Transcript
Page 1: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Neonatal Screening Neonatal Screening for for

Prenatal Alcohol Exposure Prenatal Alcohol Exposure - -

UpdateUpdate Joey Gareri HBSc., MSc.Joey Gareri HBSc., MSc.

Motherisk LaboratoryMotherisk LaboratoryDivision of Clinical Pharmacology & Toxicology, Hospital for Sick ChildrenDivision of Clinical Pharmacology & Toxicology, Hospital for Sick Children

Department of Pharmacology, University of TorontoDepartment of Pharmacology, University of Toronto

Page 2: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

FASD Diagnosis:FASD Diagnosis:Canadian Guidelines (2005)Canadian Guidelines (2005)

(Chudley (Chudley et al. et al. 2005)2005)

A.A. Presence of the 3 characteristic facial features (short palpebral fissures, smooth or Presence of the 3 characteristic facial features (short palpebral fissures, smooth or flattened philtrum, thin vermilion border).flattened philtrum, thin vermilion border).

B.B. Evidence of significant prenatal exposureEvidence of significant prenatal exposure to alcoholto alcohol at levels known to be at levels known to be associated with physical or developmental effects, or both.associated with physical or developmental effects, or both.

C.C. Presence of 1 or more facial features with growth deficits Presence of 1 or more facial features with growth deficits plus known or probable plus known or probable significant prenatal alcohol exposure.significant prenatal alcohol exposure.

D.D. Presence of 1 or more facial features with 1 or more central nervous system deficits Presence of 1 or more facial features with 1 or more central nervous system deficits plus known or probable significant prenatal alcohol exposure.plus known or probable significant prenatal alcohol exposure.

E.E. Presence of 1 or more facial features with pre- or postnatal growth deficits or both Presence of 1 or more facial features with pre- or postnatal growth deficits or both (at the 10th percentile or below [1.5 SD below the mean]) and 1 or more central (at the 10th percentile or below [1.5 SD below the mean]) and 1 or more central nervous system deficits nervous system deficits plus known or probable significant prenatal alcohol plus known or probable significant prenatal alcohol exposure.exposure.

Page 3: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

FASD DiagnosisFASD Diagnosis

METHODS:METHODS:1)1) Cranio-facial featuresCranio-facial features2)2) Confirmation of Confirmation of in utero in utero alcohol exposurealcohol exposure

-maternal self-reporting-maternal self-reporting-maternal biomarkers of alcoholism -maternal biomarkers of alcoholism

**The use of any single or multiple maternal markers is not The use of any single or multiple maternal markers is not very effective in the identification of a drinking mother very effective in the identification of a drinking mother

(Stoler et al., 1998)(Stoler et al., 1998)

BIOMARKER SPECIFIC TO PREGNANCYBIOMARKER SPECIFIC TO PREGNANCY

Page 4: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Detecting Alcohol AbuseDetecting Alcohol Abuse

One standard drink One standard drink (Canadian definition)(Canadian definition)

13.6 grams of ethanol13.6 grams of ethanol 12 oz. beer (5%)12 oz. beer (5%) 5 oz. wine (12-15%)5 oz. wine (12-15%) 1.5 oz. liquor (40%)1.5 oz. liquor (40%)

Alcohol Elimination Rate: ~7 g per hourAlcohol Elimination Rate: ~7 g per hour e.g. 5 drinks in 1 hour e.g. 5 drinks in 1 hour (i.e. binge episode)(i.e. binge episode)

0 BAC within 10 hours0 BAC within 10 hours 0 UAC within 12 hours0 UAC within 12 hours

Page 5: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Ethanol Metabolism & EliminationEthanol Metabolism & Elimination

Oxidative Metabolism

Urine/Breath/Sweat

Non-oxidative Metabolism

Page 6: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

FAEE productionFAEE production

ETHANOL

ADH and Microsomal Oxidation (e.g. CYP 2E1)ACETALDEHYDE

FAEE Synthases

FAEE

Non-Oxidative

FATTY ACIDS

Oxidative

Acyl-coenzyme A:ethanol O-acyltransferase (AEAT)

FATTY ACYL CoA

POTENTIALBIOLOGICAL

MARKERS

Page 7: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

The Matrices:The Matrices:FAEE AnalysisFAEE Analysis

1)1) Neonatal MeconiumNeonatal Meconium 22ndnd & 3 & 3rdrd trimester prenatal ethanol exposure trimester prenatal ethanol exposure

2)2) Neonatal HairNeonatal Hair 33rdrd trimester prenatal ethanol exposure trimester prenatal ethanol exposure

Chan Chan et al. et al. 2004: 2004: FAEE do not cross placenta FAEE do not cross placenta

neonatal FAEE = fetal exposureneonatal FAEE = fetal exposure

3)3) Maternal HairMaternal Hair < 6 month history of general drinking behaviour< 6 month history of general drinking behaviour

Page 8: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Meconium FAEEMeconium FAEE

1)1) MeconiumMeconium analysis analysis Begins formation at ~13 weeks of pregnancyBegins formation at ~13 weeks of pregnancy 22ndnd & 3 & 3rdrd trimester exposure trimester exposure Available within 72 hours of birthAvailable within 72 hours of birth Discarded materialDiscarded material

Page 9: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Meconium FAEE:Meconium FAEE:Maternal Alcohol ConsumptionMaternal Alcohol Consumption

Bearer Bearer et al. et al. 1999: 1999: Prospective Study (United Prospective Study (United States)States) Ethyl linolate; Ethyl linolate; >> 1 drink/week 1 drink/week N = 248N = 248

n = 39 confirmed drinkersn = 39 confirmed drinkers Sensitivity 72%; Specificity 51%Sensitivity 72%; Specificity 51%

Klein Klein et al. et al. 1999: 1999: Case report (Canada)Case report (Canada) High [FAEE] in meconium w/reported prenatal ethanol High [FAEE] in meconium w/reported prenatal ethanol

consumptionconsumption [FAEE] 34-fold higher than non-drinking control group[FAEE] 34-fold higher than non-drinking control group

Page 10: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Meconium FAEE:Meconium FAEE:Maternal Alcohol ConsumptionMaternal Alcohol Consumption

Bearer Bearer et al. et al. 2003: 2003: Prospective study (South Africa)Prospective study (South Africa) Ethyl oleate; Ethyl oleate; >> 1.5 oz. ethanol/drinking day 1.5 oz. ethanol/drinking day N = 27N = 27

n = 21 confirmed drinkersn = 21 confirmed drinkers Sensitivity 84.2%; Specificity 83.3%Sensitivity 84.2%; Specificity 83.3%

Chan Chan et al. et al. 2003: 2003: Prospective study (Canada, Israel)Prospective study (Canada, Israel) Meconium [FAEE] baseline = < 2.00 nmol/gram Meconium [FAEE] baseline = < 2.00 nmol/gram n = 206n = 206

n = 84 non-drinkers; Toronton = 84 non-drinkers; Toronto n = 99 non-drinkers; Jerusalemn = 99 non-drinkers; Jerusalem n = 17 social drinkers; Toronton = 17 social drinkers; Toronto n = 6 confirmed drinkers; Toronton = 6 confirmed drinkers; Toronto

Sensitivity 100%; Specificity 98.4%Sensitivity 100%; Specificity 98.4%

Page 11: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Meconium FAEE:Meconium FAEE:Population-Based StudiesPopulation-Based Studies

Chan Chan et al. et al. 2003 2003 (Canada)(Canada) N = 142 meconium samples with suspicion of prenatal N = 142 meconium samples with suspicion of prenatal

exposure exposure 71% samples positive for at least one illicit drug71% samples positive for at least one illicit drug 14% samples positive for FAEE > 2.0 nmol/gram14% samples positive for FAEE > 2.0 nmol/gram

Moore Moore et alet al. 2003. 2003 (United States) (United States) 2 hospitals: Utah, Hawaii2 hospitals: Utah, Hawaii Universal anonymous screeningUniversal anonymous screening N = 725N = 725 44thth quartile = meconium [FAEE] > 10,000 ng/g quartile = meconium [FAEE] > 10,000 ng/g

Page 12: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Meconium FAEE:Meconium FAEE:Population-Based StudiesPopulation-Based Studies

Gareri Gareri et al. et al. in progressin progress (Canada) (Canada) 5 hospitals: Grey Bruce Region, ON5 hospitals: Grey Bruce Region, ON Universal anonymous screeningUniversal anonymous screening N = 683N = 683 2.5 - 3.5% prevalence of fetal alcohol exposure 2.5 - 3.5% prevalence of fetal alcohol exposure

Meconium [FAEE] > 2.0 nmol/gMeconium [FAEE] > 2.0 nmol/g 5-fold > than clinical reporting5-fold > than clinical reporting

Hutson Hutson et al. et al. in progressin progress (Uruguay) (Uruguay) Prospective study; One hospital serving low SES populationProspective study; One hospital serving low SES population N ~900N ~900 Preliminary resultsPreliminary results

> 30.0% prevalence of fetal alcohol exposure> 30.0% prevalence of fetal alcohol exposure Meconium [FAEE] > 2.0 nmol/gMeconium [FAEE] > 2.0 nmol/g

Neonatal outcomes available for comparisonNeonatal outcomes available for comparison

Page 13: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Meconium FAEE:Meconium FAEE:FASD OutcomesFASD Outcomes

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

Noland Noland et al. et al. 2003 2003 (United States)(United States) Decreased score on executive functioning taskDecreased score on executive functioning task

Tapping inhibition (age 4 years)Tapping inhibition (age 4 years) Lower birth weight, length, head circumferenceLower birth weight, length, head circumference N = 316N = 316

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

Page 14: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Meconium FAEE:Meconium FAEE:FASD OutcomesFASD Outcomes

Jacobson Jacobson et al. et al. 2006 2006 (South Africa)(South Africa) ↑ ↑ [ethyl oleate] in FAS or pFAS diagnosed children [ethyl oleate] in FAS or pFAS diagnosed children

(age 5 years; p < 0.005)(age 5 years; p < 0.005) [ethyl oleate] > maternal self-report correlates to:[ethyl oleate] > maternal self-report correlates to:

Recognition memory, Processing speed, Complexity of symbolic playRecognition memory, Processing speed, Complexity of symbolic play N = 55N = 55

Brien Brien et al. et al. 20062006 (Canada) (Canada) Animal study: guinea pigAnimal study: guinea pig ↑ ↑ Meconium [FAEE] = ↓ neonatal brain weightMeconium [FAEE] = ↓ neonatal brain weight N = 51N = 51

n = 25 ethanol-exposedn = 25 ethanol-exposed n = 23 pair-fed controln = 23 pair-fed control n = 3 water controln = 3 water control

Page 15: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Hair FAEEHair FAEE

2)2) Neonatal HairNeonatal Hair Begins formation at ~20 weeks of pregnancyBegins formation at ~20 weeks of pregnancy 33rdrd trimester exposure trimester exposure Available for up to 3 months after birthAvailable for up to 3 months after birth Small quantities availableSmall quantities available

3)3) Maternal HairMaternal Hair Grows at ~1.0 cm/monthGrows at ~1.0 cm/month Contains history of substance useContains history of substance use

Page 16: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Hair FAEE & Hair FAEE & Maternal Alcohol ConsumptionMaternal Alcohol Consumption

Pragst Pragst et al. et al. 2001; Wurst 2001; Wurst et al. et al. 20042004 < 6 cm hair analysis = maximum 6 mos. History< 6 cm hair analysis = maximum 6 mos. History [FAEE] > 1.0 ng/mg[FAEE] > 1.0 ng/mg

75% sensitivity; 100% specificity75% sensitivity; 100% specificity [FAEE] > 0.5 ng/mg[FAEE] > 0.5 ng/mg

90% sensitivity; 90% specificity90% sensitivity; 90% specificity

Kulaga Kulaga et al. et al. 20062006 Comparison of animal (guinea pig) vs. human dataComparison of animal (guinea pig) vs. human data FAEE incorporation in hair 11-fold higher in humansFAEE incorporation in hair 11-fold higher in humans [ethyl oleate] correlates with total systemic ethanol [ethyl oleate] correlates with total systemic ethanol

exposureexposure

Page 17: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Hair FAEE:Hair FAEE:Neonatal ValidationNeonatal Validation

Caprara Caprara et al. et al. 20052005 Animal Study (guinea pig)Animal Study (guinea pig) Neonatal [FAEE] 10-fold higher in ethanol-exposed littersNeonatal [FAEE] 10-fold higher in ethanol-exposed litters

Caprara Caprara et al. et al. 20052005 Pilot Study; baseline establishmentPilot Study; baseline establishment Community-based pediatric clinicCommunity-based pediatric clinic N = 56N = 56

n = 33 non-drinkersn = 33 non-drinkers n = 23 social drinkers (≤ 2 drinks per week)n = 23 social drinkers (≤ 2 drinks per week)

Range [FAEE] = 0.00 – 2.95 pmol/mgRange [FAEE] = 0.00 – 2.95 pmol/mg Mean [FAEE] = 0.32 pmol/mgMean [FAEE] = 0.32 pmol/mg Median [FAEE] = 0.008 pmol/mgMedian [FAEE] = 0.008 pmol/mg

Page 18: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Future DirectionsFuture Directions

Complete validation of neonatal hair analysis Complete validation of neonatal hair analysis for FAEEfor FAEE Baseline establishment in large populationBaseline establishment in large population

Determine predictive value between [FAEE] Determine predictive value between [FAEE] and FASDand FASD

Page 19: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

AcknowledgementsAcknowledgements

Canadian Institute for Health ResearchCanadian Institute for Health Research

Dr. Gideon KorenDr. Gideon Koren

Dr. James BrienDr. James Brien

Janine HutsonJanine Hutson

Susan SantiagoSusan Santiago

Dr. Bhushan KapurDr. Bhushan Kapur

THANK YOU THANK YOU

THE ENDTHE END

Page 20: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

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

Page 21: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

OVERVIEWOVERVIEWNeonatal Screening for Fetal Alcohol Neonatal Screening for Fetal Alcohol

ExposureExposurePROSPROS

maximize diagnosis/intervention maximize diagnosis/intervention across socioeconomic linesacross socioeconomic lines

opportunity to initiate therapy at opportunity to initiate therapy at earliest possible time in development earliest possible time in development (improved prognosis for outcome)(improved prognosis for outcome)

avoids marginalization of high-risk avoids marginalization of high-risk women (as opposed to targeted women (as opposed to targeted screening)screening)

birth provides a window of opportunity birth provides a window of opportunity in engaging high-risk womenin engaging high-risk women

optimal intervention timing for optimal intervention timing for behaviour changes in motherbehaviour changes in mother

can provide adoptive parents with can provide adoptive parents with valuable background informationvaluable background information

enormous research potential in enormous research potential in engaging an elusive study populationengaging an elusive study population

CONSCONS

potential labeling/stigmatization of potential labeling/stigmatization of mother and childmother and child

potential for conflict due to perceived potential for conflict due to perceived or potential implications of a positive or potential implications of a positive test test

low disease specificity associated with low disease specificity associated with alcohol exposure (<60% unaffected)alcohol exposure (<60% unaffected)

not diagnostic for specific treatmentnot diagnostic for specific treatment intensive follow-up required, high costintensive follow-up required, high cost

can potentially decrease the likelihood can potentially decrease the likelihood of adoption for exposed infantsof adoption for exposed infants

Page 22: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Prevention by InterventionPrevention by Intervention

NEONATAL INTERVENTION CANNOT PREVENT NEONATAL INTERVENTION CANNOT PREVENT PRIMARY ALCOHOL-INDUCED DAMAGEPRIMARY ALCOHOL-INDUCED DAMAGE

Mothers of alcohol-affected children are significantly more Mothers of alcohol-affected children are significantly more likely to likely to produce subsequentproduce subsequent alcohol affected children alcohol affected children

Substance-addicted women have an Substance-addicted women have an 85%85% incidence of incidence of multiple pregnancies (average = 4) and multiple pregnancies (average = 4) and 25%25% incidence of incidence of child apprehension by social serviceschild apprehension by social services

EARLY MATERNAL INTERVENTION (e.g. 1EARLY MATERNAL INTERVENTION (e.g. 1stst pregnancy) can pregnancy) can potentially prevent future cases of FASDpotentially prevent future cases of FASD

Page 23: Neonatal Screening  for  Prenatal Alcohol Exposure -  Update

Prevention by InterventionPrevention by Intervention

In FASD In FASD 50-70% incidence of substance addiction50-70% incidence of substance addiction 50% incidence of inappropriate or promiscuous 50% incidence of inappropriate or promiscuous

sexual behavioursexual behaviour FASD INTERVENTION is capable of alleviating FASD INTERVENTION is capable of alleviating

secondary disabilities which perpetuate FASDsecondary disabilities which perpetuate FASD


Top Related