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)
(Chudley et al. 2005)
A. Presence of the 3 characteristic facial features (short palpebral fissures, smooth or
flattened philtrum, thin vermilion border).
B. Evidence of significant prenatal exposure to alcohol at levels known to be
associated with physical or developmental effects, or both.
C. Presence of 1 or more facial features with growth deficits plus known or probable
significant prenatal alcohol exposure.
D. Presence of 1 or more facial features with 1 or more central nervous system deficits
plus known or probable significant prenatal alcohol exposure.
E. 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
nervous system deficits plus known or probable significant prenatal alcohol
exposure.
FASD Diagnosis
METHODS:
1) Cranio-facial features
2) 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 Abuse

One standard drink (Canadian definition)

13.6 grams of ethanol




12 oz. beer (5%)
5 oz. wine (12-15%)
1.5 oz. liquor (40%)
Alcohol Elimination Rate: ~7 g per hour

e.g. 5 drinks in 1 hour (i.e. binge episode)


0 BAC within 10 hours
0 UAC within 12 hours
Ethanol Metabolism & Elimination
Oxidative Metabolism
Urine/Breath/Sweat
Non-oxidative Metabolism
FAEE production
Oxidative
ACETALDEHYDE
ADH and Microsomal Oxidation (e.g. CYP 2E1)
FATTY ACYL CoA
ETHANOL
Acyl-coenzyme A:ethanol
O-acyltransferase (AEAT)
FAEE
FATTY ACIDS
FAEE Synthases
Non-Oxidative
POTENTIAL
BIOLOGICAL
MARKERS
The Matrices:
FAEE Analysis
Neonatal Meconium
1)

2nd & 3rd trimester prenatal ethanol exposure
Neonatal Hair
2)

3rd trimester prenatal ethanol exposure
Chan et al. 2004:
FAEE do not cross placenta
neonatal FAEE = fetal exposure
Maternal Hair
3)

< 6 month history of general drinking behaviour
Meconium FAEE
1)
Meconium analysis




Begins formation at ~13 weeks of pregnancy
2nd & 3rd trimester exposure
Available within 72 hours of birth
Discarded material
Meconium FAEE:
Maternal Alcohol Consumption

Bearer et al. 1999: Prospective Study (United
States)


Ethyl linolate; > 1 drink/week
N = 248



n = 39 confirmed drinkers
Sensitivity 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 Consumption

Bearer et al. 2003: Prospective study (South Africa)


Ethyl oleate; > 1.5 oz. ethanol/drinking day
N = 27



n = 21 confirmed drinkers
Sensitivity 84.2%; Specificity 83.3%
Chan et al. 2003: Prospective study (Canada, Israel)


Meconium [FAEE] baseline = < 2.00 nmol/gram
n = 206





n = 84 non-drinkers; Toronto
n = 99 non-drinkers; Jerusalem
n = 17 social drinkers; Toronto
n = 6 confirmed drinkers; Toronto
Sensitivity 100%; Specificity 98.4%
Meconium FAEE:
Population-Based Studies

Chan et al. 2003 (Canada)

N = 142 meconium samples with suspicion of prenatal
exposure



71% samples positive for at least one illicit drug
14% samples positive for FAEE > 2.0 nmol/gram
Moore et al. 2003 (United States)




2 hospitals: Utah, Hawaii
Universal anonymous screening
N = 725
4th quartile = meconium [FAEE] > 10,000 ng/g
Meconium FAEE:
Population-Based Studies

Gareri et al. in progress (Canada)




5 hospitals: Grey Bruce Region, ON
Universal anonymous screening
N = 683
2.5 - 3.5% prevalence of fetal alcohol exposure



Meconium [FAEE] > 2.0 nmol/g
5-fold > than clinical reporting
Hutson et al. in progress (Uruguay)



Prospective study; One hospital serving low SES population
N ~900
Preliminary results

> 30.0% prevalence of fetal alcohol exposure


Meconium [FAEE] > 2.0 nmol/g
Neonatal outcomes available for comparison
Meconium FAEE:
FASD Outcomes

Derauf 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 task




Tapping inhibition (age 4 years)
Lower birth weight, length, head circumference
N = 316
Peterson et al. 2005 (United States)


Decreased psychomotor performance (age 2 years; P < 0.04)
N = 202
Meconium FAEE:
FASD Outcomes

Jacobson et al. 2006 (South Africa)

↑ [ethyl oleate] in FAS or pFAS diagnosed children


[ethyl oleate] > maternal self-report correlates to:



(age 5 years; p < 0.005)
Recognition memory, Processing speed, Complexity of symbolic play
N = 55
Brien et al. 2006 (Canada)



Animal study: guinea pig
↑ Meconium [FAEE] = ↓ neonatal brain weight
N = 51



n = 25 ethanol-exposed
n = 23 pair-fed control
n = 3 water control
Hair FAEE
2)
Neonatal Hair




3)
Begins formation at ~20 weeks of pregnancy
3rd trimester exposure
Available for up to 3 months after birth
Small quantities available
Maternal Hair


Grows at ~1.0 cm/month
Contains history of substance use
Hair FAEE &
Maternal Alcohol Consumption

Pragst et al. 2001; Wurst et al. 2004


< 6 cm hair analysis = maximum 6 mos. History
[FAEE] > 1.0 ng/mg


[FAEE] > 0.5 ng/mg


75% sensitivity; 100% specificity
90% sensitivity; 90% specificity
Kulaga et al. 2006



Comparison of animal (guinea pig) vs. human data
FAEE incorporation in hair 11-fold higher in humans
[ethyl oleate] correlates with total systemic ethanol
exposure
Hair FAEE:
Neonatal Validation

Caprara et al. 2005



Animal Study (guinea pig)
Neonatal [FAEE] 10-fold higher in ethanol-exposed litters
Caprara et al. 2005



Pilot Study; baseline establishment
Community-based pediatric clinic
N = 56





n = 33 non-drinkers
n = 23 social drinkers (≤ 2 drinks per week)
Range [FAEE] = 0.00 – 2.95 pmol/mg
Mean [FAEE] = 0.32 pmol/mg
Median [FAEE] = 0.008 pmol/mg
Future Directions

Complete validation of neonatal hair analysis
for FAEE


Baseline 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
Portrait of the Addicted Mother











Unemployed (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%)
OVERVIEW
Neonatal Screening for Fetal Alcohol
Exposure
PROS







maximize diagnosis/intervention
across socioeconomic lines
opportunity 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
women
optimal intervention timing for
behaviour changes in mother
can provide adoptive parents with
valuable background information
enormous research potential in
engaging an elusive study population
CONS






potential labeling/stigmatization of
mother and child
potential for conflict due to perceived
or potential implications of a positive
test
low disease specificity associated
with alcohol exposure (<60%
unaffected)
not diagnostic for specific treatment
intensive follow-up required, high
cost
can potentially decrease the
likelihood of adoption for exposed
infants
Prevention by Intervention
NEONATAL INTERVENTION CANNOT PREVENT
PRIMARY ALCOHOL-INDUCED DAMAGE


Mothers of alcohol-affected children are significantly
more likely to produce subsequent alcohol affected
children
Substance-addicted women have an 85% incidence
of multiple pregnancies (average = 4) and 25%
incidence of child apprehension by social services

EARLY 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 behaviour

FASD INTERVENTION is capable of alleviating
secondary disabilities which perpetuate FASD