neonatal screening for prenatal alcohol exposure - update

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Neonatal Screening for Prenatal Alcohol Exposure - Update. Joey Gareri HBSc., MSc. Motherisk Laboratory Division of Clinical Pharmacology & Toxicology, Hospital for Sick Children Department of Pharmacology, University of Toronto. FASD Diagnosis: Canadian Guidelines (2005). - PowerPoint PPT Presentation

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  • Neonatal Screening for Prenatal Alcohol Exposure - Update Joey Gareri HBSc., MSc.Motherisk LaboratoryDivision of Clinical Pharmacology & Toxicology, Hospital for Sick ChildrenDepartment of Pharmacology, University of Toronto

  • FASD Diagnosis:Canadian Guidelines (2005)(Chudley et al. 2005)

  • FASD DiagnosisMETHODS:1)Cranio-facial features2)Confirmation of in utero alcohol exposure-maternal self-reporting-maternal biomarkers of alcoholism *The use of any single or multiple maternal markers is not very effective in the identification of a drinking mother (Stoler et al., 1998)

    BIOMARKER SPECIFIC TO PREGNANCY

  • Detecting Alcohol AbuseOne standard drink (Canadian definition)13.6 grams of ethanol12 oz. beer (5%)5 oz. wine (12-15%)1.5 oz. liquor (40%)

    Alcohol Elimination Rate: ~7 g per houre.g. 5 drinks in 1 hour (i.e. binge episode)0 BAC within 10 hours0 UAC within 12 hours

  • Ethanol Metabolism & Elimination

  • FAEE productionETHANOLADH and Microsomal Oxidation (e.g. CYP 2E1)ACETALDEHYDEFAEE SynthasesFAEENon-OxidativeFATTY ACIDSOxidativeAcyl-coenzyme A:ethanol O-acyltransferase (AEAT)FATTY ACYL CoAPOTENTIALBIOLOGICALMARKERS

  • The Matrices:FAEE AnalysisNeonatal Meconium2nd & 3rd trimester prenatal ethanol exposure

    Neonatal Hair3rd trimester prenatal ethanol exposure

    Chan et al. 2004: FAEE do not cross placenta neonatal FAEE = fetal exposure

    Maternal Hair < 6 month history of general drinking behaviour

  • Meconium FAEEMeconium analysisBegins formation at ~13 weeks of pregnancy2nd & 3rd trimester exposureAvailable within 72 hours of birthDiscarded material

  • Meconium FAEE:Maternal Alcohol Consumption

    Bearer et al. 1999: Prospective Study (United States)Ethyl linolate; > 1 drink/week N = 248n = 39 confirmed drinkersSensitivity 72%; Specificity 51%

    Klein et al. 1999: Case report (Canada)High [FAEE] in meconium w/reported prenatal ethanol consumption[FAEE] 34-fold higher than non-drinking control group

  • Meconium FAEE:Maternal Alcohol ConsumptionBearer et al. 2003: Prospective study (South Africa)Ethyl oleate; > 1.5 oz. ethanol/drinking dayN = 27n = 21 confirmed drinkersSensitivity 84.2%; Specificity 83.3%

    Chan et al. 2003: Prospective study (Canada, Israel)Meconium [FAEE] baseline = < 2.00 nmol/gram n = 206n = 84 non-drinkers; Toronton = 99 non-drinkers; Jerusalemn = 17 social drinkers; Toronton = 6 confirmed drinkers; TorontoSensitivity 100%; Specificity 98.4%

  • Meconium FAEE:Population-Based StudiesChan et al. 2003 (Canada)N = 142 meconium samples with suspicion of prenatal exposure 71% samples positive for at least one illicit drug14% samples positive for FAEE > 2.0 nmol/gram

    Moore et al. 2003 (United States)2 hospitals: Utah, HawaiiUniversal anonymous screeningN = 7254th quartile = meconium [FAEE] > 10,000 ng/g

  • Meconium FAEE:Population-Based StudiesGareri et al. in progress (Canada)5 hospitals: Grey Bruce Region, ONUniversal anonymous screeningN = 6832.5 - 3.5% prevalence of fetal alcohol exposure Meconium [FAEE] > 2.0 nmol/g5-fold > than clinical reporting

    Hutson et al. in progress (Uruguay)Prospective study; One hospital serving low SES populationN ~900Preliminary results> 30.0% prevalence of fetal alcohol exposureMeconium [FAEE] > 2.0 nmol/gNeonatal outcomes available for comparison

  • Meconium FAEE:FASD OutcomesDerauf et al. 2003 (United States)Lower one-minute Apgar scores (p = 0.003)[ethyl oleate] assoc. w/low birth weight (p = 0.006)N = 422

    Noland et al. 2003 (United States)Decreased score on executive functioning taskTapping inhibition (age 4 years)Lower birth weight, length, head circumferenceN = 316

    Peterson et al. 2005 (United States)Decreased psychomotor performance (age 2 years; P < 0.04)N = 202

  • Meconium FAEE:FASD OutcomesJacobson et al. 2006 (South Africa) [ethyl oleate] in FAS or pFAS diagnosed children (age 5 years; p < 0.005)[ethyl oleate] > maternal self-report correlates to:Recognition memory, Processing speed, Complexity of symbolic playN = 55

    Brien et al. 2006 (Canada)Animal study: guinea pig Meconium [FAEE] = neonatal brain weightN = 51n = 25 ethanol-exposedn = 23 pair-fed controln = 3 water control

  • Hair FAEENeonatal HairBegins formation at ~20 weeks of pregnancy3rd trimester exposureAvailable for up to 3 months after birthSmall quantities available

    Maternal HairGrows at ~1.0 cm/monthContains history of substance use

  • Hair FAEE & Maternal Alcohol ConsumptionPragst et al. 2001; Wurst et al. 2004< 6 cm hair analysis = maximum 6 mos. History[FAEE] > 1.0 ng/mg75% sensitivity; 100% specificity[FAEE] > 0.5 ng/mg90% sensitivity; 90% specificity

    Kulaga et al. 2006Comparison of animal (guinea pig) vs. human dataFAEE incorporation in hair 11-fold higher in humans[ethyl oleate] correlates with total systemic ethanol exposure

  • Hair FAEE:Neonatal ValidationCaprara et al. 2005Animal Study (guinea pig)Neonatal [FAEE] 10-fold higher in ethanol-exposed litters

    Caprara et al. 2005Pilot Study; baseline establishmentCommunity-based pediatric clinicN = 56n = 33 non-drinkersn = 23 social drinkers ( 2 drinks per week)Range [FAEE] = 0.00 2.95 pmol/mgMean [FAEE] = 0.32 pmol/mgMedian [FAEE] = 0.008 pmol/mg

  • Future DirectionsComplete validation of neonatal hair analysis for FAEEBaseline establishment in large population

    Determine predictive value between [FAEE] and FASD

  • Acknowledgements

    Canadian Institute for Health Research

    Dr. Gideon Koren

    Dr. James Brien

    Janine Hutson

    Susan Santiago

    Dr. Bhushan Kapur

    THANK YOU THE END

  • Portrait of the Addicted MotherUnemployed (93%)Annual Income < $15,000/yr (CAD) (96%)Grade 12 education or less (92%)Single/Divorced/Separated (74%)No permanent residence (23%)Multiple pregnancies (87%)Apprehended children (25%) Children living with other family members (74%)Abused by partner (60%)Depressed (78%)Suicidal thinking (25%)

  • OVERVIEWNeonatal Screening for Fetal Alcohol ExposurePROS

    maximize diagnosis/intervention across socioeconomic linesopportunity to initiate therapy at earliest possible time in development (improved prognosis for outcome)avoids marginalization of high-risk women (as opposed to targeted screening)birth provides a window of opportunity in engaging high-risk womenoptimal intervention timing for behaviour changes in mothercan provide adoptive parents with valuable background informationenormous research potential in engaging an elusive study population

    CONS

    potential labeling/stigmatization of mother and childpotential for conflict due to perceived or potential implications of a positive test low disease specificity associated with alcohol exposure (

  • Prevention by InterventionNEONATAL INTERVENTION CANNOT PREVENT PRIMARY ALCOHOL-INDUCED DAMAGE

    Mothers of alcohol-affected children are significantly more likely to produce subsequent alcohol affected childrenSubstance-addicted women have an 85% incidence of multiple pregnancies (average = 4) and 25% incidence of child apprehension by social servicesEARLY MATERNAL INTERVENTION (e.g. 1st pregnancy) can potentially prevent future cases of FASD

  • Prevention by Intervention

    In FASD 50-70% incidence of substance addiction 50% incidence of inappropriate or promiscuous sexual behaviourFASD INTERVENTION is capable of alleviating secondary disabilities which perpetuate FASD