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

Abstract

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.

Alterations in Excitatory and Inhibitory Synaptic Development Within the Mesolimbic Dopamine Pathway in a Mouse Model of Prenatal Drug Exposure

“…Considerable research efforts have been made to increase the understanding of the pathophysiology of NAS as well as methods to improve treatment of NAS symptoms (1,(7)(8)(9)(10). However, knowledge concerning the long-term effects of prenatal exposure to drugs of abuse on neurological development is limited (11).…”

Prenatal exposure to nitrofurantoin and risk of childhood leukaemia: a registry-based cohort study in four Nordic countries

“…Though most animal studies have investigated medicines used in opioid maintenance treatment rather than analgesic opioids [248], animal studies may still point to areas of interest for future investigation. These areas include memory [248,249], anxiety or depression [249], and hyperactivity [248]. Future epidemiologic studies should also carefully consider the choice of comparators, seeing that only pregnant women with severe pain will be prescribed analgesic opioids.…”

Maternal and iatrogenic neonatal opioid withdrawal syndrome: Differences and similarities in recognition, management, and consequences

“…For a complete overview of the neurodevelopmental mechanism behind neonatal opioid withdrawal and the consequences of opioid withdrawal in early life on infant physiology, we refer the reader to a recently published review on this topic (Boggess & Risher, 2020).…”