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Maternal buprenorphine treatment and fetal neurobehavioral development

Published:February 07, 2017DOI:https://doi.org/10.1016/j.ajog.2017.01.040

      Background

      Gestational opioid use/misuse is escalating in the United States; however, little is understood about the fetal effects of medications used to treat maternal opioid use disorders.

      Objective

      The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development.

      Study Design

      Forty-nine buprenorphine-maintained women who attended a substance use disorder treatment facility with generally uncomplicated pregnancies underwent fetal monitoring for 60 minutes at times of trough and peak maternal buprenorphine levels. Data were collected at 24, 28, 32, and 36 weeks gestation. Fetal neurobehavioral indicators (ie, heart rate, motor activity, and their integration [fetal movement–fetal heart rate coupling]) were collected via an actocardiograph, digitized and quantified. Longitudinal data analysis relied on hierarchic linear modeling.

      Results

      Fetal heart rate, heart rate variability, and heart rate accelerations were significantly reduced at peak vs trough maternal buprenorphine levels. Effects were significant either by or after 28 weeks gestation and tended to intensify with advancing gestation. Fetal motor activity and fetal movement–fetal heart rate coupling were depressed from peak to trough at 36 weeks gestation. Polysubstance exposure did not significantly affect fetal neurobehavioral parameters, with the exception that fetuses of heavier smokers moved significantly less than those of lighter smokers at 36 weeks gestation. By the end of gestation, higher maternal buprenorphine dose was related to depression of baseline fetal cardiac measures at trough.

      Conclusion

      Maternal buprenorphine administration has acute suppressive effects on fetal heart rate and movement, and the magnitude of these effects increases as gestation progresses. Higher dose (≥13 mg) appears to exert greater depressive effects on measures of fetal heart rate and variability. These findings should be balanced against comparisons to gestational methadone effects, relatively good outcomes of buprenorphine-exposed infants, and recognition of the benefits of medication-assisted treatment for pregnant women with opioid use disorders in optimizing pregnancy outcomes.

      Key words

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      References

        • Patrick S.W.
        • Schumacher R.E.
        • Benneyworth B.D.
        • Krans E.E.
        • McAlllister J.M.
        • Davis M.M.
        Neonatal abstinence syndrome an associated health care expenditures United States, 2000-2009.
        JAMA. 2012; 307: 1934-1940
        • Patrick S.W.
        • Dudley J.
        • Martin P.R.
        • et al.
        Prescription opioid epidemic and infant outcomes.
        Pediatrics. 2015; 135: 842-850
        • Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality
        Treatment Episode Data Set (TEDS): 2000-2010. National Admissions to Substance Abuse Treatment Services. DASIS Series S-61, HHS Publication No. (SMA) 12-4701.
        Substance Abuse and Mental Health Services Administration, Rockville (MD)2012
        • Ko J.Y.
        • Patrick S.W.
        • Tong V.T.
        • Patel R.
        • Lind J.N.
        • Barfield W.D.
        Incidence of neonatal abstinence syndrome – 28 states, 1999-2013.
        MMWR Morb Mortal Wkly Rep. 2016; 65: 799-802
        • Krans E.E.
        • Bogen D.
        • Richardson G.
        • Park S.Y.
        • Dunn S.L.
        • Day N.
        Factors associated with buprenorphine versus methadone use in pregnancy.
        Subst Abus. 2016; 37: 550-557
        • World Health Organization (WHO)
        Guidelines for the identification and management of substance use and substance use disorders in pregnancy.
        World Health Organization, Geneva, Switzerland2014
      1. American Society of Addiction Medicine (ASAM). The ASAM National Practice Guidelines for the use of medications in the treatment of addiction involving opioid use. Available at: http://www.asam.org/docs/default-source/practice-support/guidelines-and-consensus-docs/asam-national-practice-guideline-supplement.pdf. Accessed March 10, 2017.

        • Jones H.E.
        • Kaltenbach K.
        • Heil S.H.
        • et al.
        Neonatal abstinence syndrome after methadone or buprenorphine exposure.
        N Engl J Med. 2010; 363: 2320-2331
        • DiPietro J.A.
        • Kivlighan K.T.
        • Costigan K.A.
        • et al.
        Prenatal antecedents of newborn neurological maturation.
        Child Dev. 2010; 81: 115-130
        • Jansson L.M.
        • DiPietro J.A.
        • Velez M.
        • et al.
        Fetal neurobehavioral effects of exposure to methadone or buprenorphine.
        Neurotoxicol Teratol. 2011; 33: 240-243
        • Salisbury A.L.
        • Coyle M.G.
        • O’Grady K.E.
        • et al.
        Fetal assessment before or after dosing with buprenorphine or methadone.
        Addiction. 2012; 107: 36-44
        • Jansson L.M.
        • Svikis D.
        • Lee J.
        • Paluzzi P.
        • Rutigliano P.
        • Hackerman F.
        Pregnancy and Addiction: A Comprehensive Care Model.
        J Subst Abuse Treat. 1996; 13: 321-329
        • Tompkins D.A.
        • Bigelow G.E.
        • Harrison J.A.
        • Johnson R.E.
        • Fudala P.J.
        • Strain E.C.
        Concurrent validation of the Clinical Opiate Withdrawal Scale (COWS) and single-item indices against the Clinical Institute Narcotic Assessment (CINA) opioid withdrawal instrument.
        Drug Alcohol Depend. 2009; 105: 154-159
        • Besinger R.
        • Johnson T.
        Doppler recordings of fetal movement: clinical correlation with real-time ultrasound.
        Obstet Gynecol. 1989; 74: 277-280
        • DiPietro J.
        • Hodgson D.
        • Costigan K.
        • Hilton S.
        • Johnson T.
        Development of fetal movement-fetal heart rate coupling from 20 weeks through term.
        Early Hum Dev. 1996; 44: 139-151
        • Locatelli A.
        • Roncaglia N.
        • Arreghini A.
        • Bellini P.
        • Vergani P.
        • Ghidini A.
        Hepatitis C virus infection is associated with a higher incidence of cholestasis of pregnancy.
        BJOG. 1999; 106: 498-500
        • Paternoster D.
        • Fabris F.
        • Palu G.
        • et al.
        Intra-hepatic cholestasis of pregnancy in hepatitis C virus infection.
        Acta Obstet Gynecol Scand. 2002; 81: 99-103
        • Ropponen A.
        • Sund R.
        • Ylikorkala O.
        • Aittomaki K.
        Intrahepatic cholestasis of pregnancy as an indicator of liver and biliary diseases: a population based study.
        Hepatology. 2006; 43: 723-728
        • Wiiarnpreecha K.
        • Thongprayoon C.
        • Sanguankeo A.
        • Upala S.
        • Ungprasert P.
        • Cheungpastiporn W.
        Hepatitis C infection and intrahepatic cholestasis of pregnancy: a systematic review and meta-analysis.
        Clin Res Hepatol Gastroenterol. 2017; 41: 39-45
        • Jansson L.M.
        • Elko A.
        • DiPietro J.
        Fetal response to maternal methadone administration.
        Obstet Gynecol. 2005; 193: 611-617
        • DiPietro J.A.
        • Costigan K.A.
        • Voegtline K.M.
        Studies in fetal behavior: revisited, renewed and reimagined.
        Monogr Soc Res Child Dev. 2015; 80: 1-94
        • Jansson L.M.
        • Spencer N.
        • McConnell K.
        • et al.
        Maternal buprenorphine maintenance and lactation.
        J Hum Lact. 2016; 32: 675-681
        • Jansson L.M.
        • Choo R.
        • Velez M.L.
        • et al.
        Methadone maintenance and breastfeeding in the neonatal period.
        Pediatrics. 2008; 121: 106-114
        • Habek D.
        Effects of smoking and fetal hypokinesia in early pregnancy.
        Arch Med Res. 2007; 38: 864-867
        • Kelly J.
        • Mathews K.A.
        • O’Conor M.
        Smoking in pregnancy: effects on mother and fetus.
        BJOG. 1984; 91: 111-117