Could genetic variations explain variability in neonatal opiate withdrawal syndrome?

Abstract

Over the past decade, increased use and misuse of opioids during pregnancy have resulted in more than a 5-fold increase in neonatal opioid withdrawal syndrome (NOWS). In 2014, more than 8 out of every 1000 births were affected by maternal opioid abuse, which has created an urgent need for methods to accurately detect, monitor, and treat symptoms of neonatal opiate withdrawal. Current methods of NOWS assessment are based on behavioral findings of irritability, tachypnea, crying, and hyperphagia, and are inherently subjective. In addition, it remains unclear why some infants appear to be severely affected by NOWS and difficult to adequately treat. In this volume of The Journal, Yen et al evaluated salivary gene expression profiles in 100 infants; 50 with neonatal opiate withdrawal and a positive maternal toxicology screen and 50 without antenatal opiate exposure. Male infants with NOWS were more likely to require pharmacotherapy, and these male infants had elevated expression of dopamine receptor type 2 (DRD2), a hypothalamic and reward gene that governs feeding behavior in infants. Moreover, although prenatal opioid exposure upregulated DRD2 in males, it downregulated expression in females. This intriguing finding could explain why a higher proportion of males vs females with NOWS have high feeding intakes that drive the need for pharmacotherapy and suggests symptoms of NOWS may be different in male vs female infants. Opioid-mediated changes in DRD2 expression could help explain why men are more prone than women to substance use disorders as adults. Although this study included a small population, it suggests the possibility that treatment for NOWS may eventually be informed by noninvasive genetic testing and personalized care. Article page 60▸ Sex-Dependent Gene Expression in Infants with Neonatal Opioid Withdrawal SyndromeThe Journal of PediatricsVol. 214PreviewTo evaluate salivary biomarkers that elucidate the molecular mechanisms by which in utero opioid exposure exerts sex-specific effects on select hypothalamic and reward genes driving hyperphagia, a hallmark symptom of infants suffering from neonatal opioid withdrawal syndrome (NOWS). Full-Text PDF