Association between early-phase opioid use and outcomes in extremely preterm infants: A nationwide study

Abstract Background Opioids are often administered for extremely preterm infants to prevent morbidities (e.g., intraventricular hemorrhage); however, their short-term outcome remains unclear. We aimed to assess the association between early-phase opioid use and in-hospital outcomes in extremely preterm infants. Methods This retrospective nationwide cohort study analyzed data from the Diagnosis Procedure Combination database in Japan. A total of 18,794 extremely preterm infants hospitalized between July 2010 and March 2021 were included. The patients were divided into those who received early-phase opioids ( n = 4806) and those who did not ( n = 13,988). We performed a 1:2 propensity score-matched analysis adjusting for patient backgrounds. Results In-hospital mortality, intraventricular hemorrhage, and periventricular leukomalacia occurred in 8.5%, 13%, and 2.1% of the patients, respectively. The incidences of in-hospital mortality (12% vs. 12%) and intraventricular hemorrhage (14% vs. 15%) did not differ between the two groups after 1:2 propensity score matching. The patients who received early-phase opioids had a lower incidence of periventricular leukomalacia than those who did not (1.7% vs. 2.2%). However, bronchopulmonary dysplasia occurrence (65% vs. 58%), home assistive technology use (19% vs. 15%), and length of hospital stay (125 vs. 122 days) were increased for patients who received early-phase opioids. Conclusion In this large retrospective study, early-phase opioid use in extremely preterm infants was not associated with increased mortality or intraventricular hemorrhage. Periventricular leukomalacia slightly decreased. Impact This large retrospective nationwide study of 13,988 extremely preterm infants revealed that using early-phase opioids was not significantly associated with in-hospital mortality or intraventricular hemorrhage but was significantly associated with a decrease in periventricular leukomalacia. Early-phase opioids may not increase mortality or intraventricular hemorrhage, in contrast to the results of previous studies. Thus, these results could help clinicians select opioids as sedative agents for extremely preterm infants.