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Randomized Controlled Trial
. 2025 Aug:283:114629.
doi: 10.1016/j.jpeds.2025.114629. Epub 2025 Apr 28.

Furosemide Safety in Preterm Infants at Risk for Bronchopulmonary Dysplasia: A Randomized Clinical Trial

Rachel G Greenberg  1 , Jason Lang  2 , P Brian Smith  2 , Prem Shekhawat  3 , Sherry E Courtney  4 , Mark L Hudak  5 , Fernando Moya  6 , Anjali Iyengar  7 , Alaa Eldemerdash  8 , Barry Bloom  9 , Mitzi Go  10 , Mina Hanna  11 , Lawrence Rhein  12 , Sofia Aliaga  13 , Tamorah Lewis  14 , Aprille Febre  15 , Autumn S Kiefer  16 , Varsha Bhatt-Mehta  17 , Joseph A Khoury  18 , David Selewski  19 , Ravinder Anand  20 , Karen Martz  20 , Elizabeth H Payne  20 , Kanecia O Zimmerman  2 , Daniel K Benjamin Jr  2 , Matthew Laughon  13 ; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Collaborators, Affiliations
Randomized Controlled Trial

Furosemide Safety in Preterm Infants at Risk for Bronchopulmonary Dysplasia: A Randomized Clinical Trial

Rachel G Greenberg et al. J Pediatr. 2025 Aug.

Erratum in

Abstract

Objective: To evaluate the safety of furosemide in preterm infants at the risk of developing bronchopulmonary dysplasia (BPD).

Study design: This multicenter, randomized, dose-escalating, placebo-controlled trial enrolled infants born <29 weeks gestational age at 7-28 days postnatal age and at risk for BPD. Infants were randomized 3:1 (furosemide:placebo) into 2 cohorts with escalating doses of furosemide to a maximum of 1 mg/kg intravenous (IV; or 2 mg/kg enteral) every 24 hours (cohort 1; n = 40) or 1 mg/kg IV (or 2 mg/kg enteral) every 6 hours (cohort 2; n = 40) for 28 days. Effects of furosemide on total adverse events (AEs; primary outcome), BPD, death, hearing loss, serum electrolyte AEs, and nephrocalcinosis were estimated using logistic regression adjusted for gestational age.

Results: We found 293 AEs in 74 of 80 (93%) infants, including 223 AEs among 56 of 61 (92%) infants who received furosemide and 70 AEs among 18 of 19 (95%) infants who received placebo (P > .99). Adjusted analysis among all groups showed no difference in the odds of having moderate-to-severe BPD or death at 36 weeks post-menstrual age (P = .32), hearing loss (P = .78), or nephrocalcinosis (P = .39). For serum electrolyte AE, OR (furosemide vs placebo) was 4.46 (95% CI, 1.06-21.70; P = .048) for cohort 1 and 7.89 (95% CI, 1.50-61.91; P = .023) for cohort 2.

Conclusions: In preterm infants, furosemide did not increase the overall incidence of AEs, hearing loss, or nephrocalcinosis, but did increase the incidence of electrolyte abnormalities. Furosemide given for 28 consecutive days was not associated with a difference in moderate-to-severe BPD or death at 36 weeks postmenstrual age.

Clinicaltrials: GOV: NCT02527798.

Keywords: bronchopulmonary dysplasia; electrolytes; furosemide; preterm infants; safety.

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Conflict of interest statement

Declaration of Competing Interest This work was funded under a contract [HHSN275201000003I] from the National Institute of Child Health and Human Development (NICHD) for the Pediatric Trials Network (PI Danny Benjamin) and the United States Food and Drug Administration (FDA R01FD005101; PI Matthew Laughon). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or FDA. The study funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

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