Association of Prenatal Fentanyl Exposure With Neonatal Opioid Withdrawal Syndrome Severity

Opioid use disorder (OUD) in pregnancy has increased substantially, with illicit fentanyl now the most common illicit opioid. Limited data exist on the impact of antenatal fentanyl exposure on neonatal opioid withdrawal syndrome (NOWS). We aimed to evaluate whether antenatal fentanyl exposure is associated with increased NOWS severity.

We conducted a retrospective cohort study of mother-infant dyads with OUD between 2017 and 2024. Fentanyl exposure was determined by urine toxicology during the pregnancy and on admission. Infants were monitored using the Eat, Sleep, Console tool and a standardized NOWS protocol. NOWS hospitalization outcomes were compared between the fentanyl-exposed and nonexposed groups with adjustment for breastfeeding, year of birth, and relevant co-exposures.

Among 504 dyads, 131 (26.0%) had fentanyl exposure. Maternal demographics were similar between groups, but fentanyl was associated with higher rates of polysubstance use. Fentanyl-exposed infants were more likely to receive pharmacologic NOWS treatment (61.1% vs 40.8%, P < .01), scheduled methadone dosing, secondary pharmacologic agents (15.4% vs 7.4%, P = .03), and feeding tubes (40.0% vs 24.5%, P < .001). Hospital length of stay (22.1 vs 13.3 days, P < .01) and opioid treatment duration (14.2 vs 9.4 days, P < .01) were longer in the fentanyl-exposed cohort. In adjusted regression models, fentanyl exposure remained independently associated with prolonged hospitalization (mean difference 5.1 days [95% CI 1.7-8.5]) and increased odds of pharmacologic treatment (adjusted odds ratio 2.1 [95% CI 1.2-3.8]).

Antenatal fentanyl exposure is strongly associated with intensive pharmacologic management and extended hospitalization. These findings are suggestive of more severe NOWS.