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

Abstract

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. 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. 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. 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.