Maternal buprenorphine treatment and fetal neurobehavioral development

Abstract

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.

Trial registration: ClinicalTrials.gov NCT15671079.

Keywords: buprenorphine; fetal heart rate; fetal movement; fetal neurobehavior; fetus; treatment.