Correlations of maternal buprenorphine dose, buprenorphine, and metabolite concentrations in meconium with neonatal outcomes

Clin Pharmacol Ther. 2008 Nov;84(5):604-12. doi: 10.1038/clpt.2008.156. Epub 2008 Aug 13.


For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Buprenorphine / metabolism*
  • Buprenorphine / therapeutic use
  • Cocaine / urine*
  • Double-Blind Method
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Maternal Behavior
  • Maternal-Fetal Exchange
  • Meconium / chemistry*
  • Methadone / therapeutic use
  • Narcotic Antagonists / metabolism*
  • Narcotic Antagonists / therapeutic use
  • Neonatal Abstinence Syndrome / diagnosis
  • Neonatal Abstinence Syndrome / drug therapy
  • Nicotine / metabolism*
  • Opiate Alkaloids / urine*
  • Opioid-Related Disorders / drug therapy*
  • Opioid-Related Disorders / rehabilitation
  • Opioid-Related Disorders / urine
  • Pregnancy
  • Smoking / metabolism


  • Narcotic Antagonists
  • Opiate Alkaloids
  • Buprenorphine
  • Nicotine
  • Cocaine
  • Methadone