state of the art determination of fetal drug and alcohol exposure douglas lewis united states drug...
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State of the Art Determination of Fetal Drug
and Alcohol Exposure
Douglas LewisUnited States Drug
Testing Laboratories
Diagnosing Fetal Drug & Alcohol Exposure
• Prior to early 1970’s, diagnosis relied on maternal self-report
• 1972 Physical diagnosis on facial dysmorphology for FAS published
• 1972 EMIT urine immunoassays introduced.
Diagnosing Fetal Drug & Alcohol Exposure
• Mid 1970’s 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
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
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
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)
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 FAEE’s in meconium
• 1998 FAEE’s in meconium available from reference lab
(MecStat-EtOHsm)
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
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
Laboratory StudiesFAEE’s in Meconium
1059 1139 3133 30766628 7674
62115
50143
0
10000
20000
30000
40000
50000
60000
70000
ng/g
1st Qtr 2nd Qtr 3rd Qtr 4th Qtr
Quartiles
HawaiiUtah
0
2
4
6
8
10
12
14
16
18
20
AMP COC OPI PCP THC BAR BZP MTD PPX FAEE
Meconium Positivity Rate
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
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
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
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
Diagnosing Fetal Drug & Alcohol Exposure
• New Developments
• Testing Umbilical Cord– Provides >Equal Sensitivity as Meconium– Available on Every Newborn Immediately– Provides More Rapid Results– Lowers Nursing Costs
Umbilical Cord v. Meconium
AMPHETAMINES
+ -
%AGREEMENT = 96.6
+ 20 3
- 1 94
MECONIUM
UCORD
CORD
Umbilical Cord v. Meconium
OPIATES
+ -
%AGREEMENT = 94.9
+ 7 4
- 2 99
MECONIUM
UCORD
CORD
Umbilical Cord v. Meconium
COCAINE
+ -
%AGREEMENT = 99.2
+ 3 0
- 1 99
MECONIUM
UCORD
CORD
Umbilical Cord v. Meconium
CANNABINOIDS
+ -
%AGREEMENT = 90.7
+ 14 9
- 2 93
MECONIUM
UCORD
CORD
Umbilical Cord v. Meconium
PHENCYCLIDINE (PCP)
+ -
%AGREEMENT = 100
+ 0 0
- 0 99
MECONIUM
UCORD
CORD
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.
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.
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
Diagnosing Fetal Drug & Alcohol Exposure
• Why can’t you just test the mom early in the pregnancy?– It requires informed consent. If mom
doesn’t self-report, she’ll usually refuse permission.
– 50% of moms who have no prenatal care are drug/alcohol users.
Drug Detection Times
0 20 40 60 80 100 120 140
Urine
Blood
Amniotic fluid
Hair
U-Cord
Meconium
