State of the Art Determination of Fetal Drug and Alcohol Exposure

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State of the Art Determination of Fetal Drug and
Alcohol Exposure

• Douglas Lewis
• United States Drug Testing Laboratories

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Diagnosing Fetal Drug Alcohol Exposure

• Prior to early 1970s, diagnosis relied on
  maternal self-report
• 1972 Physical diagnosis on facial dysmorphology
  for FAS published
• 1972 EMIT urine immunoassays introduced.

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Diagnosing Fetal Drug Alcohol Exposure

• Mid 1970s EMIT allows newborn maternal urine
  tests for drugs of abuse
• Maternal testing requires informed consent
• Newborn testing does not require maternal consent
• Newborn urine testing slowly adopted

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Diagnosing Fetal Drug Alcohol Exposure

• 1982 Cocaine babies arrive
• Huge demand for newborn testing starts
• Only 50 of urine tests ordered on NICU admits
  actually administered.
• Good data on drug exposure for neonates needed,
  but not being obtained
• Outcome measures deficient due to lack of true
  exposure data

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Diagnosing Fetal Drug Alcohol Exposure

• Outcomes originally ascribed to maternal drug use
  - just wrong.
• Urine lacked a long term direct marker for
  alcohol exposure
• Many cocaine effects were actually fetal alcohol
  effects
• A clear need arose for improved neonatal drug and
  alcohol exposure testing

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Diagnosing Fetal Drug Alcohol Exposure

• 1988 1st report on meconium screening for
  drugs of abuse
• 1990 1st report on meconium GC/MS
  confirmation for cocaine
• 1991 Meconium 5 drug panel available from
  reference lab (MecStat-5sm)

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Diagnosing Fetal Drug Alcohol Exposure

• 1992 1st experiments for determining Fatty Acid
  Ethyl Esters in meconium for alcohol exposure
• 1996 NIAAA funds SBIR phase I grant for FAEEs
  in meconium
• 1998 FAEEs in meconium available from
  reference lab (MecStat-EtOHsm)

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Diagnosing Fetal Drug Alcohol Exposure

• USDTL - Over 50,000 Drug EtOH Exposed Newborns
  Identified using Meconium since 1991
• Expanded Drug Panels
• Oxycodone, Hydrocodone, Hydromorphone
• Benzodiazepines
• Methadone, Meperidine, Tramadol
• Propoxyphene

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Diagnosing Fetal Drug Alcohol Exposure

• Meconium has become the Gold Standard for Drug
  EtOH Identification
• IDEAL Study of Methamphetamine Exposure During
  Pregnancy
• Two States and a Canadian Province Conducted
  Fetal Alcohol Prevalence Studies

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Laboratory StudiesFAEEs in Meconium
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Meconium Positivity Rate
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Diagnosing Fetal Drug Alcohol Exposure

• MecStat Turnaround of Results
• Negative Screens - Same Day Report
• Positive Screens - 24 to 48 hours GC/MS Confirmed
  Quantitative Results

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Meconium Specimen Collection Storage

• At least 3 grams of meconium should be collected,
  total passage optimum specimen
• Specimens for FAEE analysis should be frozen upon
  collection and shipped frozen.
• Drugs of abuse are stable in meconium for at
  least 2 weeks at room temperature

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Diagnosing Fetal Drug Alcohol Exposure

• Recent Findings
• Pre-gestational Diabetic Moms can Auto-brew
  Alcohol
• Fetal Alcohol Exposure can Result by Diffusion
  from Bladder of Mom
• May Help Explain High Risk of Teratogenic Outcomes

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Diagnosing Fetal Drug Alcohol Exposure

• Meconium testing has drawbacks
• Up to 10 of births pass meconium in utero - No
  specimen available
• In utero passage of meconium a sign of fetal
  distress - also can be a sign of drug exposure
• Need a universally available specimen with same
  (or better) diagnostic power as meconium

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Diagnosing Fetal Drug Alcohol Exposure

• New Developments
• Testing Umbilical Cord
• Provides gtEqual Sensitivity as Meconium
• Available on Every Newborn Immediately
• Provides More Rapid Results
• Lowers Nursing Costs

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Umbilical Cord v. Meconium
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Umbilical Cord v. Meconium
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Umbilical Cord v. Meconium
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Umbilical Cord v. Meconium
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Umbilical Cord v. Meconium
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Phosphatidylethanol (PEth) in Umbilical Cord

• Phosphatidyethanol is a unique phospholipid only
  formed when EtOH is present within cells
• Humans have no enzyme to destroy PEth
• PEth incorporates into cell membranes and remains
  until cell death.

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Phosphatidylethanol (PEth) in Umbilical Cord

• PEth found in red blood cells and virtually all
  tissues of heavy EtOH users
• PEth concentrations closely follow EtOH dosing
• Umbilical cord forms PEth
• PEth in umbilical cord is extractable and
  detectable.

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Phosphatidylethanol (PEth) in Umbilical Cord

• Current NIAAA grant to determine feasibility of
  PEth in umbilical cord as diagnostic test.
• 200 paired meconium-umbilical cord specimens from
  drug/EtOH suspected exposed newborns.
• Results in Fall 2007

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Diagnosing Fetal Drug Alcohol Exposure

• Why cant you just test the mom early in the
  pregnancy?
• It requires informed consent. If mom doesnt
  self-report, shell usually refuse permission.
• 50 of moms who have no prenatal care are
  drug/alcohol users.

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Drug Detection Times
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QUESTIONS

• Douglas Lewis
• 1-847-375-0770
• douglas.lewis_at_usdtl.com