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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    ABSTRACT: Methadone maintenance treatment (MMT) is the standard of care during pregnancy for opioid-dependency, showing efficacy in improving prenatal care and reducing risk of relapse. By design, however, MMT is only intended to prevent withdrawal thus facilitating cognitive behavioural interventions. In order to maximize the benefits of MMT, it is essential that methadone is both properly prescribed and that additional addiction treatment is concurrently administered. This study aims to determine the effectiveness of MMT engagement in high-risk pregnant women in reducing polydrug use by objective laboratory examination of neonatal meconium. Over a 29-month period, the Motherisk Laboratory at the Hospital for Sick Children in Toronto analyzed meconium samples as per request by social services and hospitals for drugs of abuse. Of the 904 meconium samples received, 273 were tested for methadone with 164 positive and 109 negative for methadone. Almost half of the methadone positive samples (46.34%) were also positive for at least one other opioid compound, which did not differ statistically from the methadone-negative control samples (46.79%; Chi square test, p=0.94). No differences were found between the methadone positive and negative groups in rates of concurrent amphetamines, cocaine, cannabis, and alcohol use indicating a similar risk of polydrug use between pregnant women taking or not taking methadone in this population. The high rates of additional opioid and other drug use in the MMT group, suggest that MMT is failing this population of patients. It is possible that methadone doses during pregnancy are not appropriately adjusted for changes in pharmacokinetic parameters (e.g. blood volume, renal function) during the second and third trimesters. This may result in sub-therapeutic dosing creating withdrawal symptoms leading to additional substance use. Alternatively, these results may be demonstrating a substantial lack in delivery of addiction support services in this vulnerable population.
    PLoS ONE 12/2013; 8(12):e82647. DOI:10.1371/journal.pone.0082647 · 3.23 Impact Factor
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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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    ABSTRACT: Buprenorphine pharmacotherapy for opioid-dependent pregnant women is associated with maternal and neonatal outcomes superior to untreated opioid dependence. However, the literature is inconsistent regarding the possible existence of a dose-response relationship between maternal buprenorphine dose and neonatal clinical outcomes. The present secondary analysis study (1) examined the relationship between maternal buprenorphine dose at delivery and neonatal abstinence syndrome (NAS) peak score, estimated gestational age at delivery, Apgar scores at 1 and 5min, neonatal head circumference, length, and weight at birth, amount of morphine needed to treat NAS, duration of NAS treatment, and duration of neonatal hospital stay and (2) compared neonates who required pharmacotherapy for NAS to neonates who did not require such pharmacotherapy on these same outcomes, in 58 opioid-dependent pregnant women receiving buprenorphine as participants in a randomized clinical trial. (1) Analyses failed to provide evidence of a relationship between maternal buprenorphine dose at delivery and any of the 10 outcomes (all p-values>.48) and (2) significant mean differences between the untreated (n=31) and treated (n=27) for NAS groups were found for duration of neonatal hospital stay and NAS peak score (both p-values<.001). (1) Findings failed to support the existence of a dose-response relationship between maternal buprenorphine dose at delivery and any of 10 neonatal clinical outcomes, including NAS severity and (2) that infants treated for NAS had a higher mean NAS peak score and, spent a longer time in the hospital than did the group not treated for NAS is unsurprising.
    Drug and alcohol dependence 11/2013; 134. DOI:10.1016/j.drugalcdep.2013.11.006 · 3.42 Impact Factor
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