1. State of the Art Determination of Fetal Drug and Alcohol Exposure Douglas Lewis United States Drug Testing Laboratories

2. 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.

3. 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

4. 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

5. 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

6. Diagnosing Fetal Drug & Alcohol Exposure 19881st report on meconium screening for drugs of abuse 1990 1st report on meconium GC/MS confirmation for cocaine 1991Meconium 5 drug panel available from reference lab (MecStat-5 sm )

7. Diagnosing Fetal Drug & Alcohol Exposure 19921st experiments for determining Fatty Acid Ethyl Esters in meconium for alcohol exposure 1996NIAAA funds SBIR phase I grant for FAEE’s in meconium 1998FAEE’s in meconium available from reference lab (MecStat-EtOH sm )

8. 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

9. 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

10. Laboratory Studies FAEE’s in Meconium

11. Meconium Positivity Rate

12. 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

13. 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

14. 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

15. 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

16. 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

17. Umbilical Cord v. Meconium

22. 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.

23. 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.

24. 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

25. 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.

26. Drug Detection Times

27. QUESTIONS Douglas Lewis 1-847-375-0770 douglas.lewis@usdtl.com