Prenatal methadone exposure, meconium biomarker concentrations and neonatal abstinence syndrome.
OBJECTIVE
Methadone is standard pharmacotherapy for opioid-dependent pregnant women, yet the relationship between maternal methadone dose and neonatal abstinence syndrome (NAS) severity is still unclear. This research evaluated whether quantification of fetal methadone and drug exposure via meconium would reflect maternal dose and predict neonatal outcomes.


METHODS
Prospective clinical study.


METHODS
An urban drug treatment facility treating pregnant and post-partum women and their children.


METHODS
Forty-nine opioid-dependent pregnant women received 30-110 mg methadone daily.


METHODS
Maternal methadone dose, infant birth parameters and NAS assessments were extracted from medical records. Thrice-weekly urine specimens were screened for opioids and cocaine. Newborn meconium specimens were quantified for methadone, opioid, cocaine and tobacco biomarkers.


RESULTS
There was no relationship between meconium methadone concentrations, presence of opioids, cocaine and/or tobacco in meconium, maternal methadone dose or NAS severity. Opioid and cocaine were also found in 36.7 and 38.8 of meconium specimens, respectively, and were associated with positive urine specimens in the third trimester. The presence of opioids other than methadone in meconium correlated with increased rates of preterm birth, longer infant hospital stays and decreased maternal time in drug treatment.


CONCLUSIONS
Methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) concentrations in meconium did not predict infant birth parameters or NAS severity. Prospective urine testing defined meconium drug detection windows for opiates and cocaine as 3 months, rather than the currently accepted 6 months. The presence of opioids in meconium could be used as a biomarker for infants at elevated risk in the newborn period.
Gray
Teresa R
TR
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Choo
Robin E
RE
Concheiro
Marta
M
Williams
Erica
E
Elko
Andrea
A
Jansson
Lauren M
LM
Jones
Hendreé E
HE
Huestis
Marilyn A
MA
D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000032:analysis; D003042:Cocaine / Q000009:adverse effects / Q000032:analysis; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000652:urine; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007902:Length of Stay; D008470:Meconium / Q000737:chemistry*; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis*; D009294:Narcotics / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis*; D009357:Neonatal Abstinence Syndrome / Q000453:epidemiology*; D058850:Opiate Substitution Treatment; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000652:urine; D011237:Predictive Value of Tests; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D047928:Premature Birth / Q000453:epidemiology; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology; D011446:Prospective Studies; D015813:Substance Abuse Detection / Q000379:methods*; D055815:Young Adult
D000701:Analgesics, Opioid; D009294:Narcotics; D003042:Cocaine; D008691:Methadone