title: Maternal buprenorphine treatment and fetal neurobehavioral development.
abstract: 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.
  
  
  
  The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: ljansson@jhmi.edu.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Jansson
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Martha
authors.initials: M
authors.lastname: Velez
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Krystle
authors.initials: K
authors.lastname: McConnell
authors.affiliation: Johns Hopkins Bayview Hospital, Department of Nursing, Baltimore, MD.
authors.forename: Nancy
authors.initials: N
authors.lastname: Spencer
authors.affiliation: University of Maryland School of Social Work, Baltimore, MD.
authors.forename: Michelle
authors.initials: M
authors.lastname: Tuten
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD; University of North Carolina Chapel Hill, Department of Obstetrics and Gynecology.
authors.forename: Hendree E
authors.initials: HE
authors.lastname: Jones
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Van L
authors.initials: VL
authors.lastname: King
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Gandotra
authors.affiliation: Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: Milio
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Kristin
authors.initials: K
authors.lastname: Voegtline
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Janet A
authors.initials: JA
authors.lastname: DiPietro
mesh_terms: D002047:Buprenorphine / Q000008:administration & dosage*; D015148:Cardiotocography; D004305:Dose-Response Relationship, Drug; D005260:Female; D005324:Fetal Movement / Q000187:drug effects*; D005865:Gestational Age; D006340:Heart Rate, Fetal / Q000187:drug effects*; D006801:Humans; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D058850:Opiate Substitution Treatment; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D002047:Buprenorphine
keywords: buprenorphine; fetal heart rate; fetal movement; fetal neurobehavior; fetus; treatment