by hypotension and right heart failure. Because of the continued instability, new fluid boluses were again administered, this time also colloids, which is not indicated in a patient with data of right heart failure because it increases risk of pulmonary edema. However, response to the intervention was inadequate and the patient continued to deteriorate, requiring maximal doses of amines and initiation of vasopressin at physiological doses (as described in the study of Carcillo) to counter the depletion of reserves of vasopressin and improve vasomotor tone. Hydrocortisone was also initiated as indicated in the guidelines for management of septic shock, in order to improve the hemodynamic variables and decrease the requirement for vasopressors as cortisol levels improve. Also, increase in serum creatinine, FENa of 1.22 and BUN/creatinine index ratio of 5 was observed, which points to acute renal injury probably due to shock. Strict control of urinary output and fluid balance should have been done. The patient then presented with oligoanuria, metabolic acidosis, doubling of serum creatinine, positive fluid balance and data of acute pulmonary edema. Consultation with the nephrology department should then have been done to initiate renal replacement method. The indication, in this case, was renal failure with oligoanuria and hypervolemia plus cardiac failure. It has been observed that early onset of renal replacement method in patients with heart failure improves survival. Hyponatremia with elevated urine sodium is notable and may have been related to the administration of crystalloid boluses (probably physiological solution) and fluid retention due to renal failure, which translates to hypervolemic hyponatremia—in which case there is a fluid overload, not a sodium deficit. For this reason, treatment should be on the basis of fluid restriction. It is concluded that the sodium correction done was not indicated. Finally, a peritoneal dialysis catheter was placed and large amounts of clear liquid were obtained, probably because of the fluid leak secondary to endothelial lesion due to shock. At that time it was impossible to rule out the presence of a capillary leak toward virtual spaces such as the pleura, pericardium or interstitium, which would worsen the prognosis. The ideal method for this patient, because of the hemodynamic instability, was to carry out hemo- 581 Sarbelio Moreno Espinosa, Bárbara Inés Morales Mérida, Carlos Alberto Serrano Bello, Orlando Domínguez Pacheco, Olga Camaño Andrade, Rubí Rojas Padilla, Ernesto Calderón Jaimes diafiltration. However, this was not available; therefore, peritoneal dialysis was begun as a rescue measure because the patient would not have tolerated the fluid exchanges of hemodialysis. Peritoneal dialysis was started. However, because the indication was hypervolemia, it should have been done with a hypertonic solution and more frequent exchanges to extract fluids and negate the balance with a minimal volume of 20 ml/kg per exchange. Considering the low cardiac output, poor pulmonary function and hypoperfused peritoneum as demonstrated by this patient, probability of worsening hemodynamic conditions and causing greater ventilatory restriction (mechanical) was very high and the probability of it being successful as a dialysis measure was very low. Final diagnoses were as follows: • Eutrophic female infant • Infection due to Bordetella pertussis • Acute lobar pneumonia • Acute respiratory distress syndrome • Probable pulmonary hypertension • Septic shock refractory to catecholamines • Disseminated intravascular coagulation • Multiple organ failure due to • Acute respiratory infection • Cardiovascular dysfunction • Pulmonary dysfunction • Hematological dysfunction with pneumonia can develop hypervolemic hyponatremia and, the more severe the pneumonia, the greater the risk of developing this condition. Department of Integrated Patient Care (Dr. Erick Rosales Uribe) Some important aspects that were not elaborated were the risk factors. Children <4 months presenting with leukocytosis and/or thrombocytosis have a high probability of death, close to 90%, or as expressed in another way, 90% of children who die are <4 months old. Serology was not the most appropriate method for detection of B. pertussis in this patient. The possibility of requesting PCR should have been planned for or, failing that, a culture—although this is not the most suitable method. An important fact is mentioned about prevention and the high level of success of vaccination campaigns with coverage for the first dose between 95% and 96% and up to the fourth dose of ~95%. Because of this, we see B. pertussis less frequently in children although we do see other types of Bordetella. Coordinator (Dr. Sarbelio Moreno Espinosa) Additional Information Multiplex PCR results (Respifinder): sample from February 15, 2011 1) B. pertussis 2) Coronavirus OC43 Causes of death were as follows: • Respiratory failure secondary to B. pertussis infection • Multiple organ failure 15 days later: serological test results (described as serology by InDRE with unknown origin) 1) Bordetella pertussis 2) Enterovirus Subdirector of Ambulatory Pediatrics (Dr. Edgar Bustos Cordova) We considered doing this in an open session due to the obvious diagnosis, but for clinical practice and because the etiology, outcome and prognosis were unknown, we decided to leave this information to the end. When referring to management of hyponatremia, the term “dilution” is no longer used. Today we mention hypervolemic hyponatremia and, obviously, as mentioned, the patient developed hyponatremia due to excess fluid administration. In addition, the studies were poorly evaluated. Elevated urinary sodium represents a hypervolemic (not hypovolemic) hypernatremia. We would be least interested in additional sodium intake. Usually, in these cases, a high sodium intake worsens, rather than improving, the condition as occurred in this patient. An additional factor is that it is reported that up to 25% of cases of patients 582 Pathological Findings (Dr. Carlos Alberto Serrano Bello) We describe a normally developed female weighing 5500 kg with a height of 58 cm who presented with a sutured, infraumbilical wound (0.7 x 0.7 cm) without apparent alterations and with generalized edema. Upon neck dissection, the trachea and epiglottis showed significant edema (Figure 4) which, together with the thickness of the secretions, caused the characteristic cough of the desBol Med Hosp Infant Mex Acute respiratory failure secondary to Bordetella pertussis infection in a 4-month-old infant Figure 4. Edematous epiglottis. cribed disease as well as congestion of the lower mucosa. On histological cuts we observed minimal intraepithelial inflammatory infiltrate apoptosis of some respiratory cells. Bilateral pleural effusion (45 mL) was found in the thoracic cavity. Lung parenchyma showed extensive reddish-brown areas of consolidation and indistinct borders involving both lungs, predominantly basal (Figure 5). Trachea and main bronchi exhibited only congestion. In histological sections, we observed that the majority of the alveolar spaces were filled with an intense inflammatory infiltrate, which consisted mainly of neutrophils with formation of microabscesses, necrosis of pneumocytes, cellular debris and intraalveolar edema (Figure 6). To understand the damage to the respiratory epithelium caused by microorganisms, we must remember the primary defense mechanisms present in the respiratory system, which can be synthesized for practical purposes into four major factors: 1. The respiratory epithelium itself, due to its available and histological nature, is arranged in a pseudostratified manner and with strong intercellular junctions that function as a mechanical barrier against aggressive pathogens 2. Goblet cells, epithelial cells and mucus-secreting glands project towards the lumen of the bronchial Vol. 69, November-December 2012 Figure 5. Pulmonary parenchyma with multiple areas of consolidation. Figure 6. Histological cut with alveolae occupied by inflammatory infiltrate, cellular detritus and mucus. tree mucosa, which added to cilia propulsion act as an efficient means of sweeping, but also produce ~100 chemical substances with antimicrobial effect such as defencins, lysozyme, lactoferrin, nitric oxide, IgA, etc.4,5 3. Toll-like receptors (or TLR2) that, without need of opsonins, directly recognize the microorganisms and, in turn, activate nuclear transcription factors 583 Sarbelio Moreno Espinosa, Bárbara Inés Morales Mérida, Carlos Alberto Serrano Bello, Orlando Domínguez Pacheco, Olga Camaño Andrade, Rubí Rojas Padilla, Ernesto Calderón Jaimes and interferon pathways that activate or regulate the cellular immune response 4. Finally, there are the intracytoplasmic receptors such as MDA5, which directly detect microorganisms including virus5 and these receptors can also activate the interferon pathway (Figure 7) Now, when infection exists, microorganisms and virus have the capacity of altering the first immune response so that certain viruses can increase mucus production and cause it to be thicker, making ciliary movement difficult and fostering stagnation of the mucus. This functions as a growth medium for other bacteria, facilitating their adherence to the epithelium as well as hindering molecular bactericidal activity. Other bacteria have the ability of producing certain molecules such as STAT and IFR3 that block the interferon pathway, which impedes regulation of the immune response.5 These bacteria also have proteolytic enzymes that degrade the intercellular junctions, thereby causing loss of integrity of the epithelium and facilitating invasion by microorganisms. Other microorganisms are conducive to overexpression of receptors such as I-CAM and C-CAM (Figure 8) that facilitate bacterial adhesion, causing superinfection.5 Moreover, B. pertussis has characteristic enzymes that aggravate the histopathological status of the respiratory epithelium such as pertussis toxin, filamentous hemagglutinin (FH), and pertactin, which make it more conducive to adhesion of bacteria to the respiratory epithelium. LPS and toxins cause cell death, adenylate cyclase toxin interferes with proper leukocyte activation, and tracheal cytotoxin acts on the inhibition of the ciliary motility.6 Table 5 summarizes the mechanisms of action of these toxins. In making a correlation, with alterations of the primary immune response and the action of toxins and enzymes that characterize B. pertussis, we can explain the observed histological changes in the lung, i.e., alveoli are filled with inflammatory cells. These are probably not fulfilling their function by interference of the adenylate cyclase enzyme. The presence of cellular debris, mucus and epithelial necrosis is favored by toxins such as dermonecrosis, LPS, and the pertussis toxin itself, in addition to ciliostasis (probably produced by the action of tracheal cytotoxin) and prevents clearance of these same components. This inevitably leads to poor gas exchange and, therefore, the state of complete tissue hypoxia in the patient (Figure 9). The remainder of the organs showed signs of shock secondary to a persistent 584 Figure 7. Primary defense mechanisms of respiratory epithelium. Figure 8. Overexpression of receptors such as I-CAM and C-CAM that facilitate bacterial adhesion, resulting in superinfection. state of hypoxia and hypoperfusion to which the patient was subjected (Table 6). In the myocardium, vacuolization of cardiomyocytes with macronucleation was observed. In the thymus there was calcification of Hassall’s corpuscles and reduction of lymphoid tissue. In the digestive tract, characteristic changes of hypoxic intestinal myopathy were observed characterized by contraction bands that refer to the alternating pattern of cytoplasmic staining between muscle fibers with ischemia and others more viable or better perfused. Macroscopically, the liver showed no abnormalities. In histological sections, microvesicular steatosis and dilated sinusoids were observed. In the spleen there was a decrease in lymphoid tissue in the white pulp and dilation with sinusoidal congestion. Pancreas and adrenals showed no gross or microscopic abnormalities. There was medullary congestion in the kidneys and microscopy showed acute tubular necrosis characterized by lysis and detachment of the tubular epithelium. No morphological Bol Med Hosp Infant Mex Acute respiratory failure secondary to Bordetella pertussis infection in a 4-month-old infant Table 5. Actions of virulence factors of Bordetella pertussis in the respiratory epithelium Virulence factor Biological effects Pertussis toxin Protein fixation (interference with signal transmission) FHA Media adherence to epithelial LPS Pertactin Activity of endotoxin Adherence to epithelial and immunogenic cells Contracción de musculo liso vascular Alterations of chemotaxis and leukocyte function Ciliostasis Changes in the synthesis of DNA of cellular cilia Dermonecrotic toxin Adenylate cyclase toxin Tracheal cytotoxin LPS, lipopolysaccharide; FHA, Filamentous hemagglutinin. alterations were observed in the central nervous system. However, in histological cuts, changes were demonstrated such as clear pericellular and perivascular halos with pyknosis of a variable number of neurons. Bone marrow showed secondary myeloid hyperplasia or a response to the acute inflammatory process experienced by the patient. As an independent finding, there were multiple cystic follicles in the ovaries. Results of postmortem culture media were negative, although it must be kept in mind that the B. pertussis bacteria grow on special media such as Regan Lowe or Bordet Gengou. As a principal disease, we can state that the patient had bilateral multilobar pneumonia with multiple foci along with the history of B. pertussis infection. As concomitant alterations of the principal diagnosis, we may mention the massive alveolar damage characterized by cytotoxicity and secondary ischemia of the respiratory epithelium that led to acute respiratory insufficiency due to a deficiency of the respiratory epithelial system. The remaining organs were noted to have changes due to a state of sustained hypoxia. Subdirector of Medical Assistance (Dra. Mónica Villa Guillén) Were there data of pulmonary hypertension? Dr. Carlos Alberto Serrano Bello Histologically, no data of pulmonary hypertension or pulmonary vascular disease were demonstrated. Coordinator (Dr. Sarbelio Moreno Espinosa) Figure 9. Cellular hypoxia. (A) Necrosis of pneumocytes. (B) Cellular detritus, accumulation of mucus due to ciliostasis. (C) Inadequate leukocyte function. Table 6. Histological changes secondary to persistent hypoxia Organ Histology Thymus Fluid depletion, califications of hassal corpuscles Liver Kidneys Digestive tract CNS DHS ATN Hyproxic myopathy Grave hypoxic encephalopathy DHS, diffuse hepatic steatosis; ATN, acute tubular necrosis; CNS, central nervous system Vol. 69, November-December 2012 As can be seen, a cascade of events occurred. B. pertussis can cause changes, locally as well as distant, that may explain these series of events. Chief of Ambulatory Care and Emergency Department (Dr. Victor Olivar Lopez) I see the opposite situation. Here is a patient with B. pertussis complicated by pneumonia due to coronavirus. It is difficult for me to think otherwise, especially because there is a history of three patients with infection due to B. pertussis in the referral hospital. In contrast, up to 25% of patients with B. pertussis have some type of complication, some with bacteria and other viruses. From the clinical condition in which the patient arrived, I think there was an added viral picture, which explains the bronchospasm mentioned by Dr. Barbara Morales. With respect to the 585 Sarbelio Moreno Espinosa, Bárbara Inés Morales Mérida, Carlos Alberto Serrano Bello, Orlando Domínguez Pacheco, Olga Camaño Andrade, Rubí Rojas Padilla, Ernesto Calderón Jaimes approach, this case is very interesting because it exemplifies what we are seeing today, but also in a patient whose age places her in a high-risk age group for dying. The first thing we must evaluate, in terms of respiratory distress and respiratory failure, is the approach to the airway and oxygen. Obviously, as soon as there is suspicion, the patient should be placed under isolation. We had the advantage of knowing the history. I also clarify that, in the hospital, there is a basic monitoring system, which has pulse oximetry. In fact, it is stated here that the patient desaturated when this catastrophic event occurred. In this type of patient with this serious condition, we refer to it as chronic pertussis.7 The natural history of these patients includes the expected symptoms of apnea, desaturation, cyanosis and bradycardia. Fortunately, it occurs in only 1% of patients. It is my opinion that the patient was monitored. However, these events cannot be avoided, probably due to the interaction of some pertussis strains that favor the development of multiple organ failure, as previously mentioned. Under the best of situations, even in patients with extracorporeal oxygenation systems, 70% of patients will die. Regarding oxygenation systems, it is initially free flow and such systems are incorporated as required. I postpone the CPAP because the respiratory pause from the cough of the patient with B. pertussis is precisely an inspiratory pause, and the individual objective is to increase the inspiratory, not expiratory, pressure. If this patient had prolonged expiration and some stigmatas, in my opinion it was because there was an added viral infection. The patient should be admitted, a differential diagnosis made, and the patient should be kept under strict isolation. Mandatory reporting is made, as was done in this patient. The patient is monitored for any complications that may arise and is managed in the emergency room. tional literature increasingly better clarifies this fact. It is believed that up to 70% in this series of illnesses is caused purely by infections due to B. pertussis, without relation to a different superimposed bacteria.6 The term “coqueluchoide syndrome” encompasses signs and symptoms that occur in whooping cough, which may be caused by other agents such as adenovirus, Chlamydia, Mycoplasma and others. Due to the lack of access to appropriate diagnostic methods and the belief of the infallibility of the vaccine that it confers lifelong immunity, we have taken refuge in this term. With the introduction of molecular methods and a better understanding of this agent and its epidemiological changes, it is increasingly more difficult for us to confuse this disease. It can be proven that in the majority of cases in which patients present convulsive or paroxysmal coughing, with vomiting after coughing and stridor at the end of the inspiration, we are dealing with a B. pertussis infection because a clinical picture of whooping cough can only be compared with another clinical picture of whooping cough. For this reason, the term coqueluchoide syndrome is becoming less effective. Coordinator: (Dr. Sarbelio Moreno Espinosa) Coordinator (Dr. Sarbelio Moreno Espinosa) Typically, a viral infection is the pivot for establishment of a bacterial infection. It has been seen that coronavirus infections, which is not the coronavirus of SARS, but that which causes the common cold, rhinovirus, parainfluenza and others, cause ciliostasis favoring the introduction of a bacterial infection. When there is pneumonia superimposed on a clinical picture of pertussis, we have a bacterial infection. Although a clinical picture of pertussis may be complicated by a superimposed bacterial pneumonia, B. pertussis per se can cause pneumonia. In fact, the interna- 586 Commentary (Dr. Erick Rosales Uribe) When we speak about coqueluchoide syndrome, we refer to a clinical spectrum that includes, in addition to B. pertussis, viral agents such as adenovirus, parainfluenza and respiratory syncytial virus. We also include Mycoplasma pneumoniae and other Bordetella species such as parapertussis, bronchiseptica and holemsi. According to the characteristic clinical picture, one could declare that we are dealing with B. pertussis. Because there was access to PCR it would be interesting to know which primer was used to determine if it was B. pertussis or another species of Bordetella. On this occasion, in addition to the IS481 that identifies a common element of insertion to other Bordetella species and has the highest sensitivity, we used ptxS1 primer that identifies the subunit 1 promoter of the pertussis toxin, giving the specificity for B. pertussis. Commentary (Dr. Ernesto Calderón Jaimes) There are several aspects to consider in this case. From the epidemiological point of view, the disease acquired characteristics of severe illness. Situations of the pathogen Bol Med Hosp Infant Mex Acute respiratory failure secondary to Bordetella pertussis infection in a 4-month-old infant and host are combined. B. pertussis has, in the filamentous hemagglutinin (FHA) and in several of the fimbriae (FIM), two of the most potent adhesins. The first is a protein secreted at the surface and the second is a filamentous, also superficial, structure. Both are highly immunogenic. Pertussis toxin and pertactin are elements of pathogenicity and virulence as well as LPS and other toxins. There are receptors in the tracheobronchial mucosa, specifically in the ciliated cells and in mucin-producing cells. B. pertussis acts locally: it does not invade and it adheres firmly in situ and, from there, releases its toxins. B. pertussis has various phenotypes. During minor outbreaks, a clone with a gene vir/Bvg dominates, which makes products such as FHA, FIM, FRN, PT and LPS, function as a superantigen, increases the capacity for adherence and directly activates T lymphocytes. This results in an intense, uncontrollable and aberrant cascade of different water-soluble products that modulate the response, both at the interstitial level as well as in the mucociliary apparatus. Exotoxins are responsible for a marker of severity expressed in blood studies with leukemoid, leukocytosis and lymphocytosis counts. On the side of the host there are crucial aspects: 1) age, 2) not having been vaccinated with pertussis toxoid vaccine, and 3) being involved in an outbreak with virulent clones where three of four children died. The mucociliary apparatus suffers the assault. Its response disrupts ciliary function, and the mucins are now more abundant, thick and difficult to expectorate. The lung “obstructs” with interstitial edema and occupied alveolar syndrome, dramatically altering the gas exchange. Cyanosis is prevalent and pulmonary hypertension leads to a cardiopulmonary component, becoming irreversible on not stopping the inflammatory cascade. Although pertussis is typically described as a highly infectious disease, transmission requires intimate contact and prolonged exposure. Neither the disease nor the vaccination confers permanent immunity, explaining why the accumulation of susceptibility allows an outbreak to occur every 2-5 years. The only postvaccine change occurs in the population exposed to disease risk. Prior to 1980, the most affected population was young children, including children <1 year of age, most of whom were unvaccinated. Vaccination now changes the population of adolescents and adults who are contracting the disease. Vol. 69, November-December 2012 Undoubtedly, B. pertussis is internationally accepted as well as cases of whooping cough in adolescents and adults. Recognition of cases is based on patients who are “coughers” with an evolution of >2 weeks. Pediatric Commentary (Dra. Rubí Rojas Padilla) Prior to the availability of the vaccine, B. pertussis was a common cause of morbidity and mortality in children. After the introduction of the vaccine in the 1940s, incidence of the disease began to decrease and reached an incidence of one case/100,000 population between 1980 and 1990. However, the incidence has been increasing since the 1980s. Between 2001 and 2003 the highest annual incidence was found in patients <1 year of age and, particularly, in those <6 months (100 cases/100,000). In recent years, the incidence has increased in adolescents and adults, a reason why vaccination in these age groups has become very important to prevent transmission to young children. The acellular vaccine has inactivated components of B. pertussi cells. It is combined with tetanus and diphtheria toxoids and is used in children between 6 weeks and 6–7 years of age. Recommended doses are at 2 months, 4 months, 6 months, and between 15 and 18 months of age. For adolescents and adults, the acellular vaccine is combined with tetanus toxoid and a smaller quantity of diphtheria toxoid, compared with the pediatric vaccines. It is recommended in persons between 10 and 64 years of age. In persons between 11 and 18 years of age who completed the vaccination schedule against Bordetella pertussis in childhood, the application of a single dose of Tdap vaccine is recommended. Similarly, its application is recommended in patients between 7 and 10 years of age who did not receive a complete vaccination scheme against B. pertussis and in adults 65 years of age or older who are expected to have contact with a child <12 months of age. All women of childbearing age should receive a dose of Tdap. Women who did not receive the vaccine should receive the dose in the immediate postpartum. Td administration is recommended during pregnancy but, under certain circumstances, Tdap can be administered, especially if a B. pertussis outbreak is documented in the community or in pregnant adolescents. Health care workers who work in hospitals and have direct patient contact should receive a single dose of Tdap as soon as possible, especially personnel in contact with patients <12 months of age. 587 Sarbelio Moreno Espinosa, Bárbara Inés Morales Mérida, Carlos Alberto Serrano Bello, Orlando Domínguez Pacheco, Olga Camaño Andrade, Rubí Rojas Padilla, Ernesto Calderón Jaimes The epidemiological justification for booster vaccination against whooping cough is based on the fact that the individual effectiveness of the vaccine is between 70 and 80% with protection of limited duration. Because of this, there has been a disease transition to older age groups, who transmit it to vulnerable infants. The new epidemiology of whooping cough has a close relationship with the vaccine coverage. Where coverage is low, there will be a high incidence in children. However, in areas where the coverage is high, we see a low incidence in children with a gradual decrease in the immunity of adolescents and adults who may have the disease and transmit it to infants who are not vaccinated or have been partially vaccinated. Also, it is important to take into account that 75% of infant cases were infected by family members, of which the mother was the most frequent transmitter because she has the closest contact with this vulnerable age group. Regarding the duration of the immune response, recent studies suggest that the acquired immunity for infection could be as short as 3.5 years in children, and the protection provided by the vaccine between 4 and 12 years. Also, the protective immunity after a natural infection decreases after 7 to 20 years. For all these reasons, the use of acellular vaccines and boosters is a priority for protection of adolescents and adults as well as for the protection of children who are not vaccinated or who are only partially vaccinated. Intensive Therapy Physician (Dr. Alberto Jarillo Quijada) Mention needs to be made on the pathophysiological aspect as to why the patient expired. We have focused only on the refractory hypoxemia, and though Dr. Rosales already mentioned the poor prognostic factors, which are pneumonia, hypoxemia and secondary convulsive crisis in children <2 years of age, we focused and made the serious mistake of concentrating only on the resolution of the hypoxemia, managing the patient from a ventilatory standpoint. Another important risk factor that causes death in children is hyperleukocytosis. The patient had a leukocyte count of 100,000. In these cases, saline pheresis was then proposed, although with the technical complications due to the fact of dealing with an infant <4 months who needs to have an 8 Fr catheter placed. The other is leukopheresis 588 as seen here. There is significant alveolar lymphocytic infiltrate as well as intravascular. This patient behaved like a patient with DIC, with platelet consumption. What is done is thrombotic microangiopathy with capillary flow obstruction, both pulmonary and systemic. In this patient, as with those patients who come in with leukemoid reaction in leukemia and refractory hypoxemia managed with adequate ventilation parameters, leukopheresis is carried out, blood viscosity is decreased, and leukocyte binding to pulmonary capillary level and inflammatory response are reduced. This possibility should have been taken into consideration. Technical difficulties are very important in a 4-month-old infant. If we consider that pertussis is making a “come back”, we should also be prepared in this regard. Coordinador: (Dr. Sarbelio Moreno Espinosa) This case brings to mind several pathophysiological aspects of childhood disease, not only from the infectious viewpoint. It also allowed the interaction of various services. We must be prepared to deal with such cases, especially taking into account the reemergence of this disease. REFERENCES 1. 2. 3. 4. 5. 6. 7. Kuhlman JE, Reyes BL, Hruban RH, Askin FB, Zerhouni EA, Fishman EK, et al. Abnormal air-filled spaces in the lung. Radiographics 1993;13:47-75. Romano MJ, Weber MD, Weisse ME, Siu BL. Pertussis pneumonia, hypoxemia, hyperleukocytosis, and pulmonary hypertension: improvement in oxygenation after a double volume exchange transfusion. Pediatrics 2004;114:e264-e266. John SD, Ramanathan J, Swischuk LE. Spectrum of clinical and radiographic findings in pediatric mycoplasma pneumonia. Radiographics 2001;21:121-131. Fahy JV, Dickey BF. Air mucus function and dysfunction. N Engl J Med 2010;363:2233-2247. Vareille M, Kieninger E, Edwards M, Regamy N. The airway epithelium: soldier in fight against respiratory viruses. Clin Microbiol Rev 2011;24:210-229. Paddock CD, Sanden GN, Cherry JD, Gal AA, Langston C, Tatti KM, et al. Pathology and pathogenesis of fatal Bordetella pertussis infection in infants. Clin Infect Dis 2008;47:328-338. Burr JS, Jenkins TL, Harrison R, Meert K, Anand KJS, Berger JT, et al. The Collaborative Pediatric Critical Care Research Network (CPCCRN) Critical Pertussis Study: collaborative research in Pediatric Critical Care Medicine. Pediatr Crit Care Med 2011;12:387-392. Bol Med Hosp Infant Mex Bol Med Hosp Infant Mex 2012;69(6):589-594 Pediatric theme Renal tubular acidosis Dr. Luis Velásquez Jones ABSTRACT Renal tubular acidosis (RTA) refers to a group of clinical entities in which hyperchloremic metabolic acidosis occurs with normal anion gap as a result of defective transport of the proximal tubular reabsorption of bicarbonate (proximal RTA or type 2), distal secretion of hydrogen ions (distal RTA or type 1), or hyperkalemic RTA (or type 4). These RTA types can be inherited or acquired. Primary forms of proximal RTA are extremely rare, with the majority of cases in children found associated with Fanconi syndrome. Primary distal RTA is the most common distal RTA found in children. Hyperkalemic RTA is found together with aldosterone deficiency or aldosterone resistance, which causes hyperkalemia, low synthesis and low levels of urinary ammonium and salts and titratable acids. RTA may manifest early in infancy with vomiting, polyuria and polydipsia, dehydration crisis, failure to thrive and growth retardation. Children with distal RTA may present with nephrocalcinosis. Long-term treatment with alkalizing solutions (citrate or bicarbonate of sodium and potassium) to maintain normal values of serum bicarbonate concentration induces catch-up growth, corrects the electrolyte abnormalities of the different types of RTA (hypocitraturia, hypercalciuria) and arrests progressive nephrocalcinosis in patients with distal RTA. Key words: renal tubular acidosis, proximal or type 2, distal or type 1, hyperkalemic or type 4. INTRODUCTION Proximal RTA Renal tubular acidosis (RTA) includes a group of clinical entities in which hyperchloremic metabolic acidosis occurs, i.e., with normal serum anion gap. These are characterized by alterations in bicarbonate resorption in the proximal tubule of the nephron [proximal RTA (pRTA) or type 2] or defect of hydrogen ion secretion in the distal tubules of the nephron [distal RTA (dRTA) or type 1] and hyperkalemic RTA (or type 4). Previously, type 3 RTA was used to define children with type 1dRTA who, as infants, also presented proximal loss of bicarbonate in the urine; however, because this loss is transitory, this category has been eliminated.1,2 Causes Head, Departamento de Nefrología, Hospital Infantil de México Federico Gómez, México, D.F., México Correspondence to: Dr. Luis Velásquez Jones Departamento de Nefrología Hospital Infantil de México Federico Gómez México, D.F., México E-mail: [email protected] Received for publication: 10-23-12 Accepted for publication: 10-30-12 Vol. 69, November-December 2012 Approximately 75-80% of the filtered bicarbonate is resorbed normally and therefore “returned” to the blood by the proximal tubule of the nephron. If the resorptive capacity of this segment of the nephron is reduced (as seen in primary pRTA and Fanconi syndrome), increased release of bicarbonate would occur to the distal segments of the nephron, which exceeds the possibilities of their absorption, developing bicarbonaturia and metabolic acidosis. The contraction of the extracellular water volume induces increased resorption of chlorine, resulting in the development of hyperchloremic metabolic acidosis. In pRTA, also called type 2, the primary forms are included and are hereditary and sporadic variants and secondary forms. Primary forms are rare in children, with the majority of cases seen as part of Fanconi syndrome (Table 1).1-3 Autosomal dominant and autosomal recessive variants have been described in some families of patients with pRTA. The autosomal dominant variant has been described in only a limited number of affected families.4 The recessive variant is associated with mental retardation and ocular problems and is caused by a defect in the co-transporter Na+ + HCO3-(NBC1); this 589 Dr. Luis Velásquez Jones Table 1. Causes of proximal RTA 1. Primary a) Hereditary forms: autosomal dominant, autosomal recessive, osteopetrosis, Leigh syndromes, metachromatic leukodystrophy b) Sporadic: persistent idiopathic, transitory 2. Secondary a) Component of Fanconi syndrome: cystinosis, glycogenesis type I, tyrosinemia, hereditary fructose intolerance, galactosemia, Wilson’s disease b) Other diseases: nephrotic syndrome, cyanogenic cardiopathy, CVA, paroxysmal nocturnal hemoglobinuria, postrenal transplant c) Drugs: isophosphamide, heavy metals d) Carbon anhydrase inhibition: acetazolamide, sulfanylamide, mafenide, topiramate RTA, renal tubular acidosis; CVA, cerebrovascular accident. transporter allows output (resorption) of the bicarbonate ion together with sodium ions from the tubular cell to the peritubular renal blood circulation. The gene SLC4A4, which encodes for NBC1, is located on chromosome 4.3,5,6 Affected children with this autosomal recessive variant present, in addition to pRTA, short stature, glaucoma, cataract, band keratopathy, psychomotor retardation, calcification of the basal ganglia and hyperamylasemia.4 These alterations manifest because, in addition to its expression in the proximal renal tubule of the nephron, the NBC1 cotransporter is also present in ocular structures, brain and pancreas.4 Patients with osteopetrosis associated with carbonic anhydrase II deficiency exhibit both pRTA and dRTA because carbonic anhydrase II is important for renal tubular resorption of bicarbonate and hydrogen ion secretion. For this reason, it has also been called “mixed” renal tubular acidosis.6 In the proximal tubule of the nephron, cytosolic carbonic anhydrase II provides intracellular hydrogen ion secretion continuously into the tubular lumen and bicarbonate ion for its extrusion through the basolateral membrane into the circulation. Both ions are derived from CO2 and water.7 The clinical picture of pRTA has also been described in patients with Leigh syndrome and metachromic leukodystrophy.3 Sporadic variants, also called isolated variants, may be either persistent or transitory. The transient variation is usually manifested during breastfeeding age and is predominant in males. Affected patients have low stature 590 and have repeated episodes of vomiting and dehydration.8 Indicated treatment is alkalizing solutions and the alteration disappears after several years. It is speculated that there is an immaturity of transporter NBC1 in these children, which persists beyond the neonatal period, but the alteration corrects itself spontaneously some years later.4 Development of proximal RTA has been observed in infants with cyanotic heart disease and renal vascular accidents.1 Secondary causes of pRTA include Fanconi syndrome and its various etiologies, other diseases such as nephrotic syndrome, post-renal transplant, drugs and inhibition of carbonic anhydrase. Acetazolamide and some anticonvulsant medications such as topiramate induce the clinical picture of pRTA by inhibiting the action of carbonic anhydrase IV. Carbonic anhydrase IV is located in the apical or luminal and basolateral membranes of the proximal tubule cells and thick ascending branch of the loop of Henle. In the basolateral membrane, release of the bicarbonate ion from the tubular cell is facilitated.7-9 Clinical Manifestations and Laboratory Findings Proximal RTA is usually manifested during infancy mainly with growth retardation and is commonly associated with low dietary intake by the presence of marked hyperoxia, nausea and persistent vomiting. Polyuria is frequently present.1 Laboratory tests typically show metabolic acidosis: arterial blood pH ≤7.30 and arterial blood bicarbonate <21 mEq/L. Hyperchloremia is also present, which conditions the finding of anion gap to be within normal limits (8-16 mEq/L) and with mild hypokalemia. Total CO2 contents can also be examined in venous blood (normal range 2130 mEq/L or mmol/L)10 to document the decline in blood bicarbonate concentration. Urine pH can be <5.5. Typically no changes are observed in the serum concentrations of calcium, phosphate and vitamin D. To determine the ability of the kidney to resorb filtered bicarbonate, fractional excretion of bicarbonate (FE-HCO3-) should be performed. This test should be performed after the serum bicarbonate concentration has been normalized (22-25 mEq/L or mmol/L) after starting treatment with alkalizing solutions. Normally, FE-HCO3values are <5%. In contrast, in patients with pRTA, this value is usually between 12 and 15%.1 Bol Med Hosp Infant Mex Renal tubular acidosis Treatment The main goal of treatment for patients with pRTA is to maintain normal pH and serum bicarbonate concentration. This can be achieved only with the administration of relatively high volumes of alkalizing solutions containing bicarbonate or organic anion equivalent, such as citrate, which consumes hydrogen ions during metabolism in the liver.11 The typical dose ranges from 8-15 mEq/kg/day, with even higher doses to normalize serum bicarbonate concentration.1 The composition of the solutions usually indicated is as follows: a) Bicarbonate solution: 43 g sodium bicarbonate, potassium bicarbonate 53 g and 500 mL water b) Citrate solution: citric acid (70 g), sodium citrate (98 g), potassium citrate (108 g), water and currant syrup (1000 mL) The solution provides 1 mEq sodium, 1 mEq potassium and 2 mEq bicarbonate/mL, whereas the citrate solution contains 1 mEq of sodium, 1 mEq potassium and 2 mEq of citrate/mL. The daily dose should be divided into 6-h doses.1 In situations that require increasing amounts in an attempt to normalize serum bicarbonate concentration, it may be necessary to add a thiazide diuretic to the treatment.6 The diuretic induces a chronic state of depletion of the extracellular water volume, which decreases the glomerular filtration rate and the filtered bicarbonate load. Although the disease prognosis will vary according to the causative factor, pRTA itself will not produce serious consequences for the patient if the electrolytic and acidbase alteration is corrected. In children with the isolated idiopathic form, normal growth for age is recovered. It has been observed that, with this variant, the tubular defect of bicarbonate resorption improves with age.11 Distal RTA Distal RTA (dRTA) is also called classic or type 1. It is characterized by the presence of hyperchloremic and hypokalemic metabolic acidosis with inability to reduce urinary pH to values <6.0. This is due to a defect in the transporters involved in the elimination of hydrogen ions in the urine and the associated bicarbonate regeneration. In this regard, when the ability of the distal nephron to reduce urinary pH is altered, various metabolic consequences are presented: a) the bicarbonate that escapes resorption of the proximal tube is not resorbed, with bicarVol. 69, November-December 2012 bonaturia occurring despite the acidosis, b) tubular renal secretion of ammonia and titratable acids is reduced, c) hypokalemia occurs due to the presence of nonabsorbable anion (bicarbonate, sulfate) in the distal nephron, which promotes excessive potassium secretion and d) hyperchloremic metabolic acidosis occurs because the contraction of the extracellular space induces greater renal tubular resorption of chlorine.1 Causes The causes of dRTA include both the persistent sporadic forms as well as the genetic forms, those associated with heredity, autoimmune factors and renal tubulointerstitial diseases, and also diseases accompanied by hypercalcemia and nephrocalcinosis and drugs and toxic effects (Table 2).1,2,12,13 The disease can be transmitted in an autosomal dominant or autosomal recessive manner. In the dominant variant, a defect was observed in the SLC4A1 gene located on chromosome 17, which encodes the action of Cl-/HCO3(AE1) exchanger located on the basolateral surface of the alpha intercalated cells and erythrocytes and allows the release (resorption) of the bicarbonate ion to the blood of the peritubular capillaries in exchange with chlorine.3,14 SLC4A1 gene mutations also cause anemia and spheTable 2. Causes of distal RTA 1. Primary a) Sporadic (persistent) b) Genetic: autosomal dominant, autosomal recessive with or without or deafness 2. Diseases associated with hypercalciuria and nephrocalcinosis, primary hyperparathyroidism, medullary sponge kidney, idiopathic hypercalciuria, vitamin D intoxication 3. Renal tubulointerstitial diseases: obstructive nephropathy, chronic pyelonephritis, renal transplant rejection, hyperoxaluria 4. Autoimmune diseases: SLE, chronic active hepatitis, hyperglobulinemia purpura 5. Other diseases: a) Ehlers-Danlos syndrome b) Hematologic diseases: spherocytosis, ovalocytosis, hemolytic anemia c) Renal cystic diseases: nephrocytosis, cystic medullary disease d) Glycogenesis type I e) Familiar hypercalciuria f) Congenital cyanogenic cardiopathy 6. Medications and toxins: amphotericin, lithium salts, cyclamates, foscarnet, amiloride, toluene RTA, renal tubular acidosis; SLE, systemic lupus erythematosus. 591 Dr. Luis Velásquez Jones rocytosis and ovalocytosis hemolytic anemia, which are hereditary autosomal dominant diseases.2,15 In the autosomal recessive variant of dRTA, two genes have been implicated: ATP6V1B1 and ATP6V0A4. These codify the β1- and α4-subunits of H+-ATPase located in the apical membrane of the intercalated renal tubular cells, which participate in the transference of hydrogen ions to the urine. It has been observed that children with this variant have a more severe clinical picture with severe growth retardation, metabolic acidosis and accentuated hypokalemia, along with a tendency to depletion of the intravascular volume. There is also early development of nephrocalcinosis with renal function compromise. Finally, in most cases, progressive sensorineural hearing loss can be observed.6,16 Clinical Manifestations Clinical manifestations can be observed from infancy with growth retardation, hyperoxia, nausea and vomiting and, in some cases, concomitantly with severe metabolic acidosis and accentuated hypokalemia. 1,17 Rhabdomyolysis has been noted in children with dRTA and severe hypokalemia. 18 Severe acidosis in young children is due to the fact that, apart from the defect to acidify the urine, during these ages, an additional loss of bicarbonate with fractional excretion of bicarbonate is seen, which can reach values of 5-15%. Chronic metabolic acidosis alters bone mineralization, leading to the development of rickets in children and osteomalacia in adults. In a recently published study that included children from 5 months to 9 years of age with a diagnosis of primary RTA, there was a high frequency (up to 28%) of sensitivity to various allergens such as cow’s milk, wheat and egg whites.19 However, it will be necessary to confirm these findings in future diagnostic studies with greater sensitivity and specificity.19 Laboratory and Imaging Findings Disruption of hydrogen ion secretion in the distal nephron leads to reduced ammonia excretion and titratable acid in the urine, with increased bicarbonate excretion, all of which lead to metabolic acidosis. It has been mentioned that the main feature of the classic dRTA or type 1 is the inability of the kidney to reduce urine pH <6.0 in the presence of systemic acidosis. 592 In these cases of metabolic acidosis with normal plasma anion gap, it is useful to calculate the urine anion gap [(Na+/K+) - Cl-].17 Thus, the urine anion gap can be used as an indirect estimation of ammonia excretion, which usually is excreted as ammonium chloride. In patients with metabolic acidosis caused by dRTA, the acidemia is mainly due to inadequate excretion of hydrogen and ammonium ions. In these cases, the urinary anion gap gives positive values, i.e., the sum of sodium and potassium is greater than the chlorine concentration.20 In dRTA, acidosis is also related to significant loss of sodium at the renal level, which leads to increased secretion of renin and aldosterone and aggravates hypokalemia. Renal loss of sodium and the tendency to hypovolemia are more pronounced also in patients with nephrocalcinosis.1 Moreover, chronic acidosis is associated with increased citrate resorption at the level of the proximal renal tubule so as to help cushion acidosis. This leads to reduced availability of citrate at the distal tubular level, and hypocitraturia induces increased urinary excretion of calcium.8 Also, because bicarbonate buffer reserves are used to compensate for chronic metabolic acidosis, liberation of hydroxyapatite from bone takes place to release calcium and hydroxyl ions and buffer metabolic acidosis. This also causes hypercalciuria, which favors the development of nephrocalcinosis and nephrolithiasis in these patients.3,8 In some patients with dRTA, particularly genetic forms, hypercalciuria may not present itself in the initial stages of the disease.21 Renal ultrasound should be performed to rule out nephrocalcinosis. We recommend repeating this study each year during treatment and follow-up of the patient. Treatment It has been mentioned that, in infants and toddlers, the concomitant presence of renal loss of bicarbonate in addition to the distal urinary acidification defect, higher doses of alkalizing solutions may be required, on the order of 5-10 mEq/kg /daily, divided every 6 h. This allows maintaining normal growth rate. In this respect, it has been observed after the age of 5 to 6 years, the required amount of alkalizing solutions per kilogram of weight decreases. After these ages, it is noted that, unlike what occurs in patients with pRTA, the quantity of bicarbonate or citrate to administer in dRTA is less, with doses between 1 and 3 mEq/kg/day to correct the acidosis.1 Bol Med Hosp Infant Mex Renal tubular acidosis It is also noted that correction of acidosis improves the increased losses of sodium and potassium in the urine and particularly increases citrate production in the kidney and corrects hypercalciuria. It should be emphasized that treatment with alkalizing solutions in children with dRTA should be directed not only to achieve pH normalization and serum concentration of bicarbonate but also, and primarily, to correct the hypercalciuria. This will prevent the deposition of calcium in renal tissue. It must be remembered that if there is development of nephrocalcinosis, usually with recurrent stone formation of calcium oxalate or phosphate, it can influence the progressive destruction of functional renal mass with progression to chronic end stage renal disease. Therefore, in laboratory tests for children with dRTA, in addition to the pH determination in serum and especially the concentration of bicarbonate and electrolytes, determination of calcium excretion in urine for a 24-h period (normal value ≤4 mg/kg/24 h) should also be determined or the ratio of urinary calcium to creatinine (normal value with the same units of measure, i.e., mg/dL in both determinations, is <0.2).1 With proper treatment, recovery of growth velocity in these children can be achieved. Moreover, early diagnosis and treatment will prevent the development of nephrocalcinosis and renal stones. In children with autosomal dominant or recessive dRTA and development of sensorineural deafness, it will be necessary to provide early support with speech therapy. In severe and progressive cases a cochlear implant may be required.1 Table 3. Causes of hyperkalemic RTA 1. Aldosteron deficiency a) Addison´s disease b) Congenital adrenal hyperplasia c) Congenital lipod adrenal hyperplasia d) Medications: ACE inhibitors, nonsteroidal antiinflammatories, beta-blockers, heparin e) Medications: ACE inhibitors, nonsteroidal antiinflammatories, beta-blockers, heparin. 2. Resistence to aldosterone a) Pseudohypoaldosteronism: autosomal dominant, autosomal recessive b) Renal tubulointerstitial disease: Kidney transplant rejection, obstructive uropathy, nephrocalcinosis, nephropathy due to analgesics, nephropathy due to sickle cell disease c) Medications: spironolactone, triamterene, amiloride, cyclosporin, tacrolimus, heparin, trimethoprim, indomethacin, captopril RTA, renal tubular acidosis; SLE, systemic lupus erythematosus; ACE, angiotensin-converting enzyme. also decreases the intake of the ammonia ion from the medullary interstitium towards the interior of the cells of the medullary collector tubules through its defect in the secretion of potassium ion through the Na+-K+/ATPase located on the basolateral portion of the tubular cellular membrane. The net effect of these actions is the decrease in urinary excretion of ammonia ions and titratable acids with development of metabolic acidosis.3 Clinical Manifestations Clinical manifestations are directly related to the underlying condition causing the altered acid-base balance. Hyperkalemic RTA Hyperkalemic RTA or type 4 (or IV) is characterized by the development of mild to moderate hyperchloremic metabolic acidosis associated with hyperkalemia. Kidney patients affected retain the ability to reduce urinary pH <5.5.1 Causes Hyperkalemic RTA type 4 is seen in diseases accompanied by aldosterone deficiency or resistance to its action in target organs (Table 3).1,3,22-24 In these cases the resultant hyperkalemia induces a decrease of production of the ammonia ion in the proximal renal tubule due to the defect in action of aldosterone. The potassium also competes with the ammonia ion for the Na+/2Cl/K+ transporter in the ascending branch of the loop of Henle, thereby reducing the medullary gradient of the ammonia ion. Hyperkalemia Vol. 69, November-December 2012 Laboratory Findings It has been mentioned that the clinical picture of metabolic acidosis is usually mild to moderate. A characteristic fact is also the finding of hyperkalemia. Although in these patients there is also reduction of urinary excretion of ammonia and titratable acids, the urine can generally be acidified, noting a pH <6.0. It is proposed that the response of the cortical collecting tubule of the nephron can be evaluated through determination of transtubular potassium gradient (TTKG) using the following equation:1,2,23 TTKG = [K+ urine]/[K+ plasma] Uosm/Posm where the numerator indicates potassium concentrations in urine and plasma and the denominator indicates 593 Dr. Luis Velásquez Jones urine and plasma osmolality. It is considered that a TTKG value ≥8 indicates there are normal values of aldosterone and that in patients with hyperkalemia the cortical tubule is properly responding to increased plasma potassium concentration. However, values <8 suggest aldosterone deficiency or lack of renal tubular response to its action.1,6 Treatment The treatment indicated is also based on the correction of the precipitating cause. The intake of alkalizing solution (bicarbonate solution or citrate without potassium) may be necessary for correction of metabolic acidosis. It has been observed that patients with aldosterone deficiency will have an increase in the TTKG after several days of initiating glucocorticoid treatment or mineralocorticoid replacement. However, this response is not observed in cases of insensitivity to the action of aldosterone. REFERENCES 1. Velásquez JL. Alteraciones Hidroelectrolíticas en Pediatría. México: Prado; 2010. p. 425. 2. Chan JC, Santos F, Hand M. Fluid, electrolyte, and acid-base disorders in children. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM, eds. Brenner & Rector’s The Kidney. Philadelphia: Elsevier Saunders; 2012. pp. 2572-2621. 3. Foreman JW. Renal tubular acidosis. In: Kher KK, Schnaper HW, Makker SB, eds. Clinical Pediatrics Nephrology. London: Informa Healthcare; 2007. pp. 302-316. 4. Gross P, Meye C. Proximal RTA: are all the charts completed yet? Nephrol Dial Transplant 2008;23:1101-1102. 5. Alper SL. Familial renal tubular acidosis. J Nephrol 2010;23(suppl 16):S57-S76. 6. Karet FE. Disorders of water and acid-base homeostasis. Nephron Physiol 2011;118:28-34. 7. Hamm LL. Mecanismos de acidificación renal. In: Brenner BM, ed. Brenner y Rector. El Riñón. Tratado de Nefrología. Madrid: Elsevier; 2005. pp. 497-534. 8. Quigley R. Renal tubular acidosis. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, eds. Pediatric Nephrololgy. Berlin: Springer; 2009. pp. 979-1003. 9. Schwartz GJ, Kittelberger AM, Barnhart DA, Vijayakumar S. Carbonic anhydrase IV is expressed in H(+)-secreting cells of rabbit kidney. Am J Physiol Renal Physiol 2000;278:F894-F904. 10. Kratz A, Ferraro M, Sluss PM, Lewandrowski KB. Normal reference laboratory values. N Engl J Med 2004;351:1548-1563. 594 11. DuBose TD, Alpern RJ. Renal tubular acidosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Diseases. New York: McGrawHill; 2001. pp. 4983-5021. 12. Ambühi PM. Posttransplant metabolic acidosis: a neglected factor in renal transplantation? Curr Opin Nephrol Hypertens 2007;16:379-387. 13. Keven K, Ozturk R, Sengul S, Kutlay S, Ergun I, Erturk S, et al. Renal tubular acidosis after kidney transplantation—incidence, risk factors and clinical implications. Nephrol Dial Transplant 2007;22:906-910. 14. Fry AC, Su Y, Yiu V, Cuthbert AW, Trachtman H, Karet Frankl FE. Mutation conferring apical-targeting motif on AE1 exchanger causes autosomal dominant distal RTA. J Am Soc Nephrol 2012;23:1238-1249. 15. Fawaz NA, Beshlawi IO, Al Zadjali S, Al Ghaithi HK, Elnaggari MA, Elnour I, et al. dRTA and hemolytic anemia: first detailed description of SLC4A1 A858D mutation in homozygous state. Eur J Haematol 2012;88:350-355. 16. Mohebbi N, Vargas-Poussou R, Hegemann S, Schuknecht B, Kistler A, Wüthrich R, et al. Homozygous and compound heterozygous mutations in the ATP6V1B1 gene in patients with renal tubular acidosis and sensorineural hearing loss. Clin Genet 2012. doi: 10.1111/j.1399-0004.2012.01891.x. 17. Mul D, Grote FK, Goudriaan JR, de Muinck Keizer-Schrama SM, Wit JM, Oostdijk W. Should blood gas analysis be part of the diagnostic workup of short children? Auxological data and blood gas analysis in children with renal tubular acidosis. Horm Res Paediatr 2010;74:351-357. 18. von Vigier RO, Ortisi MT, La Manna A, Bianchetti MG, Bettinelli A. Hypokalemic rhabdomyolysis in congenital tubular disorders: a case series and a systematic review. Pediatr Nephrol 2010;25:861-866. 19. Bojórquez OA, Morfin MBM, García CR, Hernández T, Barbosa C, Zaltzman GS. Prevalence of sensitization to inhaled and food allergens in a group of children with primary renal tubular acidosis. Rev Alerg Mex 2011;58:87-92. 20. Rose BD, Post TW. Rose & Post Trastornos de los Electrólitos y del Equilibro Ácido-Base. Madrid: Marbán Libros; 2005. p. 590. 21. Tsai HY, Lin SH, Lin CC, Huang FY, Lee MD, Tsai JD. Why is hypercalciuria absent at diagnosis in some children with ATP6V1B1 mutation? Pediatr Nephrol 2011;26:1903-1907. 22. Nalcacioglu H, Genc G, Meydan BC, Ozkaya O. Hyperkalaemia in a female patient with systemic lupus erythematosus: questions. Pediatr Nephrol 2012;27:1499-1500. 23. Nalcacioglu H, Genc G, Meydan BC, Ozkaya O. Hyperkalaemia in a female patient with systemic lupus erythematosus: answers. Pediatr Nephrol 2012;27:1501-1503. 24. Riveiro-Barciela M, Campos-Varela I, Tovar JL, Vargas V, Simón-Talero M, Ventura-Cots M, et al. Hyperkalemic distal renal tubular acidosis caused by immunosuppressant treatment with tacrolimus in a liver transplant patient: case report. Transplant Proc 2011;43:4016-4018. Bol Med Hosp Infant Mex Bol Med Hosp Infant Mex 2012;69(6):595-598 Vital statistics Mortality due to exposure to smoke, fire and flames in children under 15 years of age during the period 1998-2010 Sonia B. Fernández Cantón,1 Ana Ma. Hernández Martínez,1 Ricardo Viguri Uribe2 INTRODUCTION On previous occasions, mention has been made of one of the biggest public health problems facing our country: deaths due to accidents. These are the leading cause of death among the population <15 years (except for those <1 year of age). It is therefore important to analyze and disseminate the behavior of the causes, which in a disaggregated manner make up this great sector of mortality. In this manner, the present paper addresses the issue of mortality due to exposure to smoke, fire and flames This analysis was carried out using official data from vital statistics (mortality) generated by the National Institute of Geography and Informatics (INEGI) from death certificates distributed by the Ministry of Health. The codes considered for this paper are those between the X00 and X09 of the International Classification of Diseases (ICD) (10th revision) (ICD-10) (Table 1). Time period comprises 1998–2010 to correspond to the year 1 2 Dirección de Información Epidemiológica, Secretaría de Salud, Mexico, D.F., Mexico Departamento de Ediciones Médicas, Hospital Infantil de México Federico Gómez, México, D. F., México Correspondence: Dra. Sonia B. Fernández Cantón Dirección de Información Epidemiológica Secretaría de Salud Mexico, D.F., Mexico E-mail: [email protected]; sonia_fernandez@ prodigy.net.mx Received for publication: 8-7-12 Accepted for publication: 8-14-12 Vol. 69, November-December 2012 in which the ICD-10 began and the last year of data with final figures, respectively. Although deaths caused by exposure to smoke, fire and flames represent a quantitatively smaller figure to other causes that have been addressed in this space, the human suffering provoked by the severity of the process that leads to death and the impact of its consequences within the family are reason enough to pursue the subject. In the context of the general population, 1.8% of accidental deaths had as the underlying cause exposure to smoke, fire or flames (8453 deaths of a total of 475,923 from 19982010). Within the group of children under 15 years, this percentage rose to 2.4%, i.e., 1543 deaths that occurred in a 13 year period, from a total of 65,236 accidents in the same period (Table 2). It is noteworthy that almost one in five deaths from this cause (smoke, fire, flames) occurred in the age group under 15 years of age (18.3%) According to available information, between 1998 and 2010, on average, just under 120 deaths were recorded annually, so that together, that age group accumulated over the period a total of 1543 deaths, equivalent to a rate of 3.6 deaths per million population of that age group, that is 0.36 deaths per hundred thousand population <15 years of age (Table 3). The trend analysis shows that, in general, a decrease over the period, although with some fluctuations: a rebound in 2005-2007 (rate of 0.25 to 0.37), followed by a decrease (to 0.28) and a new increase in 2009 (to a rate of 0.40), with the two extremes in the years 1999 with 182 deaths (and a rate of 0.54) against the lowest on record in 2004 with 83 deaths (and with a rate of 0.25). The year 2010, latest available figure, had 92 deaths (Table 4). Fig 1 shows, in detail, the behavior of the fluctuations described above. 595 Sonia B. Fernández Cantón, Ana Ma. Hernández Martínez, Ricardo Viguri Uribe Table 1. Deaths due to exposure to smoke, fire and flames in the population <15 years of age, 1998-2010 Deaths 3-digit ICD code < 1 year X00 Exposure to uncontrolled fire in an area of a bulding or other construction X01 Exposure to uncontrolled fire not in an area of a building or other construction X02 Exposure to controlled fire in an area of a building or other construction X03 Exposure to controlled fire in an area that is not a building or other construction X04 Exposure to highly inflammable ignitable material X05 Exposure to ignition or fusion of sleepwear X06 Exposure to ignition or fusion of other clothes and accessories X08 Exposure to other specified smoke, fire or flames X09 Exposure to unspecified smoke, fire or flames Total 31 1 2 5-year age group 1-4 5-9 10 - 14 years years years 101 1 3 3 2 45 1 2 1 2 27 3 1 2 2 1 27 674 812 1 8 268 328 3 162 200 3 13 153 203 < 15 years 204 6 8 6 6 3 2 51 1,257 1,543 Source: SINAIS/SSA/INEGI/sistema de defunciones/Sistema Dinámico de Información (Cubes), ICD-10 cause: X00 to X09. http://dgis.salud.gob.mx/cubos Table 2. Relative weight of deaths due to smoke, fire and flames exposure with respect to the total accidental deaths in children <15 years of age, 1998 - 2010 Year 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Total Deaths in children <15 years of age Exposure to smoke, Accidental Relative fire and flames deaths weight (%) 154 182 160 139 109 85 83 106 106 116 88 123 92 1,543 5,848 6,022 5,590 5,667 5,646 5,186 5,053 4,762 4,846 4,483 4,156 4,161 3,816 65,236 2.63 3.02 2.86 2.45 1.93 1.64 1.64 2.23 2.19 2.59 2.12 2.96 2.41 2.37 Source: SINAIS/SSA/INEGI/sistema de defunciones/Sistema Dinámico de Información (Cubes), ICD-10 cause: X00 to X09 http://dgis.salud.gob.mx/cubos While over the period analyzed, the number of deaths of children under 15 years caused by exposure to smoke, fire and flames have fallen by 40%, going from 154 deaths in 1998 to 92 in 2010 (figure higher than the decrease of 35% of accidental deaths as a whole), it is noteworthy 596 that the relative weight of the former out of the total has remained virtually unchanged, and has remained around 2.4% (with values ranging from 1.64 in 2003–2004 and 3 in 1999) (Table 2). It is important to point out that the decline in mortality was observed in both males and females and in all age groups, although with different intensities: the greatest reduction occurred in the group <1 year of age (56%) followed by the 1- to 4-yearold age group (43%), 5- to 9-year-old group (30%), and 10- to 14-year-old group, which showed the lowest reduction (only 22%). In particular, there were differences in mortality rates according to gender. In males there was a 49% decrease observed and in females only a 28% reduction of deaths. With respect to the distribution of deaths by age, this is heterogeneous within groups. More than half of the deaths (52%) occurred in the 1- to 4-year-old age group followed by the 5- to 9-year-old age group, affecting >20%. The remaining 26% is distributed equally among children <1 year and the 10- to 14-year-old age group (Figure 2). Regarding gender distribution, this was similar to all deaths that occurred due to external causes, whether or not accidental. In deaths due to exposure to smoke, fire and flames, there is a clear prevalence of male/female deaths: 880 and 663 deaths, respectively (Table 5); 57% of the deaths occurred in males and 43% in females (Figure 3). In other words, there is a mortality rate in males of 133 (per 100 female deaths). The most accepted explanation is Bol Med Hosp Infant Mex Year reported <1 year 1-4 years 5-9 years 10 - 14 years < 15 years Rate* 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Total 25 23 22 24 11 14 13 18 10 12 10 10 11 203 84 98 71 73 59 49 48 54 56 64 47 61 48 812 27 34 43 23 31 15 12 21 24 25 20 34 19 328 18 27 24 19 8 7 10 13 16 15 11 18 14 200 154 182 160 139 109 85 83 106 106 116 88 123 92 1,543 0.46 0.54 0.48 0.41 0.33 0.26 0.25 0.33 0.33 0.37 0.28 0.40 0.30 0.36 Number of deaths Table 3. Deaths and mortality rate due to smoke, fire and flames exposure in children <15 years of age, 1998-2010 4 200 0.60 0.5 8 180 0.46 4 . 0 0.50 1 160 0 0.4 4 . 0 140 .37 0.40 3 3 3 0 0.3 120 0.3 0.3 8 .30 2 0 . 6 5 0 0.30 100 0.2 0.2 80 0.20 60 40 0.10 20 0.00 0 8 99 00 01 02 03 04 05 06 07 08 09 10 9 19 19 20 20 20 20 20 20 20 20 20 20 20 Deaths Year México 1998 -2010 Deaths Rate 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Total 154 182 160 139 109 85 83 106 106 116 88 123 92 1,543 0.46 0.54 0.48 0.41 0.33 0.26 0.25 0.33 0.33 0.37 0.28 0.40 0.30 0.36 Source: SINAIS/SSA/INEGI/sistema de defunciones/Sistema Dinámico de Información en Sistemas de Salud (Cubes), ICD-10 cause: X00 to X09 http://dgis.salud.gob.mx/cubos Vol. 69, November-December 2012 Rate Figure 1. Mortality rate and deaths due to exposure to smoke, fire and flames in children <15 years of age (Mexico 1998-2010). Source: SINAIS/SSA/INEGI/Sistema de defunciones/Sistema Dinámico de Información (Cubes), ICD-10 cause: X00 to X09. http://dgis.salud.gob.mx/cubos *Rate per 100,000 population of the group of children <15 years of age Table 4. Deaths and morality rate due to exposure to smoke, fire and flames in children <15 years of age Percentages Mortality due to exposure to smoke, fire and flames in children under 15 years of age during the period 1998-2010 <1 year 13.2% 10-14 years 13.0% 1-4 years 52.6% 5-9 years 21.3% Figure 2. Percentage distribution of deaths due to exposure to smoke, fire and flames broken down according to age groups (1998-2010). linked to learned behaviors by males and females, which accepts that males are often at greater risk as a result of playing with fire and risk-taking behaviors. Similarly, there are frequent injuries associated with group activities where the boys use gasoline or other flammable products, such as fireworks. 597 Sonia B. Fernández Cantón, Ana Ma. Hernández Martínez, Ricardo Viguri Uribe Table 5. Deaths due to exposure to smoke, fire and flames in children <15 years of age according to gender (1998-2010) Year reported Male Female Total 1998 1999* 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Total 88 109 95 77 60 55 52 73 54 59 44 69 45 880 66 73 65 62 49 30 31 33 52 57 44 54 47 663 154 182 160 139 109 85 83 106 106 116 88 123 92 1,543 Fuente: SINAIS/SSA/INEGI/Sistema de defunciones/Sistema Dinámico de Información (Cubos), Cause CIE: X00 a X09 http://dgis.salud.gob.mx/cubos * includes a death of unespecified gender. Moreover, despite the importance that knowing the specific breakdown of the causes that led to the death by exposure to smoke, fire and flames would have, Table 1 demonstrates the serious problems in registration and the 598 Males 57.0% Females 43.0% Figure 3. Percentage of deaths due to exposure to smoke, fire and flames in children under 15 years of age (1998-2010). Percentage of deaths due to exposure to smoke, fire and flames in children under 15 years of age, 1998-2010 lack of precision in the medical certification. It is observed that >80% of deaths appear as "causes related to smoke, fire and flames unspecified." This represents a major limitation for prevention and control of risks. Bol Med Hosp Infant Mex Guidelines to authors Boletín Médico del Hospital Infantil de México is the official publication of the Hospital Infantil de México “Federico Gómez.” The journal has been continuously published on a bi-monthly basis since 1944 and publishes studies relating to pediatrics according to the following areas: biomedical, clinical, public health, clinical epidemiology, health education and clinical ethics. The following guidelines are in accordance with the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals,” published by the International Committee of Medical Journal Editors (http://www.icmje.org). Types of articles Types of articles published are as follows: Review Articles, Clinical Case Reports, Clinicopathological Cases, Pediatric Themes and Letters to the Editor. Published articles appear both in print and on-line in Spanish and on-line in English. Submissions should be sent via electronic mail to: bolmedhim@ yahoo.com.mx with the following requirements: 1. Letter addressed to Dr. Gonzalo Gutiérrez Trujillo, Editor, Boletín Médico del Hospital Infantil de México, Departamento de Ediciones Médicas. The letter, signed by the corresponding author, should include the following information: a) The enclosed article is being submitted for evaluation for eventual publication in Boletín Médico del Hospital Infantil de México. b) The authors declare that the work has not been previously published, has not been previously accepted for publication and has not been submitted simultaneously to another publication. c) Type of study should be indicated along with the corresponding pertinent area of pediatrics. d) Confirm that the Guidelines to Authors have been reviewed and adhered to prior to submission. e) If applicable, the authors should declare any conflict of interest or submit a statement that no conflict of interest exists. In the event of a conflict of interest, the authors must disclose any external financial or economic interest. f) All external funding sources should be clearly indicated. g) All authors must affirm that they are in agreement with the submission of the manuscript and that they have reviewed and approved the work. Please be reminded that without the appropriately signed author letter, the initial editorial process will be delayed. Manuscript preparation All manuscripts should be prepared with standard programs (Word 97 or higher) using the word processor function of your computer. Double space all sections of the manuscript including References, Tables and Figure Legends. Do not justify right margins and use one-inch margins all around. Keep formatting to a minimum. Pages should be numbered consecutively beginning with the first page and numbers should appear in the lower right corner of the page. Abbreviations Complex terms used frequently in the manuscript may be abbreviated. Abbreviations are placed in parentheses at first use in the abstract and again at first use in the text. Confirm that any abbreviations used in Tables are appropriately spelled-out in the Table legend underneath. Organization of the manuscript The first page should include the following: a) Title of the manuscript (Spanish and English) b) Type of manuscript: Original Article, Review Article, Clinical Case Report, etc. c) Name(s) of all authors in their order of appearance in relation to the publication d) Affiliation of each author (degrees and honors should be omitted) e) Name, E-mail address, postal address and telephone number of the corresponding author to whom any correspondence can be directed during the review process of the manuscript. The second page should contain the Abstract. Note that the Abstract is the most-often read part of the manuscript. For this reason, it must be clear, concise and contain information relevant to the article. Do not use references in the Abstract. In the case of Original Articles and Clinical Case Reports, the Abstract should be structured according to the following sections: Background, Methods, Results, Conclusions, or Background, Clinical Case and Conclusions. Abstracts for Review Articles and Pediatric Themes should be unstructured and include only one paragraph. The Abstract should be limited to 200 words and include only relevant aspects of each of the principal sections of the body of the manuscript. Authors should provide 3–6 keywords following the Abstract and use Medical Subject Headings (MeSH) terms as a guide. Visit: http://www.nlm.nih.gov/mesh/meshhome.html. The manuscript should include the following sections: 1) Original articles: Introduction, Methods, Results, Discussion and References. 2) Clinical case reports: Introduction, Clinical case, Discussion and References. 3) Clinicopathological cases: Clinical case, Discussion and References. An Acknowledgment section may be included directly following the Reference section. Granting institutions or other financial aid may be listed under Acknowledgments. If there are persons, other than the authors, who assisted with the study or preparation of the manuscript (i.e., technicians, nurses, ancillary health personnel, editorial assistance), they may be listed here. References References should be numbered consecutively, double spaced, and listed in the order in which they appear in the text using arabic numbers (in the text, references are indicated by superscript arabic numbers after any punctuation). The Reference section should follow the last section of the manuscript. It is not necessary to begin the References on a separate page. The references should be formatted according to the instructions from the U.S. National Library of Medicine. Abbreviated journal names should reflect the style of Index Medicus (visit http://www.nlm.nih.gov/ tsd/serials/lji.html) When a reference cites six or fewer authors, names should be included for all authors. When there are seven or more authors, use the first six names followed by et al. Authors are responsible for the accuracy of references. Please use the following examples for presentation of references: Journals: • Klimo P, Rao G, Brockmeyer D. Congenital anomalies of the cervical spine. Neurosurg Clin North Am 2007;18:463478. • Published book: • Bell RM. Holy Anorexia. Chicago: University of Chicago Press; 1985. • Book chapter: • Hudson JI, Hudson RA, Pope HG. Psychiatric comorbidity and eating disorders. In: Wonderlich S, Mitchell J, eds. Eating Disorders Review. Part 1. Oxford: Radcliffe Publishing; 2005. pp. 43-58. • Internet consult: • McKusick VA. Klippel Feil syndrome. Online. Mendelian inheritance in man (accessed: March 26, 2008). Available at: http://www.ncbi.nlm.nih.gov/entrez/dispomim. cgi?id=148900. Tables and Figures All tables and figures including schemes, diagrams and table legends must be presented in an editable form. Do not “copy and paste” material from external sources. Tables Tables should be numbered using arabic numbers in the order in which they are cited in the text and include a short descriptive title. Tables should not reiterate information presented in the Results section. For preparation of Tables containing only data, use the “Table Editor” function of your word processing program. Do not insert any vertical lines. Use horizontal lines only for clarity of information under table headings. Confirm that information provided below each table heading is properly aligned and clearly identifiable. Tables containing schemes or diagrams should be prepared in PowerPoint; graphics with shading, bars, dispersions, etc. should be prepared using Excel. Each Table should be prepared on a separate page, following the Reference section. Table footnotes should include any abbreviations that need to be explained and notes relating to the Table should be presented alphabetically using superscript letters. Figures Authors should number figures in the order in which they appear in the text. Figures include graphs, charts, photographs, and illustrations. Each figure should be accompanied by a selfexplanatory legend. Digital images should be legible and printed with a resolution of not less than 300 dpi, using .jpg (jpeg) or .bmp extension. If photographs submitted correspond to actual patients, the anonymity of the patients should be protected or written permission from the patient and/or family/legal guardian to publish the photograph(s) should be submitted. Figure legends with corresponding figure numbers should be typed consecutively on a separate page following the last Table (or following the Acknowledgments if there are no Tables). 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For studies involving human subjects, state the manner in which informed consent was obtained from the study participants (i.e., oral or written). All manuscripts reporting data from studies involving humans or animals are subject to formal review and approval by an appropriate institutional review board or ethics committee and should be described at the end of the Methods section. For investigators who do not have formal ethics review committees, the principles outlined in the Declaration of Helsinki as well as in the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council) should be followed. Review process The first review of the manuscript is performed by the Editor to assure that the manuscript corresponds to the theme of the journal and that all required information has been properly submitted in accordance with the Guidelines to Authors. 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