Clinical and basic research investigations into the long-term effects of prenatal opioid exposure on brain development

Coincident with the opioid epidemic in the United States has been a dramatic increase in the number of children born with neonatal abstinence syndrome (NAS), a form of withdrawal resulting from opioid exposure during pregnancy. Many research efforts on NAS have focused on short-term care, including acute symptom treatment and weaning of the infants off their drug dependency prior to authorizing their release. However, investigations into the long-term effects of prenatal opioid exposure (POE) on brain development, from the cellular to the behavioral level, have not been as frequent. Given the importance of the perinatal period for human brain development, opioid-induced disturbances in the formation and function of nascent synaptic networks and glia have the potential to impact brain connectivity and cognition long after the drug supply is cutoff shortly after birth. In this review, we will summarize the current state of NAS research, bringing together findings from human studies and preclinical animal models to highlight what is known about how POE can induce significant, prolonged deficits in brain structure and function. With rates of NAS continuing to rise, particularly in regions that already face substantial socioeconomic challenges, we speculate as to the most promising avenues for future research to alleviate this growing multigenerational threat.