Overexpression of a gene in the centers of the brain responsible for regulating hunger, satiety and pleasure may be the cause of abnormal feeding habits of many babies suffering from withdrawal symptoms known as neonatal abstinence syndrome (NAS) due to prenatal opioid exposure, according to a new study led by Tufts Children's Hospital Neonatologist Elizabeth Yen, MD, an investigator in the Mother Infant Research Institute at Tufts Medical Center. The Journal of Pediatrics published the study, “Sex-Dependent Gene Expression in Infants with Neonatal Opioid Withdrawal Syndrome,” on August 29, 2019.
“As a direct result of the opioid epidemic, there has been a fivefold increase in NAS cases over the past 10 years, to the point where an infant is born with NAS every 15 minutes,” said Dr. Yen. “Newborns with NAS often have unique feeding behaviors – feeding difficulties, immediately followed by excessive feeding in which they consume 2-to-2.5 times the calorie requirements of a healthy newborn. We wanted to determine why this behavior occurred and why male babies with NAS were more susceptible.”
Upon analyzing just a few drops of infant saliva, Dr. Yen and her colleagues, Executive Director of the Mother Infant Research Institute Jill Maron, MD, MPH and physician-scientist Laboratory Director Tomoko Kaneko-Tarui, MD, PhD, discovered that the normal balance of the genes involved in feeding regulation seems disrupted in infants with NAS. These genes were found in the hypothalamus, the center in the brain that sends hunger and satiety signals, primarily based on energy requirements. However, with prenatal opioid exposure, reward signaling appeared to become more predominant, causing the newborns to eat even when they felt full.
Male infants with NAS were found to have a higher expression of a particular reward gene compared to females, and the expression of this gene directly correlated with the amount of food these newborns consumed. These findings indicate that after birth food may replace the opioid supply these infants once received in the womb, serving as the new reward trigger and leading to excessive eating behavior in these male babies. Essentially, food has become their new drug.
“Our study provides an insight into the impact of opioids on the developing newborn brain, and the reward gene in particular, and shows that males and females are not affected the same way by in utero opioid exposure,” said Dr. Yen. “In the future, we hope to be able to use saliva analysis to accurately predict which infants with NAS will experience the most severe withdrawal, and track gene expression to see if these babies are more prone to addictive behavior when they grow up.This research is an important first step towards understanding why a certain population has a greater risk for future addictive behavior."
The three-year study involved 100 babies - 50 newborns with NAS and 50 infants without any prenatal opioid exposure.