Aberrant Feeding and Growth in Neonates With Prenatal Opioid Exposure: Evidence of Neuromodulation and Behavioral Changes

Opioid use disorder (OUD) among pregnant women over the last decade has led to more than a fivefold increase in the number of neonates born with withdrawal signs known as Neonatal Abstinence Syndrome (NAS) or Neonatal Opioid Withdrawal Syndrome (NOWS). The impact of prenatal opioid exposure on these neonates remains a public health and research priority due to both its short and long-term effects on offspring. Among the adverse long-term effects associated with OUD is a metabolic syndrome with accompanying cardiovascular comorbidities. The susceptibility to metabolic diseases may begin as early as conception. Neonates born in a setting of prenatal opioid exposure are known to have aberrant early growth, e.g., lower birth weight and smaller head size, and dysregulated feeding behavior that ranges from feeding difficulty to hyperphagia which may predispose these neonates to metabolic syndrome in adulthood. However, studies on this topic are lacking. In this article, we describe the reported association between OUD and metabolic syndrome in adults, animal data linking opioid receptors with the development of diet-induced obesity, the inflammatory modulation of opioids and finally, neonatal salivary transcriptomic data from our laboratory that highlighted the sex-specific impact of opioids on the hypothalamic and reward receptors that regulate feeding behavior in opioid-exposed neonates. There is a great need for future research linking opioids with epigenetic and gene expression changes, as well as neuromodulatory effects in the developing brain, that may underlie the dysregulated feeding, growth, and long-term metabolic and cardiovascular risks for these neonates.