Download The 2 Pan Arab Pediatric Infectious Diseases Society Meeting

 The 2nd Pan Arab Pediatric Infectious Diseases Society Meeting Dear Reader: Below is a collection of the Abstracts of presentations delivered in the 2nd Conference of the Pan Arab Pediatric Infectious Diseases Society, May 5‐8, 2009; Amman, Jordan. The abstracts are presented as it were sent by the authors. The authors are responsible for the format, typing and the contents of the abstracts. Immunization in the Arab World & the MDG 4 By Dr Ezzeddine Mohsni, Regional Adviser, Vaccine Preventable Diseases & Immunization, WHO EMRO Out of the estimated 10.4 million under‐five deaths that occurred globally in 2000, around 25% were due to vaccine preventable diseases, which confirms the important role that immunization is expected to play in reaching MDG4. WHO & UNICEF Global Immunization Vision and Strategies 2006‐2015 (GIVS) highlight that and provide countries and immunization stakeholders with comprehensive information on basic strategies and actions that should be implemented to make sure that immunization plays its full role in reaching MDG4. The main strategies include improving routine immunization coverage to more than 90%, fully implement accelerated disease control initiatives like measles elimination and introduce new life saving vaccines like Hib, pneumococcal and rotavirus vaccines. The presentation reviews the progress made in the Arab World and focus on the precious achievement done in terms of measles mortality reduction as well as improving routine immunization coverage. It highlights the huge challenges the Arab World, and in particular the middle income Arab countries are facing in terms of introducing the new recommended and highly needed Hib, pneumococcal and rotavirus vaccines. It goes through the main initiatives in process by the WHO Eastern Mediterranean Office in collaboration with its partners like UNICEF and CDC Atlanta, to assist member states in optimizing the use of this strong and precious tool that is immunization. The paper calls for a more regular and stronger collaboration with the Union of Arab Pediatricians in this regard. MUSCULOSKELETAL INFGECTIONS IN CHILDREN Dr. Esam Banyan Musculoskeletal infections are serious pediatric infections with potential for serious sequelae. Timely diagnosis and appropriate management are essential. The epidemiology of these infections in children will be reviewed. We will show that these infections are mostly hematogenous in children (AHO) and less commonly due to trauma, and rarely due to vascular insufficiency. We will review the etiological agents showing that it is mostly bacterial in etiology; however can rarely be due to fungi or mycobacterium We will also discuss updates on the approach to an accurate diagnosis, particularly with regards to imaging modalities. Therapeutic approaches to management of this important infection will be discussed taking into consideration the emergence of antibiotic resistance among common etiological agents. Until recently, the antibiotic treatment of osteoarticular infections caused by S. aureus acquired in the community was straightforward, because virtually all S. aureus isolates were susceptible to beta‐lactam antibiotics. However, during the past 5 years methicillin resistant S. aureus has emerged as a major pathogen in the community (CA‐MRSA) in many areas of the world. Although skin and soft tissue infections predominated in the initial descriptions of the clinical spectrum of infections caused by CA‐MRSA, increasing numbers of children with invasive infection caused by CA‐MRSA have been reported. Controversies on when to use oral therapy vs. intravenous therapy will be reviewed in addition to optimal duration, follow up and potential complications. Infections In Immunocompromised Patients Ibrahim Bin‐Hussain, MBBS, ABCP, FAAP Consultant, Pediatric Infectious Diseases Chairman, Working for Infections in Immunocompromised Pediatric Patients King Faisal Specialist Hospital & Research Centre, Riyadh The presence of an underlying immunodeficiency should be seriously considered when an unusual organism, or one of generally low pathogenecity in a normal child, causes a serious or life‐threatening illness. The predominant pathogens in immunocompromised patients vary by type of immunosuppression and often by degree and duration of the immunodeficiency. Therefore the net state of immunosuppression should be determined. The source of the infection may be exogenous or endogenous. A very wide range of organisms can cause infection in immunocompromised patients. Opportunistic pathogens must not be overlooked. Broad‐spectrum antibiotic use increases the risk of secondary fungal infections. As these patients are often in‐patients, Healthcare associated infections are a particular risk. The types of infections that occur in the immunocompromissed host usually reflect the underlying immunodeficiency, and can help in identifying what part of immune system may be compromised. For example intracellular pathogens, e.g. viruses, fungi, and mycobacteria cause opportunistic infections in patients with T‐cell deficiency. Bacterial pathogens cause infections in patients with neutrophil or immunoglobulin deficiency. Recurrent sino‐pulmonary infections may indicate an immunodeficiency state. Fever is often the only symptom of infection in the immunocompromised patient and always requires further investigation. No pathognomonic pattern or degree of fever can be associated with specific infection and fever may be absent during infection in the profoundly immunocompromised. Skin and mucous membrane infections can be very widespread and highly visible. In contrast, it is often difficult to identify the site of infection. Signs of inflammation other than fever are often mild or absent. The microbiology department should be alerted to the patient’s clinical history and extent of immunosuppression. Initiation of treatment should not be delayed pending laboratory results. Specimens should be selected based on the signs and symptoms presented and should reflect the disease process. Blood samples should always be taken and both bacterial and fungal cultures should be assessed. Blood counts are useful to assess the degree of neutropenia. Generally, the treatment should target the pathogen most likely to be involved, depending upon the host condition and duration of immunosuppression. Resistant or opportunistic organisms should always be considered. Specimens should be selected based on the signs and symptoms presented and should reflect the disease process. Blood samples should always be taken and both bacterial and fungal cultures should be assessed. Blood counts are useful to assess the degree of neutropenia. Generally, the treatment should target the pathogen most likely to be involved, depending upon the host condition and duration of immunosuppression. Resistant or opportunistic organisms should always be considered. TREATMENT OF UPPER RESPIRATORY TRACT INFECTIONS IN CHILDREN Dr. Esam Banyan The common upper respiratory tract infections (URTI) discussed in this presentation include: Acute Otitis Media, Pharyngitis and Sinusitis. They are particularly important because they are: • The most frequent cause of outpatient visits, approximately 5 –6 million episodes of AOM per year in the U.S. Costing about 3 billion dollars. • The most common indication for out patient antibiotic therapy. • And more importantly an opportunity to apply the principles of judicious use of antibiotics, which I think is critical in this day and age of increasing antibiotic resistance There was a time not long ago when it was thought that we had conquered most bacterial infections. Unfortunately that era has not come and we are actually loosing ground to these same infectious agents that were easily treated in the past. You are now very likely in your practice to encounter multiply drug‐
resistant Streptococcus pneumoniae, antimicrobial resistance among common respiratory pathogens, Vancomycin‐resistant enterococci (VRE), Glycopeptide‐intermediate or resistant Staphylococcus aureus (GISA, VRSA) and MDR tuberculosis. This has lead to treatment dilemmas and failures, serious invasive disease with antibiotic resistant strains and further spread of resistant strains in the community. This has required practitioners to change their approach to the therapy of common pediatric infections such as URTI, meningitis and osteomyelitis. The widespread use of antibiotics has been clearly proven to promote the emergence of resistant strains. This has been documented in both the inpatient and outpatient settings in a multitude of studies. Similarly the judicious use of antibiotics has been proven to limit antimicrobial resistant strains In this presentation we will discuss the accurate diagnosis of the common URTI and the approach to management taking into consideration the emerging resistance of the common pathogens. We also emphasize the judicious use of antibiotics yet show that this does not mean withholding antibiotics. Rather this means limiting the use of these agents to patients who have a high likelihood of benefiting from treatment, thereby reducing antibiotic pressure in the community. In addition the impact of the introduction of the seven valent pneumococcal conjugate vaccine on the epidemiology, diagnosis and management of URTI will be discussed. It is primary care providers who hold in their hands the ability and significant impact, in limiting the spread of this serious problem thru the implementation of the principles of judicious antibiotic use and by improving awareness among their patients. Prevention and Control of Childhood Pneumonia ‐ A focus on prevention of Hib and pneumococcal disease in the Arab World Rana A. Hajjeh, M.D. Director, Div. of Bacterial Diseases, NCIRD, CDC, Atlanta, GA Pneumonia is the commonest cause of childhood mortality, particularly in countries with the highest child mortality, and it has been identified as the major “forgotten killer of children” by the United Nations Children’s Fund (UNICEF) and WHO. Almost all (99.9%) child pneumonia deaths occur in developing and least developed countries. Although various pathogens may cause pneumonia, either singly or in combination, the available evidence, including the effectiveness of case management, suggests that two bacteria are the leading causes: Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus). WHO estimates that in 2000, Hib and pneumococcus together accounted for more than 50% of pneumonia deaths among children aged 1 month to 5 years. Several effective vaccines are available for the prevention of childhood pneumonia, including two vaccines provided in immunization programmes in all countries, Bordetella pertussis and measles vaccines, and two relatively new vaccines, Hib conjugate vaccine (HibCV) which has been introduced in most Arab countries over the last decade and pneumococcal conjugate vaccines (PCVs), which have been introduced in routine immunization programs in many developed countries starting in 2000, and recently in only a few Arab countries in the Gulf region. In those countries, the impact of Hib and pneumococcal vaccines on overall incidence of disease has been dramatic. For pneumococcal vaccines, several changes were observed in the spectrum of serotypes causing invasive pneumococcal disease. This presentation will review progress with Hib and pneumococcal vaccine and disease issues over the last decade and the resulting changes in the epidemiology of pneumococcal disease, as well as a global update on pneumococcal vaccine issues. Prevention and Control of Bacterial Meningitis ‐ A focus on vaccine preventable disease and issues for the Arab World Rana A. Hajjeh, M.D. Director, Div. of Bacterial Diseases, NCIRD, CDC, Atlanta, GA Bacterial meningitis remains an important public health problem worldwide, mainly caused by Streptococcus pneumoniae (SP), Haemophilus influenzae serotype b (Hib) and Neisseria meningitidis (NM). Even with antimicrobial therapy and availability of advanced intensive care, case fatality rates (CFR) are 5‐10% in industrialized countries and are much higher in the developing world. Between 10‐
20% of the survivors develop permanent disabling neurologic sequelae such as epilepsy, mental retardation or deafness. In the Arab World, localized epidemics of meningococcal meningitis have been reported from various countries and Saudi Arabia has experienced large meningococcal meningitis epidemics during the Hajj seasons, the most recent one was the first ever reported outbreak of serogroup W135. Almost all bacterial meningitis can now be prevented with very effective vaccines, including Hib conjugate vaccine, pneumococcal conjugate vaccines, and meningococcal conjugate vaccines. Hib vaccines have been introduced in most Arab countries over the last decade, however pneumococcal conjugate vaccines are only used in very few countries as part of routine immunization. In many countries where these vaccines were introduced, they have had a dramatic impact on incidence of disease. Laboratory‐based surveillance of meningitis is critical not only to determine the initial burden of disease, but also to detect outbreaks of meningococcal disease and to monitor the impact of vaccines once introduced. Though it has traditionally been difficult to isolate these organisms from CSF, the recent addition of polymerase chain reaction (PCR) testing was found to increase the yield of testing. This presentation will review progress with Hib and meningococcal vaccine and disease issues over the last decade with a focus on the Arab World and recent implementation issues. Influenza and influenza vaccines in pediatric patients Natasha Halasa Influenza viruses cause yearly epidemics globally and are responsible for multiple pandemics in the past. Currently, two types of trivalent influenza vaccines exist – inactivated influenza vaccine (TIV) and cold‐adapted live attenuated influenza vaccines (LAIV). In the United States, TIV is licensed for individuals 6 months of age and older and LAIV is approved for healthy individuals 2‐49 years of age. During this lecture, we will review the epidemiology of influenza, especially in the Middle East, and the associated morbidity and mortality of influenza illness. In addition, we will review the efficacy of both influenza vaccines. Acute Flaccid Paralysis ( AFP ) Surveillance in Amman : Two years Epidemiological Study DR . Atallah M . Abu – Sbeih , Medical Epidemiologist , Capital Health Directorate , MOH Disease Surveillance and Immmunization Department Emaile : [email protected] Mobile : 0796511552 P.O.Box : 630543, Jabal Al‐zohour Post Office, (11163 ) Background : Jordan is Polio free country , last case reported was in 1992 . Reasons behind this situation was high coverage with 4 doses of OPV and strong AFP surveillance . NIDs , SNIDs were also carried out . All health sectors ( MOH , Military , JUH , and Private hospital ) are informed to report all AFP cases to our department . Non – Polio AFP rate ( WHO ) 2/100000 child under 15 years , e.g target population for Amman 600000 children under 15 years, i.e we need to report 12 cases at least each year . Methods : AFP case was defined as any limb flaccid weakness for any reason , mostly Guillian – Baree syndrome GBS , in a child under 15 years of age . These cases were investigated using standard questionnaire for different variables : age , sex , stool adequacy …….etc. Two adequate stool samples, 24 hours apart , within 14 days of onset , were collected for viral study in polio lab , MOH . Follow ups after 60 days from onset was done to detect any residual paralysis in these cases by Experts Committee . Results : total number of cases reported in the last to years was 50 , each year 25 cases , 10 cases from Amman in 2007 , 12 cases in 2008 . From the governmental hospitals 38 cases and 12 cases from the private hospitals 8 of which from the Islamic hospital. 100 % of these cases were reported and investigated within 14 days from the date of onset of weakness. Two adequate stool samples were collected within 14 days from onset , and sent within 3 days from collection to polio lab to all these cases . Result of stool cultures was negative for polio virus. No residual paralysis was found after 60 days of follow up in any case. Non polio AFP rate of 2/100000 was fulfilled in Amman area in 2008. Conclusion / Recommendations : We have strong, competent, and timely AFP surveillance system. No surveillance failures was reported. Continuous reporting and monitoring of AFP cases is indicated to achieve WHO country certification. More involvement and participation of private sector (hospitals , clinics ) is highly needed . The Clinical importance of Urinary Calcium/Creatinine Ratio in Urinary Tract Infection Zuhair Nusair MD, Sameer Kofahi MD, Nazih Abu Al‐Shiekh MD Background: Urinary tract infection (UTI) is one of the most common infections in children. It approximately occurs in 3‐17% of girls and 1‐1.6% of boys. Hypercalciuria is believed to be the cause of a variety of urinary tract complaints in pediatric patients including urinary frequency, urgency, dysuria, enuresis, sterile pyuria and renal calculi. Hypercalciuria can be induced due to physiologic stimuli, increased filtered load, impaired renal tubular reabsorption of calcium, idiopathic hypercalciuria and unknown causes. Objective: The aim of this study was to evaluate the prevalence of hypercalciuria in children with pyelonephritis. Methods: This is a before and after study conducted between January‐December of 2008 on children afflicted with pyelonephritis, admitted in Pediatric Department at Prince Rashed Bin Al‐Hassan hospital. All children were treated with intravenous Ceftriaxone (75 mg/kg). The first fresh morning urine sample was collected before any treatment and analyzed for calcium and creatinine. The second urine sample was collected at the 4th day of admission. In our study the method of sampling was census, plan for data collection was observation and we used T‐test, Chi‐square and Regression analysis for statistic analysis. Results: A 42 children age ranged from 4‐8 years. (71.4%) of our patients were girls and 12 (28.6%) were boys. On the first day of admission 27 children (64.3%) had hypercalciuria and 15 children (35.7%) did not. There is a significant difference between first (before treatment) and second (after treatment) urinary Ca/Cr (p<0.0001). There was a significant correlation between first urinary Ca/Cr and BUN (p=0.010), CRP (p=0.004) and blood neutrophilia (Pearson Correlation r=0.358 and p=0.020). Conclusions: We conclude that hypercalciuria may be an important contributing factor in pyelonephritis and often it ameliorates after treatment of infection. The inflammation of the kidney and presence of infectious interstitial nephritis may explain this complication. Clinicians should be aware of this complication of pyelonephritis as an etiology of hypercalciuria and evaluation of hypercalciuria should be postponed up to resolution of infection. Surveillance of mumps cases in Amman area for the years 1999 ‐ 2008 D. Samir Khalil / epidemiology specialist Mobile: 0795846473 Fax‐5606029 Capital Health Department Introduction: Communicable diseases are reported by the decline of cases that refer to health centers and hospitals, in both public and private sectors, through the mechanism of the weekly reporting in the control Disease Department in Amman. MMR vaccine has been introduced in the National Vaccination Program in 2000, to be given to the child at the age of 18 months, and a second dose of this vaccine has been introduced in 2008, and given to the child at the age of one year. and the MMR vaccine is given as well as within the school health program for children in first grade of primary (those who did not take the MMR vaccine previously), as well as tenth grade students of both sexes. Methods: This study was conducted to reflect the impact of the introduction of MMR vaccine upon mumps cases, have been recorded in the period between 1999‐2008. A special questionnaire has been prepared for these cases, containing the main epidemic indicators of the disease: The number of cases, the distribution of cases by age and sex, distribution of cases by months, and vaccination status of the child. Analysis of these data and comparisons for the years 1999 ‐ 2008 , was done using epi‐info, and epidemic level for comparisons. The results of the study: Show a significant decrease in the number of cases of mumps in the last three years (2006,2007,2008), compared to previous years which reflects the positive effect of the introduction of MMR vaccine according to the schedule that has been explained above 63% of the total mumps cases were males, rest were females from age groups of 5 to 14 years, most of whom are students of primary schools and junior high, as expected Conclusion : ‐ The success of the National Vaccination Program against mumps with MMR vaccine in reducing the number of cases of this disease by concrete. ‐ The need to report the cases that refer to the health centers or hospitals, ‐ follow‐up to vaccinate the retarded. Susceptibility of Bacterial Pathogens in Children with Urinary Tract Infection in North of Jordan Nazih Abu Al‐Shiekh MD, Sameer Kofahi MD Zuhair Nusair MD, Amal Hatamleh Bcs, Fathi Abdel‐Algani Msc, Lara Obeidat Bcs. Abstract Background: Urinary Tract Infections (UTI) are one of the most common infections among children and the clinicians are basing their initial antibiotic therapy for UTI on probability grounds, but emerging resistance is not unusual. On other hand unnecessary prescriptions for antibiotics create new drug‐
resistant strains of common diseases. Prescribing antibiotics carefully and using them wisely is the key to preventing the spread of antibiotic‐resistant illnesses. Objectives: to asses the susceptibility of urinary pathogens to antibiotics in children with UTI in North of Jordan. Methods: The study sample included 100 children with UTI. The UTI was diagnosed by urine culture. Antimicrobial susceptibility of the isolates was investigated by Antibiotic Desk performed at the Lab of Prince Rashed Bin Al‐Hassan Military Hospital in North of Jordan. Results: The pathogens recovered in children with UTI as of the follow: Escherichia coli was the highest frequency (82%), Klebsiella (11%), Proteus (6%) and Pseudomonous was the least frequency (1%). The pathogens isolated from the children with UTI were 86% susceptible to Nitrofurantion, 83% to Gentamicine, 79% to Norfloxacine, 72% to Ceftriaxone, 48% to Cephalothin, 42% to Naladixic acid, 30% Septrin, and 16% susceptibility to Ampicilline respectively. Conclusions: This study shows a decrease in bacterial susceptibility to some antibiotics in children with UTI. This is important in empirical initial antibiotic treatment of children with UTI. Correspondence should be addressed to: Dr. Zuhair Nusair, Email: [email protected] Mobile: +962‐777215127. Invasive Fungal Infections and Antifungal Therapy Ibrahim Bin‐Hussain, MBBS, ABCP, FAAP Consultant, Pediatric Infectious Diseases and Clinical Mycology King Faisal Specialist Hospital & Research Centre, Riyadh Invasive fungal infection is a serious life‐threatening complication in immunocompromised children. Children with AIDS, leukemia, chronic granulomatous disease, severe combined immunodeficiency and preterm infant are the highest risk groups. During the last two decades, the incidence of invasive fungal infections has increased and continued to increase explosively. Two factors have had a dominating influence on the changing epidemiology of fungal disease. First, the number of at‐risk patients for invasive fungal infection has increased, as more patients have undergone chemotherapy and transplantation and received a growing array of immunosuppressive agents. Second, the increase in fungal disease is in no small way a by‐product of the ever‐improving technology available to practitioners, including intravascular catheters and the drugs used to suppress the otherwise efficient host defense system. Children with hematology/oncology disorder including BMT recipients are prone to fungal infections because of profound, prolonged immunosuppression due to cytotoxic drugs, steroids, radiotherapy, use of central venous catheters, GVHD and immunosuppressive therapy given as prevention and/or treatment of GVHD. Other predisposing factors are prolonged neutropenia and the wide use of broad‐
spectrum antibiotics. Most fungal infections in pediatric patients are caused by Candida spp. and Aspergillus spescies. Diagnosis of invasive fungal is sometimes quite difficult as presenting symptoms can be non‐specific, especially in neutropenic patients. Amphotericin B deoxycholate (D‐AmB; Fungizone) was the cornerstone of treatment for both suspected and proven invasive fungal infection. Amphotericin B has considerable toxicities. Adequate renal blood flow should be maintained and serum levels of co‐administered aminoglycosides, vancomycin and cyclosporins should be monitored. Because of infusion related and non‐infusion related toxilities of D‐
AmB, the pharmaceutical company tried to modify the toxicity of D‐AmB by incorporating it in lipid formulation. There are three variety of the lipid formulations of AmB tested as potential alternatives to D‐AmB: liposomal AmB; AmB lipid complex (ABLC) and AmB colloidal dispersion (ABCD). Fluconazole is well tolerated and has been shown to be effective as both treatment and prophylaxis against Candida albicans but has less activity against other species such as C. krusei and C. galabrata and is not effective against Aspergillus spp. Itraconazole has a broader spectrum of activity and is active against both Candida and Aspergillus but the capsule formulation has unpredictable absorption, is inconvenient to administer to young children and may be difficult for patients with mucositis to swallow. An oral and IV solution of itraconazole with better bioavailability than the capsules is now available for use against deep fungal infections in adult patients with neutropenia. The newer azoles, itraconazole, and voriconazole, are very attractive because they have oral, as well as intravenous, formulations; the echinocandins are attractive because of their excellent safety profile. Both voriconazole, posaconazole, and echinocandins have broad spectrum of activities against Candida spp. and Aspergillus spp. Echinocandins (caspofungin, micafungin, anidulafungin) are synthetic compounds that inhibit the synthesis of β‐1,3 glucan, by inhibiting the activity of glucan synthase. Their clinical use is primarily limited to Candida spp and Aspergillus spp and they lack activity against the Zygomycete, and Cryptococcus spp. Echinocandins have poor oral absorption and current agents are available only in the IV formulation. Voriconazole has become the drug of choice for most cases of invasive aspergillosis based on recent data comparing voriconazole to conventional amphotericin B, followed by other antifungal therapy in patients who have invasive aspergillosis. Voriconazole in children has demonstrated linear pharmacokinetics, in adults nonlinear metabolism is observed, likely secondary to saturable metabolic enzymes required for drug clearance. These new compound voriconozole, posaconazole, caspofungin, micafungin, and anidulafungin will be discussed during presentation. Restoration of host defenses is paramount and includes a) the discontinuation of corticosteroids, if feasible and b) treatment with G‐CSF or GM‐CSF in patients with diminished neutrophil counts to achieve normal levels of circulating granulocytes. Prevention of a GVHD is an important factor determining transplant‐related morbidity and mortality caused by IFI. This is not only due to a decreased administration of immunosuppressive drugs but also to the immunosuppressive effect of a GVHD by itself. Infections In Immunocompromised Patients Ibrahim Bin‐Hussain, MBBS, ABCP, FAAP Consultant, Pediatric Infectious Diseases Chairman, Working for Infections in Immunocompromised Pediatric Patients King Faisal Specialist Hospital & Research Centre, Riyadh The presence of an underlying immunodeficiency should be seriously considered when an unusual organism, or one of generally low pathogenecity in a normal child, causes a serious or life‐threatening illness. The predominant pathogens in immunocompromised patients vary by type of immunosuppression and often by degree and duration of the immunodeficiency. Therefore the net state of immunosuppression should be determined. The source of the infection may be exogenous or endogenous. A very wide range of organisms can cause infection in immunocompromised patients. Opportunistic pathogens must not be overlooked. Broad‐
spectrum antibiotic use increases the risk of secondary fungal infections. As these patients are often in‐patients, Healthcare associated infections are a particular risk. The types of infections that occur in the immunocompromissed host usually reflect the underlying immunodeficiency, and can help in identifying what part of immune system may be compromised. For example intracellular pathogens, e.g. viruses, fungi, and mycobacteria cause opportunistic infections in patients with T‐cell deficiency. Bacterial pathogens cause infections in patients with neutrophil or immunoglobulin deficiency. Recurrent sino‐pulmonary infections may indicate an immunodeficiency state. Fever is often the only symptom of infection in the immunocompromised patient and always requires further investigation. No pathognomonic pattern or degree of fever can be associated with specific infection and fever may be absent during infection in the profoundly immunocompromised. Skin and mucous membrane infections can be very widespread and highly visible. In contrast, it is often difficult to identify the site of infection. Signs of inflammation other than fever are often mild or absent. The microbiology department should be alerted to the patient’s clinical history and extent of immunosuppression. Initiation of treatment should not be delayed pending laboratory results. Specimens should be selected based on the signs and symptoms presented and should reflect the disease process. Blood samples should always be taken and both bacterial and fungal cultures should be assessed. Blood counts are useful to assess the degree of neutropenia. Generally, the treatment should target the pathogen most likely to be involved, depending upon the host condition and duration of immunosuppression. Resistant or opportunistic organisms should always be considered. Consideration of local factors ie. underlying disease state, presence of an intravascular device, local bacterial ecology and known resistance patterns. In cancer patients, infection is one of the most important causes of morbidity and mortality. Neutropenia is the primary risk factor for infection, as there is a close relationship between the level and duration of neutropenia and the frequency of infection in cancer patients. Risk is highest for severe neutropenia (absolute neutrophils <500 cells per mm3). Tremendous progress has been made in the treatment of febrile neutropenia in the last three decades. In the 1960s infection in neutropenic patients was associated with a mortality rate of more than 80%, whereas new treatment and medical advances have now reduced the mortality rate to nearer 5%. In addition to neutropenia, cancer patients can also have lymphopenia and humoral deficiency on top of altered physical integrity due to immuno‐suppressive therapy. The presentation will address and concentrate on the following issues: Who is really at risk for infection? What impact does the emergence of multi‐resistant organisms have on antimicrobial selection? Are modifications of initial therapy a failure or an expectation? Acute Flaccid Paralysis ( AFP ) Surveillance in Amman : Two years Epidemiological Study DR . Atallah M . Abu – Sbeih , Medical Epidemiologist , Capital Health Directorate , MOH Disease Surveillance and Immmunization Department Emaile : [email protected] Mobile : 0796511552 P.O.Box : 630543, Jabal Al‐zohour Post Office, (11163 ) Abstract Background : Jordan is Polio free country , last case reported was in 1992 . Reasons behind this situation was high coverage with 4 doses of OPV and strong AFP surveillance . NIDs , SNIDs were also carried out . All health sectors ( MOH , Military , JUH , and Private hospital ) are informed to report all AFP cases to our department . Non – Polio AFP rate ( WHO ) 2/100000 child under 15 years , e.g target population for Amman 600000 children under 15 years, i.e we need to report 12 cases at least each year . Methods : AFP case was defined as any limb flaccid weakness for any reason , mostly Guillian – Baree syndrome GBS , in a child under 15 years of age . These cases were investigated using standard questionnaire for different variables : age , sex , stool adequacy …….etc. Two adequate stool samples, 24 hours apart , within 14 days of onset , were collected for viral study in polio lab , MOH . Follow ups after 60 days from onset was done to detect any residual paralysis in these cases by Experts Committee . Results : total number of cases reported in the last to years was 50 , each year 25 cases , 10 cases from Amman in 2007 , 12 cases in 2008 . From the governmental hospitals 38 cases and 12 cases from the private hospitals 8 of which from the Islamic hospital . 100 % of these cases were reported and investigated within 14 days from the date of onset of weakness. Two adequate stool samples were collected within 14 days from onset , and sent within 3 days from collection to polio lab to all these cases . Result of stool cultures were negative for polio virus. No residual paralysis was found after 60 days of follow up in any case. Non polio AFP rate of 2/100000 was fulfilled in Amman area in 2008 . Conclusion / Recommendations : We have strong , competent , and timely AFP surveillance system. No surveillance failures was reported . Continuous reporting and monitoring of AFP cases is indicated to achieve WHO country certification . More involvement and participation of private sector ( hospitals , clinics ) is highly needed . The 6th Meeting of the Pan Arab Neonatology Forum Dear Reader: Below is a collection of the Abstracts of presentations delivered in the 6th Conference of the Arab Neonatology Forum, May 5‐8, 2009; Amman, Jordan. The abstracts are presented as it were sent by the authors. The authors are responsible for the format, typing and the contents of the abstracts. Cyanotic Congenital Heart Disease With PDA Dependent Pulmonary Circulation Fakhri Al‐ Hakim MD,FACC. Queen Alia Heart Institute Pulmonary Atresia intact ventricular septum,critical pulmonary stenosis,severe TOF,tricuspid atresia & pulmonary atresia,single ventricle & pulmonary atresia all are cyanotic congenital heart diseases with PDA dependent pulmonary circulation. Pulmonary atresia intact septum first described by Hunter in 1784. With D‐Transposition of great arteries and pulmonary atresia with ventricular septal defect are most common cardiac causes of cyanotic congenital heart diseases. The patient with pulmonary Atresia often presents as a cyanotic newborn,may do well for hours or days as long as there is substantial blood flow through a PDA ,but then becomes increasingly hypoxemic as the ductus constricts and closure of the ductus will be lethal. Use of prostaglandin E1 is critical in the early neonatal period to maintain ductal patency and stabilization of the patient prior surgery or catheter perforation of pulmonary valve. Evaluation of Brain Functions in NICU Safaa A. EL Meneza, Faculty of Medicine for Girls, AL Azhar University, Cairo, Egypt High risk newborn infants are liable to neurological complications, which may impair their motor, sensory and cognitive development. The primary focus of neurocritical care for CNS problems is the prevention, identification, and treatment. Therefore it is important to monitor high risk newborn infants for primary brain injury and for secondary brain injury after a prior neurologic insult. In clinical practice, predicting outcome in the acute period is most reliably based on assessment of the initial degree of brain injury and the persistence of brain dysfunction during the ensuing first few days. It is difficult to assess the cerebral function in critically ill neonates due to lack of clear guidelines and protocols that provide helps to choose the ideal neurodiagnostic tools. Also there are economic constrains in majority of NICUs worldwide that limit the cerebral function evaluations. With the increasing availability of neuromonitoring technology, it is essential for neonatal intensive care staff to understand the rationale for its use, as well as the fundamentals of application and interpretation of each tool. Guidelines include the neurological applications as encephalopathy, seizures drug effects, and neurological deterioration. There are different clinical situations that necessitate evaluation of brain functions as, preterm babies, low Apgar score, asphyxia, hypothermia, sepsis, metabolic diseases, and intubated infants. The neuromonitoring in NICU based upon, neurological examination, EEG monitoring and neuroimaging.The EEG has an important role in the diagnosis and management of neurological disorders in newborns. It has proven superior to clinical examination in newborns for the early detection and prognosis of brain dysfunction, and provides an important measure of quality of the brain function in critically ill infants. This is in contrast to other techniques, such as head ultra‐sonography and neuroimaging studies, which assess brain structure. Variable issues have to be considered when choose the ideal neuromonitoring tool as the degree of brain maturation ,the sensitivity and specificity regarding acute stages of illness and the anatomical location of the injury . This presentation will discuss the ideal tools in relation to GA, and patterns of cerebral injury. I will mention our experience in AL Zhraa University hospital in relation to the literatures. Severe hyperbilirubinemia in Egypt: Risk for Bilirubin Encephalopathy Seoud I, Iskander I, Gamal el din R, Khairy D, Khairy M , Wennberg R Objective: To examine the relationship of total serum bilirubin (BT) to bilirubin encephalopathy (BE) in a population with high prevalence of severe hyperbilirubinemia.. Methods: We reviewed the early outcomes of all patients admitted with severe hyperbilirubinemia admitted to the NICU of Cairo Children’s Hospital during a 24‐month period from January 2005 to December 2006 and estimated the sensitivity and specificity of BT in determining risk for BE in term/near term infants. Results: 685 neonates were admitted to the NICU with a primary diagnosis of severe hyperbilirubinemia, representing 40% of all NICU admissions. 147 patients had a TSB ranging 25‐29.9 mg/dL and 134 patients had TSB of 30 mg/dL or higher. All patients were treated by phototherapy; 229 (82% of infants with BT > 25 mg/dL) received one or more exchange transfusions. Neurological manifestations indicative of acute bilirubin induced encephalopathy were present in 29 infants. However signs of acute BE resolved in 13 cases following treatment. Seven of the remaining 16 cases died (BT ranged 34‐58, median 39 mg/dL) while 9 survivors had persistent evidence of BE when discharged. The sensitivity of BT>25 mg/dL in correctly identifying patients with BE was 100% in our population (92‐
97% in published series). The false positive rate was 95% if only patients with death from BE or signs of BE at discharge are included, and 90% if all patients with signs of early BE are included. This compares with FPRs of about 94% reported in the literature. A logical error in these calculations is that risk will increase with increased BT, and the calculations include patients with TSB ranging as high as 58 mg/dL. If data are confined to patients with TSB 25‐30 mg/dL, a region where most clinical decisions arise with 25 being the putative discriminating value, then false positives may be as high as 98%. Conclusion: In our population, a BT of 25 mg/dL was a sensitive risk indicator but with poor specificity indicating that factors other than BT play important roles in modifying the risk for BE. Clinical characteristics of Glucose‐6‐phosphate dehydrogenase deficiency in male Hasawiyah neonates Sameer Al‐Abdi, Taher Mousa, Maryam Al‐Amri, Najeeb Rehman, and Ayman Abumehrem. Department of pediatrics, King Abdulaziz Medical City, Alhasa, Saudi Arabia Background: Glucose‐6‐phosphate dehydrogenase (G‐6‐PD) deficiency is an X ‐linked recessive enzymopathy that may cause severe neonatal hyperbilirubinemia and kernicterus. Its clinical feature may differ according to the geographic area and genetic mutation. Its incidence in male in Alhasa area (Eastern Province of Saudi Arabia) is 23.3% and the most common mutation is Mediterranean (84%). However its clinical characteristics in native male neonates in Alhasa (Hasawiyah) are underreported. Objective: To report the clinical characteristics of G‐6‐PD deficient male Hasawiyah neonates. Design/Methods: This is a retrospective chart review of all male Hasawiyah live born at ≥ 35 weeks' gestation or ≥ 2500 grams birth weight who had cord blood G‐6‐PD screening via fluorescent spot test at King Abdulaziz medical city, Alhasa from 01 May‐31December 2008. The clinical characteristics of G‐6‐
PD deficient male Hasawiyah neonates (GD) were compared with G‐6‐PD normal male Hasawiyah neonates (GN). Results: During the study period, there were 1791 live births of which 538 (447 civilian & 91 bedouins) male Hasawiyah neonates met the inclusion criteria. All the 106 GD (20%) were civilians. Compared with GN, GD were more likely to develop total serum bilirubin (TSB) ≥ 257 mol/L [Odd Ratio (OD) 3 (95%CI: 2‐
6), Risk Ratio (RR) 3 (95%CI: 2‐4), p<0.0001] and TSB ≥ 95 percentile (Bhutani nomogram) in the first day of life [OD 4 (95%CI: 2‐10), RR 4 (95%CI 2‐9), p = 0.003]. Rebound hyperbilirubinemia requiring phototherapy was more in GD than GN but did not reach statistical significant [OD 1.7 (95%CI: 0.8‐3.4), RR 1.5(95%CI: 0.9‐2.8), p = 0.1]. Phototherapy requirement was considerably higher in GD than GN [80% versus 21%, OD 15 (95%CI: 9‐36), RR 4 (95%CI: 3‐5), p<0.0001], particularly in the early hours of life [Interquartile Range (IQR) (8‐13 hours) vs. (13‐43), p<0.0001]. Mean total hours of phototherapy duration was longer in GD, yet this difference was not statistically significant [56±87 (mean±SD) vs. 42±33, IQR (54‐25) vs. (54‐21), p = 0.1]. None required blood exchange or developed kernicterus in studied population. Demographic GD(106) Birth weight(g) (mean SD) 3119 438 Gestational age 39 1.5 Hgb(g/L) 165 22 Retic index 5.3 1.8 pDAT (%) 2.8 IDM (%) 6.6 pDAT=positive Direct antigen test, IDM=Infant of diabetic mother GN(432) 3226 484 39 1.5 162 29 5.2 2.6 3.2 9.3 Conclusions: G‐6‐PD deficient male Hasawiyah neonates are at considerable risk of hyperbilirubinemia that requires phototherapy in few hours of life and might rebound later on. Noteworthy they are all civilians which might argue against malria/G‐6‐PD development hypothesis. Neural tube defects , myelomeningocele : management and prognosis Myelomeningocele is one of the most common birth defects of the central nervous System. Research and studies in Arabic countries remain scarce . Prevention , management and prognosis need to be reevaluated in order to achieve the best benefits And health care for our children . Lecture’s objective : the aim of this lecture is to overview what has been published On this subject in Arabic world , compare it with our experience in Syria and Demonstrate What has been achieved in developed countries to overcome the burden of this health problem . Results will be discussed in order to conclude the best way of management . Conclusion and recommendation will be discussed afterwards Type of presentation : oral presentation , Power point . Duration of lecture : 15‐20 minutes Language : English Dr Mohamed Anas Barakat Neonatologist . The Syrian association of neonatology Survival and short‐term outcomes of Very Low Birth Weight Infants in Alhasa Area, Saudi Arabia and benchmark with the NICHD Neonatal Research Network Sameer Al‐Abdi, Ayman Abou Mehrem*, Kamal Dabelah, Mustafa Al‐Aghbari, and Maryam Al‐Amri. Department of pediatrics, Neonatal division, King Abdulaziz Hospital for National Guard (KAH), Alhasa, Saudi Arabia OBJECTIVE: To report our survival rate and incidence of short‐term morbidities for infants born at ≤ 1500 g birth weight (VLBWI) at King Abdulaziz Hospital for National Guard (KAH), Alhasa, Saudi Arabia and to benchmark our data with data reported from the Neonatal Research Network of the National Institute of Child Health and Human Development (NRN). STUDY DESIGN: Retrospective analysis of KAH electronic neonatal database for survival and selected short‐term morbidities to 120 days of life, discharge, or death from January 2003 through December 2008 for VLBWI and benchmark the data of KAH with the data of the NRN for (1997‐2002) cohort. RESULTS: The total deliveries at KAH were 10,551; 255(2.4%) out of them were VLBWI. Rate of Survival to discharge was 83% at KAH versus 82% at NRN. The Survival rate at KAH vs. NRN for infants weighing (501‐750 g) was 61% vs. 55%, for (751‐1000 g) 79% vs.88%, for (1001‐1250 g) 94% at both, and for (1251–1500 g) 93% vs. 96%.The Rate of intact Survival, that is, survival without bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH), and proven necrotizing enterocolitis (NEC) was 70 % at KAH and NRN. Similar to the NRN; more females survived at KAH (85% female vs. 81% male). Incidence of Bell’s stage 2 or more NEC, Papile grade III‐IV IVH and periventricular leukomalacia (PVL) at KAH were analogous to NRN data; 7%, 11%, and 3% respectively. At KAH, the Incidence of pneumothorax was 7.5% which is higher than NRN upper range 5% (1% ‐ 7%). The incidence of culture proven late‐onset septicemia (LOS) at KAH was higher then NRN 28% vs. 22 %; however, it is still within the range of benchmarking centers (12% ‐ 32%). The incidence of mild BPD, moderate BPD, and severe BPD was 13.7%, 5.9% and 4.7% respectively at KAH. Compared to NRN; antenatal corticosteroid use was less at KAH 70.2% vs. 79%. CONCLUSION: Survival rate of VLBWI born at KAH and important short‐term morbidities were computed. The Survival rates and incidence of definite NEC, severe IVH and PVL at KAH were analogous to the satisfactory data of NRN. On the other hand; incidence of pneumothorax and LOS were not; therefore further studies addressing the long‐term consequences of VLBWI in the context of high incidence of pneumothorax and LOS and at KAH are required Maternal Vitamin D deficiency 1Wadah M. KHRIESAT, MD, CHSM.2Isam M. LATAIFEH. MD, CGO. 1Sirin Alzoubi, M.D. 1Jomana Al‐
Sulaiman, MD 1Departmnet of Pediatrics,2Department of Obstetrics and Gynecology,Jordan University of Science and Technology, Faculty of Medicine,Irbid,Jordan Maternal vitamin D insufficiency is not uncommon. Infants born to mothers who are deficient in vitamin D, and in addition are breastfed, are at risk of developing vitamin D deficiency and hypocalcemia. The correlation between maternal vitamin D and neonatal vitamin D and hypocalcemia is not well documented. We present a case of neonatal hypocalcemic seizures secondary to vitamin D deficiency. PubMed Search PubMed, is developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM), located at the U.S. National Institutes of Health (NIH). Entrez is the text‐
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Use the Single Citation Matcher for finding the citation for a particular article using title words or citation information, or to find an entire volume or issue of a journal, or to generate a bibliography by a first author. Glycogen storage disease type III among Palestinian Children; a report of 24 cases Imad Dweikat MD, Inas Naser MD, Adeeb Naser Eddin MD Pediatric Department, Metabolic unit, Makassed Hospital, Jerusalem, Palestine Background: Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency of glycogen debranching enzyme, amylo‐1,6‐glucosidase which results in incomplete degradation of glycogen molecule. This enzyme is critical in both liver and muscle tissues. Deficiency of the enzyme in both tissues produces a variant known as GSD IIIa which can involve skeletal and cardiac muscles. Another less common variant known as GSD IIIb is caused by a deficiency of the enzyme in the liver only and is not associated with muscle involvement. Objectives: To discuss the characteristic clinical and laboratory findings that should alert the physicians for the diagnosis of the disease and its management. Methods: Retrospective study of 24 confirmed cases of GSDIII. The study was approved by the local ethics committee. Subjects: 24 patients (14 males, 10 females) belonging to 18 families whom were diagnosed at Makassed Islamic Charitable Hospital between1994‐2008. Parental consent was taken. Results and analysis: The mean age at diagnosis was 22 months. 18 children were born to consanguineous parents and most cases were from Bethlehem area. All cases had abdominal distension and hepatomegaly. Growth retardation was common. Elevated liver enzymes and hyperlipidemia were present in all cases and fasting hypoglycemia in 75%. Conclusion: Glycogen Storage Disease type III is relatively common among Palestinian children because of high rates of consanguineous marriages. It should be suspected in children presenting with abdominal distension, hepatomegaly, elevated liver enzymes, hypoglycemia and hyperlipidemia. G6PD Deficiency and Early Neonatal Hyperbilirubinemia Mansour A Al Qurashi, MD; Jubara Alallah, MD; Eman Nooreddeen,MD Salma H El Beely, MD; Ahmad A Moustafa, MD; Aliyah N Musba, MD; Ehab H Hanafi, MD; Hanin Al Ghamdi, BNSC; Musbah Al Shamrani, MD; Wasil Justaniah, MD INTRODUCTION: G6PD deficiency is a common enzyme deficiency causing anemia worldwide. We launched a program to test for G6PD deficiency in cord blood samples of all newborns delivered at King Abdulaziz Medical City (KAMC‐WR) in Jeddah, Saudi Arabia. OBJECTIVES: 1) To determine the prevalence of G6PD deficiency among infants born at KAMC‐WR over 7 years period (2001‐2007), and 2) to evaluate the risk of hyperbilirubinemia during early neonatal period in the G6PD deficient infants. DESIGN AND METHODOLOGY: Cord blood samples from infants were collected as part of a standard protocol, which included qualitative G6PD enzyme assessment in all neonates. We analyzed the data on the relationship between G6PD, hyperbilirubinemia, and its management. RESULTS: A total of 14,964 newborns (49% male and 51% females) had qualitative G6PD screening; of them 489 (3.3%) infants had G6PD deficiency. G6PD deficiency was more frequent in males compared to females (5.6% vs. 1%, p=<0.05). Phototherapy was administered in 41% of infants with G6PD deficiency. Jaundice presented in 18% of G6PD infants within 24 hours of life and 19% required admission to NICU for management of severe jaundice. Late preterm infants (35‐38 wks) with G6PD needed more frequent phototherapy (P=.008) and more admission to NICU due to severe jaundice (P<0.001). CONCLUSION: G6PD deficiency is more common among Saudi newborn infants compared to global figures. Significant portion of these infants required treatment for hyperbilirubinemia and were admitted to NICU. Male gender and late preterm gestation are the major risk factors for the development of jaundice and requirement of intervention in this population. Our data support the need to embrace G6PD screening program using cord blood at a national scale. Fluconazole Prophylaxis is Effective in Reducing Systemic Fungal Infection in VLBW Infants. A Single Center, 4 Years Retrospective Study. Mansour A Al Qurashi, MD; Jubara Alallah, MD; Eman Nooreddeen,MD Salma H El Beely, MD; Ahmad A Moustafa, MD; Aliyah N Musba, MD; Ehab H Hanafi, MD; Hanin Al Ghamdi, BNSC; Musbah Al Shamrani, MD; Wasil Justaniah, MD – King Abdulaziz Medical City – WR, National Guard Health Affairs Jeddah INTRODUCTION: The prevalence of systemic fungal infection in very low birth weight (VLBW) infants is increasing. It has high morbidity and mortality costs in this vulnerable group. The use of fluconazole to prevent fungal infection in preterm infants is gaining widespread popularity among neonatologists. However, It is not yet recommended as a standard of care. We have reviewed 4 years series to evaluate the effectiveness of this strategy in preventing systemic fungal infection in our NICU. OBJECTIVES: To asses the effectiveness of fluconazole prophylaxis in preventing systemic fungal infection in VLBW infants. METHODOLOGY: This retrospective study of 196 preterm infants who weighed < 1500gms at birth and admitted to our NICU in the period from January of 2003 until December of 2006 (4 years). Those who were born between 2003‐2004 and didn’t receive fluconazole prophylaxis (group A, n=94) were compared with those who were born between 2005‐ 2006 and given fluconazole prophylaxis for 4‐6 weeks of life (group B, n=102). The incidence of Systemic Fungal Infection (SFI) and mortality rate attributable to fungal infection has been estimated for both groups. RESULTS: Overall systemic fungal infection was significantly lower in group B (fluccnazole group), [2 of 102, 1.96 %] than in group A (Non‐fluconazole group), [13 of 94, 14%] with an ARR of 12%, relative risk of 0.19, 95% CI (0.054‐0.7) and P‐value of 0.007 and the number need to treat (NNT) is 8.3 . Major risk factors for SFI, which includes use of 3rd generation cephalosporins, duration of central lines placement, use of T.P.N., use of systemic steroids, rate of NEC and other risk factor where comparable and not significantly differs in both groups. CONCLUSIONS: Fluconazole prophylaxis significantly reduced the incidence of systemic fungal infection in VLBW infants. This retrospective cohort study adds to the increasing body of evidence to support its use in this exquisitely vulnerable group, particularly in units with high rate of invasive fungal infants, further studies are required to refine the identification of infants who at highest risk for IFI for whom prophylaxis would be optimally suited. An Update on Paediatric Resuscitation Ezzedin A Gouta, Barnsley Hospital, England, UK The most important changes in recommendations for paediatric resuscitation over the last several years include: Increased emphasis on performing high quality Cardio‐Pulmonary Resuscitation (CPR): “Push hard, push fast, minimize interruptions of chest compression; allow full chest recoil, and don’t provide excessive ventilation”, Chest compression‐ventilation ratio: for lone rescuers with victims of all ages: 30:2 and for health care providers performing 2‐rescuer CPR for infants and children: 15:2,, either a 2‐ or 1‐hand technique is acceptable for chest compressions in children, use of 1 shock followed by immediate CPR is recommended for each defibrillation attempt, instead of 3stacked shocks, biphasic shocks with an automated external defibrillator (AED) are acceptable for children 1 year of age, attenuated shocks using child cables or activation of a key or switch are recommended in children <8 years old, routine use of high‐dose intravenous (IV) epinephrine is no longer recommended , intravascular (IV and intraosseous) route of drug administration is preferred to the endotracheal route, cuffed endotracheal tubes can be used in infants and children provided correct tube size and cuff inflation pressure are used, exhaled CO2 detection is recommended for confirmation of endotracheal tube placement and consider induced hypothermia for 12 to 24 hours in patients who remain comatose following resuscitation. References: 1. Pediatric Basic and Advanced Life Support. The International Liaison Committee on Resuscitation. Pediatrics 2006;117;e955‐e977 2. Resuscitation Council (UK). Resuscitation Guidelines 2005. www.resus.org.uk The European Consensus Guidelines on the Management of Neonatal Respiratory Distress Syndrome Ezzedin A Gouta, Barnsley Hospital, England, UK Preterm babies are at risk of developing Respiratory Distress Syndrome (RDS). Pre‐labour management includes, if possible, delaying birth by using tocolytics and antibiotics to allow the maximum benefit of prenatal corticosteroid therapy. At birth, resuscitate gently, avoiding excessive tidal volumes and exposure to 100% O2 if possible, provided there is an adequate heart rate response (>100/min). For extremely preterm infants, consider intubation in delivery room for prophylactic surfactant administration. For more mature babies, CPAP should be initiated early, and early rescue surfactant administered if signs of RDS develop. Natural surfactants should be used and given as early as possible in the course of RDS. More mature babies can often be extubated to CPAP immediately following surfactant, and a judgment needs to be made if an individual baby will tolerate this. For those who require mechanical ventilation, aim to ventilate for as short a time as possible, aiming to avoid hyperoxia and hypocapnia. Repeat doses of surfactant may be required if there is ongoing evidence of RDS. Following extubation, babies should be maintained on CPAP until it is clear that they are stable. Whilst managing RDS good supportive care is also essential. Antibiotics should be initiated until sepsis has been ruled out. Body temperature should be maintained in the normal range at all times and careful fluid balance with nutritional support, initially in the form of parenteral nutrition, should be instigated. Blood pressure should be monitored regularly, aiming to maintain normal tissue perfusion, if necessary using inotropes and consideration should be given to whether pharmacological closure of the ductus arteriosus is indicated. References: European consensus guidelines on the management of neonatal respiratory distress syndrome. David Sweet, Giulio Bevilacqua, Virgilio Carnielli, Gorm Greisen, Richard Plavka, Ola Didrik Saugstad, Umberto Simeoni, Christian P. Speer, Adolf Valls‐i‐Soler and Henry Halliday. J. Perinat. Med. 35 (2007) 175–186 Jordan National New Born Screening Programme Sana' Al Hait, Itidal Zaidan, Basem Zou'bi, Raja' Badarneh, Hind Othman. Ministry of Health, Jordan New Born Screening for Hypothyroidism (HT) and Phenylketonuria (PKU) started as a pilot study in two governorates in 2006. Five thousand new born infants were screened. Detected infants with HT and with PKU were seven and two respectively. Education and training plan was designed and a training team was formed. Courses were conducted in 22 Health Directorate all over the country. Stepwise governorates involvement in the screening programme was completed in June 2008. Screening was officially nationalized by the Ministry of Health in Aug 2008. New Born Screening and management of detected infants have been integrated in the free of charge health services. Method: comprised Guthrie dry blood spots collection and ELISA measurement of TSH and Phenylalanine, with cut off points of 10 IU and 240 umol respectively. Only twenty three thousand new born babies have been screened. Thirty four new born infant have been protected from mental handicap of both diseases. Conclusion : Jordan has initiated its National New Born Screening Programme for HT and PKU in 2008. It is the second national genetic prevention programme in this country. Though it is early to consider an accurate incidence, it could be higher than expected. Recommendations : ‐Enhanced maintained community wide health education and sustained education of health sectors are recommended. ‐ Ninety percent coverage in three years, can be an achievable goal. ‐ Mandatory New Born Screening, could it be a suitable policy in the Jordanian community ? ‐ Introduction of other screen able common disorders in the foreseeable future is suggested. Third Epidemic of Retinopathy of Prematurity (ROP) Oommen Mathew Professor of Pediatrics, Children’s Medical Center BIW 6033, Medical College of Georgia ROP is a common blinding disease in children in developed countries and is becoming increasingly prevalent in the developing countries, accounting for approximately 50,000 blind children globally. The first wave occurred in the late 40s and 50s. Several publications in the 50s showed a strong association between oxygen use and retrolental fibroplasia. A re‐emergence of ROP was noted in the late 70s. Oxygen toxicity was not the primary factor in this re‐emergence of ROP. One of the important changes during this period was the increased survival of low birth weight infants. ROP blinded infants in the USA in 1981 was 883 compared to 397 in 1971. A third epidemic is now emerging primarily in developing countries; infants are being exposed to risk factors which are now largely controlled in industrialized countries. Our understanding of the pathogenesis and treatment has improved dramatically over the years. Premature birth interrupts normal retinal vascular development. ROP has two phases: the first phase begins with delayed retinal vascular growth after birth and partial regression of existing vessels, and the second phase consists of hypoxia‐induced pathological vessel growth. Both oxygen‐regulated and non‐
oxygen‐regulated factors contribute to the development of ROP. Vascular endothelial growth factor (VEGF) is an important oxygen‐regulated factor, whereas insulin‐like growth factor (IGF‐1) is a non‐
oxygen‐regulated growth factor. Suppression of VEGF by oxygen in phase I inhibits normal vessel growth. Elevated levels of VEGF in phase II of ROP induce pathological vessel proliferation. IGF‐1 levels are low after preterm birth; low IGF‐1 levels may prevent normal vessel growth in phase I. As levels of IGF‐1 rise in phase II, it indirectly regulates VEGF stimulated pathological neovascularization. Serum levels of IGF‐1 in premature babies directly correlate with the severity of clinical ROP. Cryotherapy and laser photocoagulation have given hope to neonates with ROP who would otherwise be blind. With the advent of laser, there was a shift from cryotherapy to laser photocoagulation. Recent studies have shown that early treatment of high‐risk prethreshold ROP reduces unfavorable outcomes even further. Screening guidelines of preterm infants for ROP was originally published in 2001 and revised in 2006. As per these screening guide lines the first exam is to be performed at 31 weeks post menstrual age for infants < 28 weeks at birth and at 4 weeks chronological age for 28‐32 weeks gestational age infants. Follow up examinations are performed at intervals of one to three weeks until the growth of retinal vessels are completed to the ora serrata. It is anticipated that continued screening and new guidelines for intervention will reduce this number. Is There A Role For Inhaled Nitric Oxide For Premies? Oommen Mathew Professor of Pediatrics, Children’s Medical Center BIW 6033, Medical College of Georgia Inhaled nitric oxide (NO) was approved by the FDA in1999 for use in term and near‐term infants with hypoxic respiratory failure. Since its approval, iNO has become the standard of care among term and near‐term infants with hypoxic respiratory failure. Only infants who fail to respond to this therapy are considered for ECMO. Inhaled NO has potential clinical benefits in a number of other disease states as well. Several key observations suggested that inhaled NO is potentially beneficial in preterm infants. NO has been shown to improve oxygenation in preterm infants with respiratory failure. Furthermore, it improves surfactant function, reduces lung inflammation in the animal model and reduces hyperoxic lung injury. However, results of the majority of NO trials in critically ill preterm infants have not shown any beneficial effect including a large multicenter trial. No decrease in the rates of death or bronchopulmonary dysplasia was found with the use of inhaled nitric oxide in critically ill premature infants weighing less than 1500 g. On the other hand, Schreiber et al. showed that the incidence of chronic lung disease and death among premature infants with the respiratory distress syndrome is reduced by treatment with low‐dose inhaled nitric oxide. Two large clinical trials investigated the potential benefit of NO in reducing chronic lung disease. In both trials very small premature infants requiring mechanical ventilation were exposed to small doses of inhaled NO for relatively long periods. Kinsella et al. observed no overall difference between groups in the combined primary outcome of death or bronchopulmonary dysplasia. In contrast, Ballard et al. reported that nitric oxide treatment improved survival without bronchopulmonary dysplasia. Given the expense and the lack of benefits in critically ill neonates this treatment regimen cannot be considered cost effective. Questions still remain on the most effective dose, duration, and time of initiation of inhaled NO in less critically ill infants. Clinical And Cytogenetic Profile Of Down Syndrome At King Hussein Medical Centre Wajdi Amayreh*, MB BS, MRCPCH, Kefah Al Qa'qa'*, MD, Ali Al Hawamdeh*, MD, FRCPCH, Samah Tawalbeh*, RN Department of Paediatrics, Metabolic genetics division, King Hussein Medical Centre BACKGROUND: This study was designed to evaluate the karyotype pattern, clinical features and other systemic anomalies of patients with Down syndrome at King Hussein Medical Centre. METHODS: Prospective analysis of Down syndrome cases referred to the Genetic Clinic was performed. The following information was recorded: age at presentation; sex; maternal age; craniofacial and other physical features; presence and type of congenital heart disease, gastrointestinal abnormalities, hearing assessment, ophthalmic evaluation, complete blood count, kidney and liver function tests,thyroid function tests,abdominal ultrasound, and results of cytogenetic evaluation. RESULTS: Analysis included cases of Down syndrome attending the genetic clinic at KHMC; a total of 75 patients were studied (40 males and 35 females; M:F ratio 1.14:1). Average age at presentation was 3 months (range: 1 day‐10 years). Average maternal age at birth of the affected child was 26.8 years (range: 18‐40 years). Craniofacial features noted in >80% of the cases included mongoloid slant , ear abnormalities , epicanthic folds , and flat facial profile. Characteristic limb and dermatoglyphic anomalies were seen inabout 65% of cases. Ophthalmologic abnormalities included hypertelorism , refractive errors, nystagmus, Brushfield spots and cataracts. Congenital heart disease was found in 31 cases (40%) which was proved by echocardiography. Gastrointestinal anomalies were noted in 2 cases and included two with diaphragmatic hernia, and one with duodenal atresia. Hypothyroidism was present in 16 patients (21%) of cases. Results of cytogenetic abnormalities showed Free trisomy (non‐
dysjunction) was present in 93%, 4% had translocation, and 2.6% were mosaics. Conclusion; Early diagnosis and a proper screening for high association with systemic anomalies should be undertaken among patients diagnosed with Down syndrome. The New Genetics of Autism. Majed Desouki Autism is an early childhood complex behavioral disorder characterized by impairments in social interaction and communication as well as repetitive and stereotypic behaviors. While it is usually gradual, 30% have a "regressive" onset. The majority of affected children have essential or idiopathic autism while 5‐10% have a recognizable cause. In complex autism (30%), microcephaly, macrocephaly, dysmorphic features and brain malformations occur. Chromosomal, single gene and genomic copy number abnormalities are now recognized as causes of childhood autism. The advent of array Comparative Genomic Hybridization (aCGH) greatly enhanced our ability to identify submicroscopic genomic abnormalities as causes of autism. Many (75%) autistic children have a lifelong disability requiring intensive parental, school, and societal support. Medical and behavioral therapies for autistic children aim at promoting conversational language and social interactions while mitigating repetitive, self‐stimulatory behaviors. A comprehensive genetic evaluation of autistic children is indicated. The identification of a genetic cause should also provide families with more accurate recurrence risks. Late Preterm Infants and their complications Yousef M Abdulrazzaq, Department of Paediatrics, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates. Abstract Late preterm infants are at risk for neonatal morbidity or mortality. Preterm births have increased worldwide and late preterm births make up 71% of preterm births. Factors associated with the increased preterm birth are multiple births, caesarian sections and early induction of labour. Babies born between gestational ages 34‐36 weeks are at increased risk of Respiratory distress, jaundice, feeding difficulties, hypoglycemia, temperature instability, sepsis and increased NICU use. Compared to full term infants, these near term infants are more likely to have positional apnea, less glycogen and fat stores to prevent hypoglycemia, mild hypotonia, less alert awake periods, an uncoordinated suck, swallow, and breathe pattern, and a less mature liver. Neonatal care statistics in a hospital in UAE and comparison with Vermont Oxford Network Yousef M Abdulrazzaq, Department of Paediatrics, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates. Abstract The UAE progress in health care has been remarkable. Neonatal Mortality Rate in the year 2000 was 4.38 per 1000 live births and in 2006 it was 3.6 per 1000 live births. Very low birth weight infants (VLBWI) represent 1.5% of life births, but contributes to about half of infant mortality. Their outcome varies according to the population characteristics and closely reflects the organization of perinatal service and the quality of neonatal intensive care. The mortality rate of VLBWI born in Al Ain, UAE between 1995 and 1998 and reported 34.5 and 12.2% mortality rates in infants with birth weight 500–
999 g and 1000–1499 g, respectively. In 2006 in one hospital in the UAE, mortality in birthweight group 500‐1000 g was 33% and in 1000‐1500g birthweight group was 3.6% as compared to 32% and 5% respectively in the 2 birthweight groups of the 2005 Vermont Oxford cohort. In 1991 mortality rate in the 2 groups were 50% and 20% respectively and this had significantly reduced in 2006 to 31% and 3.6% respectively. The management of fat oxidation disorders Andrew Morris Problems associated with fatty acid oxidation disorders include •Hypoglycaemic encephalopathy, which may lead to sudden death, as in MCAD deficiency •Rhabdomyolysis and muscle weakness, as in partial CPT II deficiency and mild cases of multiple acyl‐
CoA dehydrogenase (MAD) deficiency •Cardiomyopathy in severe disorders of long‐chain fatty acid oxidation •Pigmentary retinopathy and peripheral neuropathy, as long‐term complications in LCHAD deficiency. The management of MCAD deficiency involves •A regular intake of carbohydrate during stress, such as infections •Avoiding fasting. In long‐chain fat oxidation disorders, additional dietary measures are needed. Strategies have included •Long‐chain fat restriction, with adequate essential fatty acids and vitamins •Medium chain triglycerides (MCT) •Triheptanoin •3‐Hydroxybutyrate in severe cases of MAD deficiency In a few disorders, drugs are effective •Carnitine in carnitine transporter defects •Riboflavin in some cases of MAD deficiency •Bezafibrate to prevent rhabdomyolysis in mild long‐chain disorders Outcomes in MCAD deficiency are excellent with the precautions outlined above. There are, however, limited data concerning the frequency of problems without intervention. The evidence base is much weaker for the drugs and dietary treatment used in other fatty acid oxidation disorders. Reasons include •the rarity of the conditions •variation in severity between patients with the same condition •the need for long term studies, particularly for retinopathy in LCHAD deficiency •reluctance to do randomised controlled trials due to belief that treatment works. Anecdotal case reports suggest that dietary treatment improves the clinical outcome in long‐chain fatty acid oxidation disorders. This is supported by a few small series, compared with historical controls. Some further evidence is provided by studying metabolites, such as acylcarnitines. Blood acylcarnitines may, however, be of limited relevance to pathogenesis in, for example, the retina. The investigation of suspected mitochondrial disease Andrew Morris Mitochondrial disease can present at any age, with problems affecting any part of the body and with any pattern of inheritance. The first requirement is to select which patients to investigate, as this is generally invasive, usually requiring a muscle biopsy. The easiest patients to diagnose are those with classic clinical ‘syndromes’, such as Leigh, Alpers, Pearson, Kearns‐Sayre (KS), Barth, LHON, MELAS, MERRF, NARP and GRACILE syndromes. Suspicion should also be high in patients with multisystem disease without an obvious anatomical, biochemical or embryological link. The m.3243G>A mutation, for example, is often associated with diabetes and deafness. Finally, some individual symptoms are suggestive, such as progressive external ophthalmoplegia (PEO) and renal Fanconi syndrome. Initial investigations should define the pattern of clinical involvement, exclude alternative diagnoses and seek specific markers. Raised lactate concentrations, particularly in CSF are an important clue. L:P ratios only add further information if samples are collected under ideal conditions. Many classical syndromes can be diagnosed by looking for specific mutations in blood. For other patients, including those with Leigh & KS syndromes, a muscle biopsy is generally required. Histochemistry and biochemical assays of the respiratory chain complexes both provide important, complementary results. Subsequent molecular studies should be guided by these results, together with clinical features, including the patient’s age and family history. MtDNA defects are, for example, more likely in adults, if there is no parental consanguinity and if histochemistry shows a patchwork of fibres positive and negative for cytochrome oxidase (COX = complex IV). In patients with PEO, mtDNA deletions should be sought by Southern blotting or long‐range PCR. If multiple deletions or mtDNA depletion are found, common POLG1 mutations should be sought, generally followed by sequencing as this gene is the commonest cause. In patients with isolated defects of complexes I‐III, sequencing of subunits and assembly genes may be appropriate. Unless there is parental consanguinity, it is generally appropriate to start with mtDNA encoded subunits. In patients with isolated complex IV deficiency, sequencing should generally start with assembly genes (such as SURF1 in Leigh syndrome) unless histochemistry shows a patchwork of COX positive and negative fibres. In patients with a patchwork and/or combined defects of complexes I, III & IV, mtDNA sequencing is usually appropriate, though defects of genes involved in mtDNA replication and translation can give similar findings. Normal biochemical results are seen in a few patients with mitochondrial disease, such as complex V defects. Moreover, respiratory chain abnormalities can be artifactual if samples are not processed correctly and may also occur secondary to various other disorders. Results are, therefore, sometimes equivocal: consensus criteria have been devised to estimate the likelihood of mitochondrial disease in these patients. Safe sleep practice to prevent sudden infant death, old and new Bradley Thach, MD, Washington University School of Medicine St. Louis, MO USA Abstract Over the past 17 years a number of strategies have been adapted to prevent sudden unexpected infant deaths. A few of these are back sleeping, avoidance of soft bedding and swaddling. Avoidance of “heat stress” is controversial. Swaddling styles vary from the ancient to the modern. Over many thousands of years a variety of practices for infant care were developed. Unfortunately, in recent times most of these were abandoned. U.S. pediatricians exported the practice of placing infants prone. This was a tragic mistake. Infant deaths in epidemic proportions occurred when infants were placed prone. Recognition of this lead to the return to back sleeping. With back sleeping, SIDS rates have fallen greatly in Western Countries. SIDS was originally believed to be a single entity. Now other diagnoses are used such as accidental suffocation or cause of death unknown. Accidental suffocation is believed to be due to rebreathing of expired air when soft bedding covers an infant’s face. A current problem in the U.S. is infant deaths while sharing a bed with others. This continues to be controversial. Pediatric organizations and government agencies in the U.S. strongly recommend against this practice. Epidemiology and clinical outcome of candidaemia among Jordanian newborns over a 10‐year period Eman F. Badran a; Jumana H. Al Baramki b; Abdulqader Al Shamyleh c; Asem Shehabi d; Najwa Khuri‐Bulos e , Jordan University Hospital, Amman, Jordan Background: Newborns admitted to neonatal intensive care units (NICU) are at increased risk of candidaemia . The incidence of candidaemia is influenced by several risk factors. The risk factors have changed in recent years/ The mortality rate of candidaemia was reported to be as high as 50% .Severe infections caused by non‐albicans Candida species are increasingly being reported among infants in neonatal intensive care units. Objectives: Since information on the importance of candidaemia in our region is lacking, this study was undertaken in order to determine the rate of candidaemia at Jordan University Hospital (JUH) NICU, and to describe risk factors, clinical presentation, and outcomes of Candida‐induced neonatal infection. Patients and Methods : A retrospective study was conducted at JUH, which has a 30‐ tertiary NICU bed. All patients admitted between January 1995 and June 2006 with candidaemia were included. Data were collected from patient's medical records, the infection control unit, and the clinical microbiology laboratory.For statistical analysis, we used the statistical package system version 13. The chi square test was applied when indicated. In all of the statistical tests, the null hypothesis was rejected at the 5% level (p ≤ 0.05). Continuous variables (birth weight, gestational age and total hospitalization duration) were compared between patients who survived and those who succumbed using a non‐parametric test; Mann‐Whitney U test.Research committee approval was obtained to do this study. Results. Among 24 patients included, 13 (54.2%) died. The incidence of candidaemia was 0.27%, the mean age at diagnosis 25.9 d and the mean gestational age at birth 34.6 weeks. Species most frequently isolated were Candida albicans (50%) and C. krusei (20%). Previous gastrointestinal pathology was present in 41.7% of the cases. A comparison of cases due to C. albicans with those due to other species of Candida revealed no statistical differences in terms of demographic factors, age at onset of disease, mortality, clinical manifestations or risk factors. Conclusion: This study indicates that the incidence of neonatal candidaemia in the JUH tertiary referral academic hospital is low, with stability in incidence over the study period. Half of candidaemia cases were caused by non‐albicans Candida species in which C. krusei is now the second most common pathogen (20%). Based on our results, empirical antifungal therapy should be considered in neonates who have gastrointestinal pathology and other risk factors. Neonatal Screening of Inherited Metabolic Diseases In KSA Zuhair A. Rahbeeni, MD and Mohamed S. Rashed, PhD, King Faisal Specialist Hospital and Research Centre Introduction: Healthcare providers especially Ministries of Health in the world should provide the healthcare from diagnosis till treatment and prevention of diseases for every resident. However, limitations of resources make the preventive strategies are the best to target in many parts of the world. Neonatal screening program proved without doubt that it is one of the best means for healthy children and community. In addition, it decreases the handicapped by early treatment. However the neonatal screening program should not be a test but a complete program. Method: Blood samples were extracted from neonates during the first 3 days of life to be sent to King Faisal Specialist Hospital and Research Centre with biographic data including age, sex, weight, etc. The research involved more than 24 hospitals in the Kingdom. Inclusive Dates: The period of research is from 20 August 2005 to 29 February 2008. Result: We screened 161,926 samples and there was one neonate affected among 764 neonates with one of the 16 disorders that we screened (212 positive neonates). Discussion: This study showed doubt the high incidence of Genetic disorders including inherited metabolic diseases (IMDs) in the Kingdom (and Arab worlds) if compared with Western Countries. Conclusion: This high incidence of IMDs make Neonatal Screening program in the Kingdom (and Arab Countries) necessary if the program is taking completely from diagnosis till treatment and follow up including Genetic Counseling in order to prevent these disorders in the future. Attitude of Palestinian Families Towards Terminating Antenatally Diagnosed Abnormal Fetuses: ‐ Religious, Cultural and Ethical Issues. Bassam Y. Abu‐Libdeh, MD, Makassed Islamic Charitable Hospital & Al‐Quds Medical School, Jerusalem, [email protected] Background:‐ In Islam, termination of pregnancy (TOP) was not allowed at any stage except to save the life of the mother. About 20 years ago, a Fatwah was declared by Muslim scholars permitting TOP if the fetus is diagnosed before emergence of the soul to have a dangerous and none treatable congenital abnormality. Objectives: ‐ To examine the attitude of Palestinian families living now in the Palestinian Territory (West Bank & Gaza) towards the issue of terminating antenatally diagnosed abnormal fetuses. Methods :‐ Between 1/1996‐12/2007, 1294 pregnant ladies underwent antenatal diagnosis for different indications at Makassed Hospital in Jerusalem either by amniocentesis performed between 16‐19 wks of gestation (1056 ladies) or chorionic villous sampling performed between 10‐12 wks of gestation (238 ladies). The most 4 common indications for performing the test were advanced maternal age (491/ 38%), abnormal antenatal screening (337/26%), previous child with thalassemia (197/15%) and previous child with Down Syndrome (115/9%). Subjects:‐ Pregnant ladies undergoing prenatal diagnosis for different medical indications after signing the appropriate consent. Results & Analysis:‐ The total number of abnormal fetuses was 57 (20 by amniocentesis and 37 by CVS). The single most common abnormality detected was Thalassemia (26/46%). After receiving appropriate genetic counseling and after consulting a religious authority (in most cases), the families of 55 abnormal fetuses consented to terminate the pregnancy. Only 2 families refused the termination. Conclusions :‐ We found very good acceptability for prenatal diagnosis in families at risk of having babies affected with a genetic disease. Most of these families accepted to perform the test because they were considering terminating an abnormal fetus. All couples with an affected fetus, except two, opted for abortion as long as the diagnosis was made before 120 days of conception. Perinatal and Neonatal Audit Mohamed Reda Bassiouny, MD, MHPE, Mansoura University, Egypt During the past decade, there have been dramatic changes in the field of neonatology. Health professionals must understand: How to evaluate their own performance and how their performance will be evaluated by others. An audit is a thorough assessment, count or evaluation. In an audit information is systematically collected and then presented in a manner that can be understood. An audit of health care can be conducted. To conduct Mortality or Morbidity Audit: The information (data) must be collected, analyzed, discussed and then draw conclusions. Plans must be made to correct any detected problems. Often morbidity is included as part of a mortality audit. Perinatal Mortality Meeting is a meeting to discuss all the aspects of: maternal deaths stillbirths and neonatal deaths. The extent of the problem is identified. Causes and avoidable factors and likely answers are hopefully found. There is minimal data set to be presented in an organized summary. Problems with Perinatal Mortality Meetings involve staff commitment, confidentiality, documentation. It is important to discuss the problem and NOT the staff involved. Regular reports must be prepared, based on the findings in the perinatal mortality meetings. A Feed Back Meeting should be conveyed. On the regional or national level results should be compared between different Areas. Evidence Based Medicine in Necrotising Enterocolitis Gamal Samy Aly MD, Ain Shams University,Cairo, Egypt NEC is the most common emergency of the gastrointestinal tract occurring in the neonatal period. It affects 2‐4% of all NICUs admission and its mortality rate ranges between 5 – 20%. Studies published over the last years have provided new insight into diagnosis and management of this complex disease. Evidence‐based pediatrics is the practice of child health care based on the best available evidence. The practice of evidence‐based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research. Clinicians caring for children need to be aware of the evidence about the benefits and harms of preventive maneuvers, diagnostic strategies, treatments, and rehabilitation techniques. The practice of Evidence Based Medicine comprises 5 steps: 1‐Formulating answerable clinical question containing 4 elements [(Patient, P), Intervention (I), Comparison (C) and Outcome (O)]. 2‐Searching for the best evidence, using any of available search protocols. 3‐Critical appraisal of the evidence using especial worksheets. 4‐Applying evidence to the patients. 5‐Evaluation of the whole work from step 1 to step 4. The stool pattern, abdominal ultrasonography, Doppler ultrasonography , C.T study especially after application of the new technique (by detecting the C.T. attenuation coefficient of urine after oral administration of contrast material and Magnetic Resonance Imaging (MRI) can help early and safe diagnosis and management of NEC . Culture studies (from blood, stool, duodenal aspirate and peritoneal aspirate) correlates poorly with NEC diagnosis because no specific organism associated with NEC. Rapid fall in platelet count and platelet count less than 100.000 have been suggested as predictors of intestinal necrosis in cases of NEC but have low sensitivity and specificity. Acute phase reactants as C‐reactive protein (CRP) and orosomucoid can help NEC diagnosis. Abnormalities in pH might predict gastrointestinal complications in infants < 1500g (necrotizing enterocolitis and perforation). Plasma intestinal fatty acid binding protein (IFABP) levels elevation was considered as useful biochemical marker for intestinal ischemia particularly in the early reversible phase. Serum CK‐BB (Creatinine Kinase Brain Isoenzyme) can be a useful marker in the diagnosis of NEC . Gut hormones blood levels (gastrin and neurotensin) but not vasoactive peptide (VIP) has been observed to be significantly reduced with NEC. Infants who have NEC have selective amino acid deficiencies including reduced levels of Glutamine (GLN) and Arginine (ARG). Hydrogen breath test however, was found by some authors to be useful in discriminating children who could be safely fed from those who could develop NEC. There is excellent evidence that human breast milk decreases the incidence of NEC and its morbidity and mortality Neither delayed feeding nor slow feeding has evidence to have a NEC protective effect. Early trophic feeding with breast milk or half strength formula is highly accepted .Ideal rate of feeding advancement is still unclear . Egg phospholipids added to preterm formula could be used to decrease risk of NEC. Early feeding with UAC in place does not increase the incidence of NEC. Excellent evidence for the protective effect of antenatal corticosteroid given to preterms 34w gestation or less against NEC was found. Multiple courses of antenatal corticosteroid have no benefits more than single course. According to the recent Cochrane database multisystematic review and the recent multicenter RCT, there is no evidence support the administration of oral immunoglobulin for the prevention of NEC. Oral arginine supplement could be used to decrease incidence of NEC .There is no sufficient evidence to prove that oral antibiotics could decrease the incidence of NEC. No evidence available in humans up till now to prove the protective effect of epidermal growth factor against NEC. Oral vitamin E treatment may increase the incidence of NEC in prematures with birth weight 1.5kg or less especially if used for a long period. Indomethacin as antenatal tocolytic may increase the incidence of NEC especially if used within 24h of delivery. Recombinant erythropoietin can protect against NEC in VLBW infants. Enteral theophylline may increase the incidence of NEC. No evidence of protective effect of magnesium sulfate against NEC. Probiotics as [Lactobacillus acidophilus and Bifidobacterium infantis] are considered as one of the promising preventive measures against NEC. No sufficient evidence supports the protective effect of either oligofructose or polyunsaturated fatty acid (PUFA) against NEC in the humans. In the category of treatment, critically ill infants with perforated NEC who do not tolerate laparotomy and general anesthesia, peritoneal drainage may improve the outcome of surgically treated NEC. Septic Work Up In Healthy Newborns With Severe Hyperbilirubinemia: Is It Required? Saad Alsaedi, FAAP, FRCPC, Dr. Ahlam Mazi, King Abdulaziz University Hospital, Jeddah, Saudi Arabia Background: Bacterial infection is a potential cause of neonatal jaundice. A common practice is to perform septic work up in all newborns who have significant unexplained indirect hyperbilirubinemia. Objective: To test the hypothesis that bacterial sepsis is not a cause of hyperbilirubinemia in otherwise healthy newborns admitted to the hospital for phototherapy. Method: This retrospective study was conducted on neonates (age <30 days) admitted to our institution during the period April 2000 to April 2008. We identified neonates admitted due to indirect hyperbilirubinemia, without any other manifestations. The results of blood and CSF cultures as well as CBC analysis were reviewed. Results: A total of 197 newborns, were studied the mean age on admission was 7± 4.3 days (range 1 to 30 days). Admission weight was 3.2±1.7 Kg (range 2.5 to 4.7 The mean peak serum total bilirubin was 298± 144 µmol/L(range 144 to 667 µmol/L). Eighty percent were fully or partially breast‐fed. The blood cultures from 12 infants grew coagulase ‐ negative Staphylococci (CONS) that was felt to be contaminant in repeated blood cultures. CSF culture was performed on 110 infants (56%). The CSF was sterile in 107 infants. The CSF cultures from 3 infants grew CONS which were considered contaminants and was not treated. No case of real sepsis was identified in this population. Concusion: Healthy term newborns, who require readmission to hospital for severe indirect hyperbilirubinemia do not need to be investigated for sepsis. Our data does not support that indirect hyperbilirubinemia can be the only manifestation of bacteremia or incipient sepsis. Can transcutaneous bilirubinometry reduce the need for serum bilirubin estimations in Saudi term and near term infants? Saad A. Alsaedi, FRCPC, FAAP, Faculty of medicine, king Abdulaziz University Introduction: The clinical evaluation of neonatal jaundice involves visual estimation of Skin color which is subjective. Chemical methods for measurement of serum bilirubin are the standard of care in the assessment of neonatal jaundice. Several studies had demonstrated the possibility of prediction of serum bilirubin in neonates by analysis of the spectral reflectance from the skin. The accuracy of these techniques has been complicated by the variability introduced by skin color and the dermal maturity; so, the results of studies in white infants may not be applicable to heterogeneous population. BiliCheck device has been designed to correct for these interfering factors. Objective: To investigate the accuracy of the BiliCheck device as a screening tool for transcutaneous bilirubin (TcB) measurement in healthy Saudi term and near‐term newborns Methods: The Bilicheck bilirubin analyzer was used to measure (TcB) in 202 jaundiced term and near term newborns during the first 6 days of life. Blood was taken for total serum bilirubin (TSB) measurement according to the discretion of the treating physician. Paired TcB/TSB results were reviewed over a period of 9 months. The correlation as well as the mean difference between the 2 methods were calculated. Results: Total of 202 paired TcB/TSB measurements were performed in 202 term or near term newborns. TcB was significantly correlated with TSB with a correlation coefficient of 0.88 (p < .001). Their mean difference was 0.72 mg/dl /L (SD 0.3, p < 0.001) with the 95% limits of agreement between –1.2 and 3.7 mg/dl. Conclusion: Transcutaneous measurement of bilirubin by BiliCheck correlates well with the measurement of total serum bilirubin in healthy term Saudi newborns. Although bilirubinometer – BiliCheck, might result in some difference between TcB and TSB measurement in Saudi newborns, it can be valuable tool for screening for significant neonatal jaundice and avoid unnecessary blood tests. An outbreak of Serratia marcescens infection in neonatal intensive care unit due to contaminated baby shampoo Saad Alsaedi, Tarek Madani, Laby James,RN, King Abdulaziz University Hospital, Jeddah, Saudi Arabia Background: Serratia marcescens is a recognized cause of outbreaks in neonatal intensive care units (NICUs). Many possible sources of the organism have been implicated in previous outbreaks, including contaminated breast pumps and milk, adhesive tapes, scalp vein needles, intravenous solutions, disinfectant solutions and soaps, laryngoscope blades and air‐conditioning ducts. The contaminated hands of health care workers are thought to be an important mode of spread of S marcescens Objective: In this report we share our experience in investigating an outbreak of Serratia. marcescens infection in our NICU and nursery. Methods: During the period of December 2008 until January 2009 (2 months), an outbreaks due to Serratia marcescens infection occurred in the NICU and the nursery in king Abdulaziz University Hospital, Jeddah, Saudi Arabia. This led to epidemiological measures to find and control the source of this outbreak. Specimens from different sites of the NICU and nursery were collected, particularly from sinks, floor, physicians and nurses’ hands and nose, sink, tap, soap, baby shampoo and medical equipment using pre‐moistened sterile swabs. Medical equipment included: mechanical ventilator, incubator, venous catheter, laryngoscope and feeding tube. The swabs were transported to the laboratory using sterile trans tubes, containing transport media and inoculated directly on to blood agar plates. The plates were incubated aerobically at 37 C for 48 h. The isolates were identified by conventional biochemical tests and antibiotic susceptibility was tested. Subjects: Newborns with Serratia marcescens infection in the NICU and Nursery during the outbreak. Results: During the period of December 2008 until January 2009 (2 months), 14 newborns were found to be infected by Serratia marcescens. The infections range from conjunctivitis (5 cases), sepsis (5 cases), severe sepsis and meningitis (2 cases) and urinary tract infection (2 cases). All the bacterial isolates had identical antibiotic sensitivity. Fifteen samples from one batch of a baby shampoo (specific brand) grew Serratia marcescens which had the same antibiotic sensitivity of the organism isolated from the affected newborns. All shampoo products stocks in the hospital units and main hospital stores we collected and the use of this shampoo was discontinued. No more cases of Serratia marcescens had been reported since this infection control measures had been implemented. Conclusion: Contaminated shampoo product can be a common source of health care associate infection in the NICU and nursery. This report highlights the importance of appropriate infection control measures to prevent serious infection Interventional vs Surgical Treatment in Neonates and Infants with Cyanotic Congenital Heart Disease MO Galal, MD, PhD, MBA, Prince Salman Heart Center, Riyadh, Saudi Arabia Over the last 20 years a shift in management of patients with cyanotic cardiac defects occurred. Cardiac catheterization and angiography was and remained an important role in establishing diagnosis in these patients for quite some time. Similarly for decades, the only therapy was cardiac surgery. Two‐
dimensional echocardiography revolutionized the diagnosis and management of congenital heart diseases. The shift in therapeutic management is noticeable in a variety of cyanotic cardiac diseases, as tetralogy of Fallot, transposition of the great arteries, tricuspid atresia and pulmonary atresia. Tetralogy of Fallot remains the domain of cardiac surgeon, when the anatomy allows total repair. In case of hypoplastic pulmonary arteries with patent ductus arteriosus (PDA), stent of the PDA can be performed, sparing the child a Blalock‐Taussig shunt. Additionally, balloon dilation of the right ventricular outflow tract can be offered. In case of transposition of the great arteries, balloon atrial septostomy has been shown to be performed under echocardiographic guidance. This is needed if a cardiac surgeon is not available in the center and helps in stabilizing the patient prior to transferring to a higher center. In case of tricuspid atresia, balloon atrial septostomy is rarely needed. Instead of a Blalock Taussig shunt, stenting of the PDA can be offered. At a later stage a Glenn procedure is performed. Pulmonary atresia with intact ventricular septum is another example for change in management of the years. Also here instead of surgical options, different interventional options can be applied. Balloon atrial septostomy is indicated in case the child is planned for a univentricular track of repair. Perforation of the pulmonary membrane through transcatheter approach can be contemplated in case the right ventricle size allows later a biventricular repair. If desaturation remains an option, either additional stenting of the patent ductus arteriosus or adding an alpha blocker to the medication regimen can be contemplated. Conclusion: In the last years the trend towards less invasive technique is present. Interventional techniques could replace cardiac surgery in many occasions. Both modalities remain complementary to each other for the benefit of the patients. Proposal for Madinah neonatal network, “The future of newborn care in Madinah” Mustafa Zubier , Aziza Al Harby, NICU, Madinah maternity and children hospital , Madinah, KSA The Neonatal services aim to offer high quality care for some of the most vulnerable babies in our society. Approximately ten per cent of babies require some form of specialist support at birth with nearly three per cent of these requiring neonatal intensive care . Increasing capability of technology and development of health care expertise has led to greater numbers of very small and sick babies being born alive and surviving, therefore the care of very small or sick babies is extremely challenging, not least because the effects of care in these earliest days can be marked and long‐lasting Currently in Madinah region most of the general hospitals offer some level of neonatal care ranging from special care to intensive care. These hospitals differ in the numbers of babies cared for and the frequency with which they are treating babies with intensive care needs. They also had shortage of staff and equipments along with varying level of expertise who look after these sick newborns. The current situation in Madinah region showed that some mothers and / or their babies are travelling long distances for their care –often not in a planned way or to the closest possible destination. Most of the time their transfer carried out by inexperienced staff which may risk the mother’s life and limit the chance of the newborn survival. This had led to an increase influx of babies mostly not very sick to the main hospital in the region which became overcrowded with an increases in the infection rate. To bring higher quality neonatal intensive care to Madinah region, we planned to set up a Madinah neonatal network in which all the hospital and health professionals within the region work together in co‐ordinated manner to provide neonatal care at different levels based on resources, capacity, population and geography and the availability of appropriately skilled and trained staff in aim to deliver high quality and clinically effective neonatal services. The network ensures that every infant has access to the right level of care with the right resources and that they are cared for by staff with the right skills. AS the geographical distribution of these hospitals in Madinah region offer an excellent opportunity to do so as Madinah region has an excellent road link, A Network management team will be formed to make recommendations for delivery of services and to implement the network plans and strategy for the future. The Current State Of Antifungal Therapy For Neonates Eman F. Badran; Department of Pediatrics, Neonatal Unit, Jordan University Hospital, Amman, Jordan. The pattern of nosocomial infection in neonatal units has changed over the past decades. The dominance of virulent bacterial pathogens in the 1960s has gradually been replaced by that of opportunistic organisms in the 1990s. Although the majority of nosocomial infections are of bacterial origin, disseminated fungal increased in frequency and severity over the past two decades as a result of an is an increasing problems carrying high morbidity and mortality in modern day NICU due to increasing interventions and survival of smaller babies. Similarity in presentation to bacterial sepsis and availability of few systemically active antifungal agents leads to difficulty in diagnosis and treatment. The last decade has seen the development of several new antifungal agents for the treatment of these infections. However, there is a paucity of data on the treatment of invasive fungal infections in neonates This presentation provides a brief overview of the current state of antifungal therapy for neonates. Also this presentation well define the rate of candidaemia, risk factors, clinical presentation, and outcomes of Candida‐induced neonatal infection in all newborns with culture proved candidaemia who were admitted to the neonatal intensive care unit of Jordan University Hospital through the period January 1995 to June 2006. OUTCOME AND ETHICAL DECISIONS IN INFANTS BORN AT THE THRESHOLD OF VIABILITY Professor Tom Clarke, Rotunda Hospital, and Royal College of Surgeons in Ireland. An infant born at threshold viability presents a variety of complex medical, social and ethical decisions. Although the incidence of such births is low the number of extremely preterm births has increased and the impact of surviving infants on family, the health care system and society is profound. In Ireland in 2006 about 150 of 66,000 infants born (with birth weight greater than 500 grams) were between 22 and 27 weeks gestation. The Canadian Paediatric Society and the Society of Obstetricians and Gynaecologists of Canada in October 1993 recommended, for the woman with threatened birth of an extremely low gestational age infant (22‐26 weeks completed weeks), that “for infants born 22 weeks or less and with a birth weight of less than 500 grams suggest that only comfort care be given. For those born at 23 or 24 weeks suggest flexibility with regards to resuscitation, with careful consideration of the views of the family and the condition of the infants at birth. For infants born at 24 or 25 weeks full resuscitation is warranted.” The highly publicised report of the Epicure study in the UK and Ireland (NEJM 2005) highlighted the poor outcome of infants born at 25 or less completed weeks gestation. The rates of severe (indicating dependence on caregivers), moderate, and mild disability were 22 percent, 24 percent, and 34 percent, respectively; disabling cerebral palsy was present in 30 children (12 percent). Accurate international, and more importantly, local data will help in counselling parents, particularly those with unrealistic expectations about current ability to nurture immature infants outside the womb. The future for intensive care of extremely low birth weight babies should be aimed at resolving these issues. We should strive towards a more accurate ability to predict outcome, such as the increasing use of MRI scanning. A more informed public is required rather than necessarily setting arbitrary limits on gestation for treatment. Immediately though, it is societies role that can change. The individual decision on when to resuscitate or when to withdraw care may lie with doctors and parents but the overall policies are set by society; if as a society we save these children then we must provide for them. As with all data, there are different ways of interpretation. Having an infant born extremely premature is a very stressful and frightening experience for parents. On the one hand, there is a risk of up to 10% for the baby to be destined for a life of continuing total dependency, while on the other hand, most. MANAGEMENT OF THE TINY INFANT – HOW CAN WE IMPROVE? Professor Tom Clarke, Rotunda Hospital, and Royal College of Surgeons in Ireland VLBW infants account for more than half of normally formed infant deaths and also for a large amount of the morbidity attributable to the perinatal period. Antenatal steroids and endotracheal surfactant have been the major advances over the past 25 years. There is still a large variation in outcome in survival between centres of excellence, e.g. Avery et al (Pediatrics 1987) found a significant difference in CLD between institutions even when birth weight, race and sex were taken into consideration In the Rotunda Hospital, sixty infants died due to prematurity in a recent six year period; (two thirds were less than 26 weeks gestation). The main causes of mortality in infants between 27 to 30 weeks gestation were pulmonary hypoplasia with prolonged rupture of membranes (4), NEC (3), intraventricular haemorrhage (3), pneumothorax/PIE (3), and coagulopathy (2). This is the gestation at which, we believe, there is room for improvement in survival currently. Budin, a French obstetrician, in 1892 enunciated the basic principles of newborn care, temperature control, nutrition, and prevention of infection. Apgar emphasised the importance of resuscitation and of the first ten or twelve minutes of a baby's life. Blood pressure and perfusion and assisted ventilation have been addressed over the past few decades. Perinatal audit is the systematic critical analysis of the quality of perinatal care, including the procedure used for diagnosis and treatment, use of resources and the resultant outcome and quality of life for women and their babies. The Rotunda has been a member of the Vermont Oxford Neonatal Network since 1996. This collaborative brings together multidisciplinary teams of health professionals from a broad range of NICUs. The goal is to make measurable improvements in the quality, cost and safety of neonatal intensive care. Improvement teams typically consist of 3 to 9 people who routinely work in the relevant care process; improvement in care often depends on the coordinated activities of many different people. Conclusion: The key in improving outcome is having a highly skilled, well trained nursing and medical team, with regular monitoring of out come and comparison with best international standards to determine where further improvements can be made. Humidified High flow nasal cannula for respiratory support in infants Ramzi A. Kilani, MD, FAAP Associate Professor of Pediatrics – Attending neonatologist Department of Pediatrics, Neonatology, Children's Mercy Hospitals and Clinics, University of Missouri at Kansas City, Missouri, USA Abstract Humidified high flow nasal cannula (HHFNC) has been suggested as an alternative form of respiratory support for preterm infants with apnea, respiratory distress syndrome or chronic lung disease. They appear to be easy to apply and care for. Although, HHFNC may provide positive end‐expiratory pressure (PEEP), limited evidence is available to support the specific role, efficacy, and safety of HHFNC in newborns. The evidence suggests that HHFNC provides inconsistent and relatively unpredictable positive airway pressure, but may be effective in the treatment of some neonatal respiratory conditions while being more user‐friendly for caregivers than conventional nCPAP. Caution should be exercised in the use of HHFNC in neonates until further evidence is available to clearly delineate its role, as well as to support its safety and efficacy. The current controversy and the available data regarding the use of HHFNC in providing non‐invasive respiratory support in newborn infants are reviewed and presented. Lung protective strategies in mechanical ventilation Ramzi A. Kilani, MD, FAAP Associate Professor of Pediatrics – Attending neonatologist Department of Pediatrics, Neonatology, Children's Mercy Hospitals and Clinics, University of Missouri at Kansas City, Missouri, USA Abstract Ventilator‐induced lung injury remains an important cause of morbidity and mortality in neonates requiring assisted mechanical ventilation. Historically, neonatal ventilation began as pressure‐limited. Pressure, but not volume, was controlled. Hence, the term baro (airway pressure) trauma (lung injury). Animal studies showed, however, that changes in lung volume, and not pressure, caused lung injury. This has led to a new term, volutrauma. Changes in pressure produce changes in volume as reflected by the compliance of the respiratory system. Once the uninjured lung is recruited, it tends to stay open during exhalation. Surfactant and the structure of the lung and chest wall confer this deflation stability and define functional residual capacity (FRC). When FRC is optimized, end expiatory pressure can be decreased without a great loss of lung volume, as long as the pressure is not decreased below the critical closing pressure of the lung. Therefore, ventilator induced lung injury sequence can occur at the beginning and end of each assisted breath. If inadequate numbers of alveoli were recruited in the previous breath, or if the positive end expiratory pressure was insufficient to maintain recruitment, atelectasis may occur, and can by itself propagate a lung injury sequence. Once the airway epithelium and pulmonary capillary endothelium are injured, a lung injury sequence is initiated leading to alveolar capillary leak, surfactant disruption, inflammatory response and distal organ injury through efflux of inflammatory mediators from the alveolar space into the general circulation. Oxidant injury may be another serious cause of lung injury. Immature and developing lungs are particularly susceptible to acquired injury. An understanding of the basic pathophysiology of the underlying respiratory disorder is essential to optimize the ventilatory strategy. Aim for an adequate gas exchange without injuring the lungs. Phenyl Ketonuria (PKU): 2009 update Majed J. Dasouki, M.D. Associate Professor of Pediatrics & Medicine, Biochemical, Clinical Geneticist & Cytogeneticist. The University of Kansas Medical Center, Departments of Pediatrics & Internal Medicine. Genetics, Endocrinology & Metabolism Phenylketonuria (PKU) is one of the most common inborn errors of metabolism usually caused by various mutations in the hepatic phenylalanine hydroxylase “PAH” gene. Newborn screening and early introduction of dietary phenylalanine restriction are effective in allowing affected children to have near normal growth and development. Tetrahydrobiopterin, a cofactor of phenylalanine hydroxylase, is a new therapeutic option for some patients with PKU. Phenylalanine Ammonia Lyase [PAL] is another promising investigational therapeutic drug for patients with PKU as well. The status of these established and novel therapies will be reviewd. The genetic basis of Congenital Heart Disease Majed J. Dasouki, M.D. Associate Professor of Pediatrics & Medicine, Biochemical, Clinical Geneticist & Cytogeneticist. The University of Kansas Medical Center, Departments of Pediatrics & Internal Medicine. Genetics, Endocrinology & Metabolism Congenital heart disease (CHD) is the most common developmental defect,occurring in almost 3‐5% of neonates. CHD contributes significantly to morbidity and mortality in this age group as well. Presentation of children with congenital heart disease includes: cyanosis, respiratory distress, arrhythmia and failure to thrive. CHD may be an isolated abnormality or syndromic where other birth defects coexist. While congenital heart disease is usually sporadic, familial forms had been recognized as well. While conventional chromosomal analysis had been useful in characterizing some forms of congenital heart disease, the use of more advanced molecular techniques such as DNA linkage analysis, FISH (Fluorescent‐In‐Situ Hybridization), DNA sequencing and aCGH (Array Comparative Genomic Hybridization) resulted in the identification of several genes and genomic regions implicated in the pathogenesis of common forms of congenital heart disease. Identification of the molecular basis for a common birth defect such as congenital heart disease is useful in the management of these patients and their families. What should I know about “Lysosomal Storage Diseases”? Majed J. Dasouki, M.D. Associate Professor of Pediatrics & Medicine, Biochemical, Clinical Geneticist & Cytogeneticist. The University of Kansas Medical Center, Departments of Pediatrics & Internal Lysosomal Storage Disorders (LSDs) are a heterogeneous group of metabolic diseases caused by deficiency of one of several lysosomal acid hydrolases. They are usually recessively inherited and may occur at any age. While individually they are considered to be rare, as a group they are somewhat common. This deficiency results in accumulation of the respective substrate (such as sphinglipids, mucopolysaccharides, glycogen) and secondary cytokine abnormalities. The diagnosis of an LSD is suspected when some of the clinical manifestations of these disorders are recognized which include: developmental delay, seizures, facial dysmorphism, visceromegaly and skeletal abnomalities. Until recently, the treatment of these disorders was largely supportive. Currently, enzyme replacement therapy is available for some of the more common LSDs such as Gaucher disease, Pompe disease, Fabry disease, Hunter and Hurler and Maroteaux‐Lamy syndromes. Bone marrow transplantation is used in some patients with LSDs and significant brain involvement. Promising novel therapies using oral chaperones and other agents that cause substrate reduction are also being developed. Early diagnosis and treatment of patients with lysosomal storage disorders may significantly help reduce morbidity and mortality associated with some of these conditions. Clinical evaluation of the child with global developmental delay Majed J. Dasouki, M.D. Associate Professor of Pediatrics & Medicine, Biochemical, Clinical Geneticist & Cytogeneticist. The University of Kansas Medical Center, Departments of Pediatrics & Internal Global developmental delay is a common and potentially serious medical problem for children and their families. The role of genetic causes of global developmental delay is being increasingly recognized. Often times, the parents seek specific information about treatment, prognosis, and genetic recurrence risk. This necessitates that when possible, a precise diagnosis should be made. As a result, unnecessary testing will be avoided and the health and functional outcomes of affected children can be improved. The essential components of the diagnostic evaluation for such a child should include: medical and developmental history, 3‐generation family history, dysmorphologic/genetic and neurologic examinations, and judicious use of the laboratory and neuroimaging. In addition to routine laboratory tests (complete blood count, comprehensive metabolic profile), specific genetic studies including organic acids, amino acids testing, karyotype and array Comparative Genomic Hybridization can aid in establishing a diagnosis. As diagnostic tools continue to improve, undiagnosed children deserve ongoing follow‐up for the purpose of establishing a definitive diagnosis and directing medical care. Evidence Based Medicine, A concept in evolution: The case of systematic reviews and meta‐analyses. By: Hassan Baaqeel, MBBS, FRCSC, FRCOG. Dean, College of Medicine – Jeddah, King Saud bin Abdulaziz University for Health Sciences – Saudi Arabia. Evidence based approach to health care is being increasingly adopted in contemporary health care practice. The uptake of this concept in developing countries compared to developed ones shows a significant disparity. After the initial euphoria of evidence based medicine particularly among the zealot enthusiasts, it became clear that some of the tools of implementing evidence into practice (such as systematic reviews and meta‐analyses) are not as user friendly as once thought. This presentation will address this evolution using systematic reviews as a case in point. The pros and cons of this tool will be addressed. Abstract The use of clinical indicators to improve quality of care Hassan Baaqeel, MBBS, FRCSC, FRCOG. Dean, College of Medicine – Jeddah, King Saud bin Abdulaziz University for Health Sciences – Saudi Arabia. Interest in quality improvement and accreditation of health care facilities is increasing in our region. This change in the prevailing culture is likely to have an unprecedented effect on clinical practice in term of reputation, earnings and credentialing of health care provision of both individual health care providers and institutions. Most of us were not taught about quality improvement during our professional education and training. The crux of the matter is that the well‐being and the lives of the patients we care for everyday depends on quality improvement. This presentation will address the following points 1. What is quality improvement? 2. Why should we work for quality improvement ? 3. How is quality improvement measured? 4. How can we tell if we've achieved the improvements we desire? 5. What tools do we need to improve care in our practice? Quality is measurable, much like the vital signs of a patient. Newborn Screening – a 2009 Update Hani K. Atrash, MD, MPH, Director, Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, E‐87, Atlanta, GA 30333, Tel. 404‐498‐3075, Fax 404‐498‐3070, E‐Mail [email protected] Abstract: Newborn screening (NBS) is the process of testing newborn babies for screenable, treatable genetic, endocrinologic, metabolic and hematologic diseases. The goal of newborn screening is to prevent or reduce death and other catastrophic consequences of heritable disorders to individuals and families and to improve the quality of life for affected individuals and their families. NBS is a vital public health program which does not stop at early identification and it is not just a laboratory service; it is a comprehensive system of care that includes follow up, definitive diagnosis, treatment, long term management, quality assurance and evaluation, education and financing. These components of NBS systems complement each other and fit together like pieces of a puzzle. Furthermore, NBS is a comprehensive system of care which includes multiple partners who support each other; the value of the service is reduced substantially if one of these partners does not exist or is not cooperative. Robert Guthrie is given much of the credit for pioneering the earliest screening for phenylketonuria in the late 1960s using blood samples on filter paper obtained by pricking a newborn baby's heel on the second day of life to get a few drops of blood. In the 1970s, Technology improved allowing program expansion and programs began expanding to higher incidence disorders – congenital hypothyroidism – and disorders that result in death – CAH, GAL. In the 1980s programs became computerized and expansion continued including DNA studies. In the 1990s Tandem mass spectrometry was developed by Edwin Naylor and others allowing simultaneous detection of multiple disorders. This led to a large expansion of potentially detectable congenital metabolic diseases that affect blood levels of organic acids. Most recently, NBS expanded beyond metabolic newborn screening (for example, newborn hearing screening) and a new movement to expand testing with MS/MS emerged with an emphasis on program integration (especially data), concerns about privacy, and data sharing. Criteria for determining which conditions to screen for vary. In 1968 the World Health Organization articulated the first criteria for population‐screening programs that focused on public health benefits (known as the original Wilson‐Jungner criteria – importance of the health problem, availability of an acceptable treatment, availability of diagnosis and treatment facilities, existence of recognizable latent or early symptomatic state, availability of a suitable test or examination, acceptability of the screening test, adequate understanding of the natural history of the disease, existence of an agreed policy on whom to treat as patients, and the cost balanced relative to possible expense for medical care). Other criteria used include: cost of test, cost of follow up, false positive diagnosis, public education and interest, professional education and interest, political education and interest, intangible cost such as parents distress in false positives, cost‐savings, scientific evidence, and potentially business interest. In 2002 the American College of Medical Genetics (ACMG) outlined a process of standardization of outcomes and guidelines for newborn screening programs. ACMG reviewed 84 conditions recommended for NBS and, using specific criteria identified 29 “core” conditions for which they recommended universal newborn screening. ACMG also identified 25 “secondary” conditions for which they recommended that results should be reported. However, there are some concerns related to the recommended expansion of newborn screening. For example, screening for additional conditions that occur with greater frequency in different ethnic groups could lead to discriminatory practices against individuals as well as the ethnic groups associated with particular disorders. Furthermore, historically, screening has focused on conditions for which the improvement in outcome for the infant has been substantial. However, newborn screening could identify many conditions for which the improved outcomes may be more incremental, including disorders that are associated with mental retardation, such as fragile X syndrome, for which early intervention programs may improve long‐term cognitive outcomes, but not with the expectation of a normal outcome. Finally, the nature of genetic disease is such that knowledge of its presence can be of value to other family members. Proposals to expand newborn screening represent a paradigm shift in how newborn screening is justified. The historical rationale for newborn screening was the prevention of devastating harm to affected infants by providing immediate treatment after birth, an urgent response to avert a potential emergency of public health importance. Although newborn screening for most disorders still prevents deaths and disability, screening for certain disorders under the new paradigm may carry less dramatic or immediate benefit, as well as benefits beyond those to the newborn. The Role of Preconception Health and Health Care in The Prevention of Birth Defects Hani K. Atrash, MD, MPH, Director, Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, E‐87, Atlanta, GA 30333, Tel. 404‐498‐3075, Fax 404‐498‐3070, E‐Mail [email protected] Abstract: The promotion of Preconception Health and Health Care is based on the premise that further improvements in pregnancy outcomes depend on improving the health of women before pregnancy and on helping couples and women avoid behaviors and exposures known to adversely affect pregnancy outcomes. Today, we have scientific evidence that an array of interventions before pregnancy can improve pregnancy outcomes. Furthermore, the implementation of many of these interventions will result in reducing the incidence of or totally preventing the occurrence of birth defects. A review of the literature in 2004 identified 14 interventions which have scientific evidence indicating that if implemented before pregnancy or early in pregnancy, these interventions would result in improved pregnancy outcomes: Folic acid supplementation, rubella immunization, HIV/AIDS screening and treatment, hepatitis B vaccination, diabetes management, hypothyroidism management, maternal phenylkentonuria management, obesity control, sexually transmitted infection screening and management, alcohol cessation, avoiding teratogenic medications such as anti‐epileptic drugs, Accutane, and oral anticoagulants, and smoking cessation. More recently, the Clinical Workgroup of the Centers for Disease Control and Prevention Select Panel on Preconception Care identified 83 conditions currently recommended to be a part of preconception care. They reviewed over 700 publications to determine the quality of scientific evidence and the strength of recommendation for including these interventions in preconception care services. The criteria used to determine the quality of the evidence and the strength of the recommendation were adapted from those used in the report of the US Preventive Services Task Force Guide of Clinical Preventive Services. In summary, the strength of recommendation was A if there is good evidence to support the recommendation that the condition be specifically considered in a preconception care evaluation, B for fair evidence to include, C for insufficient evidence to include, D for fair evidence NOT to include, and E for good evidence NOT to include. For 35 of the 83 interventions reviewed, the workgroup determined that there was good evidence (level A) to include the intervention as a component of preconception care. For 25 conditions the level of recommendation was B, and for the remaining 23 conditions, the level of recommendation was C, D, or E. These findings were published recently in a special supplement to the American Journal of Obstetrics and Gynecology (Volume 199, Number 6B, December 2008): http://www.ajog.org/issues/contents?issue_key=S0002‐9378(08)X0011‐0 Today, we know that a woman’s health before pregnancy, her behaviors, and her exposure to various environmental factors (including exposures to chemicals at home and at work, alcohol and tobacco use, over the counter and prescription drugs) will affect the outcome of her pregnancy including an increased risk of having a baby with a birth defect. We also know that for many of these factors, we have existing practice guidelines to help us reduce this risk if we act before pregnancy. To reduce the number of babies born with birth defects and to further improve pregnancy outcomes for mothers and babies, it is essential that we move beyond the current paradigm of “anticipation and management” during pregnancy to “health promotion and prevention” in the preconception period and throughout a woman’s life. Diagnosis and outcome of neonatal sepsis caused by resistant gram negative bacteria, a Jordanian perspective Mohammad Khassawneh, assistant professor and assistant dean in faculty of medicine, Jordan University of Science and Technology, Po box 3030, Irbid, Jordan Abstract Neonatal sepsis is a major cause of mortality and morbidity. Sepsis caused by multi drug resistant bacteria is more commonly described in neonatal sepsis in Jordan and the region. Diagnosis of neonatal sepsis still relies mainly on positive blood culture. New markers are more commonly used which include micro array technology, polymerase chain reaction (PCR0, serial C‐reactive protein. Outcome of neonatal sepsis caused by multi‐drug resistant is still not well understood. Fulminant presentation with death within 3 day of postive culture need to be explored. Early treatment with apropriate emperic antimicrobial can improve outcome of neonatal sepsis. Newre antibiotics like Piperacillin/ tazobactam or Carbapenem are becoming more and more popular. This presentation will cover new issues of neonatal sepsis with special emphasis on data colleted from tertiary NICU in Jordan. The role diagnosis, type of organism, resistance profile, and outcome will be presented. New data on the use of different empiric antibiotic protocol will be Shawn. NEC & PROBIOTICS Colonization of the premature GI tract Aziz Klilat Necrotizing enterocolitis (NEC) is one of the most frustrating diseases in the neonatal intensive care unit. Initial description was in 1975, Unfortunately, the exact etiology of the disease or how to prevent it still in lot of debate NEC is primarily a disease of premature infants, although up to 10% of cases present in term and near‐
term babies. Signs include: abdominal distension, blood‐ or bile‐stained emesis, bloody stools, and pneumatosis intestinalis, the pathognomic radiographic sign of the disease. Medical management is largely supportive; however, surgery is required for intestinal necrosis and mortality may approach 35%. NEC is likely initiated with intestinal mucosal injury from any number of factors. Following this injury, bacteria in the gut proliferate with formula or breast milk as a substrate. The bacteria invade the damaged mucosa causing inflammation and, ultimately, necrosis of the infected area. Because of the association of feeding and bacterial infection with NEC, prevention strategies have focused on manipulating the feeding of premature infants as well as trying to manipulate the bacterial environment of the intestine. Although some early trials showed a decreased incidence of NEC with slow advancement of feedings, recent randomized studies have shown no difference in the incidence of NEC with fast vs. slow or early vs. delayed feedings. Interest has focused on giving probiotic bacteria to premature infants. Probiotic bacteria, such as Bifidobacteria and Lactobacillus, are live microbial supplements that colonize the intestines and provide benefit to the infant. The hope is to prevent the overgrowth of pathogenic organisms that have been associated with NEC. There have been a modest number of studies that primarily have looked at the safety of probiotics in newborns; and to date, it appears safe to administer these bacteria; and to date, it appears safe to administer these bacteria The 6th Meeting of the Pan Arab Gastroenterology and Nutri Dear Reader: Below is a collection of the Abstracts of presentations delivered in the sixth meeting of the pan arab gastroenterology and nutri, May 5‐8, 2009; Amman, Jordan. The abstracts are presented as it were sent by the authors. The authors are responsible for the format, typing and the contents of the abstracts. Recent Advances in Inflammatory Bowel Disease Fayez K. Ghishan, M.D. Professor and Head, Pediatrics Director, Steele Children’s Research Center The University of Arizona Health Sciences Center Tucson, AZ Recent evidence suggests that the incidence of Inflammatory Bowel Disease (IBD) is on the rise in the entire world. The cause of IBD is most likely related to a genetic component, driven by environmental factors related to host‐microbial interactions resulting in dysregulated immune response. The genetic factors are related to the identification of a number of genes, including mutations in NOD2, OCTN, DLG5 and IL‐23R. Those genetic mutations are likely to be informative in regards to the phenotypic features of IBD patients. Most of IBD patients present during the adolescent period, with the majority of patients seen between the ages 15 – 20. The presentation of IBD will be discussed and the differentiation between Crohn's Disease (CD) and Ulcerative Colitis (UC) will be explored. There are a number of gastrointestinal and extraintestinal manifestations of CD, as well as UC. It is important to remember that growth failure in children is a very important feature seen in IBD patients. Similarly, bone disease is most likely related to the TNF‐α and it is downregulation of specific genes in bone formation. The diagnosis of IBD patients rests on endoscopic, radiological and serological markers which will be discussed. A number of advances in treatment will be discussed in relationship to the biological agents which appear to be highly effective in the treatment of both UC and CD. Those highly effective biological agents include inflixumab, adalimumab, certolizumab, and natalizumab. Finally, novel approaches for IBD will be discussed. Dietary management for IBD patients will rest on decreasing foods which are likely to cause symptoms, while increasing the intake of omega3 fatty acids, monosaturated fatty acids, and antioxidants in the diet. The role of elemental diet and future therapeutic targets will be discussed. Title: Growing pains: IBD in adolescence Principal investigator: Professor Ian Sanderson Institution: Centre for Gastroenterology; Institute of Cell andMolecular Science; Barts and The London School of Medicine and Dentistry, Queen Mary, University of London Adolescence is a difficult time in one’s life. A chronic illness makes it worse. Inflammatory bowel disease presenting in adolescence has some similarities to the condition presenting in adults: for example its epidemiology, the symptoms of clinical disease and the modes of treatment. But there are also significant differences. These include the onset of puberty; differences in presentation and management; and a context and style of management that is fundamentally different. A major event in adolescence is the growth spurt followed by a short window before growth ceases. Treatment is therefore modified at this time to maximise linear growth. This often means undertaking more radical therapy, like surgery, than one would in a fully grown patient with the same extent of disease. Adolescence is characterised by risk taking behaviour. This attribute extends to adherence with medications, particularly those used prophylactically. In addition, the ability to think abstractly like an adult is often not developed. In younger children, whose parents are responsible for giving medication, this is less important. But in adolescence, the responsibility of taking drugs shifts to the patient often before the patient has moved from concrete thinking to more deductive (abstract) thinking. The effects of IBD on growth and development are therefore not in one direction; but there is also a reciprocal effect of developmental issues on IBD. Finally, the strong drive of teenagers to establish independence from parents also extends to doctors. This has practical implications for how a consultation is conducted. Title: INFLAMMATORY BOWEL DISEASE what’s new on the Horizon Principal investigator: ABDEL HAI HAMMO, MD Institution. Assistant Professor, Tufts University, Chief of Pediatrics, Brockton Hospital, MA Director, Pediatric GI Background: Inflammatory bowel disease (IBD) comprises Crohn’s disease and ulcerative colitis, 2 chronic inflammatory conditions of the intestine. They are characterized by abdominal pain, diarrhea, weight loss, and rectal bleeding. The incidence of Crohn’s disease in North America is between 3.1 and 14.6 cases per 100,000 person‐years, resulting in estimated 400,000‐600,000 patients living with this condition. IBD can have a significant impact on patient’s quality of life and can have long‐term sequelae. Over the past 10 years there have been significant advances in our understanding of the pathogenesis of IBD. Although the exact cause of IBD is still unknown, it is now widely accepted that a complex interplay of genetic predisposition, environmental triggers, and aberrant immune activation is involved. Corticosteroid therapy has constituted the first‐line treatment for patients with moderate to severe Crohn’s disease and Ulcerative Colitis. They are associated with rapid clinical improvement, with 58% attaining complete remission. However, there are side effects and toxicity issue to consider. The Immunosuppressive agents have demonstrated a clinical benefit of reducing patients’ dependence on steroids. However, data over the last 25 years indicate that these agents have no long‐term effect on the course of disease or disease progression to hospitalization or surgery. The development of biologic agents has substantially improved treatment options for patients with Crohn’s and Ulcerative Colitis disease. These agents are monoclonal antibodies directed against TNF‐Alfa, including: infliximab, Adalimumab, and certolizumab. A fourth agent, natalizumab is a humanized monoclonal antibody targeting alfa‐4 integrin. Conclusions. The new biologic agents have demonstrated considerable efficacy, but they carry significant safety risks that, in rare cases, have been serious or fatal. Appropriate patient selection and screening monitoring of adverse events are essential. Long term efficacy and safety and their optimal use in terms of patient selection and sequencing of agents, continue to be investigated Outcomes Research in Pediatrics Endoscopy: Making Sense of What We Do Gilger, Mark A. Baylor College of Medicine Texas Children’s Hospital, Houston, Texas Children's Hospital Outcomes research studies the “end result” of medical care as well as the effect of health care process on the well being of the individual patient. It is comprehensive, with data collected on all aspects of health care (e.g. health care financing, patient encounters). The laboratory of outcomes research is the “real world” (e.g. hospital, doctor’s office, even the home). The methodology is evolving, but frequently involves a computer‐assisted large database.
Why study “outcomes? An important reason is limited health care dollars. Outcomes research can provide evidence for informed decisions & data for therapeutic regimens. It asks, does what we do make sense? PEDS‐CORI (Pediatric Endoscopy Database System – Clinical Outcomes Research Initiative) began in December 1999 with two aims: (1) to develop and maintain a North American database of pediatric endoscopy procedures & (2) to promote scientific inquiry into the need, efficacy, costs and outcomes of pediatric endoscopy.
This lecture will discuss outcomes research, and then use PEDS‐CORI as an example of pediatric endoscopy outcomes work.
PAEDIATRIC LIVER TRANSPLANTATION Giorgina Mieli‐Vergani MD PhD FRCP FRCPCH Diego Vergani MD PhD FRCP FRCPath Institute of Liver Studies, King's College Hospital,
London SE5 9RS, UK Liver transplantation (LT) has become a standard mode of treatment in paediatrics in the early ‘90s. Indications for LT comprise end‐stage chronic liver disease of different aetiologies (e.g. biliary atresia after failed Kasai porto‐enterostomy, alpha‐1 antitrypsin deficiency, sclerosing cholangitis, familial cholestasis, Wilson disease, autoimmune hepatitis, cystic fibrosis etc), life‐threatening metabolic disorders due to enzymatic deficiency confined only or mainly to the liver (e.g. Crigler Najjar type 1, familial hypercholesterolaemia, propionic acidaemia, urea cycle defects etc), chemotherapy responsive tumours, acute liver failure, complications of liver disease associated to poor quality of life (e.g. pruritus and xanthoma in Alagille syndrome). In paediatrics, the decision to transplant is not only taken on the basis of short life expectancy, but also on the basis of the need to grow and to live a life as normal as possible to allow full integration in the society. The child and the family need careful medical and psychological assessment before listing for LT and to accept doctor and hospital dependency for many years to come.
Over the past 20 years, a number of technical advances have improved dramatically the availability and the outcome of LT in children. Reduced, split and living‐related LT have all increased the pool of organs for children. Particularly exciting is the procedure of auxiliary transplantation, which allows to correct life threatening metabolic disorders associated to normal liver function, like Crigler Najjar type 1 or familial hypercholesterolaemia, without the risks associated to whole organ removal and transplantation, and to offer to patients with acute liver failure a bridge to full recovery of their own liver, avoiding long term immunosuppression. New techniques are currently being tried. These include hepatocyte transplantation for metabolic disorders, which has been employed successfully in children with Crigler Najjar type 1 and glycogen storage disease type 1, and gene therapy, which is currently widely experimented in animals.
Though LT has dramatically decreased the mortality for liver disease in paediatric age, it is important to remember that it is not a cure: having somebody else’s liver is a disease status. Short‐
term complications are numerous, including primary malfunction, resistant cellular rejection, infection, portal vein and/or hepatic artery thrombosis, biliary strictures, cholangiolitis, etc. Several long‐term complications are also described, including recurrent disease, infection, post transplant lymphoproliferative disease, cancer, chronic ductopaenic rejection, de novo autoimmune hepatitis, poor compliance, etc. Eosinophilic Esophagitis Issam Halabi, MD, FAAP
Professor and Chief , Pediatric gastroenterology University of Illinois
Eosinphilic esophagitis is a relatively newly recognized condition. In late eighties was described as unusual form of reflux esophagitis. More recently a better understanding of this condition has developed. It is universally recognized. It is defined as the presence of more than 20 eosinophils per HPF. Incidence ranges from 0.9‐
1.4/10000. This disease is not self limiting and progresses to complications. Epigastric pain and vomiting are the two most common presentations in children younger than 10. Teenagers present with heartburn and dysphagia. There is clear association with allergic conditions. Endoscopic findings are characteristic. GERD is the main differential diagnosis. Complications include strictures. Treatment includes dietary elimination both universe and testing guided. It also includes steroid therapy. Steroids can be given systematic or topical.
Title: DIAGNOSIS AND MANAGEMENT OF PEDIATRIC GASTROINTESTINAL DYSMOTILITY SYNDROMS
Principal investigator: ABDEL HAI HAMMO, MD Institution. Assistant Professor, Tufts University, Chief of Pediatrics, Brockton Hospital, MA Director, Pediatric GI. Background: Functional gastrointestinal disorders (FGIDs) are complex in their physiology and clinical presentation. Pediatric gastrointestinal motility disorders are common and can range from relatively benign conditions such as functional constipation, recurrent abdominal pain, cyclical vomiting, to more serious disorders such as achalasia, Hirschsprung’s disease, and chronic intestinal pseudo obstruction. Understanding the neurophysiology and neuropathology of the disease by Performing and interpreting motility evaluations in children present a better understanding of these disorders, and so the management. Primary diseases such as congenital pseudo obstruction or Hirschsprung disease occur more often in children, but as with adults, abnormal motility may be secondary to other processes. Diagnostic studies include radiographic studies, manometry, breath testing, myoelectrical testing, and histologic evaluation. Although recent advances in technology, genetics, and biology are making an important impact and have allowed for a better understanding of the pathophysiology and therapy of gastrointestinal motility disorders in children, further research and new therapeutic agents are needed. Conclusions. Treatment of motility disorder in children should be targeted to pathophysiologic defects whenever possible. Available therapies include lifestyle alterations, dietary modifications, enzyme preparations, adsorbents and agents which reduce surface tension, treatments that alter gut flora, and drugs that modulate gut transit. PATHOGENESIS OF AUTOIMMUNE LIVER DISEASE Diego Vergani, MD PhD FRCPath Giorgina Mieli‐Vergani, MD PhD FRCP FRCPCH Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK An unknown but powerful stimulus must be promoting the formation of the massive inflammatory cell infiltrate present at diagnosis in AIH. Whatever the initial trigger, the high number of activated inflammatory cells are likely to initiate and perpetuate liver damage. An autoimmune attack can follow different pathways to inflict damage on hepatocytes. It is believed that liver damage is orchestrated by CD4+ T lymphocytes recognising a self antigenic peptide on hepatocytes. To trigger an autoimmune response, the peptide must be embraced by an HLA class II molecule and presented to uncommitted (naïve) CD4+T helper (Th0) cells by professional antigen‐presenting cells (APC), with the co‐stimulation of ligand‐ligand (CD28+ on Th0, CD80+ on APC) fostering interaction between the two cells. Th0 cells become activated, differentiate into functional phenotypes according to the cytokines prevailing in the microenvironment and the nature of the antigen, and initiate a cascade of immune reactions determined by the cytokines these activated T cells produce. Th1 cells, arising in the presence of the macrophage‐produced interleukin 12 (IL‐12), secrete mainly IL‐2 and interferon (IFN) ‐gamma, which activate macrophages, enhance expression of HLA class I (increasing liver cell vulnerability to a CD8+ T cell cytotoxic attack) and induce expression of HLA class II molecules on hepatocytes. Th2 cells, which differentiate from Th0 if the microenvironment is rich in IL‐4, produce mainly IL‐4, IL‐10 and IL‐13 which favour autoantibody production by B lymphocytes. Physiologically Th1 and Th2 antagonise each other. Th17 cells, a recently described population, arise in the presence of transforming growth factor beta (TGF‐beta) and IL‐6 and appear to have an important effector role in inflammation and autoimmunity. The process of autoantigen recognition is strictly controlled by regulatory mechanisms, such as those exerted by CD4+CD25+ regulatory T cells, which are derived from Th0 in the presence of TGF‐beta, but in the absence of IL‐6. If regulatory mechanisms fail, the autoimmune attack is perpetuated. Over the past three decades different aspects of the above pathogenic scenario have been investigated. In particular, a defect in immunoregulation affecting CD4+CD25+ regulatory T‐cells (T‐regs) has been demonstrated in AIH. These cells are numerically and functionally defective in patients with AIH, particularly at diagnosis or during relapse. Advances in the study of autoreactive T cells have occurred mostly in AIH type 2, since the knowledge that CYP2D6 is the main autoantigen has enabled the characterization of both CD4 and CD8 T‐cells targeting this cytochrome. One study has shown that CD4 T cells from patients with type 2 AIH positive for the predisposing HLA allele DRB1*0701 recognize seven regions of CYP2D6, five of which have later been shown to be also recognized by CD8 T cells. High numbers of interferon‐gamma producing CD4 T cells and CD8 T cells are associated with biochemical evidence of liver damage, suggesting a combined cellular immune attack. CLINICAL ASPECTS OF AUTOIMMUNE LIVER DISEASE IN CHILDHOOD Giorgina Mieli‐Vergani MD PhD FRCP FRCPCH Diego Vergani MD PhD FRCP FRCPath Institute of Liver Studies King’s College Hospital, Denmark Hill, London SE5 9RS, UK Autoimmune liver disorders are inflammatory liver diseases characterized histologically by a dense mononuclear cell infiltrate in the portal tract (interface hepatitis) and serologically by the presence of non organ and liver‐specific autoantibodies and increased levels of IgG, in the absence of a known etiology. These disorders usually respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. The onset of these conditions is often ill defined, and they frequently mimick acute hepatitis. In pediatrics there are two liver disorders in which the liver damage is likely to arise from an autoimmune attack: autoimmune hepatitis (AIH) and AIH/sclerosing cholangitis overlap syndrome (autoimmune sclerosing cholangitis, ASC). According to data collected in our tertiary center, there appear to be an increase in the yearly incidence of AIH and ASC in childhood. Thus, in the 1990s these conditions represented 2.3% of children older than 4 months referred to our unit during one year, while in the 2000s their incidence has increased to 12%. AUTOIMMUNE HEPATITIS Two types of AIH are recognized, according to the presence of either SMA and/or ANA (type 1) or anti LKM1 (type 2) antibodies. Type 1 AIH represents two thirds of the cases. Severity of disease is similar in the two types. In both there is a predominance of girls (75‐80%). LKM1‐positive patients present at a younger age, but the duration of symptoms before diagnosis and the frequency of hepatosplenomegaly are similar in the two groups. There is no significant difference in frequency of associated autoimmune disorders (about 20%) and family history of autoimmune disease (40%) between the two groups. Type 1 AIH is associated with the possession of human leukocyte antigen (HLA) DRB1*03, while type 2 AIH with DRB1*0. Clinical, laboratory and histological features of type 1 and 2 AIH are summarized in table 1. There are three clinical patterns of disease: (1) In at least 40% of patients, the presentation is indistinguishable from that of an acute viral hepatitis (non specific symptoms of malaise, nausea/vomiting, anorexia, and abdominal pain, followed by jaundice, dark urine, and pale stools), some children, particularly anti LKM1 positive, developing acute hepatic failure with grade II to IV hepatic encephalopathy from 2 ‐8 weeks from onset of symptoms. (2) In 25‐40% of patients, the onset is insidious, with an illness characterized by progressive fatigue, relapsing jaundice, headache, anorexia, and weight loss, lasting from several months and even years before diagnosis. (3) In about 10% of patients, there is no history of jaundice, and the diagnosis follows presentation with complications of portal hypertension, such as hematemesis from esophageal varices, bleeding diathesis, chronic diarrhea and weight loss. The mode of presentation of AIH in childhood is therefore variable, and the disease should be suspected and excluded in all children presenting with symptoms and signs of prolonged or severe liver disease. LKM1‐positive patients have higher levels of bilirubin and aspartate amino transferase (AST) at presentation than those who are ANA/SMA positive. A severely impaired hepatic synthetic function, as assessed by the presence of both prolonged prothrombin time and hypoalbuminemia, is more common in ANA/SMA‐positive than in LKM1‐positive patients. The vast majority of patients have increased levels of IgG, but some 20% do not, indicating that normal IgG values do not exclude the diagnosis of AIH. Partial IgA deficiency is significantly more common in LKM1‐positive patients than in ANA/SMA‐positive patients. The severity of interface hepatitis at diagnosis is similar in both types, but cirrhosis on initial biopsy is more frequent in type 1 than in type 2 AIH, suggesting a more chronic course of disease in the former. Of note is that most patients already cirrhotic at diagnosis present with a clinical picture reminiscent of that of prolonged acute viral‐like hepatitis. Multiacinar or panacinar collapse, which suggests an acute liver injury, is more frequently seen in type 2 AIH. The question as to whether the acute presentation in these patients represents a sudden deterioration of an underlying unrecognized chronic process or a genuinely acute liver damage remains open. Progression to cirrhosis during treatment is more frequent in type 1 AIH. A more severe disease and a higher tendency to relapse is associated to the possession of antibodies to soluble liver antigen (SLA), which are present in about half of the patients with AIH type 1 or 2 at diagnosis. Treatment AIH in children is exquisitely responsive to immunosuppression. The rapidity and degree of response depends on the disease severity at presentation. AIH presenting as prolonged acute hepatitis, compensated chronic liver disease, acute decompensation of chronic liver disease with severe hepatic synthetic failure, but without encephalopathy, generally responds to standard treatment with prednisolone, to which azathioprine is often added. AIH presenting as fulminant hepatitis with encephalopathy responds only exceptionally to immunosuppression and transplantation is usually the only effective management. Treatment for AIH in our centre consists of prednisolone 2 mg/Kg/day (maximum 60 mg/day), which is gradually decreased over a period of 4‐8 weeks if there is progressive normalization of the transaminases, and then the patient is maintained on the minimal dose able to sustain normal transaminase levels, usually 5 mg/day. During the first 6‐8 weeks of treatment, liver function tests are checked weekly to allow a frequent fine‐tuning of the treatment, avoiding severe steroid side effects. If progressive normalization of the liver function tests is not obtained over this period of time or if too high a dose of prednisolone is required to maintain normal transaminases, azathioprine is added at a starting dose of 0.5 mg/Kg/day, which, in the absence of signs of toxicity (myelosuppression, hepatotoxicity), is increased up to a maximum of 2 mg/Kg/day until biochemical control is achieved. Azathioprine is not recommended as first‐line treatment because of its hepatotoxicity, particularly in severely jaundiced patients. Although an 80% decrease of initial transaminase levels is obtained within 6 weeks from starting treatment in most patients, complete normalization of liver function may take several months. In the King’s series, normalization of transaminase levels occurred at medians of 0.5 years (range 0.2–7 years) in ANA/SMA positive children and 0.8 years (range 0.02–3.2 years) in LKM‐1 positive children. Side effects of steroid treatment using this schedule are mild, the only serious complication we observed being psychosis during induction of remission in two patients, which resolved after prednisolone withdrawal. All patients develop a transient increase in appetite and mild cushingoid features during the first few weeks of treatment. Relapse while on treatment is common, affecting about 40% of the patients and requiring a temporary increase of the steroid dose. The risk of relapse is higher if steroids are administered on an alternate‐day schedule, often instituted in the belief that it has a less negative effect on the child’s growth. Small daily doses should be used because they are more effective in maintaining disease control and minimize the need for high‐dose steroid pulses during relapses (with attendant more severe side effects). In the King’s experience, after five years of treatment, 56% of the patients maintained the baseline centile for height or went up across a centile line, while only 6% dropped across two centile lines. In pediatrics, an important role in monitoring the response to treatment is the measurement of autoantibody titres and IgG levels, the fluctuation of which is correlated with disease activity. At induction of remission, however, negativization of autoantibodies and normalization of IgG (both with a half life of 21‐28 days) lag behind normalization of transaminases. If a liver biopsy shows minimal or no inflammatory changes after 1 year of normal liver function tests, cessation of treatment should be considered but not during or immediately before puberty, when relapses are more common. We have been able to stop treatment in 20% of children with AIH type 1, but in none with AIH type 2. Despite the efficacy of current treatment, severe hepatic decompensation develops after 8‐15 years of apparently good biochemical control in about 10% of the patients, who will require transplantation. Following the observation that remission can be maintained in adult patients with azathioprine alone, we have attempted to stop prednisolone, maintaining azathioprine, but were successful only in children with AIH type 1. Remission has been reported in a pediatric series of AIH using cyclosporin A alone for 6 months followed by combined low‐dose prednisone and azathioprine for 1 month, after which cyclosporin A was stopped and the other two drugs were continued. The side effects of cyclosporin A were mild, though patients did experience transient physical alteration due to hairiness and gum hypertrophy. High‐dose steroid side effects were avoided. A disadvantage of this schedule is that all patients are eventually treated with the prednisone/azathioprine combination, whereas by using the conventional treatment schedule, 15% of the children can maintain remission with very‐low‐dose steroids alone. Moreover, longer follow‐up of the patients is necessary to establish possible long‐
term toxicity of cyclosporin A, a nephrotoxic drug that in experimental animal models has been shown to induce a paradoxical autoaggressive syndrome by increasing the number of self reactive T cells escaping thymic selection and by interfering with regulatory T cell function. Mycophenolate mofetil is a promising drug for difficult to treat patients. In our experience, the drug was able to resolve laboratory abnormalities in 21 of 25 children who did not tolerate or respond to azathioprine. Side effects of mycophenolate mofetil included mild hair loss, headache, diarrhoea, nausea, dizziness and neutropenia, the latter being the cause of permanent withdrawal of the drug in three patients. AUTOIMMUNE SCLEROSING CHOLANGITIS In a prospective study performed at King’s over a period of 16 years it was shown that half of the children who present to a tertiary hepatology service with serological (i.e. autoantibodies, high IgG levels) and histological (i.e. interface hepatitis) features of autoimmune liver disease have bile duct abnormalities if a cholangiogram is performed. It has been proposed to call this AIH/sclerosing cholangitis overalp syndrome autoimmune sclerosing cholangitis (ASC). Most children with ASC are seropositive for ANA and/or SMA. Fifty five percent are girls, and the mode of presentation is similar to that of typical AIH. Inflammatory bowel disease is present in about 45% of children with ASC compared to about 20% of those with typical AIH, and 90% of children with ASC have greatly increased serum IgG levels. Standard liver function tests do not help in discriminating between AIH and ASC, though the alkaline phosphatase/aspartate amino transferase ratio is significantly higher in ASC (table 2). Perinuclear anti‐neutrophil cytoplasmic antibodies (pANCA) are present in 74% of patients with ASC compared to 45% of patients with AIH type 1 and 11% of those with AIH type 2. Clinical, laboratory and histological features of type 1 and 2 AIH are summarized in table 1. There is only a partial concordance between the histological and radiological findings, and patients with abnormal cholangiogram may have histological features more compatible with AIH than sclerosing cholangitis. Indeed, the diagnosis of sclerosing cholangitis is often possible only because of the cholangiographic studies. Treatment Children with ASC respond to the same immunosuppressive treatment described above for typical AIH. In the King’s series, liver test abnormalities resolved in almost 90% of patients within a median of 2 months after starting treatment. This good response is in contrast to the outcome in adults with primary sclerosing cholangitis (PSC) who appear to have no beneficial effects from corticosteroid treatment. The PSC of adults, however, has a much worse bile duct involvement at diagnosis and may be the result of various etiologies. Disappointing results with immunosuppressive agents have been reported in a small number of children with sclerosing cholangitis associated with autoimmune features, but these children appear to have had more advanced disease at the start of treatment than those recruited into the King’s prospective study. Ursodeoxycholic acid (UDCA), which is used in adult PSC, is usually added at the dose of 15‐20 mg/Kg/day, though there is no information as to whether it is helpful in arresting the progression of ASC. Measurement of autoantibody titers and IgG levels is useful in monitoring disease activity and response to treatment also in ASC. Follow‐up liver biopsies in the King’s series have shown no progression to cirrhosis, although one patient did develop vanishing bile duct syndrome. Follow‐up cholangiograms have shown static bile duct disease in half of the patients and progression of the bile duct abnormalities in the other half. Interestingly, one of the children with AIH who was followed prospectively developed sclerosing cholangitis eight years after presentation despite treatment with corticosteroids and no biliary changes on several follow‐up liver biopsies. This observation suggests that AIH and ASC are part of the same pathogenic process and that prednisolone and azathioprine may be more effective in controlling the liver parenchyma inflammatory changes than the bile duct disease. The medium‐term prognosis of ASC is good. All patients in the King’s series were alive after a median follow‐up of 7 years. Four of 27 patients with ASC, however, required liver transplant after 2‐11 years of observation (median interval of follow‐up 7 years). In contrast, liver transplant was not required by any of the 28 children with typical AIH who had been followed for this same time. INTERPRETATION OF AUTOIMMUNE LIVER SEROLOGY Diego Vergani, MD PhD FRCP FRCPath Giorgina Mieli‐Vergani, MD PhD FRCP FRCPCH Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK Autoantibodies play a central role in the diagnosis and classification of autoimmune liver disease. Their detection and interpretation, however, are often difficult. The basic technique for autoantibody testing is indirect immunofluorescence, an operator‐dependent technique hard to standardize. Often, the lack of familiarity in the interpretation of the laboratory finding by the physician compounds the problem Autoimmune liver disorders are characterized by elevation of transaminases, presence of autoantibodies, increased immunoglobulin G levels and interface hepatitis on histology. Two types of autoimmune hepatitis (AIH) are recognized, according to the presence of smooth‐
muscle antibody (SMA) and/or antinuclear antibody (ANA) (type 1 AIH), or liver/kidney microsomal type 1 (LKM1) antibody (type 2 AIH). Usually the two patterns of serology are mutually exclusive, but in the rare cases in which they coexist, the disease course resembles that of type 2 AIH. There exists a third form of autoimmune liver disease, described in children and characterised by clinical, histological and serological similarities with type 1 AIH, but concomitant radiological changes diagnostic of sclerosing cholangitis. This condition is referred to as autoimmune hepatitis/sclerosing cholangitis overlap syndrome or autoimmune sclerosing cholangitis (ASC). In addition to the classical autoantibodies used in the diagnosis of type 1 and 2 AIH and ASC, there exist other autoantibodies which are of diagnostic and/or prognostic value in paediatric autoimmune liver disease. Anti liver cytosol type 1 (LC1) has been originally described in association with AIH type 2. In the majority of cases it is present in conjunction with anti LKM1, but it can be occasionally detected in isolation in children with clinical features of type 2 AIH. Another antibody, known as anti‐soluble liver antigen (SLA) is associated with a particularly severe clinical course and a poorer outcome. The majority of anti SLA positive patients is also positive for ANA, SMA or anti LKM1, but occasionally anti SLA is present in isolation and, in this case, its detection is of diagnostic importance. Atypical perinuclear anti neutrophil cytoplasmic antibody (ANCA) can also be positive in autoimmune liver disease, being present with a similar prevalence in ASC and type 1 AIH, while it is virtually absent in type 2 AIH. Detection of autoantibodies Immunofluorescence ­ The standard technique for the detection of autoantibodies is indirect immunofluorescence using a composite substrate comprising freshly prepared liver, kidney and stomach from rodents. The use the three tissues simultaneously enables the detection of virtually all the autoantibodies relevant to liver autoimmune serology, namely SMA, ANA, anti LKM1, anti mitochondrial antibody (AMA), and anti LC1. In adults, the patient serum dilution recommended for autoantibody detection is 1:40, while in childhood titres as low as 1:20 for ANA and SMA and 1:10 for anti LKM1 are significant. ANA is readily detectable as nuclear staining in all the three tissues of the composite substrate. On the liver it is possible to identify the pattern of antinuclear reactivity as homogeneous or speckled, the former being the most frequent in AIH, even though a speckled pattern can also be seen. A clearer definition of the pattern can be achieved by the use of the cell line HEp2 that is characterised by large nuclei. However, while HEp2 cells are ideal for pattern definition, they should not be used for first‐line detection of ANA because of the high rate of positive staining observed in healthy subjects. SMA stains the muscularis mucosae of the stomach and the arterial walls of the three organs. When the vascular (V) staining within the kidney is associated with staining of glomeruli (G) and around the tubules (T) the pattern is called VGT and is considered specific for AIH type 1, though some 20% of patients with AIH type 1 do not have it. The VGT pattern corresponds to the microfilament staining of isolated fibroblasts. Both patterns have been termed ‘anti‐actin’ though there is no molecular proof that actin is indeed the target of VGT SMA. Anti LKM1 stains the third portion of the proximal renal tubules and brightly the cytoplasm of all the hepatocytes, sparing the gastric mucosa. Anti LKM1 is the most frequently misdiagnosed autoantibody, being commonly confused with AMA, the serological hallmark of primary biliary cirrhosis, a disease of middle age, mainly female, patients. AMA is extremely rare in paediatric patients and PBC practically absent. When AMA is reported in a child with clinical and histological characteristics of AIH, the serological report is almost certainly incorrect. The confusion between AMA and anti LKM1 stems from the fact that both autoantibodies stain the renal tubules, though with a different pattern. This difference is only readily appreciated if the kidney section contains both distal and proximal tubules. AMA stains the distal, smaller tubules especially well, while anti LKM1 stains the larger proximal ones. On the other hand, AMA also stains the gastric parietal cells within the stomach, which are spared by anti LKM1, while anti LKM1 stains the hepatocytes much more brightly than AMA. The analysis therefore of the three‐tissue substrate allows a correct serological interpretation. Unfortunately interpretative problems are frequent in those not infrequent laboratories where only kidney is used as substrate, particularly when the tissue is poorly oriented. In contrast to ANA and SMA, the molecular target of which is unknown, the main target of anti LKM1 has been identified as cytochrome P4502D6 (CYP2D6). Anti LC1 can be detected by indirect immunofluorescence when it occurs in isolation, but in the majority of cases it is obscured by the simultaneous presence of anti LKM1. Anti LC1 can be also detected by gel diffusion techniques such as double dimension immunodiffusion and counter immuno electrophoresis, where the liver cytosol is used as antigen and the serum is run with a positive control. The molecular target of anti LC1 is formimino‐transferase cyclodeaminase (FTCD). Anti SLA is not detectable by immunofluorescence, but only by molecularly based assays such as enzyme linked immunosorbent assay (ELISA) and radioligand assay. Its target is UGA tRNA suppressor associated antigenic protein (tRNP(Ser)Sec) and cloned. ANCA is detected by indirect immunofluorescence using neutrophils as substrate. The atypical perinuclear ANCA found in AIH and ASC gives a perinuclear staining irrespective of the type of fixation and probably reacts with nuclear membrane components, hence its proposed alternative name of perinuclear anti neutrophil nuclear antibody (p‐ANNA). Antigen based assays – Identification of the antigenic targets of several autoantibodies, including anti LKM1, anti LC1, anti SLA, AMA, has led to the establishment of molecularly based assays and their commercial availability. The results of a comparison between anti LKM1detected by immunofluorescence and anti‐CYP2D6 by ELISA show a very good agreement between the two methodologies, indicating that the much easier ELISA can take the place of the more complex indirect immunofluorescence. Of particular relevance to the frequent confusion between AMA and anti LKM1 is the fact that the molecular target of AMA has been identified as an antigen collectively known as M2, which comprises enzymes of the 2‐oxo‐acid dehydrogenase complexes. In the event of a laboratory report of AMA in a child with the clinical, biochemical and histological characteristics of AIH, the clinician should request the verification of the nature of the autoantibody using ELISAs detecting anti CYP2D6 and anti M2. Positivity for anti CYP2D6 will confirm the diagnosis of AIH type 2. TEACHING MEDICAL SKILLS Dr. Salah Nassar*, MD MB BCh, DCH, DM, MD "Pediatrics" Prof. of Pediatrics, Faculty of Medicine, Cairo University Consultant of Medical Education Development The outcome of medical education is a graduate equipped with evidence‐based knowledge, skills and attitude that enable him to function effectively at a health care setting. Skills constitute the most important, domain of teaching and learning. Health care services involve the frequent use of many skills; in their absence the human life is in real danger. Knowing a lot of facts without knowing how to apply them does not help the health care worker to do his job well in serving the society both competently and thoughtfully based on basic Quality Standards. It is absolutely essential to teach practitioners the relevant skills. The skill is the ability to perform a task through the application of knowledge and experience. Skills, in general, are of 3 types: cognitive, psychomotor, and communication skills. Teachers must accept that their job is to help students to learn the necessary skills and attitudes. Teachers must make sure that there is enough time to teach the skills. At least two‐thirds of the time of every course for continued medical education (CME) and continued professional development (CPD) should be spent teaching and practicing skills. Teachers should also use good teaching methods to teach skills. Teachers should be committed not only to describe the skill but also to demonstrate the skill and arrange practice sessions. This pattern is generally sensible although the stages cannot be separated completely. Description of the skill should include what the skill is, why the skill is important, when it should be used and stages involved in performing the skill. Skills must be demonstrated correctly and visibly and trainers must explain what they are doing and provide practice sessions. Methods used in teaching skills include role‐playing, projects, simulators, case studies, and job experience. Finally, teachers must make sure that all their trainees are able to hear what they are saying and see what they are doing. They also must repeat the Demo if some students cannot see properly. GASTROESOPHAGEAL REFLUX DISEASE (GERD) Dr. Omar Saadah, MB BS, MRCP (UK), CABP Consultant Pediatric Gastroenterologist King Abdulaziz University Hospital Gastroesophageal reflux (GER) is a common, self‐limited process in infants that usually resolves by six to 12 months of age. Effective, conservative management involves thickened feedings, positional treatment, and parental reassurance. Gastroesophageal reflux disease (GERD) is a less common, pathologic process in infants manifested by poor weight gain, signs of esophagitis, persistent respiratory symptoms, and changes in neurobehavior. Transient lower esophageal sphincter relaxations unassociated with swallowing may be the major mechanism allowing the gastric refluxate to return into the esophagus. Infants with GERD may manifest persistent regurgitation with secondary poor weight gain and failure to thrive. Other infants may manifest signs of esophagitis, including persistent irritability, pain, feeding problems, and iron deficiency anemia. A variety of respiratory symptoms occur in infants with GERD such as apnea with cyanotic episodes, stridor, wheezing and chronic cough. Aspiration of refluxate may lead to pneumonia, especially in infants with neurologic impairment. After infancy, more classic symptoms of esophagitis predominate, including lower chest pain, heartburn, odynophagia, dysphagia, and signs of anemia and esophageal obstruction from stricture formation. A test may be useful to document the occurrence of GER, to detect complications of GER, to establish a causal relationship between GER and symptoms, to evaluate therapy or to exclude other causes of symptoms. Upper GI examination is best utilized to identify anatomic abnormalities that may present with symptoms similar to those of GERD. The 24‐hour pH probe monitoring may be considered the gold standard test for quantitating reflux and for evaluating atypical symptoms such as apnea, stridor, or cough. Endoscopy is useful in evaluating symptoms of pain, dysphagia, and hematemesis, and to differentiate GERD from other conditions that clinically mimic GERD.The role of nuclear scintigraphy in the diagnosis and management of GERD in infants and children is unclear. However it is useful in investigating infants and children for possible aspiration secondary to GER. The clinical implication of Intraluminal Impedance Technique in studying GER still under investigation, but appears promising as an adjunct to extended pH study. Management involved life style changes in addition to the use of acid‐suppressant therapy such as H2‐receptor antagonists and proton pump inhibitors. Prokinetic agents may be helpful in subset of patients. Fundoplication remains an option for infants and children with GERD unresponsive to medical therapy. Gastroesophageal Reflux Disease in Childhood Diagnosis and Management Issam Halabi, MD, FAAP
Professor and Chief , Pediatric gastroenterology University of Illinois
Gastroesophageal reflux disease is a very common condition that affects infants and young children. It is more common in early childhood because of weak gastroesophageal sphincter, small gastric volume and predominantly supine position. Spitting up is the most common presentation. Distinction has to be made between reflux and reflux disease. A good history and physical exam are adequate to establish the diagnosis. Diagnostic tests are only needed in certain situations. This includes irritability, cough, aspiration and vomiting not responding to reflux treatment. Diagnostic tools include: PH probe, Impedance, UGI and endoscopy. Treatment includes diet modification, pharmaceutical agents and surgical. Most cases are treated with simple means. Surgery is rarely needed.
Morbidity of GERD IN Morocco Nezha Mouane ­ N.Erreimi – T. Meskini ­ S.Ettair Pediatric Gastroenterology Nutrition Unit University Hospital – Rabat – Morocco The gastro‐oesophageal reflux and anomalies of the oesogastric junction are the most common pathology of the oesophagus in childhood. It is very common in infants, currently manifested by regurgitation. If the GERD frequently disappear in most cases at the age of 1year, signs may persist throughout childhood. In its uncomplicated digestive form, no exploration is necessary. The pH meter is indicated in case of diagnostic doubt or extra digestive events. Digestive Endoscopy is indicated in cases of suspected esophagitis. We conduct a retrospective study of the results of the digestive endoscopy, performed cause of GERD pathology, at our paediatric endoscopy unit, between January 2004 and April 2009. Material and Methods: We identified the incidence of GERD with severe peptic complication: peptic esophagitis grade II, III or IV and cases of peptic stricture, according to Savary and Miller endoscopic classification in 4 grades. Results: This study revealed that the incidence of peptic complications of GERD remains high, including 140 cases of severe esophagitis grade II or III and 92 cases of peptic stricture. The pathology of GERD, is still a concern among our children, the peptic complications are not rare, which raises the interest of enhancing all health professionals skills regarding diagnosis and medical care of GERD, vigilance must be the norm, with the introduction of a policy advocacy. In regard to our epidemiology, the danger would be to trivialize this disorder. Prospective Study to Evaluate the Efficacy of Quadruple Therapy in Treatment of Helicobacter pylori Gastritis in Children in whom Triple Therapy has failed
R. Abdelhadi1, MD; M. Miqdady2, MD; V. Tolia3, MD
1 Clinical Assistant Professor of Pediatrics and Communicable Diseases, University of Michigan Health System, CS Mott Children’s Hospital, Ann Arbor, Michigan
2 Clinical Assistant Professor of Pediatrics, Jordan University of Science and Technology, King Abdullah University Hospital, Irbid, Jordan
3 Adjunct Professor of Pediatrics, Michigan State University, Providence Hospital, Southfield, Michigan
Background:
Helicobacter pylori infects half of the world population; it is associated with diverse pathologies of varying severity. The therapeutic regimens used in treatment have evolved over the last decade aiming towards the most tolerable drug association for the shortest duration with best eradication rates. Traditional first line treatment includes combination triple therapy using a proton pump inhibitor (PPI) and two antibiotics. Emerging resistance to antibiotics among Helicobacter pylori strains has necessitated the use of more than one course of triple therapy. Aims: To investigate the efficacy of quadruple therapy in children with Helicobacter pylori gastritis when two courses of primary triple anti‐ Helicobacter pylori therapy using different antibiotic combinations had failed. Methods: Gastric biopsies were obtained for CLO test, histology and culture in children diagnosed or suspected to have Helicobacter pylori gastritis using following criteria at the time of endoscopy being performed for routine indications. Helicobacter pylori gastritis was diagnosed if two of the following three criteria were present: CLO test positive, Helicobacter pylori seen at histology, Helicobacter pylori culture positive. If positive by two of the above criteria, then triple therapy with a PPI and two antibiotics was started. We selected only those who had received two courses of triple therapy with PPI and a combination of two of the following antibiotics: Amoxicillin, Clarithromycin, Metronidazole, Tetracycline. This group received quadruple therapy with a PPI, two of the above mentioned antibiotics based on antibiotic susceptibilities, as well as Peptobismol bid for two weeks after starting treatment for the third time. Results: Twenty patients met the criteria for having received quadruple therapy from a cohort of 176 patients. Age range was 4‐18 years, mean 12.8 years. 12 females/ 8 males, 14 African American, 3 Caucasian, 3 Hispanic. These patients have been evaluated with follow‐up endoscopies to assess eradication; 16 were cured with complete eradication of Helicobacter pylori at follow‐up endoscopy, CLO, and culture; and 4/12 showed persistence of infection on repeat endoscopy. Conclusions: Multiple factors play a role in the outcome of Helicobacter pylori as eradication or persistence including antimicrobial susceptibility, patient compliance, and inherent qualities in the H. pylori strain itself. Rescue therapy with four drugs can be effective in those who failed to eradicate with triple therapy. The quadruple therapy was well tolerated without significant side effects. Abdelaziz Elamin, Hashim Javid From the Department of Pediatrics, University of Khartoum, Sudan Background: The incidence of type 1 diabetes in children is increasing alarmingly all over the world. It is a significant health problem in many countries in the region. Several GIT problems are encountered in diabetic children of which Helicobacter pylori infection is the most common. Objective: Helicobacter pylori induces gastric inflammation and the production of cytokines in infected individuals. Theoretically, this increased production of cytokines could be deleterious for the metabolic control of the patients with diabetes. This study aimed to describe the insulin requirement among patients with type 1 diabetes mellitus and H pylori infection compared with uninfected counterparts. Ethical approval was granted from the local committee and informed consent obtained from participants & their caregivers. Methods: Cross‐sectional design. Demographic information (age, gender, race, annual family income, and number of individuals per room in the household) and clinical information (age at diagnosis of diabetes, duration of illness, weight, height, compliance with clinical appointments, daily insulin units per kilogram of body weight [IU/kg/d], and glycosylated hemoglobin A level) was obtained from children and adolescents with diagnosis of type 1 diabetes mellitus who were seen at the diabetes referred clinic of the university hospital. A total of 2 mL of blood was also collected and sera were tested for H pylori‐specific immunoglobulin G antibodies using an enzyme immunoassay. The daily insulin requirement among infected and uninfected children was compared, and the effect of other variables was evaluated with multiple linear regression. Results: Of the 71 subjects who were evaluated (median age: 11 years), 11 (15.5%) were found to be infected. H pylori infection was more frequent among subjects who were older, who came from large families, and who had low socioeconomic status. Infected children were found to require more insulin (1.2 vs 0.9 IU/Kg/d) and their glycosylated hemoglobin A level was higher (14.5 vs 11.2) than the level found in uninfected subjects. Multiple linear regression analysis identified H pylori infection duration of illness, social class, body mass index, and gender (female), to be associated independently with increased daily insulin requirement (IU/kg/d). Conclusion: In our study population, children with type 1 diabetes and H pylori infection had an increased daily insulin requirement and higher HbA1c level compared with the findings of their uninfected peers. The reason for this association requires additional investigation. Procedural sedation for pediatric GI endoscopy is a reality in a developing country M. Miqdady MD, W. Hayajneh MD, R. Abdelhadi MD, M. Gilger, MD Background:
Procedural sedation is a technique that is used during uncomfortable, frightening or painful procedure. It creates a clinical status of decreased level of awareness for a certain period of time yet maintaining protective airway reflexes and cardiopulmonary functions. Midazolam and ketamine provide the above‐mentioned effects. Will present data regarding their efficacy and safety in pediatric endoscopy unit in Jordan. Methods: A retrospective cohort study of all pediatric endoscopic procedures performed over a period of six years (August 1st 2002‐July 31st 2008) at the endoscopy suite of King Abdullah University Hospital (affiliated with Jordan University of Science and Technology) in Jordan was performed.
Analysis of the data included demographic details (age, gender, weight), doses of each medication/kg, procedure performed, effectiveness of sedation, need for other sedative medications, side effects and complications was conducted. Results:Three hundred and three patients received conscious sedation. There were 161 males and 142 females (1.13: 1), age range 3 months to eighteen years and a mean age of 9.26 years. The average dose of midazolam used was 0.16 mg/kg, (range 0.07‐0.38 mg/kg), while the average dose of ketamine used was 1.06 mg/kg, (range 0.31‐2.67 mg/kg). Maximum recommended dose for Midazolam was exceeded in 17.5 % and for Ketamine in only 2.6 %. In 2.1 %, the procedure was not completed because of concerns about safety. Desaturation happened in 12 %, procedure was terminated in 1.3%. Respiratory distress developed in 1.3 % after termination of procedure. All were upper endoscopy. Reversal of benzodiazepines was needed in 2.3%. None of the patients developed apnea, bradycardia or cardiac arrest. None of our patients developed emergence psychosis during recovery period in the hospital. Conclusions: Midazolam and ketamine combination is effective and safe in pediatric endoscopy. Continuous monitoring is required although there is low risk of complications. Title: Nutritional modulation of intestinal gene expression Principal investigator: Professor Ian Sanderson Institution: Centre for Gastroenterology; Institute of Cell and Molecular Science; Barts and The London School Of Medicine and Dentistry, Queen Mary, University of London The mucosal immune system is arguably the largest immune component in the body. It defends not only the intestine to invasion by infections, but also plays a similar role in the respiratory system, mouth, eyes and reproductive tract. However, it is that of the intestine that is most widely characterised.
The immune system of the gut divides into the physical barrier of the intestine and active immune components, which include both innate and adaptive immune responses. The physical barrier is central to the protection of the body to infections. Acid in the stomach, active peristalsis, mucus secretion and the tightly connected monolayer of the epithelium each play a major role in preventing microbial organisms from entering the body.
The cells of the immune system are organised in a complex pattern within the intestine. Specialised lymphoid tissue with germinal centres, the Peyer’s patches, reside below specialised epithelia. This lymphoid associated epithelium includes M cells whose structure enables sampling of small particles. Furthermore, other lymphocytes are present both in the lamina propria and associated with the epithelium itself. All cells of the immune system are found in the lamina propria. Infancy is a time of great change in nutrient intake. Not only does the intestine receive food for the first time at birth, but also at weaning the diet increases markedly in complexity. Dietary intake affects the luminal environment both directly and through the gastrointestinal microflora. Dietary changes affect both bacterial populations present and vary the substrates that bacteria metabolize. Our laboratory has hypothesized that the intestinal epithelium senses these changes and relays them as signals to the mucosal immune system. By this means the luminal environment alters the expression of genes in the epithelial cell that encodes epithelial‐immune cell signals. Examples of such signaling include chemokines, and class II MHC. In addition, components of the intestinal lumen can breach the epithelial barrier and alter the actions of immune cells beneath. In physiological transfer, molecules are shuttled by mechanisms developed in the intestine for this purpose: for example M cells for the uptake of macromolecules, or transporters for nutrient absorption. Potentially pathological uptake occurs when the passage of luminal contents crosses a poorly functioning or damaged epithelium. Recent Advances in Acute and Chronic Diarrhea:
In Infants and Children Fayez K. Ghishan, M.D. Professor and Head, Pediatrics Director, Steele Children’s Research Center
The University of Arizona Health Sciences Center Tucson, AZ
Diarrhea disorders are a major cause of morbidity and mortality for children around the world. Understanding the pathophysiological mechanisms underlying diarrheal disorders will depend on understanding the normal transport function of nutrients and electrolytes across the gastrointestinal tract. The capacity of the gastrointestinal tract to transport more than three liters per day of fluid in a 10 kg baby illustrates the important function of the transport proteins which reside at the brush border membrane of the gastrointestinal tract. The sodium‐glucose, sodium‐
amino acid cotransporters and the sodium hydrogen exchangers (NHE) coupled with the chloride bicarbonate exchangers play a major role in the absorptive function of the gastrointestinal tract. The NHE’s, specifically sodium NHE3, are responsible for the majority of water and electrolyte transport following a meal. NHE3 resides in the micro‐domain of the small intestine and the colon and its inhibition during diarrheal illnesses appears to play a role in the entrance of pathogen through the gastrointestinal tract via alterations of the apical junctional complexes. Short chain fatty acid (sodium butyrate) plays a role in up‐regulation of NHE3 which plays a role in decreasing sodium losses. On the other hand, secretory processes occur via second messengers allowing chloride secretion from the crypt cells. Recent advances in the etiology of acute diarrhea will be discussed with emphasis in the role of rotavirus vaccines. Finally, the mechanisms of chronic diarrhea will be explored, coupled with physiological approaches for the treatment of chronic diarrheas in childhood. AN OVERVEW ON ROTAVIRUS GASTROENTERITIS IN UAE Dr. Sherif Mosaad (Consultant Pediatrician, UAE) Rotavirus is the most common cause of severe diarrhea disease in infants and young children all over the world. Rotavirus most often infects infants and young children, and in children ages 3 months to 2 years, is one of the most common causes of diarrhea. It leads to outbreaks of diarrhea during the winter and spring months. Almost all children have had a rotavirus infection by the time they are 5 years old. Severe infection, rotavirus gastroenteritis, is the leading cause of severe, dehydrating diarrhea in infants and young children. Globally Rotavirus is responsible for 40% of total gastroenteritis hospitalization. Approximate 125 million cases of diarrhea in the world are due to RV and 600,000‐800,000 children die from RV GE each year. Symptoms can include watery diarrhea, vomiting and fever; Diarrhea can persist for up to 7 days, often resulting in severe illness and the need for intravenous rehydration. Children who are infected may also have a cough and runny nose. Rotavirus infection is very contagious. The virus passes in the stool of infected persons before and after they have symptoms of the illness. Children can become infected if they put their fingers in their mouths after touching something that has been contaminated by the stool of an infected person From this point the opinion started to study the nearly incidence of RV GE in our admission in SAQR hospital, UAE……………………………………….. The American Academy of Pediatrics (AAP) recommends that the rotavirus vaccine be included in the lineup of routine immunizations given to all infants. The recommendation calls for three doses by mouth at around 2, 4, and 6 months of age. Dr. Sherif Mosaad UAE , RAK, Mobile +97150‐6479555, Fax +9717‐2443534, email [email protected] Non­invasive Parameters as Predictors for Esophageal Varices in Children with Chronic Liver Disease Mohamed El Guindi Vice Dean, Professor of Pediatrics, National Liver Institute, Menoufiya University, Egypt. •
•
Background: Portal hypertension commonly accompanies liver cirrhosis, and the development of esophageal varices (EV). Cirrhotic patients are recommended to undergo screening endoscopy for the presence of EV. This recommendation requires that the patient repeatedly undergo an unpleasant procedure of endoscopy, even though 50% may still not have developed EV. Noninvasive predictors of varices would reduce the need for unnecessary screening endoscopies in children without varices. Several studies have evaluated possible non invasive marker of EOV in adults but not sufficiently investigated in pediatric patients. Aim: To identify the clinical, biochemical and ultrasonograpic parameters which might noninvasively predict the presence of esophageal varices in children with chronic liver disease and to limit screening to those at risk.
Endoscopic Treatment for UGI Bleeding in Children Gilger, Mark A. Baylor College of Medicine Texas Children’s Hospital, Houston, Texas Gastrointestinal (GI) bleeding is a common occurrence in children, often worrisome but rarely life threatening. Upper gastrointestinal bleeding is rare in children. Using the Pediatric Endoscopy Database System–Clinical Outcomes Research Initiative (PEDS‐CORI), Bancroft and colleagues found that hematemesis accounts for only about 5% (327 of 6,337) of indications for upper endoscopy in children. In children hospitalized in the intensive care unit, UGI bleeding is con¬siderably more common, with an incidence ranging from 6 to 25%. However, even in this critically ill population, life‐threatening UGI bleeding occurred in only 0.4% of children. Esophagogastroduodenoscopy (EGD) is the preferred method to evaluate the UGI tract for a source of bleeding. Hematemesis is considered a “red flag” sign and is an indi¬cation for early EGD. EGD is generally indicated for assessment of acute UGI bleeding requiring transfusion or unexplained recurrent bleeding. EGD can determine the source of the bleeding in 90% of cases. A variety of endoscopic therapies are available for the treatment of GI bleeding. These include electrocoagula¬tion (heater probe, monopolar probe, and bipolar electo¬coagulation [BICAP] probe), laser photocoagulation, argon plasma coagulation, injection of epinephrine and sclerosants, band ligation, and mechanical clipping. Unfortunately, there is little published experience with these techniques in children. As a result, which approach is best remains unknown. This lecture will address UGI bleeding in children and recommended endoscopic intervention.
Pediatric Gastrointestinal endoscopy experience Royal Hospital,Muscat Oman. Dr.Tawfiq Taki Al­Lawati. Senior Consultant, paediatric gastroenterology in Oman. Background Paediatric Endoscopy is still a developing issue in the Arabic countries and particularity in the Arabic gulf. Pediatric Endoscopy in Oman started in February 2005.This study is the first to report the paediatric Endoscopy in Oman from the major tertiary centre in the country. During the study Royal Hospital was the only centre that provides this service. Aim: To report the pattern of endoscopic experience in Royal Hospital. Objectives: • Report the total amount of endoscopic procedures done • Report the common indications of the procedures • Develop mechanisms to improve the service. Method All data from 1/4/2005 till31/10/2006 (20 months) were retrieved from the endoscopy registry book. Results Total of 185 procedures were done on 138 patients with average age of 5.6 yrs over the period of study. Ninety were diagnostic procedures and 95 were therapeutic procedures. Most of the diagnostic procedure were for abdominal pain.Other indications included screening for varices and others.The therapeutic procedures were for mainly for esophageal variceal banding followed by tracheo‐esophegal fistula stenosis dilatations. Only 9 procedures were done over the study period. The main indication was upper GI bleed followed with forien body ingestion. All peocedures were done under general anaesthesia. In conclusion The local experience in Oman has a significant amount of therapeutic procedure and is mainly related to a disease pattern in Oman. There is however a major knowledge gap in the general paediatrician about the role of endoscopy in paediatrics VIRUS­HOST INTERACTION IN LIVER DISEASE Diego Vergani MD PhD FRCP FRCPath Giorgina Mieli‐Vergani, MD PhD FRCP FRCPCH
Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK Infections with the first three viruses of the hepatitis alphabet, namely hepatitis A, B and C, provide a good illustration of distinct patterns of host‐virus interaction. Hepatitis A virus
The hepatitis A virus (HAV) replicates mainly within the hepatocytes, though some evidence suggests that HAV may also replicate in the intestine. Once HAV has replicated within the liver, it is released into the bile. Being a non‐enveloped virus it is resistant to the action of bile salts and thus enters intact the enterohepatic cycle, which continues with gastrointestinal uptake, transport through the intestinal epithelium, transfer to the liver, shedding into the bile and so on until a neutralizing antibody stops the cycle.
In the acute phase of hepatitis A, a dominant IgM and IgG immune response is observed against VP1, a major HAV capsid polypeptide. The hepatitis A‐specific IgM response is limited to the initial infection in most cases, thus acting as a useful marker of acute disease. The IgG anti‐VP1 antibody is neutralizing. Vaccination is highly effective in healthy individuals with 95% efficacy after a single inoculation and practically 100% after a second dose. Efficacy decreases in patients with chronic liver diseases (93%), immunocompromised individuals (88%) and especially in transplanted patients (26%).
HAV is considered a cytopathic virus. The viral load largely dictates the clinical range of manifestations, from a subclinical hepatitis, to symptomatic hepatitis, to, occasionally, fulminant hepatic failure. The acute event is followed by sustained immunity to the virus, capable of preventing reinfection. In addition to the humoral anti‐HAV response, it is clear that the cellular arm of the immune system is involved in protection. Thus, in vaccinated individuals protection persists long after the disappearance of neutralizing antibodies. Hepatitis B virus
The hepatitis B virus (HBV) belongs to the Hepadnaviridae family. Hepadnaviruses are hepatotropic DNA viruses that preferentially infect liver cells, though they can be present in small quantities in kidney, pancreas and mononuclear blood cells. In primary infection, after an incubation of 4‐8 weeks, HBsAg becomes detectable in the blood shortly preceding the appearance of IgM antibodies to the HBV core antigen (anti‐HBc antibodies). During acute infection the viral load is very high, at times reaching 1010 copies per milliliter. Circulating HBeAg becomes detectable in most cases. Elevation of transaminases occurs only when an HBV specific T‐cell population is sufficiently expanded and mature to launch an attack on HBV infected hepatocytes. When the infection is under control, HBsAg and HBeAg decrease and then disappear from the circulation, and anti‐HBs antibodies become detectable. Even in self‐limited infection, as defined by the appearance of anti‐HBs antibodies, low number of HBV DNA copies can be detected for years in the circulation. This observation has generated the notion that the immune system is in control of the virus – but has not cleared it. Hence the preferable use of ‘viral control’ over that of ‘viral clearance’. Whether exposure to blood containing the small number of viral copies detectable in subjects who have controlled the viral infection may result in infection remains to be established. The possibility exists that individuals who have ‘cleared’ the virus may have a viral rebound if they become immuno‐
compromised.
Acute hepatitis is the most common clinical occurrence upon exposure to HBV in adults, though some 5% of them develop persistent infection, with a continuing HBsAg and HBV‐DNA presence in the blood. Chronic persistence of the virus is, however, the rule when infection occurs in infancy. In chronic infection the viral load tends to be smaller than during primary infection, especially in those patients who develop anti‐HBe antibodies. The continued presence of HBeAg on the other hand may indicate high titers of HBV DNA. In persistently infected individuals, HBeAg tends to disappear over time, with a yearly 5‐10% seroconversion to anti‐HBe. The loss of HBeAg is frequently heralded by a transient increase in transaminases, known as flare, a reflection of an immune attack on infected hepatocytes.
The clinical observation that HBV carriers can be asymptomatic and have minimal liver injury, despite extensive and ongoing intrahepatic replication of the virus clearly indicates that the HBV replication cycle is not directly cytotoxic to the hepatocytes. The immune response against virus‐
infected cells is deemed responsible for their destruction, even though this immune response has not been completely clarified. In acutely infected patients who successfully control the virus, the T cell response to HBV is vigorous, polyclonal, and multispecific. This response is executed by both CD4+ helper T cells and CD8+ cytotoxic T lymphocytes, which recognize short viral sequences respectively presented by major‐histocompatibility‐complex (MHC) class II or MHC class I molecules. The immune attack is mainly executed by the CD8+ cytotoxic T lymphocytes (CTL), which are generally thought to mediate viral clearance by killing infected cells.
It has been shown that CTL can also inhibit HBV gene expression and replication in the liver of transgenic mice non cytopathically by secreting antiviral cytokines that interrupt the HBV life cycle. Similar data have also been obtained in man. Also from the murine model is the observation that the number of hepatocytes killed by direct engagement between cytotoxic T lymphocytes and their targets is very small and unable to account for the extensive liver damage. The recruitment of antigen‐nonspecific inflammatory cells appears to play a pivotal role in the liver injury through the release of cytokines, free radicals and proteases. Hepatitis C
The hepatitis C virus (HCV) is a positive‐stranded RNA virus within the genus hepacivirus of the Flaviviridae family. It contains genes encoding structural (ie, nucleocapsid protein and envelope glycoproteins) and nonstructural (NS) proteins. HCV shows extensive genetic variation resulting in multiple distinct genotypes. Due to the low fidelity of the RNA replicative machinery on the one side and to the pressure of the immune system on the other, HCV in an individual exists as a heterogeneous mixture of divergent RNA genomes, which has been termed quasispecies. Evolution to quasispecies has a number of possible repercussions, including the development of 1) escape mutants 2) “defective” viral particles 3) drug resistance 4) variation of cell tropism. Quasispecies formation at the level of the hypervariable region 1 (HVR1) sharply declines in patients with self‐
limited acute infection in whom viremia spontaneously resolves, while progresses in patients who become chronically infected. The arrest of quasispecies formation has been attributed to an efficient immune response eliminating one by one the individual variants. Intriguingly, the rare patients with fulminant HCV hepatitis have very high serum HCV RNA levels with a very low degree of genetic diversity, this possibly being the result of the emergence of a particularly virulent strain that is uncontrolled by the immune response. Probably the most remarkable feature of HCV infection is its tendency to become chronic. Importantly, the large majority of chronically HCV infected patients, develop histological evidence of liver disease, ultimately leading to cirrhosis, hepatocellular carcinoma, and liver failure requiring liver transplantation. The outcome of the infection is determined to a large extent by the host’s immune response. Recent data show that Natural Killer (NK) cells, essential elements of the innate immunity, are involved in HCV‐host interaction. The binding of the HCV‐E2 protein to the co‐stimulatory CD81 molecule, present on the NK cell surface, blocks activation, proliferation, cytokine production, and cytotoxic granule release of these cells. The CD81‐ mediated blockade is detectable both in activated and resting cells suggesting that this inhibitory effect may occur at all stages of the infection. Dendritic cells, vital to antigen processing and presentation, are also functionally impaired in HCV‐infected individuals, at least when tested in an allostimulatory response. The role of adaptive immune responses has been investigated at both humoral and cellular level. High titers of HCV‐specific antibodies are present in chronic infection, but no antibody is able to confer stable immunity to HCV. Indeed anti‐HCV antibodies are used as markers of ongoing infection. Anti‐HCV antibodies can be lost over time, as shown in the cohort of women accidentally administered HCV genotype 1b–contaminated Rh immunoglobulin. Eighteen to 20 years after the accident, the antibody disappeared in a high proportion of cases together with the viral RNA, the only trace of exposure to the virus being detectable at the level of T cells.
A vigorous, polyclonal, and multispecific CD4 T cell response to HCV in acutely infected patients is central to disease resolution, being characteristically found in self‐limited disease. Individuals who become HCV RNA negative and normalize serum alanine aminotransferase levels more frequently show stronger CD4 T‐cell proliferative responses to the HCV antigens E2, NS3, NS4, and NS5 compared with those patients who develop persistent viremia and biochemical evidence of chronic liver injury. Conversely, HCV‐RNA recurs in patients, who lose virus‐specific CD4 memory T‐cells, a finding supporting the concept that HCV‐specific immunological memory must be sustained to maintain recovery from acute infection.
The role of CD8 T‐cells in HCV infection is not completely understood. Although an HCV‐specific CD8 T‐cell activity has been linked to markers of hepatocellular damage, such as signs of histological and biochemical activity, and inversely to serum viral levels, these associations are not consistent. The importance of non cytolytic effector T‐cell functions in controlling HCV replication has been highlighted by studies in chimpanzee, and by the demonstration that IFN‐gamma production efficiently inhibits the replication of HCV in the Huh‐7 cell line. Recent data suggest two possible roles for HCV‐specific CTLs: while CTLs capable of producing interferon gamma would be associated with viral clearance, those unable to produce antiviral TH1 cytokines would fail to eradicate the virus, while maintaining cytolytic properties and thus the ability to destroy infected hepatocytes (stunned phenotype). Studies are in progress to define phenotype and effector functions of HCV‐specific T cells that could induce viral clearance without causing extensive tissue damage.
Treatment of viral hepatitis in childhood Giorgina Mieli‐Vergani MD PhD FRCP FRCPCH Diego Vergani MD PhD FRCP FRCPath Institute of Liver Studies, King's College Hospital, London SE5 9RS, UK Hepatitis B
Hepatitis B virus infection is a major public health problem with an estimated 300 million HBsAg carriers worldwide. In endemic areas like China and Africa, where the HBsAg carrier rate is as high as 15‐20%, hepatitis B is primarily a disease of childhood, acquired either perinatally from HBsAg positive mothers or horizontally from infected mates or family members. In areas of intermediate endemicity (Italy, Japan, Spain, Greece, Portugal), where 2‐10% of the population is HBsAg carrier, infection occurs in both adults and children. In low endemicity areas, including the UK, infection in infancy and childhood is uncommon and <1% of the population has chronic HBV infection, which usually, though not exclusively, affects ethnic minorities originating from endemic countries or travellers to endemic areas. These epidemiological data are, however, rapidly changing with the introduction of universal hepatitis B vaccination in some countries, but not in others, and with an increase in travel facilities and international adoption. While HBV infection in children has dramatically decreased in countries like Taiwan, Italy or the USA that have introduced infant, or infant and adolescent universal vaccination, the number of infected children is not declining in the UK, where no universal vaccination policy is in place, and is possibly increasing, though no recent epidemiological data are available. Until universal vaccination is introduced worldwide, HBV infection will continue to be a serious problem. The virus is highly infectious, much more than hepatitis C virus (HCV) or human immunodeficiency virus (HIV), and chronically infected individuals readily infect unvaccinated family members, mates and sexual partners. The probability of becoming a chronic HBV carrier is correlated to the age at infection and the efficiency of the immune system, being highest in children infected within the first year of life, who tend to become ‘tolerant’ to the virus. Thus, more than 90% of infected infants, including the 5% who do not respond to HBV vaccination, become chronic carriers as compared to 6‐10% if the infection occurs after the 6th year of life. Chronically infected children are usually asymptomatic with normal or minimally abnormal liver function tests, but their liver histology often shows progressive inflammatory changes. Besides posing a serious infection risk to the community, chronically HBV infected children, particularly if male, have a high risk of progressing to cirrhosis and hepatocellular carcinoma, the likelihood of developing these complications being correlated to the length of time to achieve anti‐HBe seroconversion. Spontaneous HBeAg loss in chronically infected children occurs at an annual rate of 10‐16%, while spontaneous loss of HBsAg is as low as 0.6% per year, the children achieving earlier seroconversion being those with biochemical and/or histological evidence of active disease. Moreover, the annual HBsAg clearance rate is significantly higher in those children who are already anti‐HBe positive (= low viral load), than in those with HBeAg (= high viral load) (1.7% vs. 0.4%). A treatment able to speed up anti‐HBe serocoversion would therefore have a major impact in avoiding the spread of infection and serious complications. Interferon treatment does accelerate spontaneous HBeAg clearance. HBeAg loss has been shown in 30‐40% of Caucasoid children with chronic HBV infection at the end of short courses of IFN‐alpha or lymphoblastoid IFN, but in only 8% of Chinese children. Baseline features predicting HBe clearance during IFN treatment are the same as those associated with a higher rate of spontaneous seroconversion: histologically active disease, high transaminase activity and low HBV DNA levels. In contrast, children infected vertically, who have inactive liver histology, low transaminase values and high HBV DNA levels, and therefore also a low chance of spontaneous HBe clearance, show a poor response to IFN. Current guidelines advise not to treat children infected during the first year of life who have normal transaminase levels, high HBV DNA, mild changes on liver biopsy, particularly if of Oriental ethnicity, because the published results in these children do not justify the cost and the particularly demanding nature of IFN treatment. However, with HBV vaccination, horizontal HBV infection will become rarer, while infants infected because of vaccine failure, i.e. 5% of the vaccinated children overall but 15% of babies of HBeAg positive mothers, will represent an increasing proportion of the infected pool. A treatment strategy efficient in inducing HBV immune control in these ‘tolerant’ children is highly desirable. In HBV infected children, as in adults, lamivudine decreases HBV viral load, but when stopped a rebound of viral replication is observed. In a recent large multinational study comparing lamivudine with placebo in 286 HBV positive children with biochemically and histologically active liver disease, a significant reduction in HBV DNA level was observed at the end of 52 weeks in those treated with lamivudine compared to controls, but the proportion of patients who continued to be HBeAg and HBV DNA negative 6 months after stopping treatment was 17% among children who had been treated with lamivudine and 13% among those who had received placebo, suggesting that lamivudine on its own is not effective in accelerating HBV immune control in chronically infected children. In addition, prolonged treatment with lamivudine leads to a very high rate of YMDD mutations (over 60%). Combining the anti‐viral effect of lamivudine with the immune boosting action of IFN offers a rational therapeutic approach for children, particularly those who are less likely to respond to IFN alone due to infection at a very young age, who have normal transaminase levels, high HBV DNA and who are ‘tolerant’ to the virus. In a pilot study performed in our Unit, 23 ‘low responder’ children, all infected during the first year of life and HBsAg, HBeAg and HBV DNA positive, 15 of Oriental ethnicity, 21 with normal transaminase levels and 15 with HBV DNA > 1000pg/ml (Digene test) at baseline, were treated for 8 weeks with lamivudine (3 mg/Kg, maximum 100 mg daily), and then for 10 months with lamivudine (same dose) and Viraferon (5 Mu/m2 sub cutaneously three times per week). At the end of treatment 19 (82%) were HBV DNA negative, and 3 months later 5 (22%) continued to be HBV DNA negative. All 5 have seroconverted to anti‐HBe during a 6‐month follow up, and 4 (17%) have cleared HBsAg and become persistently anti‐HBs positive. Such a rate of anti‐HBs seroconversion (i.e. complete HBV control) is the highest observed in ‘low responder’ children over a period of 18 months and similar if not better than that observed within treatment trials of HBV infected children with active disease. In addition, none of our patients developed YMDD mutations, suggesting that lamivudine is more likely to induce these mutations in ‘non‐tolerant‘ patients or that IFN protects from lamivudine‐induced YMDD mutations.
In recent years pegylated interferon, a more child‐friendly drug requiring only one injection per week has become available. Large studies using pegylated IFN in tolerant children and in children with active disease are being pursued at the moment. Hepatitis C
End‐stage liver disease due to chronic hepatitis C virus (HCV) infection is currently the most frequent indication for liver transplantation in adult life, but unfortunately HCV infection recurs universally in the graft. Acute HCV infection has a high tendency to chronicity, and the risk of developing later complications like cirrhosis and/or hepatocellalur carcinoma is related to the length of infection. Thus, despite the declining incidence of new cases of HCV infection since the introduction of blood screening, the prevalence of cirrhosis and its complications will increase over the next 10 to 20 years. Although current treatment regimens eradicate HCV in over 50% of cases, many more patients would need to be treated to have a significant impact on disease progression. HCV infection occurs in children throughout the world, with variable prevalence data according to risk factors and geographic location. Children who have received multiple transfusions of blood products before 1992 have infection rates from 50 to 95%, while those with moderate transfusion exposure before 1992 have intermediate seroprevalence rates of 10‐20%. Studies in children without identifiable risk factors report seroprevalence rates ranging from 0% in Japan, Taiwan and Egypt, 0.2‐0.4% in the USA, 0.4% in Italy and 0.9% in Saudi Arabia to as high as 14.5% in Cameroon. Since the introduction of blood screening, virtually all new cases of HCV infection in children are due to vertical transmission. Though the risk of HCV transmission with pregnancy is low, on the order of 6%, the incidence of new infections in children through this route is substantial, given the prevalence of HCV infection in women of childbearing age that is approximately 1.2% in the USA and 0.8% in the UK. Acute HCV infection is rarely recognized in paediatric age. Most chronically infected children are asymptomatic, with normal or only mildly abnormal transaminases. The natural history of HCV infection in children appears to be relatively benign because it is rarely associated with severe or decompensated liver disease during childhood, but the infection persists for many years, causes chronic hepatic damage, and may be responsible for significant morbidity and mortality later in life. The histological features of chronic HCV infection in children, like in adults, are those of a relatively mild necrosis and inflammation, but the fibrotic changes tend to progress with increasing age and duration of infection. Moreover, chronically infected children become source of infection to others in adulthood. Hence, a treatment able to induce a sustained virological response (i.e. persistently negative HCV RNA by PCR) in childhood would be highly desirable, whatever the severity of the liver damage. Promising results have been obtained in a 48‐week treatment study with Viraferon and Ribavirin including 70 children with chronic hepatitis C and normal or minimally elevated transaminase levels, who were not expected to undergo spontaneous control of the viral infection during the trial observation period. A sustained viral response was observed in 68% of the 43 patients (61% of the overall cohort) who had received at least 80% of the prescribed dose of the treatment drugs for at least 38 weeks, but only in 19% of the 27 who did not, because of problems with compliance or side effects. Sustained viral response was observed in 38% of the patients with HCV genotype 1 and in 82% of patients with HCV genotypes 2 or 3. In an open‐labeled, uncontrolled pilot study, 62 children and adolescents (range, 2‐17 years) were treated with subcutaneous peginterferon alfa‐2b at a dose of 1.5 μg/kg body weight once per week plus oral ribavirin (15 mg/kg /day) for 48 weeks. Sixty‐one patients completed the study. Twenty‐three children discontinued therapy after 6 months according to study protocol. Sustained viral response was documented in 22 (47.8%) of 46 patients with genotype 1, in 13 (100%) of 13 with genotype 2 or 3, in 1 of 2 with genotype 4, in 19 (70.4%) of 27 children with parenteral, in 12 (48%) of 25 with vertical, and in 5 of 9 with unknown route of infection. Large studies using newer anti‐viral drugs with or without pegilated interferon are needed
Management of Malabsorption Syndromes in Pediatric Patients Fayez K. Ghishan, M.D. Professor and Head, Pediatrics Horace W. Steele Endowed Chair in Pediatric Research Director, Steele Children’s Research Center The University of Arizona Health Sciences Center Tucson, AZ This presentation will first discuss the physiology of digestion and absorption ofcarbohydrates, proteins, fats, and electrolytes. Next, the pathophysiology of malabsorption syndromes will be discussed. Followed by etiology of malabsorption syndromes and then the evaluation and presentation of malabsorption syndromes. Finally, the clinical management of malabsorption syndromes will be discussed. The discussion will evolve over the transport of monosaccharides, followed by the digestion of disaccharides and polysaccharides. The activity of brush border enzymes involved in the digestion of disaccharides will be discussed with emphasis on α‐ glucoamylase as a major enzyme responsible for the hydrolysis of glucose polymers and its high expression in the ileum which is protected in the setting of viral gastroenteritis. Next, the digestion and absorption of proteins will be discussed, with emphasis on the fact that dipeptides and tripeptides can be transported intact through the intestinal membranes. Fat digestion and absorption will then be discussed in relationship to the role of medium chain triglycerides as a source of fat, which is transported directly across the intestinal mucosa directly through the portal vein rather than through the lymphatics. Next, the transport of electrolytes across the gastrointestinal tract will be summarized as it relates to the individual transport proteins responsible for each of those electrolytes absorption in the intestinal tract including the colon. The pathophysiology of malabsorption will be discussed as it relates to the bacterial fermentation resulting in osmotically active compounds causing diarrhea with loss of nutrients. The end product of the bacterial fermentation is fatty acids which could increase cAMP, again resulting in diarrhea and failure to thrive. The etiology of malabsorption syndrome will be characterized based on luminal factors, mucosal factors, and transport defects. The initial evaluation and the comprehensive specified testing for malabsorption syndrome will be discussed. Multiple examples will be given in relationship to the etiology of chronic diarrhea causing malabsorption syndrome. The role of nutritional evaluation and their management will be discussed. Finally specific etiologies will be discussed in relationship to cystic fibrosis, celiac disease and intestinal bacterial overgrowth.
Celiac Disease – 2009 update Hisham Nazer, FRCP,DCH, FRCPCH President of PASPAGHAN Consultant Pediatric Gastroenterology Professor of Pediatrics Celiac disease is an immune­mediated chronic enteropathy of the small intestine caused by a permanent sensitivity to gluten in genetically susceptible individual. It has been well recognized that celiac disease (CD) has a strong hereditary component with reported prevalence in the first‐
degree relatives of about 10%.. Celiac disease is one of the most frequent genetic disorders of mankind , affecting 0.5% to 1% of the general population .This is even more important in a community like ours where a high rate of consanguineous marriages prevail. The purpose of this presentation is to highlight the various manifestations of Celiac disease in childhood and to discuss the difficulties that may arise in reaching a definite diagnosis that warrants keeping the child on gluten free diet (GFD) for life. CD is considered nowadays a disorder with multi system involvement. CD is no longer a disease of early childhood but also a disease of adolescents and adults. The majority of children with CD presents usually at an older age with insidious, non‐specific and milder gastrointestinal symptoms than seen in the past.. The optimal serologic tests for a definitive diagnosis of CD remains controversial. A substantial proportion (15%) of patients with true CD are endomyseal antibodies negative . Such report could well minimize the value of EMA as a screening test. Moreover Serum IgA tissue transglutaminase could not replace the needs for Intestinal biopsies to confirm diagnosis of CD. It must also be recognized that Children with CD may have a patchy villous atrophy of the duodenum. Moreover in latent CD the jejunal mucosa is normal while the child receives normal diet in contrast to silent CD where the affected child is usually asymptomatic but the intestinal mucosa is flat and reverts to normal on GFD, At present there is a universal agreement that The diagnosis of CD is considered definitive when there is complete symptom resolution after treatment with a strict GFD in a previously symptomatic individual with characteristic histological changes on small intestinal biopsy The call for mass Screening program for the asymptomatic is still controversial and considered as being "Not cost effective". Treatable Celiac Disease remains largely undiagnosed. Greater levels of Awareness and attention on gluten intolerance are needed Much research remains to be done to further refine our understanding of CD and to devise more effective strategies for diagnosis,treatment, compliance and prevention of long term complications The pattern of chronic liver diseases in Sudanese children Omayma Sabir Background: Chronic liver diseases in Sudanese children are significant problem; the etiology of which has never been determined before. Aim: to determine the pattern, clinical presentation and etiology of chronic liver diseases in children presenting to Jaffar Ibn Auf Specialized Children Hospital in Khartoum, Sudan. Subjects & Methods: Prospective study of all children below 16 yrs of age who presented to the gastro unit of JIA hospital with chronic liver disease Between Jan 2005 and Jan 2009. Results: 400 children were seen during the specified period. All of them were fully investigated and underwent a liver biopsy and clinical data was recorded. Age ranges from 6 months to 15.9 yrs and male: female ratio was 2:1. In infancy neonatal hepatitis was the commonest pathology, but biliary atresia was fairly common and tend to be diagnosed quite late. High incidence of familial hepatic disease was noted particularly in the older age group and to our surprise hepatocellular carcinoma was diagnosed in many patients. Conclusion: Chronic liver problems are prevalent and constitute a significant health problem in Sudan. Late diagnosis and referral was evident and can be explained by lack of awareness among the health personnel and the public and lack of diagnostic facilities outside Khartoum, the capital of the country. Non‐specific liver cirrhosis of unknown etiology was noted and could be a new entity or as a sequel to chronic malnutrition and infections which are prevalent in Sudan. The high incidence of liver cancer among children is alarming and immediate attention and full investigation. Keywords: hepatitis, malnutrition, obstructive jaundice.
Autoimmune Hepatitis in Children
Badriya Al Alawar
Dubai‐ UAE Autoimmune liver disorders are inflammatory liver diseases characterized histologically by a dense mononuclear cell infiltrate in the portal tract and serologically by the presence of non‐organ and liver‐specific autoantibodies and increased levels of immunoglobulin G (IgG), all in the absence of a known etiology. These disorders usually respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. The onset of these conditions is often ill defined, and they frequently mimic acute hepatitis; the previously accepted requirement of 6 months duration of symptoms before a diagnosis of autoimmune disease can be made has been abandoned. Acute Necrotizing Pancreatitis Dr.Buthaina Al Murbati Specialist Senior Registrar
Dubai Hospital­ Dubai­UAE Abstract: Acute pancreatitis is rare disease in paediatric age group, usually has a rapid onset manifested by upper abdominal pain, vomiting, fever, tachycardia, leukocytosis, and elevated serum levels of pancreatic enzymes. Pancreatic necrosis represents a severe form of acute Pancreatitis, it is characterized by well‐marginated zones of non‐enhancing parenchyma larger than 3 cm or involving more than 30% of the pancreas by contrast enhanced CT scan. It occurs in <1% of children compared to <5% in adults. Contrast‐ enhanced abdominal CT is the gold standard for the non‐invasive diagnosis of pancreatic necrosis. Aggressive medical care with antibiotics is the mainstay of management, with surgery or other types of pancreatic debridement limited to patients with infected necrosis. We report a case of an 8y old female child who had acute necrotizing Pancreatitis 4weeks after chicken pox infection.
Gastroesophageal Reflux Disease in Childhood Diagnosis and Management Issam Halabi, MD, FAAP
Professor and Chief , Pediatric gastroenterology University of Illinois
Gastroesophageal reflux disease is a very common condition that affects infants and young children. It is more common in early childhood because of weak gastroesophageal sphincter, small gastric volume and predominantly supine position. Spitting up is the most common presentation. Distinction has to be made between reflux and reflux disease. A good history and physical exam are adequate to establish the diagnosis. Diagnostic tests are only needed in certain situations. This includes irritability, cough, aspiration and vomiting not responding to reflux treatment. Diagnostic tools include: PH probe, Impedance, UGI and endoscopy. Treatment includes diet modification, pharmaceutical agents and surgical. Most cases are treated with simple means. Surgery is rarely needed.
Title: Obesity and Risk Factors of Jordanian Adolescents in Greater Amman
Principal investigator, Dr. Sa'ad Hijazi, Professor of Child Health and Nutrition. Formerly: President of the Royal Scientific Society (on a sabbatical leave from Jordan University of Science & Technology (JUST)), when he was President of the JUST.
Co­investigators:
Abstract ‐Dr. Ahmad M. Faqih, Professor of Nutrition, University of Jordan. ‐Dr. Samir Naji: Medical Biochemist, Islamic Hospital, Amman. The following study aimed at evaluating the nutritional and health status of a sample of Jordanian adolescents between the ages of 10‐17 residing in Amman Prevalence of obesity, under‐ nutrition, and hypertension were examined. Profiles of growth patterns, blood cholesterol, blood pressure, and lipid profile of the adolescents were measured as well. A stratified two‐stage cluster sampling design was applied , Amman Municipality was divided into six strata groups. Two types of schools were Employed, being private, and public schools in Amman, Jordan. The sample size comprised of 3246 male and female adolescents.Height, weight, waist circumference, and blood pressure were measured. A Socioeconomic on family status was applied. In addition to that, sub samples of 400 adolescents were used in this study. The average prevalence of underweight for the total sample was 10.7% with as apparent lower prevalence of 8.3% in the youngest group aged 10 to 11years. The average prevalence of overweight and obesity in the total sample was 12.9% and 7.6%, respectively. Thus, the total prevalence of malnutrition (underweight, overweight, and obesity) in adolescents of greater Amman is 31.2% and only about two‐thirds (68.9%) have healthy body weight. Compared to adolescent girls (7.3%), prevalence of underweight among adolescent boys (14.8%) was twice as much. Although, there was an apparent higher prevalence of overweight among adolescent girls (14.6%), only 10.7 of the boys had overweight. Gender, however, did not affect the rate of obesity; 7.9% of boys were obese as compared to 7.3% of girls who were obese. Breast–Milk and Gastro‐intestinal Health Dr. Salah Shoheib Prof. of Pediatrics, Tanta Faculty of Medicine, Tanta (Egypt) Breast –milk is an essential nutritional material that provides: nutrition, protection against infection, and establish psychological make‐up of the new born. Moreover, it protects against several chronic disease as: type I diabetes celiac disease and inflammatory bowel disease. It also accelerates the development of G.I. epithelial barrier to antigen absorption. This may be accelerated by the epidermal growth factors which protect against gut mucosal injury after birth. The presentation will focus on the interplay between breast milk and the most common gastrointestinal diseases. IS INTESTINAL IMMUNITY IMPORTANT FOR HEALTHY CHILDREN
Principal investigator,
Dr AZIZ KOLEILAT
Makassed University General HOSPITAL Pediatric Department, BEIRUT‐LEBANON
Background: •
The fact that the era of antibiotics is from last century the purpose of medicine is to improve defense (immunity) to fight infection and prevent inflammation ABSTRACT
• The newborn comes out sterile and has a more or less complete, but tiny immune system. •
Leaving the germ‐free, intrauterine environment to enter a highly contaminated extra uterine world requires strong host defenses to prevent acquisition of gastrointestinal and systemic diseases. • Its microbial flora is acquired from his mother or environment depending on the way of delivery, which is a necessary component of normal life? • The normal micro flora on various mucosal membranes plays an important role in the defence against potential pathogens. • It stimulates the infant’s immune system to respond with specific immunological tolerance, avoiding the development of allergic, inflammatory and autoimmune diseases. •
The intestinal defenses develop during gestation and at full‐term have the capacity to respond in an appropriate manner to infectious agents and foreign antigens.(Bacteria, viruses, food, parasites ) • The importance of the gastrointestinal tract, which is the largest lymphoid organ in the human body, with its balance microbial flora on fighting infection and preventing atopy and inflammation is crucial for a healthy growing child. •
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Additional stimuli occur with the introduction of enteric feeding (breast‐milk vs. formula) and at weaning. Complete colonization with a large variety of diverse organisms occurs by two years of age(adult flora non changeable ) The intestinal microbial stimuli to the intestine are necessary for such for gut defenses and balanced T helper cell response. (the immune modulation process) Protection is done by immunological and non immunological approach.. The increased incidence of atopic and autoimmune disease during the last decades has occurred in developed countries as infectious diseases have been eradicated due to better hygiene and vaccinations. • The “hygiene hypothesis” ,the family of pattern recognition receptors, toll‐like receptors, the bacterial communication with the gut (bacterial‐epithelial crosstalk) can mediate the innate immune responses(new fields of studies ) Conclusion. The development of appropriate and adequate immune competence as a result of contact with microbes might be essential not only in establishing a non atopic immune responder phenotype but also in protection againstinflammation & infectious and autoimmune disease. Also There are many ways to modulate gut‐immune responses, e.g. use of probiotics, breast feeding ,functional food to prevent the expression of these gastrointestinal diseases
New severe malnutrition management protocol application in Syrian hospitals Dr Mahmoud Bozo­ Damascus Hospital . General secretary of the Syrian society of pediatric gastro ­ enterology and nutrition mahbozo@scs­net.org The WHO protocol was applied in Syria since 2001 , it was started started in Damascus Hospital and enlarged to some limited number of centers , in 2003 ( e.g. Aleppo , Latakia ) In 2007 , Damascus Hospital in cooperation with the Syrian society of pediatruic gastroenterology and Nutrition applied the first national training program for hospital pediatricians from : Daraa , Swedah , Homs , Hamma ,Kooneterah , Aleppo , Dair Al Zor , Hasakah , Rakkah , Kameshli , latakia , Tartous , Idlib , Doomah . the protocol was applied in all this cities during 2008 , and the results were collected at the beginning of 2009 to be analyzed . results : 265 Patients were treated for severe malnutrition in different cities , ( 82 hasakah , 48 Idlib , 42 Aleppo , 19 Damascus , 25 Dair Al Zor , 30 Kameshli , 4 Hamah , 9Homs , 6 Doomah . The mortality rate was variable between different cities : 5 % Damascus , 4% Dair Al Zor, 6 % Idlib, 40 %Homs , 16 % Doomah , 0 % Hammah , 43 %Aleppo , 14 % Kameshli , 20 % Hasakah. The cure rate was different from city to city ( from survival patients ) : 94.7 % Damascus , 52% Dair Al Zor, 56 % Idlib, 80 %Homs , Doomah 86 % , Hammah 50 % , Aleppo 16 % , Kameshli 23 % , Hasakah 12.5 % . Hospitalization duration : calculated only in Damascus Hopsital , the mean duration is 16 days , the limits are 10‐60 days , the long duration ( 3 cases ) is secondary to the complications : tuberculosis , immune deficiency . The anti Tuberculosis treatment is limited in 7 % of cases . The gain weight : < 5 g/kg / day in 5 % of cases , 5‐10 / kg / day in 16.5% , > 10 g/kg / day in 78.5 % The following cities did not send results : Daraa , Tartous , Kooneterah , Rakkah . Conclusion: The application of the New severe malnutrition management protocol proved verifiable results from center to center regarding the different criteria , a quality control of the application is recommended to improve the results . Maha Abou­Zekri, MD Consultant Pediatrician,
Cairo University Children’s Hospitals Patients with IBD are at significant nutritional risk. It is estimated that from 60% ‐75% of patients with Crohn’s disease experience malnutrition. Both Crohn’s disease and UC have dramatic effect on nutritional status and often require nutritional support during periods of exacerbation. Symptoms of UC and Crohn’s usually involve diarrhea and abdominal pain which affect normal digestion and absorption, resulting malabsorption of all the nutrients and PEM. Many patients electively restrict eating to minimize symptoms. Nutritional therapy not only required for nutritional support, but may also implicated in treatment of the disease process and to minimize symptoms.
MANAGEMENT OF PROTEIN ENERGY MALNUTRITION Mahmoud El­Mougi Paediatric department Alazhar Faculty of Medicine, Cairo, Egypt The main line of management is dietary and in severe cases this usually needs hospitalisation. Patients: We treated 50 children with severe PEM (wt for length < 75% of reference) 6 of them were oedematous. Diarrhoea was present in 33 of them but the duration of diarrhoea did not reach 14 days. All patients were aged 3‐36 months. Methods: After initial stabilisation and control of any accompanying condition e.g.dehydration, hypothermia, a starter formula (F75) was used: yoghurt 30ml, sucrose 10g, oil 2ml and water to 100ml. This started as soon as possible after admission by NGT and dose was 130ml/kg (100 ml if oedematous) and divided into 12 feeds in first 2 days then divided into 6‐8 feeds/24h. Half strength in the first 2 days then increased gradually to full strength in the 5th day. After 7 days the formula was replaced by catch‐up formula: yoghurt 88ml, sucrose 7.5ml, oil 2ml and water to 100ml dose was 130ml/kg. .All patients received ampicillin and gentamicin IM. Close monitoring included pulse, respiratory rate, intake, vomiting, stools frequency and consistency and weight progress. Results: after 7 days mean weight gain was 10.4%+4.7 diarrhoea disappeared in majority but some had loose poorly formed stools that did not interfere with adequate weight gain. Oedema disappeared within 4 days. The need for NGT persisted after 7 days in only 9 cases who needed NGT for further 3‐5 days. Complicating fatal pneumonia developed in the second week in one oedematous child. All others recovered and discharged to home gaining weight. Conclusion: This protocol of management appears suitable for severe PEM. Cautious refeeding is key element to avoid heart failure and re‐feeding sydrome which may be fatal. Patients with associated persistent diarrhoea may need low or free lactose formulas. Follow up of recovered cases is recommended to avoid recurrence and or complication and for social support. Enteral Feeding in childhood Crohn's disease Principal investigator: Professor Ian Sanderson Centre for Gastroenterology, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London Enteral nutrition is now the primary therapy in the United Kingdom, and in many other countries, for children with active Crohn's disease. Clinical trials have compared it efficacy to high dose corticosteroids in both children and adults. Studies in children have shown that entering remission with a diet is not significantly less likely than with high dose steroids. The effect of enteral feeding on the intestine directly has also been examined, by intestinal permeability, by tissue cytokine profiles and by endoscopic and histological assessment. Four lines of evidence support the hypothesis that enteral formulas directly lessen inflammation: (1) enteral nutrition directly affects the inflamed intestine; (2) changes in inflammatory markers precede repletion of nutrition status; (3) molecular pathways exist linking changes in luminal contents to the expression of class II MHC genes in intestinal epithelium in animal studies; (4) and enteral formulas have a direct effect on cytokine expression by intestinal epithelial cells. In addition, enteral nutrition has a positive effect on growth, whereas corticosteroids inhibit growth when height velocity is measured 6 months after the start of treatment. The question arises therefore as to whether this benefit for growth is due only to improved nutrition. Enteral formulas directly reduce inflammation, lowering the expression of cytokines like interleukin (IL)‐6 that inhibit growth. The role of IL‐6 in growth impairment has been examined in a rat model of intestinal inflammation; where giving an anti‐IL6 antibody enhanced growth. Humans have a single nucleotide polymorphism (SNP) in the promoter of the IL‐6 gene, which affects IL‐6 production. Those children that have the polymorphism associated with greater IL‐6, are the ones who grow poorly. Neonatal Cholestasis in 2009 Issam Halabi, MD, FAAP
Professor and Chief , Pediatric gastroenterology University of Illinois
Neonatal cholestasis is a very common condition that neonatologists and pediatricians have to approach in their practice. The causes range from simple self limiting to serious that may require liver transplantation. Biliary atresia is the most serious cause. Recognition of this condition at earlier age leads to better outcome. Surgical shunting is the mainstay of treatment. However liver transplantation may be needed particularly with late diagnosis. Alpha one antitrypsin deficiency is an inherited disorder that involves a defective gene responsible for the production of anti oxidant protein. Such deficiency can lead to significant liver disease. Bile acid metabolic disorders are recently described group of disorders that involves the production of bile acids which are essential in the process of bile excretion. Genetic defect of bile acid transporters within the hepatocytes can also lead to cholestasis. Total parenteral nutrition is a well recognized predisposing factor for neonatal cholestasis. Title: Neonatal Cholestasis. Principal investigator: Nahla khayyat.
Institution: Children Hospital ; Damascus University. Background: To view importance of cholestasis. ‐ The most common causes . ‐ The available diagnostic tools" blind liver biopsy " and the role of surgical study for two years : Retrograde diagnosis and reatment " surgical biopsy ".Methods:
It included the children that were diagnosed as cholestasis or one of .( ( 138 infant
common causes and then view the clinical ,lab radiological and histological studies and some specific investigation . The role of surgery and surgical liver biopsy in the confirmation of diagnosis .
Results & Analysis: *The common causes of neonatal cholestasis : ­ Biliary atrasia 42,8 % (liver biopsy) ­ Neonatal hepatitis 10 % (liver biopsy) ­ Galactosemia 10 % (clinical , lab , liver biopsy ) ­ Tyrosenemia 2 % ( Amino acid electrophoresis ) * Blind liver biopsy has important role in the final diagnosis because Result of blind liver biopsy agree with macroscopic and with surgical biopsy in 90 % . Conclusion ; The rapid evaluation ,study and blind liver biopsy is very essential to decide either medical treatment or surgical procedure . Biliary Atresia : Management pre & post operative Cholangiogram and Kasai Dr. Ahmad Al Soufi What blood investigations & nutrition one day pre‐op.? Including all necessary practical procedures!!! What antibiotics ?gentamycin once daily and amoxicillin .to be followed by a long term prophylaxis Antibiotic. Start methyl prednisolon on day 1 ,decreasing gradually. Also about nutritional management, before and after cholangiogram &Kasai. All children undergoing investigations of conjugated hyperbilirubinemia should commence Fat soluble Vitamins,(A.D.E.) For how long we go on with =baby with successful Kasai ? = baby with unsuccessful Kasai and remain jaundiced? The objective of the presentation is to diagnose such cases as early as possible and to give a simple guide line how to manage before and after Cholangiogram and Kasai Title : Biliary atresia : work towards improving outcome . Investigator : Dr Mohamed Anas Barakat . Institution : The Syrian association of pediatric gastro­enterology, Hepatology and nutrition. Background : Biliary atresia still a major cause of morbidity and mortality among other causes of Cholestasis . Early diagnosis and good management are essential for better outcome . Abstract : This paper will focus on the prognosis of biliary atresia . An overview of what havebb been published on this topic in Arabic countries were compared with the experience Of Damascus children 's hospital 1‐ All studies demonstrate a long delay before referring patients to an experienced team . This correlates with the experience of Damascus children hospital since the median age of referral is 50 days , All children diagnosed with biliary atresia (52) patients had clinical signs of jaundice, acholic stool and dark urine colour. 2‐ There were a long delay before performing Kasai operation , this is consistent with other research papers in Arabic countries , 25 patients out of 40 were operated after three months of age , failing to catch the perfect window of opportunity for better prognosis. 3‐ 3‐ Prognosis is related directly to early diagnosis and good management ; associated malformations may contribute to the final prognosis , depending on the type of malformations . these malformations were noted in6 cases /52 . 3 cases : cardiac malformations,1 case: polyspleenia and 2 cases :.polycystic kidney with hydronephrosis. 4‐ Liver transplantations are not performed in Syria . This procedure needs cooperation between Arabic countries, highly expensive, and considered the ultimate procedure to save the life of these patient before clinical deterioration . conclusion : The need for a better strategy to refer these patients as early as possible to an experienced team. These strategy may be emphasized by spreading information about the ultimate time to refer patients , early investigation , and putting much more stress on the clinical symptoms especially acholic stool associated with jaundice and the need to clarify the cause of every jaundice that last for more than tow weeks . Title of the abstract: Celiac Disease: Approach and Management
Principal investigator: ABDEL HAI HAMMO, MD Institution: Assistant Professor, Tufts University, Chief of Pediatrics, Brockton Hospital, MA Director, Pediatric GI. Background: Celiac disease (also known as gluten‐sensitive enteropathy or non tropical sprue) is an immune‐mediated inflammation of the small intestine caused by sensitivity to dietary gluten and related proteins in genetically sensitive individuals. The disorder is common, occurring in 0.5 to 1 percent of the general population in most countries. The cause of celiac disease was unexplained until the Dutch pediatrician Willem K Dicke recognized an association between the consumption of bread and cereals and relapsing diarrhea. The primary findings were mucosal inflammation, crypt hyperplasia, and villous atrophy. Celiac disease was defined by a set of classic clinical manifestations. However, the combination of serologic, genetic, and histologic data has led to an appreciation of the highly variable clinical manifestations of the condition and the description of other categories of celiac disease, (Classic disease, Atypical disease, Silent/subclinical celiac disease, and Latent/potential disease). Celiac disease presented between 6 and 24 months of age, after the introduction of gluten into the diet. The children have chronic diarrhea, anorexia, abdominal distension and pain, and failure to thrive or weight loss. The diagnosis of celiac disease typically requires both of the following: The presence of characteristic histologic changes on small intestinal biopsy in a symptomatic individual and complete symptom resolution on a gluten free diet. Conclusions. Treatment with a gluten‐free diet is recommended for both diagnostic and therapeutic purposes for all children. Treatment of the patient with celiac disease begins with dietary counseling. Other issues that need to be considered include addressing nutritional needs (including the prevention of bone loss), monitoring of the response, and evaluating patients who do not respond Investigator Dr Hassan Zainaldeen Institution Salmaniya Medical Centre – Kingdom Of BahraiN Background A three months old Yemeni infant admitted to our pediatric department with history of recurrent vomiting and failure to thrive since birth. On examination he was emaciated, pale with sparse hair and distended abdomen. On deep palpation he had enlarged soft liver 4 cm below costal margin. Differential diagnosis were GERD, cows milk protein intolerance, cystic fibrosis, immune deficiency and inborn of metabolism. Objective: to have a simple stepwise approach to reach to a confirmed diagnosis. Method of investigation: Investigations include full blood count and urea /creatinine / electrolyte. Liver function tests, coagulation study and ammonia. Stool microscopy and urine culture. The patient had barium meal prior to his referral to our department which was suggestive of severe GERD. Our investigations showed increased ALT 110 U/L and increased ammonia113 micromoles/L.The above findings were suggestive of inborn error of metabolism with main concern of Wolman disease. The peripheral smear showed marked acanthocytosis, so upper gastrointestinal endoscopy done which confirmed a diagnosis of abetalipoproteiemia Conclusion: a simple diagnostic approach with patience and team effort most of the time can solve the complicated dilemma. Neonatal Hemochromatosis: Case series from Bahrain. Principal investigator: Dr.Hasan Mohammed Ali Isa, pediatric gastroenterologist, Sulaimaniya Medical Complex, Manama, Kingdom of Bahrain. Background: Neonatal hemochromatosis (NH) originally was described in 1957, and >100 cases have been reported. NH may be one of the most common causes of liver failure. Its' cause is not clear, and it has an aggressive course and carries a poor prognosis. Objectives of the research: To raise awareness about neonatal hemochromatosis as a possible cause of cholestasis and liver failure in newborns. Subjects and methods of investigation: Here we are reporting five cases of neonatal hemochromatosis diagnosed over the last 12 months. The diagnosis of NH was based on serum iron, serum ferritin, alpha fetoprotein levels, liver and buccal biopsies and abdominal MRI scan. The patients were treated with an antioxidant cocktail therapy. Patients' outcomes were assessed. Results & Analysis: All five patients had high ferritin levels. Serum iron and Alpha fetoprotein levels were very high in the four tested patients. Liver biopsy was done for one patient and autopsies were done for two. Buccal biopsies were performed in all patients but unfortunately only one was positive for iron. Abdominal MRI scan was done for three patients who revealed evidence of NH. Four patients received antioxidant therapy as per protocol. Three patients survived and two passed away. Conclusions: Although it is rare, NH may be one of the most common causes of liver failure in the newborn. Diagnosis generally is made after other causes of neonatal liver failure are excluded. An elevated serum ferritin will help to confirm the diagnosis. NH is nearly universally fatal, and experience with treatment is limited because many die before diagnosis. Foreign Body Ingestion in Children Gilger, Mark A. Baylor College of Medicine Texas Children’s Hospital, Houston, Texas Infants put everything in their mouths & toddlers eat anything. It’s no wonder that 80% of all foreign body (FB) ingestions occur in children between 6 months to 6 years of age. An exception is children with developmental delay or psychiatric disorders who can have multiple or recurrent ingestions. The most common foreign body ingested in the U.S. is a coin, followed by batteries, toys, buttons & button batteries, crayons, ball‐point pen caps and food, especially meat, or anything else that fits into the mouth!
Most foreign bodies pass spontaneously. About 10 to 20% require removal and < 1% require surgery. Most foreign bodies are uncomplicated, but mortality has been reported, especially with sharps, such as straight and safety pins, which have a higher perforation risk.
Most ingestions are observed and asymptomatic. Symptoms of foreign body ingestion include dysphagia, drooling & feeding refusal. Odynophagia suggests a “sharp” FB ingestion. Signs such as stridor, wheezing, choking & respiratory distress suggest tracheal compression.
Evaluation should include assessment of airway and breathing, swelling & crepitus in the neck, stridor & wheezing on chest auscultation and tenderness & bowel sounds of the abdomen. A plain x ray of neck, chest and abdomen should include anterior – posterior projection and a lateral. Contrast radiograph is done if the FB is suspected but not seen. Management is urgent if there is a sharp FB, a disc battery in the esophagus, airway compromise (tracheal compression) or risk of aspiration (e.g., food bolus). Otherwise, observation up to 24 hr is justified if the child is asymptomatic. Flexible endoscopy is recommended in most cases because it allows visualization for possible cause (e.g. stricture), assessment of mucosal injury (e.g. unknown duration of ingestion) and provides control of FB during extraction.
This lecture will review FB ingestions in children and focus on techniques for safe Capsule Endoscopy Use in childhood: Experience and Benefits Issam Halabi, MD, FAAP
Professor and Chief , Pediatric gastroenterology University of Illinois Capsule endoscopy (CI) is a new diagnostic tool that aided pediatric gastroenterologists in their pursuit of gastrointestinal diseases identification. Since inception in 2002 more conditions were diagnosed using capsule endoscopies. The most frequent indications for CI include: GI bleeding, Crohn’s Disease, small intestinal tumors and Celiac disease. The technology behind this tool will be discussed. There are two generations so far. The main difference is in the angle of visualization. The contraindications for the use of this study include GI obstruction, cardiac implants and swallowing disorders. A patency capsule can be used prior to CI to detect any potential obstruction. A review of published pediatric and adult reports will be discussed for each indication. Conclusion: The CI is an efficient, patient friendly, and clinically‐proven diagnostic solution that provides visualization of the GI tract in its natural state. Multiple studies have demonstrated the significant role of capsule endoscopy in the evaluation of small intestinal disorders. CI indications continue to expand.
Title: Malnutrition in children: Failure to thrive and Obesity Principal investigator: ABDEL HAI HAMMO, MD Institution . Assistant Professor, Tufts University, Chief of Pediatrics, Brockton Hospital, MA Director, Pediatric GI. Background: The World Health Organization defines malnutrition as "the cellular imbalance between supply of nutrients and energy and the body's demand for them to ensure growth, maintenance, and specific functions." Malnutrition is globally the most important risk factor for illness and death, contributing to more than half of deaths in children worldwide. Malnutrition affects virtually every organ system. Balanced Diet is needed to provide amino acids for synthesis of body proteins, fatty acids, and carbohydrates and other compounds that have a variety of functional roles
Growth failure, or failure to thrive (FTT), is a descriptive term and not a specific diagnosis. This term is widely used to describe inadequate growth in early childhood. However, obesity is the most prevalent nutritional disorder among children and adolescents in the United States. Currently available data report that approximately 40% of children in the United States are either overweight or obese; the prevalence of obesity is highest among specific ethnic groups. Childhood obesity predisposes to insulin resistance and type 2 diabetes, hypertension, hyperlipidemia, liver and renal disease, and reproductive dysfunction. It also increases the risk of adult obesity and cardiovascular disease. Conclusions. Overweight and FTT are one of the most common chronic diseases in children, associated with an increased risk for morbidity and mortality. Calculation of nutritional requirements is problematic and challenging due to difficulty in measuring body composition and energy expenditure. Children with FTT need continued follow‐up care to observe their growth parameters using the appropriate growth charts. Provision of selective hypocaloric feeding in the overweight population may be particularly beneficial in reducing complications of hyperglycemia, fluid overload, and reduction in fat mass. Clinical care should incorporate a team approach that addresses the special nutritional and metabolic needs of those populations
Cystic fibrosis­ associated Liver Disease AS Najada*, M Dahabreh, A Ghanma, R Hijazeen Objectives: To study the prevalence, clinical features, degree of liver involvement and the course in cystic fibrosis patients, and compare with others Patients and Methods: Chart review of all patients with cystic fibrosis followed at both the respiratory and hepatology clinic at King Hussein Medical Center between January 2002‐ January 2008 was done. Children between day 1 till 14 years of age were included. All patients with cystic fibrosis‐related liver disease were identified based on: clinical hepatomegally, abnormal liver biochemistry,or abnormal ultrasonographic changes. Liver biopsy result when performed was shown as well. Results: Thirty patients with cystic fibrosis‐related liver disease from the total of 72 cystic fibrosis patients (42%) were identified. There were 21(70%) males and 4 (30%) females. Two newborns (7%) presented with direct hyperbilirubinemia and hepatosplenomegaly that persisted into childhood. Seven (30%) manifested in infancy while 30% were between 2‐10 years old and 27% were older than 10 years. One child had a fulminant liver failure with pseudomonas chest infection and died at the age of 4 years. Asymptomatic liver involvement was seen in 14 children (47%). Clinical hepatosplenomegaly was seen in 16 children (53%). Two children had liver cirrhosis with esophageal varices at the age of 9 and 10 years respectively. Liver ultrasound findings were: hepatomegaly and increased echogenecity in 33%, coarse in‐homogeneous liver in 13% and fatty liver in 7%. Liver biopsy was performed in 4 patients: 2 results were focal fibrosis of the liver, one showed peripheral fibrosis and the 4th manifested mild cholestasis &steatosis with no focal lesions. Conclusion: The prevalence of liver disease in our CF patients is higher than others. Identification and treatment of cystic fibrosis‐related liver disease can be a challenge. Earlier presentation in our population requires established protocols for early identification and thus intervention. Glycogen storage disease type III among Palestinian Children; a report of 24 cases Imad Dweikat MD, Inas Naser MD, Adeeb Naser Eddin MD Principal investigator: Imad Dweikat MD Pediatric Department, Metabolic unit, Makassed Hospital, Jerusalem, Palestine Background: Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency of glycogen debranching enzyme, amylo‐1,6‐glucosidase which results in incomplete degradation of glycogen molecule. This enzyme is critical in both liver and muscle tissues. Deficiency of the enzyme in both tissues produces a variant known as GSD IIIa which can involve skeletal and cardiac muscles. Another less common variant known as GSD IIIb is caused by a deficiency of the enzyme in the liver only and is not associated with muscle involvement.
Objectives: To discuss the characteristic clinical and laboratory findings that should alert the physicians for the diagnosis of the disease and its management.
Methods: Retrospective study of 24 confirmed cases of GSDIII. The study was approved by the local ethics committee.
Subjects: 24 patients (14 males, 10 females) belonging to 18 families whom were diagnosed at Makassed Islamic Charitable Hospital between1994‐2008. Parental consent was taken.
Results and analysis: The mean age at diagnosis was 22 months. 18 children were born to consanguineous parents and most cases were from Bethlehem area.
All cases had abdominal distension and hepatomegaly. Growth retardation was common. Elevated liver enzymes and hyperlipidemia were present in all cases and fasting hypoglycemia in 75%.
Conclusion: Glycogen Storage Disease type III is relatively common among Palestinian children because of high rates of consanguineous marriages. It should be suspected in children presenting with abdominal distension, hepatomegaly, elevated liver enzymes, hypoglycemia and hyperlipidemia. Title : Profile of Admission of children under five years of age admitted with diarrhea and dehydration­ Hospital based study.
Principal investigator Dr. Aida Ali Al Maktari Al Kuwaiti Hospital , Sanna , Yemen. Background: Diarrheal Diseases and nutritional disorders are very common among children in Yemen . No previous studies were performed to address this issue. Objectives : 1‐ To describe cases of diarrhea and dehydration admitted to Alkuwaiti Hospital. 2‐
To study the effect of social status on outcome of dehydration . Subjects: 219 Children with diarrhea and dehydration were admitted over the study period . Results : 219 children were admitted to paediatric department at Alkuwait hospital during the years 2002‐
2004
They were 134 males (61.2%) and 85 females (38.8%) . Patients were grouped into three groups‐
age dependent : first group: <6 months , second group : 6‐12 months, third group >12 month of age.. The means age was 8.5 months ranging between 1‐42 months . 51.6% of cases were in second group (6‐12 months) . 139 patient(63.5%) had low weight in relating to age according to WHO growth chart . Dehydration was severe in 125 (57.1%) and moderate in 94 cases (4.2%). Hb level were reported in 196 children, the mean Hb was 9.8 . 146 children were anaemic with Hb value below 11u/di 190cases were discharged home in a fairly god condition, 5 cases had a complicated course and 24 died in the hospital .. Sodium was checked in 143 cases (65.3%) of total cases, 74% of them had normal sodium level, 20% had hyponatremia. NO significant association was found between Levels of sodium and potassium and the outcome . Discussion : In accordance with other studies, our study showed that children under 12 months of age are more likely to develop diarrhea resulting in dehydration than other groups of ages . Most cases were admitted with severe dehydration (57.1%) . Nutritional status was also an important factor in developing dehydration diarrhoea in our study those with weight <80% of expected weight for age were 71.7% more likely to develop dehydration than those with >80% expected weight for age. This is explained by socio‐economic status of the Yemeni community . N0 significant association was found between the level of Na, K+ and outcome. Title of the abstract: Celiac Disease: Approach and Management
Principal investigator: ABDEL HAI HAMMO, MD Institution: Assistant Professor, Tufts University, Chief of Pediatrics, Brockton Hospital, MA Director, Pediatric GI. Background: Celiac disease (also known as gluten‐sensitive enteropathy or non tropical sprue) is an immune‐mediated inflammation of the small intestine caused by sensitivity to dietary gluten and related proteins in genetically sensitive individuals. The disorder is common, occurring in 0.5 to 1 percent of the general population in most countries. The cause of celiac disease was unexplained until the Dutch pediatrician Willem K Dicke recognized an association between the consumption of bread and cereals and relapsing diarrhea. The primary findings were mucosal inflammation, crypt hyperplasia, and villous atrophy. Celiac disease was defined by a set of classic clinical manifestations. However, the combination of serologic, genetic, and histologic data has led to an appreciation of the highly variable clinical manifestations of the condition and the description of other categories of celiac disease, (Classic disease, Atypical disease, Silent/subclinical celiac disease, and Latent/potential disease). Celiac disease presented between 6 and 24 months of age, after the introduction of gluten into the diet. The children have chronic diarrhea, anorexia, abdominal distension and pain, and failure to thrive or weight loss. The diagnosis of celiac disease typically requires both of the following: The presence of characteristic histologic changes on small intestinal biopsy in a symptomatic individual and complete symptom resolution on a gluten free diet. Conclusions. Treatment with a gluten‐free diet is recommended for both diagnostic and therapeutic purposes for all children. Treatment of the patient with celiac disease begins with dietary counseling. Other issues that need to be considered include addressing nutritional needs (including the prevention of bone loss), monitoring of the response, and evaluating patients who do not respond Comprehensive software for Pediatric Hospital Ernest Geutebruck EVALUATION OF DIET QUALITY OF EGIPTIAN CHILDREN AND ADOLESCENTS USING HEALTHY EATING INDEX Mervat I., Nebal A­R, Waffa A. , Asmaa A. National Nutrition Institute – Cairo – Egypt Abstract RATIONALE & OBJECTIVES: Some dietary patterns are associated with 4 of the 10 leading causes of death. Major improvements in the health of the public can, therefore, be made by improving people’s dietary patterns. The aim of our study is to use the healthy eating index to assess the diet quality among Egyptian children and adolescents and the compliance with specific dietary guidelines, to give a single measure to monitor change in food consumption pattern and to help developing more effective nutrition promotion messages for the public. MATERIALS & METHODS: The Healthy Eating Index (HEI) of USDA was applied with slight modifications. The data were based on representative sample (2145) of children and adolescents (10 ‐18) years in 7 governorates. One day of dietary intake data (24 hours recall) was collected, during an in‐person interview. The Healthy Eating Index measures how well the studied children and adolescents' diets conform to the American Dietary Guidelines recommendations and the Food Guide Pyramid applied in our country. RESULTS & FINDINGS: the average Healthy Eating Index score was 59.1 out of a possible 100 and it ranged from 20 to 86, only 0.5 percent of the students had Healthy Eating scores above 80; while 16.9 percent of them received scores below 50 and the majority (82.5 percent) had scores on the Healthy Eating Index between 51 and 80. In an effort to provide a "rating" of the overall student's diet, a grading scale was developed, the majority of students had diets rated as "Needs Improvement", only 0.5 % received diets rated as "Good" and 16.9 % had diets rated as "Poor". Males achieved a slightly higher average Index than females (59.7 Vs 58.2). The average score for food groups is much lower than that for dietary guidelines (23.5 Vs 35.6) out of total score of 50 for each. CONCLUSION: The majority of Egyptian children and adolescent’ eating patterns, as measured by the HEI, need improvement. Keywords: Evaluation – Healthy – Eating ‐ Index – A Breastfeeding and Hospitalization for Diarrheal and Respiratory Infection Case control study .Shiekh Ammar O, MD, Nessrine hamad,MD ,Koleilat AZIZ, MD • Pediatric Department, Makassed University General Hospital, Beirut, Lebanon Background Human milk is species specific, which makes it superior to any infant formula . The World Health Organization (WHO) and the American academy of Pediatrics recommend that all infants should be exclusively breastfed for the first six months of life . However, few women follow these recommendations especially in western societies . In Lebanon, a national survey done in 2005 showed high breastfeeding initiation rates but low rates of exclusivity and short duration of breast feeding . Objective: Prior studies have shown conflicting data on the magnitude of breast feeding protective effect during infancy. This study will question whether breastfeeding protects infants against gastroenteritis and lower respiratory tract infections severe enough to require hospitalization and to study the impact of different feeding types on infant's health Study design: This is a case control study, conducted in Makassed General Hospital in Beirut, Lebanon, between September and April 2008. Subjects: Two groups of infants were studied; the first group comprised 121 infants who were admitted to hospital for gastroenteritis and lower respiratory tract infection. Control group comprised 101 infants presenting to private clinics for vaccination or check up. Results Exclusive breastfeeding did not seem to be superior to mixed feeding in terms of protection against infection but better than bottle feeding alone Conclusion: This study provides additional generalizability that the feeding mode has a pronounced influence on infant's health. Our data stress that breastfeeding offers protection against GE and LRTI severe enough to require hospitalization in infants especially in the early three months of life, resulting in significant reduction in hospital admissions. Exclusive breastfeeding seems to be similar to mixed feeding in protection against disease. Title: Study of food pyramid And calcium intake for children (4 ­ 11) Hama Syria Principal investigator: DR: LINA NAJJAR pediatrician Co: lillas tohma nutrition specialist Institution: MAHARHEH –HAMA­SYRIA Background: healthy children of wealthy and busy families depend on fast, easy and delicious food and often forget the essential groups especially milk group which is very important to get an optimal, calcium intake Objectives: This study aims to analyze the feeding situation for 100 healthy children. And know the rate of ideal feeding according to the food pyramid, disclosing the most important faults of feeding and nutrition then trying hard to find solution. On the other hand we calculated the calcium intake for the children and compared them with the recommended daily values according to the age. Methods: too many information were gathered through the oral interviews that were held with mothers of 100 children in ACCAD institute.Through different samples, information were taken for what child eats in a complete day for tow different days. There was an agreement for this work from the government and the parents. Subjects: healthy children in a learning institute 4­11 years old (we took random samples 100 children out of 500) were studied for their food according to the food pyramid rules according to sex and age and for the same children we calculated the calcium intake according to their age . 52 males ( 38 boys 4­9 years old and 14boys 9­11years old ) 48females ( 32girls 4­9 years old and 16 girls 9­11 years old). Results & Analysis: 88% of children don’t follow the rules of food pyramid; they get their energy and power from starch sugar and fat. Only 33% take the optimal intake for milk group cheese and yoghurt, and 67% take milk group less than required. 63% of children eat meat group more than required but most of them eat red meat and eggs, they should increase white meat nuts and dry beans. 46% of children don’t eat vegetables as required and only 10% take green vegetables. 44% eat grain group as required but only 14%of them eat whole grain. Calcium intake is low 76% of children and according to the age the problem is bigger over 8 years old, children should be encouraged to drink milk, yoghart and eat other foods rich in calcium like sesame and broccoli …because a low calcium intake at childhood may be a cause of osteoporosis in the adulthood. 96% of children take junk and unhealthy food like chips and biscuits at least once a day, which should be avoided. Conclusion : the study could achieve its targets . As there was a low intake of milk group in 67% of children as we expected according to the food pyramid rules correlating with 76% of children have low calcium intake as we calculated it according to the recommended daily requirements. Other mistakes were shown to encourage healthy habits for nutrition of children. Management of severe malnutation in hospital of Aleppo Principal investigator:Dr. moustafa abo zarad
Institution: hospital of aleppo
Backgroud:severa malnutrition is the most common causes of morbidity and mortality among childrin under 5 years age Objectives :apply guidelines of WHO to management of SMC Methods : Utilize weight‐for‐height z score for admission ,at ‐3SD and less
Discharge when > ‐2SD Stay in spicial room Managed as WHO recomendation Follow up after discharge Subjects:46 severe malnourished child Results & Analysis :
Gender: female \ male = 3\2 Residence: rural\urban = 2\1 Age: infant 82.5% Symptomes: all severely wasted, lesss than ‐3SD Blood glucose: 4child(8,7%) had glucose < 54mg\dl Hb: 4g\dl & less , in 4,3% Admission: 13% aweek , 30,4% 2 weeks , 32,6% 3 weeks , 23,9% 4 weeks
Rout Of feeding: feeding bottle 78,2% , feed with acup 10,8% , syring 8,7% Feeding: all given F75 , F100 , except 2, one had meat, another had spcial formula Daily weight gain: good 52,2% ‐ moderate 13,1% ‐ poor 34,7% Z‐SCOR at discharge: 30% > ‐2SD , 37% <‐3SD , 32,6% ‐2‐3 Death: 3 child ( 6,5% ) Follow up: for 52,3% Conclusions :WHO recomendation shoud be applyed worldwide Fungi identification and aflatoxin levels determination in the most common Syrian food items Kinana Tafish and Maher Korakli Department of Nutrition and Food Science, University of Kalamoon, Deir attiah, Syria. Abstract: Background: Mycotoxins are toxic secondary metabolites produced by filamentous fungi which grow on agricultural commodities. They were reported to be frequently produced in food. Aflatoxin is the most dangerous type of mycotoxins. It is considered as the most threatening toxin in food because of their carcinogenic effect on multi system organs in the body especially liver cancer and their accumulation mechanism through the life long. Clinically, they have the ability to increase the risk of Kwashiorkor incidence. Considering that, children's food items should have the most attention and conservation for this issue. The maximum tolerated limits for total aflatoxin is below 20 ppb in many countries. In Syria, there are very limited data about the presence of aflatoxin in different foodstuffs like children's food items, grains and nuts. From this point it was a must to investigate in this domain within this region. Objectives: to evaluate aflatoxin levels in the most common foodstuffs at the local markets in Syria and to identify molds spread in these markets. Materials and methods: Different samples of foods were collected from the Syrian market and fungi were isolated and identified according to their morphology. In addition, the total aflatoxin levels of the samples were determined by using affinity chromatography at “The National Commission for Biotechnology”. Samples: The samples were: raw wheat, raw whole wheat, raw walnuts, raw peanuts, raw kabseh rice, raw yellow corn, raw pistachios, raw masry rice, spiced and roasted corn, toasted pistachios, raw green coffee beans, wheat flour, and toasted and spiced peanuts. Conclusion: More education and observation on these toxins must be applied from the governmental authorities on the sellers, suppliers, farmers and even customers. Children's foodstuffs should have less expiring dates than permitted to avoid aflatoxin building in these foods as less as possible. Finally, pediatricians and dietitians have an extremely important role in raising parents' awareness about storing and handling kids' food items. In addition, they should be informed about how to differentiate foods that have inappropriate smell to riddance it, even if it's edible as the expiring date still valid. Rickets in 6­24 MONTH­OLD CHILDREN
DR.NIDAL AL‐KHANI PEDIATRECIAN
AL‐ASAD H. , HAMA, SYR dr‐nidal@scs‐net.org
DEFINITION: Rickets (Vitamin D deficiency) is the term signifying a failure in Mineralization of growing bone .The early changes of rickets are seen radiographically at the ends of long bones . Subsequently, if healing is Not initiated, clinical manifestations (Craniotabes – Rachitic rosary – Thickening of the wrists and the ankles – Bowlegs….) appear.
OBJECTIVE: To determine the prevalence of‐ clinical & sub clinical‐ rickets in infants and Children.
MATERIAL&METHODS:Wrist radiographs were performed to all ( 530) out‐ patients aged 6‐24 Months attended to the out clinic of AL‐ASAD H. , HAMA, SYR RESULTS:A total of 319 patients (60 percent) were having radio graphically index of Rickets, of whom 29 patients ( 9% )were having clinical features of Rickets. Of 530 cases (the whole number of the sample ) there were 29(5.5%) patients with clinically rickets. Fifty seven (10.7%) of the sample were given VitD (as ERGOCALCIFEROL:oral oily solution),of whom 32(57%)were rickety. Eleven(2%) of the sample were given VitD (as ERGOCALCIFEROL:intramuscular),of whom 6(54%)were rickety .There wasn't any use of VitD as prophylactic daily oral drops as recommended, while 20(3.7%)of the sample had been used oral drops of VitD for some time. CONCLUSION:There is high prevalence of clinically rickets, and more of that is sub clinically .The study indicates that hypovitaminosis D Is continue to be an important health problem in our country . Health education to encourage the use of prophylactic VitD as recommended . The 17th Conference of Union of Arab Pediatricians Dear Reader: Below is a collection of the Abstracts of presentations delivered in the 17th conference of union of arab pediatricians , May 5‐8, 2009; Amman, Jordan. The abstracts are presented as it were sent by the authors. The authors are responsible for the format, typing and the contents of the abstracts. psychiatric impact of war on children Dr. Mahmoud A. Hammouda Prof. and Head of Psychiatry Department, Al‐Azhar Faculty of Medicine The war has disastrous effects on population and the environment. These effects are more prominent on children, as they are more week and in growing stages. Many psychiatric disturbances happened to children if they were lived war disaster. These disturbances include acute post traumatic stress disorder, post traumatic stress disorder, major depressive disorder, adjustment disorder, anxiety disorders and other psychiatric disorders may occur. The presentations of these disorders differ according to age of the child and other factors will be discussed in detail. Suffering of children in Gaza War Dr. Basem Kiswany Not available SAT‐NAV ‐ The Right Care Pathway ® Specialist Care And Treatment of Neurodisability And Ventilation Dr.G.Simoes Consultant The Childrens Trust The Children’s Trust is a charity, and one of the main U.K. providers of specialist services for children and young people with severe acquired brain injury. As well as offering places at our school and our new further education unit for young people up to the age 25, we provide medical assessment, rehabilitation and outreach services for children and young people with acquired brain injury. Due to increasing demand, in 2009 the Trust will be opening a new residential rehabilitation centre featuring the latest technology, and a multi‐sensory hydrotherapy centre. We are also opening a new long term ventilation unit in the new building. It is accepted that acute hospital environments at PICU and NICU levels cannot meet all the development needs of the children. There are considerable psychological and developmental disadvantages to long term hospital based care. There is also an increasing emphasis on transferring these children to the community. The Children’s Trust Experience: The referral process was designed to allow the decision making process to be easy and simple. We work from a Flow Chart which shows the referral pathway from the PCT to our Long Term ventilation Unit. It also provides a clear understanding of our assessment and funding pathway. Our second flow chart shows the liaison between our team, family/child and the other professionals in the community; to provide a clear discharge plan home. Child survival,Child Health and Child Development: The Roles of IPA and the Pediatricians Dr Chock‐Wan Cha Not available
An Update on Paediatric Resuscitation An Abstract The most important changes in recommendations for paediatric resuscitation over the last several years include: Increased emphasis on performing high quality Cardio‐Pulmonary Resuscitation (CPR): “Push hard, push fast, minimize interruptions of chest compression; allow full chest recoil, and don’t provide excessive ventilation”, Chest compression‐ventilation ratio: for lone rescuers with victims of all ages: 30:2 and for health care providers performing 2‐rescuer CPR for infants and children: 15:2,, either a 2‐ or 1‐hand technique is acceptable for chest compressions in children, use of 1 shock followed by immediate CPR is recommended for each defibrillation attempt, instead of 3stacked shocks, biphasic shocks with an automated external defibrillator (AED) are acceptable for children 1 year of age, attenuated shocks using child cables or activation of a key or switch are recommended in children <8 years old, routine use of high‐dose intravenous (IV) epinephrine is no longer recommended , intravascular (IV and intraosseous) route of drug administration is preferred to the endotracheal route, cuffed endotracheal tubes can be used in infants and children provided correct tube size and cuff inflation pressure are used, exhaled CO2 detection is recommended for confirmation of endotracheal tube placement and consider induced hypothermia for 12 to 24 hours in patients who remain comatose following resuscitation. Evidence based medicine Dr Hasan Baaqeel Not available Amblyopia causes and detection Dr Mustafa Mehyar Not available Advanced Laparoscopic Surgery in Children Dr Najeh Alomari, MD, JBGS, JBPS, FRACS, FEBPS, IMRCSI Consultant Pediatric Surgeon, Urology & Transplant Dr Ibrahim Dradkak, MD, Dr Yanal Abaza, MD, Dr Hussein Khraisha, MD Ola Hasanat RN, Randa Ayasrah, RN, Njoud Abadi, RN, Nadia Soudani, RN Royal Medical Services Division of Pediatric Surgery King Hussein Medical Center ABSTRACT: Objectives : Minimally invasive surgery plays an important role in the daily practice of pediatric surgeons. The aim of this paper is to report our preliminary experience over the past 4years with a broad range of pediatric laparoscopic procedures. METHODS: We performed a retrospective analysis of 106 minimally invasive procedures conducted in the department of pediatric surgery from January 2005 to April 2009. RESULTS: The mean age of the patients was 4 years (range, 2 weeks ‐15 years). Diagnostic laparoscopy for undescended testes and stage surgery (n=33). Other common operations were laparoscopic high ligation of spermatic vessels (n=8), laparoscopic cholecystectomy (n=12), laparoscopic appendectomy (n=6), laparoscopic female adnexal surgery (n=5), laparoscopic assisted splenectomy (n=1). Laparoscopic Nissen fundoplication (n=3, diagnostic laparoscopy for unexplained abdominal pain (n=4), laparoscopic gastrostomy (n=2). Morgani hernia repair (n=2), laparoscopic repair for inguinal hernia (n=10). Laparoscopic assisted pull‐through for HD (n=6). Thorcoscopy for pleural empyema (n=2), Diaphragmatic plication (n=1), laparoscopic nephrectomy (n=7), laparoscopic assisted anorectoplasty (n=1), laparoscopic simple liver cyst excision (n=1). We reviewed the indications for surgery, the surgical technique, and the outcome for each procedure. All patients in this series were well at follow‐up and there was no long‐term morbidity. CONCLUSION: Although laparoscopic procedures have gained an integral place in pediatric surgery and are relatively safe and cost‐effective, advanced laparoscopic procedures should be developed, practiced and evaluated in dedicated surgical units to ensure a broad base of experience on which to base future decisions and guidelines. The clinical profile of infections in childhood primary nephrotic syndrome K F Akl1 , N K Bulos 2, M Luwama3 F Khatib4 1,2 ,3Department of Pediatrics –Jordan University Hospital‐College of Medicine‐University of Jordan 4 Department of physiology/biochemistry‐College of Medicine‐University of Jordan Objective : To review the profile of infections in childhood nephrotic syndrome . This is a preliminary report . Patients and Methods : A case control study , with retrospective medical record review of primary idiopathic nephrotic syndrome seen at the renal service at Jordan University Hospital . Results : There were 114 children with primary nephrotic syndrome . Sixteen children were excluded because of inadequate followup . Of the remaining 98 children , 66 were boys and 32 were girls . The mean age at diagnosis was 48 months ( range from 12 to 156 months) . The mean period of followup was 25 months ( range 4 to 126 months ). A total of 379 episodes of infections were observed in 87 of the 98 children . The majority of infections occurred in the ages 1‐5 The most frequent infections encountered in our series were upper respiratory tract infection (52.5%) , gastroenteritis (9.5%) , urinary tract infection(9.2%) , Peritonitis (5.5%) , sinusitis (4.2%), Otitis media (1.6%) , appendicitis (1.3%) , multiple warts (1%) . Two of the 5 deaths were attributed to infection . Conclusion : Children with nephrotic syndrome are predisposed to a wide variety of infections , ranging from mild URTI to serious and fatal septicemia . The pediatrician and primary care physician should be alert to this complication . Preferred presentation : Oral Authors Data Surname Akl First name : Kamal Address : Pobox 831373 Amman 11183 Country : Jordan Fax : +96264644710 Phone : +962795577589 Date : March 21‐ 2009 Note : Submitted by email on February 14 , but it seems you did not receive it according to Miss Suzan . Five critical cardiac problems commonly missed in office practice Dr Riyad Abu‐Suliman Sent to u Single ventricle patients for the general pediatrician Dr Khaled Salaymeh Not available Pocket echocardiography The role of pediatrician Dr Wael Abd‐elal Not available General pediatric follow‐up for the congenital heart defect patient Dr Riyad Abu Suliman sent New Guidelines for SBE Dr Eyad Ammori Not available Pediatric renal transplant Dr Isa Hazza sent Metabolic disorders involving the kidney Metabolic disorders and the Kidney Dr. Radi Hamed. Consultant Pediatric Nephrologist. Amman, Jordan The topic of inborn errors of metabolismis is challenging for most physicians. The number of known metabolic disorders is large. Many of these disorders involve the kidneys either by virtue of deposition of metabolites in the kidney, progressive glomerulopathy, or renal tubular dysfunction. Physicians know they may not encounter certain rare inborn errors of metabolism during a lifetime of practice. Nonetheless, with a collective incidence of one in 1,500 persons, at least one of these disorders will be encountered by almost all practicing physicians. Improvements in medical technology and greater knowledge of the human genome resulted in significant changes in the diagnosis, classification, and treatment of inherited metabolic disorders. Many known inborn errors of metabolism will be recognized earlier or treated differently because of these changes. It is important for primary care physicians to recognize the clinical signs of inborn errors of metabolism and to know when to pursue advanced laboratory testing or referral to the appropriate subspecialist that can take care of these critical conditions, and do the relevant diagnostic and therapeutic interventions and procedures. Pediatric enuresis an update Kamal Akl Md . Assistant Professor –Department of Pediatrics‐Jordan University Hospital –College of Medicine‐ University of Jordan Email [email protected] Objective : To review the recent terminology update in pediatric nephro‐urology , and emphasize the role of the general pediatrician in prevention . Review :Recent terminology update in pediatric nephro‐urology includes Acute Kidney Injury (AKI) , Chronic Kidney Disease (CKD) , and Lower Urinary Tract Dysfunction (LUTD) . AKI replaces the term Acute Renal Failure (ARF) . A consensus definition for AKI was proposed by the Acute Dialysis Quality Initiative in 2002 for adults : the RIFLE criteria ( R =risk , I =injury , F= failure , L=loss of function , and E= end stage ). The pediatric RIFLE (pRIFLE) was the outcome of modification of the adult criteria . The pRIFLE is based on estimated creatinine clearance (eCC) and urine output . pRIFLE stratifies AKI from mild (RIFLE R, risk ) to severe (RIFLE F , failure ) . CKD is divided into five stages based on the presence of kidney damage and an eCC . CKD I being the mildest , and CKD V the most severe . Regarding the recent standardization of terminology by the International Childrens Continence Society , some terminologies have been changed , and new ones added . Overactive bladder replaces the term diurnal enuresis . Conclusion : Recent terminologies were established to create a common language , which will facilitate research and prevention . PD in children is possible in different environment Reem Hadidi md1 ,Nareman Alhnety md, Hanan kassad ,Ibraheem al kaysee, nesreen hmedeen md Abstract This is a retrospective study and prospective study of the course of children who received peritoneal dialysis (PD) at Prince Hamza Hospital, Amman, Jordan, from August 2006 to February 2009, A total of 33 children (22 girls and 11 boys) with end‐stage renal failure (ESRF), the most common cause of ESRF in these children are dysplastic kidney (24.2%) ,reflux nephropathy (24.2%) then neurogenic bladder (15.2%)and oxalosis (15.2%).31 patient received Peritoneal dialysis ,two patient donnot received renal replacement therapy one of them due to financial problem and the other one due to the family refusal to the treatment therapy . Continous ambulatory peritoneal dialysis (CAPD) was done in 15 patient (45.5%)and 16(48.5 %)patient received automated PD and two children is still on no treatment(6.1%).. Most of the children had low socio‐economic status. The most common complication is peritonitis then exit site infections. The over all rate of peritonitis was one episode per 6 patient's treatment months for patient on CAPD and one episode per 24 patient's treatment months for patient on APD .11 patients died (33.3%),4 patients referred for hemodialysis due to ultra filtration failure(12.1%),14 patients are still on pd(42.4%). (39.4%) of mothers are Illiterate.(35.4%) Taojehe,and the rest( 25%) are Bachelor and Deploma, only 2 of our patient the care giver is the father. In 57% of patient no spareroom is available, In conclusion; PD may still be a suitable modality of renal replacement therapy for children living in low socioeconomic conditions despite the challenging problems in them.Successful renal transplantation is the treatment of choice for children with end‐stage renal disease (ESRD). Ideally, children with ESRD should be transplanted before becoming ill and requiring dialysis 1‐Address for correspondence: DR REEM HANI AL HADIDI PEDIATRIC NEPHROLOGIST PRINCE HAMZA HOSPITAL MINESTRY OF HEALTH [email protected] Jordan‐Salt. P.O.BOX: 505 (962) 53552818 (home) (962) 777634115(Mobile). Nephropathy Dr Rula Saqan Not available Familial Glomerulopathy Not available A Clinical Approach to Brain Malformations Dr. Ganesh Mochida Not available Approach to neurodegenerative disorders Dr Abdelkarim Qudah Not available Overview of Childhood Epilepsies Dr Saleh Al‐Ajlouni FRCPCH (UK), Senior Consultant Pediatric Neurologist King Hussein Medical Centre, Amman ‐ Jordan
Patients with epileptic seizures and their families are entitled to a diagnosis, prognosis and management that are specific and precise. Epilepsy is not a single disease entity. Epilepsies are many diseases. The short and long‐term management of epilepsies is syndrome – related and often differs markedly between various disorders manifesting with seizures, emphasizing the need for accurate diagnosis. salient aspects of the history and examination ,together with electroencephalograpgy, will usually determine the epilepsy syndrome. For those patients diagnosed with epilepsy, ‘broad‐spectrum’ AEDs may facilitate initial management; however, their use should not be a substitute for accurate diagnosis and optimal treatment. Epilepsy usually begins in childhood, potentially impending education, employment , social relationships and development of a sense of self worth. Prompt, accurate diagnosis with appropriate social and medical management will optimize the situation. Here in I will present some of the childhood epilepsies and epileptic syndromes and their treatment. Address: King Hussein Medical center , Amman , Jordan . 00962‐777‐264‐126 [email protected] E mail: Update in the management of status epilepticus Dr Azhar Daoud sent
Title : Paroxystic non‐epileptic events in children –The role of history and mobile phones Running title : Paroxystic non‐epileptic events Amira Masri and Mayada Abu Shanab Amira Masri , MD ( corresponding author ) Associate prof . of child neurology Department of pediatrics – division of child neurology ‐Faculty of medicine –The University of Jordan Email : [email protected] Tel : 00962777770919 P.O.Box 1612 , code 11941 Amman –Jordan Mayada Abu Shanab Pediatric resident‐ Department of pediatrics ‐Faculty of medicine –The University of Jordan Abstract Aim: To describe the paroxystic non‐epileptic disorders (PNED) encountered in children presenting to the child neurology clinic at Jordan University Hospital Patients and methods: This retrospective study included all children referred with a provisional diagnosis of epilepsy between January 2001 and June 2008. Results: A total of 100 patients (58 boys and 42 girls) were included. PNED included breath‐holding spells (37%); hyperekplexia and excessive jitteriness or startle (20%); vasovagal attack (12%); psychogenic seizures (11%); gastroesophageal reflux (10%); masturbation (3%); head nodding (2%); tic (2%); paroxysmal torticollis (1%); migraine (1%); vitamin B12 deficiency‐induced tremor (1%). While 56 (56%) patients were referred with a suspicion of epilepsy, 44 (44%) patients were referred and given a final diagnosis of epilepsy. Forty two (42%) patients received antiepileptic treatment. We performed sleep EEG for 58 (58%) patients, and video EEG for 15 (15%) patients. Witnessing the event recorded on mobile phone was helpful in 4 patients (two psychogenic seizures and two masturbations). Elements that were helpful in the diagnosis included history, examination, follow‐up, and witnessing of the attack in clinic or on mobile phones, and were present in 85% of the patients. Conclusion: In this study we reported some of the PNED that can often be misdiagnosed as epilepsy. Taking a proper history is a key factor in reaching a correct diagnosis. In addition, this study demonstrated the usefulness and importance of mobile phones when home videos are not available. Both parents and physicians should be encouraged to use it. Reproductive Hormonal Changes and Catamenial Pattern in Adolescent Females with Epilepsy
Dr .Hamed Khayyat Abstract:
Purpose: We aimed to evaluate the effect of epilepsy on the reproductive hormone levels among female patients, and to investigate the frequency of catamenial pattern of seizures.
Methods: 42 female patients with epilepsy and 21 healthy females (control group) were included. Subjects were at least 2 years post‐menarche with regular cycles. Symptoms of premenstrual syndrome (PMS) were assessed using calendar of premenstrual experience scoring. Patients were evaluated for catamenial pattern of seizures. Levels of FSH, LH, estradiol (E) and progesterone (P) were assessed for all subjects in the three phases of the cycles. Pelvi‐abdominal ultrasound was performed near time of ovulation, to follow up size of mature follicle. Results: Symptoms of PMS were not different in patients and controls, or in patients with and those without catamenial tendency. In both perimenstrual and midluteal phases, FSH and progesterone levels were lower and E/P ratio higher in patients group. There was a catamenial pattern of seizures in 31% of patients (53.8% perimenstrual C1, 46.15% inadequate luteal phase C3 pattern). Patients with C3 pattern showed lower progesterone levels in the midluteal phase compared to patients with non‐catamenial pattern, to those with C1 pattern or to controls. Patients with C1 pattern had lower progesterone levels than controls in the perimenstrual phase. Conclusion: There was evident disruption in the reproductive hormones in female patients with epilepsy with lower FSH and progesterone levels and higher E/P ratio. 31% of patients showed catamenial pattern of seizures (C1 and C3 patterns) that was significantly related to progesterone withdrawal. Treatment of fatty acid oxidation disorders Dr Andrew Morris Not available A novel mutation in the AVPR2 gene in a Palestinian family with nephrogenic diabetes insipidus Abdulsalam Abu‐Libdeh, Imad Dweikat and Bassam Abu‐Libdeh Department of Pediatrics, Makassed Charitable Islamic Hospital, Jerusalem, Palestine Background: Nephrogenic diabetes insipidus (NDI) is a urinary concentrating defect resulting from resistance of the collecting duct to the antidiuretic action of vasopressin (AVP). NDI is classified into hereditary and acquired. The X‐linked recessive form is the most frequent genetic cause of inherited NDI and is caused by mutations in the gene encoding the V2 vasopressin receptor (AVPR2 gene). We describe a novel mutation in the AVPR2 gene in a Palestinian family with NDI. Clinical Data: A Palestinian male infant presented in the neonatal period with FTT, vomiting, irritability, fever, and polyuria of 7 cc/kg/hr. His serum sodium and osmolarity were 170 mEq/L and 330mOsm/kg respectively; while his urine osmolality remained low between 45‐135mOsm/kg. The diagnosis of NDI was established based on the clinical picture, a similarly affected older brother suggesting X‐linked inheritance of the disease, and absence of response to ddAVP. Molecular Data: Sequencing the AVPR2 gene for the patient and his affected brother revealed a novel missense mutation with replacement of G by A in codon 82 of exon 2 (TGC Æ TAC), predicting Cysteine to Tyrosine substitution (C82Y). Testing of the mother showed that she is a carrier of that mutation, and it was absent in a healthy brother and the father. Conclusion: To our knowledge, this is the first confirmation of this diagnosis by molecular testing in a Palestinian family allowing genetic counseling and future prenatal diagnosis, in addition to early diagnosis of affected males to prevent severe dehydration and complications. New genetic disorders in arab families Dr Ahmad Teebi Not available Congenital Insensitivity to Pain with Anhidrosis (CIPA) The spectrum of Clinical Presentation Authors : Wael Hayel Khreisat MD JB*( pediatric neurology) , Saleh Al‐Ajlouni FRCPH 1 , Aml Hararsheh MRCPCH2 ,Manar Aqrabawy3 , Kefah Qaaqa4 Congenital insensitivity to pain with anhidrosis (CIPA) , is an exceedingly rare disease. Only 31 cases have been reported. It is disorder resulting from defective neural crest differentiation with loss of the first‐order afferent system ,CIPA is a severe autosomal recessive condition that leads to self‐mutilation in the first months of life , bone fractures, osteomyelitis, joint deformities, and limb amputation as the children grow older. Mental retardation is common. Death from hyperpyrexia occurs within the first 3 years of fife in almost 20% of the patients. . Lack of sweating, hyperthermia, and infections of bones are main features of the disorder; In this conference we will present five cases, their clinical presentation , investigation and management. Genetic diversity in arabs Dr Ahmad Teibi Not available Rota Virus infection&the promise of vaccination Dr Bernd Benningough Not available Clinical trial in Jordan Dr Mohammad Rawashdeh Not available PubMed Search Abstract PubMed, is developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM), located at the U.S. National Institutes of Health (NIH). Entrez is the text‐based search and retrieval system used at NCBI for services including PubMed, Nucleotide and Protein Sequences, Protein Structures, Complete Genomes, Taxonomy, OMIM, and many others. PubMed provides access to citations from biomedical literature. LinkOut provides access to full‐text articles at journal Web sites and other related Web resources. 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Use the Single Citation Matcher for finding the citation for a particular article using title words or citation information, or to find an entire volume or issue of a journal, or to generate a bibliography by a first author. Spinal Muscular Atrophy Type I (Werdnig Hoffmann Disease): Clinical and Genetic Review of 24 Cases Confirmed by Molecular Study ; Experience of Makassed Hospital: 2000‐2007. Abstract Objective: To study the genetic and clinical characteristics of spinal muscular atrophy type I (SMA‐I) in the Palestinian population and in doing so to compare Palestinian local data with universal one. Background: SMA‐1 is an autosomal recessive disease, linked to a genetic locus on chromosome 5q. It typically presents with progressive muscular weakness and generalized hypotonia. Its prevalence in Palestine is not known, although it sounds not infrequent. Design/Methods: We reviewed the charts of 43 patients admitted to Makassed Hospital in East Jerusalem between 2000 and 2007 who were given the provisional diagnosis of SMA‐I. Of those 11 patients were excluded, 8 of them due to lack of clinical data and 3 others as molecular study was not preformed (although SMA was confirmed by muscle biopsy). Results: The final 32 patients with genetic testing were divided into those with abnormal genetic studies; group A (n=24; 75%) and those with normal genetic studies; group B (n=8; 25%). There were 61%, 12% females and 39%, 88% males in group 1 and 2 respectively. In group A, 20/24 (83%) had homozygous deletion in both SMN1/telomeric (Exon 7 8) and NAIP (Exon 5 6) genes, 3/24 (11%) had homozygous deletion in SMN1 (Exon 7 8) genes and 1/18 (6%) had deletion in SMN1 (Exon 7). No mutations in the SMN2/centromeric (Exon 7 8) genes were found in any patients. In addition, comparative analysis on clinical basis, of both groups A and B, doesn’t show any significant clinical difference between the 2 groups. Generalized hypotonia with hypoactivity, absent deep tendon reflexes and sharp gaze were the leading clinical findings in both groups. Conclusions/Relevance: Similar genetic mutation in the SMN1 and NAIP genes were found in our patients as reported in other populations. Our clinical and genetic findings are universal. The diagnosis of SMA1 could be made in 2 steps: clinical diagnosis followed by genetic study for confirmation. In case of confirmation, prenatal diagnosis for future pregnancies could be performed. CP & ARRC management system Dr Ahmed Raouf Not available The investigation of suspected mitochondrial disease Dr Andrew morris Not available Developmental delay Dr Majed Dasouki Not available Update on the Genetic Features of Autism & Other Neurodevelopmental Disorders Dr Ramzi Nasir Not available Sanjad Sakati syndrome Dr Alia Al‐muhtaseb CONSANGUINITY & PREGNANCY OUTCOME (ORAL PRESENTATION) DR. BAHIYEH R.M. QANDALJI , MRCPCH CONSULTANT PAEDIATRICIAN , AL‐BASHIR HOSPITAL BACKGROUND AND AIM: Consanguineous marriage are common in Jordan and Middle East in general. The aim of this study is to see the effect of consanguineous marriage on pregnancy outcome. PATIENTS AND METHODS: Mothers in the postnatal ward were interviewed and a questionare was filled .They were asked whether marriage is consanguineous or not .Data regarding number of pregnancies ,abortions, stillbirths, intrauterine fetal death, multiple pregnancy and low birth weight babies were collected. RESULTS: The study included 95 mothers of consanguineous marriage and 160 non‐
consanguineous marriage. There was a statistically significant difference between the two groups of mothers regarding number of pregnancies , number of abortions, number of stillbirths, number of intrauterine fetal death, number of neonatal deaths, number of infant deaths, number of multiple pregnancies, and number of low birth weight babies. All were significantly higher in consanguineous marriage. CONCLUSION: Consanguineous marriage has adverse effect on pregnancy outcome Consanguinity should be considered as a factor of high risk pregnancy. The obstetrician and neonatologist should be alerted to this risk factor. Primary ciliary dyskinesia Dr Ibrahim Janahi Not available Cystic fibrosis an overview Dr Abd HAMID NAJADA Allergic rhinitis in children Dr Mona Khater Not available
Critical care Asthma management Dr Husein Mugrabi Not available
Sleep Disorders in children Dr Raed Sulieman Not available Asthma control Dr Mona Khater Not available ANALYTIC STUDY OF CHILDHOOD ASTHMA IN LATTAKIA Dr. Ma'moun Hakim ABSTRACT Introduction: asthma is a serious global health problem, affecting people of all ages in all countries; it is the most common chronic disease in childhood, leading cause of school absenteeism and the third leading cause of hospitalization among children. The objective of this study is to attract the attention to the importance of childhood asthma as a public health problem, and to determine the risk factors which may be responsible of increasing asthma prevalence; evaluation of asthma management and assessment of knowledge and application of preventive measures. Materiel & methods: the study used analytic, cross‐sectional design; duration 3 years, involve 244 asthmatic Childs whose ages between 2‐15 years, in AL ASSAD University Hospital in Lattakia. Results: the study demonstrates the following risk factors for asthma: gender male, live in urban areas, existence of personal and familial history of atopy, tobacco smoke exposure and respiratory infections. The study shows inappropriate daily management of asthma; ignorance or negligence of the importance of avoiding the allergens and irritants in child atmosphere; application of maintenance therapy in 12% of cases only; more than third of patients constrained to school absenteeism and a quarter to hospitalization. Laboratory findings: hyper‐eosinophilia in 50% of cases, high total IgE serum levels in 62% of cases, and the percentage of elevation is higher in males than females with (p<0.05); house dust mites is the most common allergen in prick‐tests; so allergic asthma is the most common in children especially in males. Discussion: asthma is a common problem in children and the rise of the prevalence of asthma can be explained by augmentation of allergens in child atmosphere, early respiratory infections, passive smoking and air pollution especially in urban areas. The males are more affected than females due to more elevated incidence of atopy and relative small airways in males. Allergic asthma is common in according to other studies. The management of asthma remains inappropriate because small percentage receives daily maintenance treatment, in addition, allergens and irritants avoidance remains overlooked, thus, campaign for identification and management of asthma deem necessary. Key words: asthma, child, risk factors, total IgE, allergens. FOCAL DERMAL HYPOPLASIA (GOLTZ SYNDROME) Dr. Luay Al‐Nouri University of Baghdad A seven year old girl from Baghdad , presented with a skin lesion that was present since birth. The lesion was distributed on the forehead, chest and upper abdomen, while the back was spared. All four limbs were involved. It consisted of linear areas of thinning of the skin in which there was herneation of fat in the form of yellow papules, together with dyspigmentation and telangiectasia. The nails were atrophic and thin and there was complete syndactyly of the left second and third toes , and partial fusion of the right second and third toes. The teeth were defective and many were carious. The stature was short but development was normal. The condition is not rare as 200‐500 cases were reported so far, usually females since most affected males do not survive. Papillomatous lesions in different sites may be symptomatic and may require surgical intervention. I t is an X‐linked dominant condition associated with mutation of PORCN gene mapped to locus Xp 11.23. SEASONAL VARIATION OF NEURAL TUBE DEFECTS IN NORTHERN OF JORDAN. Obeidat A Z, Haddad I, Obeidat A D, Rawashdeh M Introduction: Neural Tube Defects are serious birth defects of the brain and the spinal cord that happen if there is interference with neural tube closure around 28th day after fertilization, Seasonal variation of NTDs development was reported by many studies worldwide. Objective: To demonstrate any association between the season of conception and the development of neural tube defects in Northern of Jordan. Methods: For the seven‐year period from Jan 2000 to Dec 2006, Data of neonates born with neural tube defect were collected and retrospectively analyzed regarding dates of conception and their relation to disease development. Results: A total of 78 neonates were collected (44 females, 56.4%; 34 males, 43.6%). 10% were delivered prematurely, 61% were delivered between 37 – 40 weeks, 27 % were delivered between 40 ‐ 42 weeks. Summer was the peak season for conception of affected babies (30%), while spring was the lowest (18%), August had the highest rate of conception of affected fetuses (14%) while conception in (Nov‐March) accounts for 32% of the cases only. After year 2003 seasonal variation started to fade away. Conclusion: Seasonal fluctuations were observed in our study population especially before 2003 when flour fortification was not completed in Jordan; summer as a peak season can be explained by maternal oxidative stress from intense solar radiation, Despite the fact that (Nov‐March) is the highest flu season in most of the world, it wasn’t the highest season for development of neural tube defect. Animal‐model studies are needed to clarify the association between NTDs seasonal variation and possible etiological factors. Acknowledgments: Prof. Mohammad Rawashdeh for supervising this project Key words: Jordan, Seasonal, Neural tube defects (NTDs) The description of newborn admissions in intensive neonatal care unit at Prince Rashed Bin Al‐Hassan Military Hospital in North of Jordan Sameer Kofahi MD, Zuhair Nusair MD, Nazih Abu Al‐Shiekh MD,Faten Kashman RN, Samar Murawah RN. Royal Medical Services Background: Neonatal period of 0 to 28 days of life is the most hazardous period. Low birth weight (LBW) continues to be the major public health problems in many developing countries. It caused by intrauterine growth restriction, short gestation or both. Early onset sepsis is caused by pathogens from the maternal birth canal which is transmitted to the infant immediately prior to delivery. Premature birth, LBW, premature rupture of the amniotic membranes, chorioamnionitis and maternal colonization with group B streptococci have been identified as specific risk factors for this severe and very often fatal disease. Late (5‐7 day) onset sepsis, may be due either to maternal pathogens, or may be transmitted nosocomially and the most cases are associated with the use of intravascular catheters. Objectives: To determine the reasons of newborn admissions in intensive neonatal care unit at Prince Rashed Bin Al‐Hassan Military Hospital in North of Jordan Methods: A cross‐sectional study conducted through the year 2008, randomly selected 380 newborn babies were admitted in the Neonatal Intensive Care Unite (NICU) at Prince Rashed Bin Al‐Hassan Military Hospital in North of Jordan, among them male were 265 (69.7%) and females were 115 (30.3%). the reasons for admission were recorded and transferred to statistical Package of Social Science (SPSS) computer software. Results: The study showed that the low birth weight accounted (42.1%) of total admissions. Neonatal infections were next commonest cause of neonatal admissions which includes sepsis (26.1%), pneumonia (1.8%) and meningitis (1.1%), premature babies (26.6%), neonatal jaundice (19.7), and birth asphexia (16.1%). Other causes of neonatal admission were congenital heart disease (2.1%), meconium aspiration syndrome (1.3%), intrauterine growth retardation (1.1%) and respiratory distress syndrome (0.8%). Among total admissions (84.2%) were sent home after their complete recovery. On other hand the neonatal mortality rate was (15.8). Conclusion: Pre‐maturity, neonatal infections, neonatal jaundice and birth asphyxia were the main causes of neonatal admissions. ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ Correspondence should be addressed to: Dr. Sameer Kofahi, Email: [email protected] Mobile: +962‐777763476. Clinical Profile of Cystic Fibrosis Dr M Dahabreh MRCPCH**,Dr A Najada,**Dr M Kawar Objectives: To describe the clinical presentations, genotype, microbiological data in children with cystic fibrosis in Jordan and the recommendations for future diagnosis and management. Patients and Methods: Clinical analysis of all the charts conducted on all children with classic cystic fibrosis from 2002 till 2008. Data Collected included: age at presentation and diagnosis, delay in diagnosis, physical findings, and family history. Laboratory tests done were included: complete blood count, kidney and liver function tests, sweat chloride and genetic testing. PCR testing is done for thirty mutations of CF. Results: Eighty children (46 (57%) males and 34(43%) females) with classic cystic fibrosis were included. Ages were between 1 month of age to 14 years old. Most of the patients presented between 1 and 6 months of age (35%). Sixteen infant (24%) presented in the newborn period. 16% presented in the 2nd year of life and 13% after the age of2 years. A delay in diagnosis more than 6 months was seen in 18 patients (26%). Most common presentations included recurrent wheezy chest (28%), (18%) recurrent chest infections and (14%) chronic diarrhea. Other presentations were syndrome of anemia and hypoalbuminemia (10%), hypotonic dehydration (9%), poor weight gain (8%)|, hepatosplenomegaly (6%), meconium ileus (4%) and direct hyperbirubinemia (3%). Twenty one children (26%) had positive family history of CF, while 12(15%) gave a history of male infertility in the family. Sputum cultures were positive in 24 patients; pseudomonas aureginosa (24%), staphyloccus aureus (4%), klebsiella (1%) and methicillin resistant staphylococcus aureus in one. Positive CF mutations were found in 25 patients (31%). Delta F508 mutation was the commonest 4%. Three patients died (4%): one with respiratory failure and severe pulmonary hypertension, 2 with severe fatal sepsis. Conclusion: The variability of clinical presentations and genotypic features reflect the diversity of the Jordanian population. A complete analysis of the DNA mutation would be helpful in knowing the most common mutations in our population. A specialized cystic fibrosis clinics and center can offer better care and long term results to patients and their families. ** Pulmonology Division, Pediatric department. King Hussein medical center. Amman‐Jordan Approach to bleeding disorders Dr Ahmad Mallouh Not available Management of ITP Dr Mahmoud Sheiab Not available IRON DEFICIENCY IN CHILDREN Maysoon Mejali Iron deficiency with or without anemia is very common in infant, toddlers, and adolescent female.Iron depletionearliest stage of diminishing iron stores.Iron deficiency(without anemia): further depletion of iron stores to impair hemoglobin synthesis : Iron supply is insufficient to maintain normal level of hemoglobin
What causes the shortage:
In the developing countries: Nutritional deficiency. In the industrial countries: Insufficient dietary iron.
Early introduction of whole cows milk before 1y .
Cows milk is low in iron and interferes with iron absorption.
Diet source of iron
Diet provides two types of iron heme and nonheme.
- Absorption is enhanced by reducing substances and ascorbic acid.
Neurological effect of iron deficiency
In early infancy and early childhood :
Recent study of children age 6 – 16 y showed lower math scores among iron‐deficit children .Iron supplement improve learning and memory in non anemic iron‐deficit adolescent female .
PREVENTION
Exclusive breast feeding until 4‐6 month, continue b.f. until at least 12 month.‐ Low birth weight infant or premature on b.f. needs supplementation with iron 2‐ 4 mg/kg/d -Fully iron fortified formula (10‐12mg/dl) is recommended for none b.f .babies.
Discourage the use of low iron formula.‐ After 4‐6 m b.f. infant needs about 1mg/kg/d of iron from iron rich food. (Each teaspoon of dry cereal provides 1mg of iron). Pediatric lymphoma Dr Essam Hadadin Sent We didn’t receive it
Thalassemia syndromes Dr Ahmad Mallouh Not available