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

Hiroki Kitaoka1,2, Takaaki Konishi3, Yoshihiko Shitara4

  • 1Department of Pediatrics, The University of Tokyo Hospital, Tokyo, Japan. kitaokahir@m.u-tokyo.ac.jp.

Pediatric Research
|March 18, 2025
PubMed

Insights

Early opioid use in extremely preterm infants did not increase mortality or intraventricular hemorrhage. While periventricular leukomalacia decreased, longer hospital stays and increased bronchopulmonary dysplasia were observed.

Area of Science:

  • Neonatalogy
  • Pharmacology
  • Pediatric Critical Care

Background:

  • Opioids are frequently used for extremely preterm infants to prevent serious conditions like intraventricular hemorrhage.
  • The short-term effects of early opioid administration on infant outcomes are not well-understood.
  • This study investigates the association between early opioid use and in-hospital outcomes in this vulnerable population.

Purpose of the Study:

  • To assess the association between early-phase opioid administration and in-hospital outcomes in extremely preterm infants.
  • To determine if early opioid use impacts mortality, major morbidities, or healthcare resource utilization.
  • To provide evidence for clinical decision-making regarding opioid use in neonatal intensive care.

Main Methods:

  • A retrospective nationwide cohort study utilizing Japan's Diagnosis Procedure Combination database.
  • Inclusion of 18,794 extremely preterm infants hospitalized between July 2010 and March 2021.
  • A 1:2 propensity score-matched analysis comparing infants who received early opioids (n=4806) versus those who did not (n=13,988).

Main Results:

  • In-hospital mortality and intraventricular hemorrhage rates were similar between opioid-exposed and non-exposed groups post-matching.
  • A statistically significant decrease in periventricular leukomalacia was observed in infants receiving early opioids (1.7% vs. 2.2%).
  • However, early opioid use was associated with increased rates of bronchopulmonary dysplasia (65% vs. 58%), higher home assistive technology use (19% vs. 15%), and longer hospital stays (125 vs. 122 days).

Conclusions:

  • Early-phase opioid administration in extremely preterm infants is not linked to increased in-hospital mortality or intraventricular hemorrhage.
  • A slight reduction in periventricular leukomalacia was noted with early opioid use.
  • Despite these benefits, clinicians should consider the increased risks of bronchopulmonary dysplasia and prolonged hospitalization associated with early opioid exposure.
Abstract

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