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Alcohol consumption among pregnant women in Barcelona (Spain) Oriol Vall Paediatrics Unit, URIE, Neuropsychopharmacology Program IMIM-Hospital del Mar Barcelona Alcohol and Pregnancy Conference Brussels, 9 September 2009 Migrants Ciutat Vella Addicts Barceloneta Middle social class Gipsies Vila Olimpica H La Mina Our reality: Hospital del Mar 1.700 deliveries /yr 2.000 total paediatric admitions/yr 10.000 outpatients /yr 15.000 paediatric emergencies/yr It is high the addiction among the mothers of maternity ward Analyzed substances Tobacco Opioids and opiates (heroin, methadone) Cannabis Cocaine MDMA (Extasis) Alcohol Areca nut Mate Here comes your footer Page 4 Plan Nacional de Drogas (2006) * (Drugs Abuse National Plan) General population between 15 and 64 years (by questionnaire): 35.1 % tobacco 15.3 % alcohol 6.5 % cannabis 1.4 % cocaine 0.6 % amphetamines Questionnaire and biomarkers Drugs of abuse: Biological matrices for evaluation of prenatal exposure to drugs of abuse Meconium Hair Teeth Placenta Cord blood Human milk Ther Drug Monit 2007 Dec;29(6):711-34. Advantages: alternative bilogical matrices Non invasive collection Easy sample collection Wider time window for substance detection No degradation Some results published in medical journals Here comes your footer Page 10 [Prenatal exposure to drugs of abuse using meconium analysis in a low socioeconomic population in Barcelona] [Article in Spanish] Here comes your footer Page 11 In 353 meconium samples analyzed for detection of FAEEs, 159 (45%) showed results 2 nmol/g meconium 2 nmol/g meconium: reference value internationally considered for distinguishing during the pergnancy an alcohol important maternal consumption, from not consumption at all Here comes your footer Page 12 Prevalence of pregnant chronical consumers y gestantes with meconio as biomarcaker: Women Hawai: 16% (*) Women Canadá: 22% (**) Women Hosp. del Mar: 45% (*) Moore C,Jones J, Lewis D, Buchi K. Prevalence of fatty acid ethyl esters in meconium specimens. Clin Chem. 2003;49:133-136. (**) Chan D, Klein J, Karaskov T, Koren G. Fetal exposure to alcohol as evidenced by fatty acid athyl esters in meconium in absence of maternal drinking history in pregnancy. Ther Drug Monit 2004; 26:474-481. Is the positive FAEEs more feasible on polyconsumers pregnant women or addicted only to alcohol? - Positive Drug abuse and Positive FAAEs (45.7%) - Negative Drug abuse and Positive FAAEs (44.7%) Technicaly, ¿ How do we get the biomarkers ? FAEEs*: Liquid chromatography tandem mass spectrometry (LC/MS/MS) Ethyl Glucoronide (EtG): Immuno assay or GC/MS or LC/MS Ethyl Sulphate (EtS): Immuno assay or GC/MS or LC/MS But!! FAEEs versus EtG/EtS: NO correlation *FAEEs: Faty Acid Esters ETHYLGLUCURONIDE AND ETHYLSULFATE IN MECONIUM: NEW BIOMARKERS OF GESTATIONAL ETHANOL EXPOSURE? Papaseit E*, Joya X*, Pichini S**, Garcí García Algar O*, Morini L***, Vagnarelli F****, Vall O* and de la Torre R*. (*) Institut Municipal d’Investigació Investigació Mèdicadica- Neuropsychopharmacology Programme, Programme, Barcelona, Spain. (**) Istituto Superiore di Sanità Sanità, Rome, Italy. (***) Department of Legal Medicine and Public Health, Health, University of Pavia, Italy. Italy. [email protected] (****) Arcispedale Santa Maria Nuova, Nuova, Reggio Emilia, Italy. Objectives: To investigate: (1) the presence and the concentration of EtG and EtS in meconium from two different European newborn cohorts and (2) the eventual correlation between these two biomarkers and FAEEs from the same meconium samples. Material and methods: Liquid chromatography tandem mass spectrometry was applied to measure EtG, EtS and FAEE in meconium samples obtained from Reggio Emilia, Italy (n=60) and from Barcelona, Spain (n=50). Similar sociodemographic and ethnic characteristics LOQ for EtS in meconium samples: 1 ng/g LOQ for EtG in meconium samples: 5 ng/g Results and Discussion Prevalence of fetal alcohol exposure MECONIUM ANALYSIS in 50 samples of Barcelona Meconium analysis disclosed: 24 samples FAEE>2nmol/g sample and 26 FAEE<2nmol/g. MECONIUM ANALYSIS in 60 samples of Reggio Emilia Meconium analysis revealed: 59 FAEE<2nmol/g of 60 total samples. 1.000,00 6,00 EtG mean 45% ethanol consumption during pregnancy in accordance with previous studies*. studies*. *Garcia-Algar O, Kulaga V, Gareri J, Koren G, Vall O, Zuccaro P, Pacifici R, Pichini S. Alarming prevalence of fetal alcohol exposure in a Mediterranean city. Ther Drug Monit. 2008 Apr;30(2):249-54. The preliminary results showed values of EtG in meconium samples from Reggio Emilia were statistically lower than those from Barcelona specimens, similarly to what happen with FAEEs. EtS mean EtG ng/g 5,00 800,00 Barras 2 Barras 1 4,00 600,00 0 100 200 300 400 500 3,00 400,00 EtS ng/g 2,00 200,00 1,00 0,00 0,00 FAEE<2 FAEE MENOR 2 FAEE>2 FAEE<2 FAEE MAYOR 2 FAEE MENOR 2 FAEE>2 FAEE MAYOR 2 Fatty acid ethyl esters (nmol/g) 0 0,5 1 1,5 2 2,5 3 3,5 4 Barcelona Reggio Emilia When considering only Barcelona samples with FAEEs below 2 nmol/g, values of EtG that were still different in the two cohorts. Conversely, EtS values were similar when comparing the whole samples from the two city cohorts and also RE samples with those from BCN with FAEEs below 2 nmol/g. EtG and EtS values did not correlate with total amount of the seven FAEEs in both Reggio Emilia and Barcelona meconium samples. This could be due to the different mechanism of formation of these metabolites. The preliminary results of our study evidence for first time the presence of EtG and EtS in meconium. Further investigations are ongoing to verify the use of these two ethanol metabolites as alternative biomarkers of chronic in utero exposure to alcohol. 600 In summary FAEEs in meconium are the best markers in fetal ethanol exposure diagnosis so far FAEEs in hair could be useful as well, but further studies are needed EtG and EtS have been recently detected and quantified in meconium. Evaluation of a possible cutoff is the next step The sensitivity and specificity of EtG in hair is well-known and the determination of this metabolite in pregnant women’s hair could be very useful in the diagnosis of gestational ethanol exposure Remember…… FASD* is 100% preventable Neonatal screening for prenatal alcohol exposure Lead to An alternative: Harm Reduction approach to treat the mother, her child, and her future pregnancies * Fetal Alcohol Spectrum Disorder Alcohol: newborns FASD*: FAS, Partial FAS (PFAS), Alcohol-Related birth defects (ARBD), Alcohol-Related Neurodevelopment Disorder (ARND) Facial dysmorphology Growth retardation CNS development abnormalities FASD is very infrequent as a diagnostic in our hospitals despite of the high prenatal alcohol exposure Why? Maybe: Health care workers not trained. Adverse effects not identified or recognized (ADHD, school failure, etc.) Depend of differents habits of consumption? * Fetal Alcohol Spectrum Disorders Alcohol: newborns • Ethanol is the main known teratogen • Specially affects the neurodevelopment and has negative cognitive effects • Brain damage can not be repared... • But an adequate follow up can achieve the best possible neurodevelopment Toronto (Canada): MOTHERISK Detection Follow up Intervention Main objectives To design and to implement a prenatal diagnosis and a neonatal screening protocols of prenatal ethanol exposure To design an intervention program: - Consumption prevention (clinical guidelines) - Diagnosis (biomarkers) - Intervention (structured counseling) - Follow up (clinical protocol): “Pregnancy Without Alcohol” To check the effectiveness of the intervention To follow up of children prenatally exposed to ethanol Translational research and Integrate several areas Health Education Social problems Addiction Clinical Atenttion Public Health Resources The Proposal Is to work in conection with other clinicicians and researchers groups in order to improve: Coordination Exchenge information and Implementation Towards decreased risks for the fetus and the mother... Also decreased the risks for the adolescents… ¡¡Botellones!! And… by the time a person reaches adult life RR and 95% CI associated with alcohol intake lower than 25g/day Corrao G, Bagnardi V, Zambon A, la Vecchia C. A meta-analysis of alcohol consumption and the risk of 15 diseases. Prev Med 2004,38:613-9.