The Effects of Prenatal Buprenorphine Exposure on the Neurobehavioral Development of the Child

Background: Current guidelines for pregnant women with substance use disorder advise prenatal maintenance of opioid agonist therapy with either buprenorphine or methadone. Despite this rise in prenatal opioid agonist therapy, little is known about the effect of prenatal buprenorphine on the neurobehavioral development of the child. This poses the question: does buprenorphine have a long-lasting effect on the central and peripheral nervous system development and behavior of children who were exposed prenatally? Methods: A comprehensive literature review identified articles relating to prenatal buprenorphine and neurobehavioral outcomes. Article searches were conducted on PubMed and Dynamed. Publications from 2002 through November 2021 were pulled for further analysis since buprenorphine was approved by the Food and Drug Administration for use in 2000. The references of pulled articles were also manually searched. The search was limited to peer-reviewed, full-length articles written in English were considered. All articles assessing buprenorphine-naloxone (Suboxone) were excluded from the review due to possible teratogenic effects of naloxone. Relevant information was summarized and included in the review. The full review of the literature identified human and animal studies to gather current knowledge on the neurobehavioral outcomes of children from birth to 5 years of age exposed to buprenorphine prenatally. Results: The literature review revealed that available studies covered three stages of life: fetal, neonatal/infant, and toddler. Neonatal and infant stages were combined into one category due to studies overlapping these similar ages or using the terms interchangeably. Fetal outcomes showed prenatal buprenorphine-exposed fetuses were more likely to exhibit higher level of fetal heart rate variability that eventually normalized later in gestation; fetal motor activity was consistently lower in buprenorphine-exposed fetuses regardless of gestational age. Exposed neonates were more likely to have a depressed initial ability to self-regulate with poor quality of movement. Infants showed no significant deficiency in neurological development. Studies of exposed toddlers showed various results ranging from no significant deviations from normal neurobehavioral development to significant cognitive and motor underdevelopment. Discussion: Prenatal exposure to buprenorphine has varying results on the development of the child, some of which can have long-term detrimental effects. No general conclusion could be made regarding the overall effect of prenatal buprenorphine exposure on an individual due to the wide range of evidence at the toddler stage. While there are multiple factors to consider when assessing neurobehavioral development, there is significant evidence to show there should be serious consideration for future controlled studies of prenatal buprenorphine exposure, from the neonatal stage to older children and beyond.