Correlations of Maternal Buprenorphine Dose, Buprenorphine, and Metabolite Concentrations in Meconium With Neonatal Outcomes

Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA.
Clinical Pharmacology &#38 Therapeutics (Impact Factor: 7.9). 09/2008; 84(5):604-12. DOI: 10.1038/clpt.2008.156
Source: PubMed


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.

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Available from: Hendrée E. Jones, Feb 11, 2014
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    • "Xenobiotics and their metabolites are deposited into meconium by the biliary route or through fetal swallowing [8]. While meconium starts to form at the beginning of the second trimester, evidence suggests that meconium likely reflects third trimester fetal exposures [10]. Meconium is considered a highly sensitive matrix, demonstrating a window of detection far exceeding that afforded by traditional urinalysis and therefore, serves as an optimal matrix for population-based studies examining gestational exposures [11],[12]. "
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    • "Research on the relationship between buprenorphine dose and neonatal clinical outcomes has largely although not entirely focused on the differences between buprenorphine and methadone in NAS occurrence or severity, and to a lesser extent on morphine dose to treat NAS, and length of hospitalization for NAS treatment . Research on the relationship between buprenorphine dose and severity of NAS has typically failed to find any such relationship (Bakstad et al., 2009; Fischer et al., 2006; Kacinko et al., 2008; Lejeune et al., 2006; O'Connor et al., 2011). Metz et al. (2011) also reported a failure to find relationships between buprenorphine dose and need for and amount of NAS medication, peak NAS score, and duration of NAS treatment in a sample of 26 neonates prenatally exposed to buprenorphine as part of comprehensive treatment program for maternal opioid use disorder. "
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