Screening Newborns for Alcohol Exposure

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Screening Newborns for Alcohol Exposure
Clinical Implementation

• Sarit Shor HBSc.
• Division of Clinical Pharmacology and Toxicology
• Hospital for Sick Children, Toronto
• Department of Pharmacology
• University of Toronto
• Joey Gareri MSc.
• Irena Nulman MD.
• Gideon Koren MD., FRCPC

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Fetal Alcohol Spectrum Disorder

• FASD
• Physical
• Behavioral
• Cognitive disabilities
• Fetal alcohol syndrome (FAS)
• High rate of alcohol consumption among young
  reproductive women (60 - 75 ) (Institute of
  Medicine of the National Academy of Sciences
  Committee for Study Fetal Alcohol Syndrome, 1996
  National Centre for Health Statistics, 1990).

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Fetal Alcohol Spectrum Disorder

• Canadian data (Chudley et al., 2005).
• 14-25 women drink ethanol at some point in
  pregnancy
• 5-9 drink throughout the entire pregnancy
• 3 reporting binge drinking
• The 2003 Canadian Community Health survey
  (Statistics Canada, 2001).
• 1.96 of pregnant women used ethanol once per
  month
• 0.84 drank 2-3 times per month
• 1.26 reported drinking greater than or equal to
  one drink per week

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Incidence Societal Impact

• FASD affects up to 1 of pediatric population in
  North America (Chavez et al., 1988 Sokol
  Clarren, 1989 Sampson et al., 1994 Sampson et
  al., 1997 Williams et al., 1999).
• Canadian annual birth rates 335,000
• These estimations indicate the scope and severity
  of FASD as public health concern
• The annual cost per FASD-affected individual in
  Canada has been estimated at 14,342 CAD

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Secondary Disabilities

• A large proportion of these costs result from
  preventable secondary disabilities associated
  with FASD
• creating a significant economic impact at the
  individual, familial, and societal levels (Nulman
  et al., 1998 Stade, 2003).
• Secondary disabilities
• Incarceration
• Dependent living
• Early death
• Unemployment
• Substance addiction
• Mental health problems
• The risk of these secondary disabilities may be
  decreased with early intervention in FASD
  affected children (Institute of Medicine of the
  National Academy of Sciences Committee for Study
  Fetal Alcohol Syndrome, 1996 Streissguth et al.,
  1996).

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Intervention Treatment

• Intervention and treatment
• adapting FASD-affected individuals to their
  environment by addressing their
  neurodevelopmental issues.
• Animal studies (Hannigan et al.,1993 Christie et
  al., 1999 Rema Ebner, 1999).
• attenuation of prenatal ethanol-related
  neurodevelopmental effects in rats that
  experience enriched/stimulating post-natal
  environments
• early intervention and treatment in the first
  years of life could improve neurological
  performance, potentially reducing deficits in
  cortical function, learning, and memory
  processing

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Diagnosis

• Intervention requires diagnosis
• The optimal time period for diagnosis and
  intervention is prior to 6 years of age
• only 11 of alcohol-affected individuals are
  diagnosed by this time (Streissguth et al.,
  1996).
• Diagnosis of FASD can be challenging as several
  other medical disorders can exhibit similar
  features.

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Diagnosis

• Canadian guidelines (2005) (Chudley et al.,
  2005).
• providing recommendations to Canadian physicians
  for screening and referral practices
• in the absence of craniofacial features (present
  in only 10 of alcohol-affected individuals),
  evidence of maternal prenatal ethanol use is
  required for a diagnosis.
• Accurate ethanol exposure history is paramount to
  mounting an effective strategy to address the
  impact of FASD in the general population.

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Obtaining Exposure History

• Maternal self-reporting of prenatal alcohol
  consumption
• subjective and often unreliable due to guilt and
  fear of reprisal (Russell et al., 1996 Neumann
  Spies, 2003).
• Maternal blood markers
• ineffective at identifying alcohol use in
  pregnancy (Stoler et al., 1998 Bearer, 2001
  Cook, 2003).
• Maternal or neonatal blood and urine for ethanol
• limited usefulness due to rapid elimination
  (Kalant Khanna, 1998).

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Meconium Analysis

• Meconium
• Comprises the first few bowel movements of the
  neonate
• Formation begins around 12 weeks of pregnancy
  (Miller Holzen, 1974 Kwong Ryan, 1997)
• Provide a record of prenatal alcohol exposure
• Fatty acid ethyl esters (FAEEs)
• Formed as a result of enzyme-mediated
  esterification of ethanol and free fatty acids
• O O
• R C OH CH3CH2OH ?
  R C O CH2CH3 H2O
• Fatty Acid Ethanol FAEE
  Water
• (Best and Laposata, 2003)

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Meconium Analysis

• Use of meconium FAEE has been extensively
  validated through cohort and population-based
  studies (Bearer et al., 1992 Bearer et al.,
  1999 Klein et al., 1999 Yamashita et al., 1997
  Bearer et al., 2003 Chan et al., 2003 Chan et
  al., 2004 Brien et al., 2006).
• Studies also have shown an association between
  meconium FAEE concentrations and some
  FASD-related outcome measures (Derauf et al.,
  2003 Noland et al., 2003 Peterson et al.,
  2005  Brien et al., 2006 Jacobson et al.,
  2006).
• Lower birth weight
• Smaller head circumference
• Elevated ethyl oleate correlated with FAS or pFAS
  diagnosis at 5 years of age
• Demonstrated high specificity and sensitivity in
  identifying prenatal exposures
• 5-fold increase in prenatal alcohol exposure
  detection over standard clinical practice (Gareri
  et al., 2006).

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Neonatal Screening

• Meconium analysis of FAEE appears to be a
  valuable tool in obtaining the prenatal exposure
  history required by the Canadian Guidelines for
  FASD diagnosis in the absence of craniofacial
  features
• In clinical practice, participation in screening
  with informed consent may be limited due to
  stigmatization of prenatal drinking
• This may pose a limitation to the usefulness of
  meconium FAEE screening.

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Pilot Study - Objectives

• Primary Objective (Part 1)
• To assess the level of voluntary participation in
  prenatal alcohol exposure screening with informed
  consent.
• Secondary Objective (Part 2)
• To determine if the presence of FAEEs in meconium
  correlates with standard childhood developmental
  milestones and Bayleys test for
  neurodevelopmental screening.

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Hypotheses

• The rate of voluntary participation in meconium
  screening for prenatal alcohol exposure with
  written informed consent will be significantly
  lower compared to the rate of voluntary
  participation in previous anonymous testing
  regimens as established by Gareri et al. (2006)
  in the same region (Grey Bruce, Ontario).
• Children with FAEE positive meconium will exhibit
  clinically significant differences in
  developmental milestones in comparison to
  children with negative FAEE results.

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Method

• Study Design
• Prospective cohort study
• Subjects
• Inclusion Criteria
• All neonates born to women living in the region
  of Grey Bruce between October 2007 and September
  2008 and whose mothers provided written informed
  consent.
• Exclusion Criteria
• All neonates born to women living outside the
  region of Grey Bruce and all neonates whose
  mothers refused to provide informed consent.
• Feasibility (N 1000-1500)
• Based on the public health data provided by the
  Grey Bruce Health Unit, it is estimated that
  1000-1500 infants will be delivered per year in
  all the birth units in the region.

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Ethical Considerations

• Available Information
• Pamphlets will be given to each mother that will
  provide
• Information on FASD and the importance of early
  detection
• Contact information for the Motherisk program.
• Informed Consent
• Will be administered by a trained research
  personnel
• Information requested will include
• TWEAK questionnaire
• Antenatal 1 2 Forms
• Delivery information
• Permission to call for follow up for
  developmental milestones neurodevelopmental
  testing
• There will be complete understanding that
  positive test results will not be reported to
  Childrens Aid Society (CAS)
• Sample
• One meconium sample will be collected for each
  live birth
• Shipped to the Hospital for Sick Children for
  analysis

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Part 2 Milestones Neurodevelopment

• Subjects
• Infants who were tested positive for meconium
  FAEEs will be matched to infants who tested
  negative for presence of meconium FAEEs and whose
  mothers were tested negative on the TWEAK
  questionnaire.
• Methods
• Follow up via phone interviews for developmental
  milestones
• smile, lift head, sit, crawl, stand, speak, walk
• Trained psychometrist will administer Bayleys
  developmental screening test.

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MOTHERS Engagement Assessment

• Engagement
• Outreach worker
• Will provide general information to mothers of
  infants whose meconium tested positive for FAEE
• Will identify families at risk (and provide
  referrals)
• Multidisciplinary program
• Mediated by the Public Health Unit

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MOTHERS- Prevention by Intervention

• Biological mothers of children with FAS exhibit a
  77 risk of having subsequent FAS-affected
  offspring (Huebert Raftis, 1996 Riley McGee,
  2005)
• Substance-addicted women have an 85 incidence of
  multiple pregnancies (4 pregnancies each)
  (Pepler et al., 2002).
• Detection of a first-born child with prenatal
  ethanol exposure can thus prevent future
  alcohol-exposed pregnancies by engaging mothers
  in substance abuse treatment.
• screening has the potential to facilitate FASD
  prevention as well as intervention for both the
  mother and alcohol-affected child.

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Long Term Goals Future Studies

• Successful completion of this study will assess
  the level of voluntary participation in prenatal
  alcohol exposure screening with written informed
  consent in clinical settings.
• Recommendations will be made regarding the
  utility of this test for screening for prenatal
  ethanol exposure in pregnancy in clinical
  practice.
• In addition, children who exhibit developmental
  delays will be enrolled in early intervention
  programs and will be followed to observe their
  progress.
• Women enrolled in support services may be
  followed to observe for changes in quality of
  life.
• A cost-effectiveness evaluation will be conducted
  on this program.