A review of the literature: How does prenatal opioid exposure impact placental health and fetal brain development?

Abstract

In recent years, there has been a sixfold increase in the number of pregnant people with opioid use disorder (OUD). Rates of neonatal opioid withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), have significantly increased in virtually every state and demographic group (Healthcare Cost Utilization Project, HCUP, 2010). NOWS is a condition resulting from chronic exposure to either therapeutic opioid use (e.g., medication for OUD, chronic pain conditions) or nonprescribed opioid use. To date, there is no known prenatal treatment to help decrease the risk of infants developing NOWS and subsequent neurodevelopmental outcomes. Given the increasing support for how placental signaling, or placental programming, may play a role in downstream pathology, prospective research investigating how the placenta is affected by chronic opioid exposure morphologically, histologically, and at the cellular level may open up potential treatment opportunities in this field. In this review, we discuss literature exploring the physiological roles of nitric oxide and dopamine not only in the vascular development of the placenta, but also in fetal cerebral blood flow, neurogenesis, neuronal differentiation, and neuronal activity. We also discuss histological preclinical studies that suggest chronic opioid exposure to induce some combination of placental dysfunction and hypoxia in a manner similar to other well‐known placental pathologies, as denoted by the compensatory neovascularization and increased utilization of the placenta's supply of trophoblast cells, which play an essential role in placental angiogenesis. Overall, we found that the current literature, while limited, suggests chronic opioid exposure negatively impacts placental function and fetal brain development on a cellular and histopathological level. We conclude that it is worthwhile to consider the placenta as a therapeutic target with the ultimate goal of decreasing the incidence of NOWS and the long‐term impacts of prenatal opioid exposure.

Intrauterine exposure to maternal opioid maintenance treatment and associated risk factors may impair child growth

“…We observed relatively large placentas despite maternal smoking, which is typically associated with small placentas and birth sizes. These large size of the placentas was linked to maternal methadone treatment, concomitant substance use, and hepatitis C, which is in line with previous research 23–25 …”

“…Placental size and function also impact foetal growth and health 22,23 . We observed relatively large placentas despite maternal smoking, which is typically associated with small placentas and birth sizes.…”

“…These large size of the placentas was linked to maternal methadone treatment, concomitant substance use, and hepatitis C, which is in line with previous research. [23][24][25] After early infancy, most children in the buprenorphine groups caught up with normal growth, whereas in the methadone group growth was poorer. The most concerning finding was the slow head growth among children born SGA, and those with intrauterine methadone exposure.…”

Children had increased risks of impaired motor and visual‐motor skills after prenatal exposure to opioid maintenance therapy

“…The long‐term epigenetic effects on proteins, receptors and neurotransmitters important for cognition result in impaired learning and memory 6 . Chronic opioid exposure has also been shown to be harmful to placental function 7 . Adding to this, magnetic resonance imaging studies have reported reduced basal ganglia volumes and white matter microstructure alterations in opioid‐exposed infants and older children 8,9 …”

“…6 Chronic opioid exposure has also been shown to be harmful to placental function. 7 Adding to this, magnetic resonance imaging studies have reported reduced basal ganglia volumes and white matter microstructure alterations in opioid-exposed infants and older children. 8,9 The most undesirable neonatal outcome associated with prenatal OMT exposure in humans is Neonatal Abstinence Syndrome, with an incidence rate of 40-90%.…”