Elsevier

Drug and Alcohol Dependence

Volume 180, 1 November 2017, Pages 56-61
Drug and Alcohol Dependence

Full length article
Maternal buprenorphine treatment and infant outcome

https://doi.org/10.1016/j.drugalcdep.2017.08.001Get rights and content

Highlights

  • Study focused on a sample of buprenorphine-exposed infants.

  • Maternal gestational buprenorphine dose is a positive predictor of NAS severity.

  • Polysubstance exposure most potently predicted NAS severity.

  • Findings underscore the need for comprehensive addictions treatment during pregnancy.

Abstract

Background and objectives

Maternal buprenorphine maintenance predisposes the infant to exhibit neonatal abstinence syndrome (NAS), but there is insufficient published information regarding the nature of NAS and factors that contribute to its severity in buprenorphine-exposed infants.

Methods

The present study evaluated forty-one infants of buprenorphine-maintained women in comprehensive substance use disorder treatment who participated in an open-label study examining the effects of maternal buprenorphine maintenance on infant outcomes. Modifiers of the infant outcomes, including maternal treatment and substance use disorder parameters, were also evaluated.

Results

Fifty-nine percent of offspring exhibited NAS that required pharmacologic management. Both maternal buprenorphine dose as well as prenatal polysubstance exposure to illicit substance use/licit substance misuse were independently associated with NAS expression. Polysubstance exposure was associated with more severe NAS expression after controlling for the effects of buprenorphine dose. Other exposures, including cigarette smoking and SRI use, were not related to outcomes. Maternal buprenorphine dose was positively associated with lower birth weight and length.

Conclusions

Polysubstance exposure was the most potent predictor of NAS severity in this sample of buprenorphine-exposed neonates. This finding suggests the need for interventions that reduce maternal polysubstance use during medication assisted treatment for opioid use disorder, and highlights the necessity of a comprehensive approach, beyond buprenorphine treatment alone, for the optimal care for pregnant women with opioid use disorders.

Introduction

Gestational illicit opioid use and licit opioid misuse are on the rise in the US, with an attendant increase in the incidence of neonatal abstinence syndrome (NAS) among exposed infants (Patrick et al., 2012, Patrick et al., 2015, Ko et al., 2016). Medication assisted treatment of maternal opioid use disorders (OUDs) with either methadone, a full mu-agonist or buprenorphine, a partial mu-agonist/antagonist during gestation is the current standard of care (WHO, 2014). Buprenorphine treatment has become more common (Krans et al., 2016) since the publication of the MOTHER study (Jones et al., 2010), which found that buprenorphine treatment of women with OUDs may confer some advantage to the infant in the form of less severe NAS. NAS requiring pharmacotherapy occurs in 22–67% (Kocherlakota, 2014) among buprenorphine-exposed infants. Substances that may potentiate NAS severity in methadone-exposed infants include polysubstance exposures (Jansson et al., 2012), heavy cigarette smoking (Choo et al., 2004) and psychiatric medication, particularly SRIs (Kaltenbach et al., 2012). It is unknown whether these substances similarly predispose the infant to more severe NAS in buprenorphine-exposed pregnancies, or if other aspects of exposure, such as maternal buprenorphine dose, potentiates NAS in exposed infants.

The purpose of this longitudinal, prospective study is to comprehensively document the outcome of buprenorphine-exposed neonates. Research questions include: 1) the extent to which there is a positive association between maternal buprenorphine dose and NAS severity; 2) whether other maternal factors, including polysubstance use, severity of opioid use, and psychiatric medications potentiate NAS outcomes; and 3) the relation between maternal buprenorphine dose and size at birth. A secondary analysis addressed whether any detected associations between buprenorphine dose and NAS severity is similarly present among women who do and do not use illicit/misuse licit substances during treatment.

Section snippets

Participants and methods

Participants were drawn from a population of pregnant women with OUD entering treatment at the Center for Addiction and Pregnancy (CAP) between 2012 and 2016. CAP is a comprehensive treatment facility for pregnant and parenting women and has been comprehensively described previously (Jansson et al., 1996). Women who opted for buprenorphine (monoproduct only) maintenance as part of a study evaluating fetal and infant outcomes were eligible for enrollment. Eligibility was limited to singleton

Results

A total of 127 pregnant women provided consent for study participation; 41 completed the protocol through delivery. Participants who left the protocol did so for a variety of reasons (Fig. 1). Of the 86 participants who left the protocol for any reason, 42 remained in drug treatment but switched to methadone maintenance and 44 left drug treatment at the center. Data describing fetal neurobehavioral development in the final sample are presented elsewhere (Jansson et al., 2017).

Discussion

Treatment of maternal OUD during pregnancy with buprenorphine provides the maternal-infant dyad with major benefits, including more optimal birth weight, lower incidence of birth defects, reduced risk of preterm birth, and reduced NAS severity when compared to methadone (Laslo et al., 2017). However, there is poorly understood variability in the continuum of expression of NAS in buprenorphine-exposed infants, with no single factor or groups of factors that can reliably and accurately predict

Conclusions

In this sample, maternal buprenorphine dose was an independent predictor of NAS severity over and above mothers’ histories of substance use, but antepartum polysubstance exposure was the most potent predictor of more severe NAS expression in buprenorphine-exposed infants. In contrast to methadone treatment, which usually occurs in the context of federally licensed programs requiring patients to return daily for dosing, buprenorphine is increasingly used as an outpatient medication delivered in

Role of funding source

This study was funded by NIH/NIDA RO1DA031689, Jansson LM (PI).

Contributors

Dr. Jansson conceptualized and designed the study, obtained funding for the research, and drafted the initial manuscript. Dr. Velez assisted the research by being a liaison between the research team and the treatment program, reviewed and revised the manuscript. Ms. McConnell and Ms. Spencer performed data collection for all maternal and infant subjects, were responsible for data abstraction from medical records and data entry and storage. Dr. Jones held the IND for this study, assisted with

Conflict of interest

Lauren Jansson is a paid consultant for Chiesi, Inc., in which capacity she provides expert guidance regarding pharmacotherapy for neonatal abstinence syndrome. The other authors have no conflicts of interest to disclose.

Acknowledgements

This study was funded by NIH/NIDA RO1DA031689. Medication for this study was provided by Indivior who had no role in study design; collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. The authors thank the study participants and the staff of the Center for Addiction and Pregnancy, without whom this work would not be possible.

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