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Prevalence of Fetal Alcohol Exposure in the Region of Grey Bruce

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Regional Mass Screening
for
Establishing the Prevalence of
Alcohol Abuse in Pregnancy by
Meconium Analysis
Joey Gareri HBSc.
MSc. Candidate
Motherisk Program, Hospital for Sick Children, Toronto
Department of Pharmacology, University of Toronto, Toronto
Grey Bruce Health Unit, Owen Sound
Gideon Koren MD, FRCPC Hazel Lynn MD, MHSc.
BACKGROUND/RATIONALE
biomarker development
FASD/FAS
пЃ®
Fetal Alcohol Spectrum Disorder (FASD)
пЃ®
пЃ®
A continuum of adverse fetal outcomes encompassing craniofacial
dysmorphology, growth retardation, neurodevelopmental and cognitive
deficits
Secondary Disabilities
пЃ®
пЃ®
пЃ®
пЃ®
пЃ®
пЃ®
“disrupted school experience” and “trouble with the law”
institutionalization/incarceration
unemployment/ dependent living
inappropriate or promiscuous sexual behaviour
mental health problems/substance addiction
Fetal Alcohol Syndrome (FAS)
пЃ®
пЃ®
Represents the far end of the “Spectrum”
Extreme phenotypic expression of heavy prenatal alcohol exposure
Public Health Impact
In the general neonatal population…
пЃ® ~1/100 are affected by Fetal Alcohol Spectrum
Disorder
пЃ® ~1/1000 are affected by Fetal Alcohol Syndrome
Born to heavy-drinking mothers…
пЃ® 4% of children have FAS
пЃ® 40% of children have 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
BACKGROUND/RATIONALE
fatty acid ethyl esters (FAEE)
as a biomarker
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
Meconium as the Ideal Matrix
пЃ®
Meconium = baby’s first bowel movements (i.e. first
few stools)
пЃ® A matrix unique to the developing fetus that is already
commonly used in neonatal drug screening
пЃ® Superior to blood and urine
пЃ® Discarded material
пЃ® Collection is easy and non-invasive
пЃ® Wide window of opportunity
пЃ® Accumulation from 13th week gestation until birth
FAEE Meconium Analysis:
Summary of Development
пЃ®
Ethanol metabolites produced by both mother and baby
пЃ®
Do not cross the placenta
пЃ®
FAEE in meconium are results of ONLY fetal metabolism of ethanol
пЃ®
Higher concentration of FAEE in neonates exposed to alcohol
(Animal & Human Studies)
пЃ®
Baseline establishment (n=200)
пЃ®
пЃ®
Positive cut-off: 2.0 nmol total FAEE/g meconium
100% Sensitive (0 false negatives)
98.4% Specific (low incidence of false positives)
FAEE Meconium Analysis:
Implications of a Positive Result
пЃ®
1st trimester exposure undetectable
пЃ®
пЃ®
Social-drinkers fall below the baseline
пЃ®
пЃ®
Accidental exposure excluded
Specific to heavy-drinking population
Positive result corresponds to sustained alcohol use
through the latter two-thirds of pregnancy
пЃ®
Addiction-related use pattern
Prevalence of Fetal Alcohol Exposure
in Grey Bruce, Ontario
Grey Bruce, Ontario
пЃ®
Regional self-perception of excessive alcohol use
пЃ®
General alcohol use exceeds national average
пЃ®
CANADA:
пЃ®
пЃ®
GREY BRUCE:
пЃ®
пЃ®
74% rate of regular alcohol use (StatsCan, 2001)
Diverse populous
пЃ®
пЃ®
пЃ®
пЃ®
пЃ®
50% rate of regular alcohol use (Health Canada, 2002)
Urban centre (Owen Sound)
Rural/farming communities
Aboriginal communities
Amish communities
Proactive Public Health Unit
Making in-roads…
пЃ®
1st population-based study using FAEE as a
biomarker for heavy prenatal alcohol exposure
пЃ®
Co-operative collaboration between an urbanbased research institution and regional healthcare providers
Primary Hypothesis
The fetal alcohol exposure rate as determined
by FAEE analysis will exceed rates reported
by epidemiological survey due to the lower
sensitivity of maternal self-reporting.
Secondary Objectives
пЃ®
Reveal discernable expression patterns of the spectrum of FAEE that can be
recovered from meconium (lauric, myristic, palmitic, palmitoleic, stearic,
oleic, linoleic, linolenic, and arachidonic acid ethyl esters).
пЃ®
Assess the applicability of the FAEE meconium test as a population
screening tool.
пЃ®
Increase public awareness of FAS and FASD in the region.
пЃ®
Increase awareness and diagnosis of FAS and FASD in the medical
community of Grey-Bruce.
пЃ®
Create a model framework for future regional prevalence studies carried
out in co-operation with public health departments and regional medical
centres.
Study Design
пЃ®
Anonymous diaper collection
пЃ®
пЃ®
пЃ®
No supplemental information collected
maximal participation пѓ most accurate prevalence
value
No Consent Required
пЃ®
пЃ®
пЃ®
пЃ®
Notification of “population health study supporting
healthy child development” via posters on the wards
Assurance of anonymity
Right of refusal to provide a sample
Supplemental information (pamphlets) available upon
request
Study Design
пЃ®
Duration:
 January 1, 2004 – February 5, 2005
пЃ®
5 regional birthing centres + Grey-Simcoe
midwives
пЃ®
пЃ®
Wiarton, Owen Sound, Markdale, Walkerton, Hanover
Regional Birth Rate: ~1,000 live births/year
Study Population
пЃ®
All neonates born in the five regional birthing
centres
пЃ®
All neonates born via midwife (i.e. homebirth)
in the region of Grey Bruce
METHODS:
Sample Collection
i.
Mom comes in for delivery
ii.
Nurse advises Mom about the study and provides her with a
designated sealable bag
iii.
Baby is born
iv.
Mom or nurse changes soiled diaper
v.
Mom/nurse places the diaper in the designated sealable bag
vi.
Nurse takes the bag and places it in a freezer
vii.
frozen diapers are collected periodically and the samples are
analyzed
METHODS:
FAEE Extraction/Analysis
пЃ®
Liquid-Liquid extraction (hexane:acetone)
followed by Solid Phase extraction of FAEE
from meconium (adapted by Chan et al.)
пЃ®
FAEE Analysis by Gas Chromatography
пЃ®
Confirmation of all positive and random
negative samples via Mass Spectrometry
METHODS:
FAEE Extraction/Analysis
NEGATIVE
POSITIVE
RESULTS:
Participation/Coverage
(collection = 12 months)
Source
Births
Diapers
Viable
Samples
Diaper
Recovery
Sample
Recovery
Markdale
12
8
7
66.67%
58.33%
Owen Sound
659
625
575
94.84%
87.25%
Wiarton
13
5
4
38.46%
30.77%
Hanover
92
87
79
94.57%
85.87%
Walkerton
261
163
150
62.45%
57.47%
Midwives
39
33
29
84.62%
74.36%
1076
921
844
85.59%
78.44%
Totals
RESULTS:
Sample Loss
пЃ®
LOST SAMPLES
пЃ®
пЃ®
пЃ®
77 diapers пѓ non-sufficient quantity (<0.5 g)
~70 diapers пѓ housekeeping error
155 diapers пѓ not collected
NO REPORTED REFUSALS
Other Sources of Subject Loss
пЃ® Patient diversion
пЃ®
extra-regional hospitals
пЃ®
Tertiary care: potentially important “high-risk” mothers
PRELIMINARY RESULTS:
Prenatal Exposure Rate
FAEE analysis
пЃ®
Reported Alcohol Use in
Pregnancy (U.S. statistics)
602 samples analyzed
пЃ®
пЃ®
пЃ®
(CDC 1997 & 2002)
26 positive results
Fetal alcohol exposure
rate: 4.32%
Anonymous telephone survey
пЃ®
Prevalence of heavy drinking in
pregnancy (>14 drinks/ week) is
about 0.1% to 0.3%
>14-fold higher than reported values
PRELIMINARY RESULTS:
Positive vs. Negative Samples
пЃ®
Positive Samples (n = 26)
пЃ®
пЃ®
пЃ®
> 2 nmol/g
mean = 17.67 nmol/g
range
пЃ®
пЃ®
2.23 - 144.18 nmol/g
Negative Samples (n = 576)
пЃ®
> LOQ (1 mg/mL) (n = 126)
пЃ®
пЃ®
mean = 0.46 nmol/g
range
пЃ® 0.01 - 1.95 nmol/g
PRELIMINARY RESULTS:
Baseline Proximity
PRELIMINARY RESULTS:
FAEE species distribution
2 short-chain esters
not included in
[FAEE] calculation
Selective expression of longerchain esters in positive samples
PRELIMINARY RESULTS:
FASD awareness
Public awareness
пЃ® Public Health Rounds in Grey Bruce
пЃ® March,
2004
Health-care awareness
пЃ® Physician Grand Rounds
пЃ® February,
пЃ®
2004
GB Health Network administrators meeting
пЃ®
September, 2004
FUTURE WORK
пЃ®
пЃ®
GC-MS confirmation of positive results
Collection of further epidemiological data
from regional authorities
 comparison to “Parkin” intake questionnaire
пЃ®
пЃ®
пЃ®
Yes/No, drug/alcohol use in pregnancy
Analysis of remaining samples
Inclusion of St. Joseph’s Health Services in
London, Ontario
Acknowledgements
Canadian Institute for Health Research
Hospital for Sick Children
Dr. G. Koren MD
Daphne Chan BSc
Julia Klein MSc
Dr. Bhushan Kapur PhD
Chris Paciorek
University of Toronto
Dr. Cindy Woodland PhD
Grey Bruce Public Health Unit
Dr. Hazel Lynn
Maureen Lapointe
GBHS – Owen Sound Site
Jeff Gonder
Maryann Townsend
GBHS – Wiarton
Val Marcella
GBHS – Markdale Site
Suzie Furlong
Hanover and District Hospital
Vivian Nieson
SGBHC – Walkerton Site
Melody King
Joanne McKee
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