Impact of in utero opioid exposure on newborn outcomes: beyond neonatal opioid withdrawal syndrome

Background and objectives: Research on in utero opioid exposure impacts has focused on Neonatal Opioid Withdrawal Syndrome (NOWS). However, possible impacts on fetal growth and newborn wellbeing have emerged, with inconsistencies likely driven by methodological issues. Our goal was to compare birth outcomes between newborns with prenatal opioid exposure and a matched control group. Methods: Participants were identified via manual review of electronic medical records of all deliveries over five years within a regional health system (6 delivery hospitals across 2 states). From over 18,000 births, 300 with prenatal opioid exposure and 300 control newborns matched on exposure, medical, and background factors were included. Additional factors were statistically controlled. Outcomes included pregnancy/delivery complications, newborn size, and newborn health complications. Results: Compared to biochemically verified controls, exposed newborns had higher rates of fetal growth restriction, weighed less, had decreased length and head circumference, and had higher rates of respiratory distress, sepsis, and jaundice. No significant differences in gestational length, Apgar scores, or neonatal hypoglycemia were found. Adjusted regression analyses revealed that compared to controls, those exposed had an average 150 g decrease in birth weight, a two-fold increased risk for IUGR (OR = 2.09), a nearly three-fold (OR = 2.80) increased risk for jaundice, a more than seven-fold (OR = 7.40) increased risk for respiratory distress, and a thirty-fold (OR = 30.47) increased risk for sepsis. Conclusions: Results suggest significant pregnancy and newborn outcomes beyond NOWS following pregnancy opioid use, informing clinical screening and treatment decisions to enhance health and wellbeing in pregnancy, during the neonatal period, and beyond.