Original Investigation 

Pediatrics

High-Frequency Oscillation vs Mechanical Ventilation for Neonatal Acute Respiratory Distress Syndrome: A Randomized Clinical Trial

Jie Li, Kaizhen Liu, Qian Yang, et al

JAMA Netw Open 2026;9;(3):e260268. doi:10.1001/jamanetworkopen.2026.0268

Key Points

Question  Does elective high-frequency oscillatory ventilation (HFOV) reduce the incidence of bronchopulmonary dysplasia (BPD) and other neonatal adverse outcomes compared with conventional mechanical ventilation (CMV) among preterm infants diagnosed with neonatal acute respiratory distress syndrome?

Findings  In this randomized clinical trial of 386 preterm infants, elective HFOV reduced the risk of BPD according to the 2001 Eunice Kennedy Shriver National Institute of Child Health and Human Development definition by 8.0% and the risk of BPD according to the 2019 Jensen definition by 32.0% compared with CMV.

Meaning  The results of this study suggest that elective HFOV is a promising strategy for preventing BPD in preterm infants with neonatal acute respiratory distress syndrome, especially the more severe forms associated with increased long-term morbidity and mortality.

Abstract

Importance  Key clinical features of neonatal acute respiratory distress syndrome (NARDS) are broadly comparable to those observed in pediatric and adult ARDS; however, evidence is insufficient to recommend high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CMV) as the preferred first-line therapy.

Objective  To evaluate whether HFOV is superior to CMV in reducing bronchopulmonary dysplasia (BPD) and other neonatal adverse outcomes, including death, among preterm infants (≤34 weeks’ gestational age) with NARDS.

Design, Setting, and Participants  This single-center randomized clinical trial conducted from August 1, 2019, to December 31, 2023, enrolled preterm infants born between 25 weeks 0 days and 34 weeks 6 days of gestation with NARDS who were stabilized with CMV. Data were analyzed from October to December 2024.

Intervention  Participants were randomly assigned to continue CMV or transition to elective HFOV.

Main Outcomes and Measures  The primary outcome was BPD, assessed using 2 definitions: definition 1, that of the 2001 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and definition 2, one based on 2019 research. Secondary outcomes included death, retinopathy of prematurity (higher than stage 2), necrotizing enterocolitis (stage 2 or higher), intraventricular hemorrhage (grade 3 or higher), air leak, and hemodynamically significant patent ductus arteriosus. Modified Poisson regression, ordinal regression, and Cox proportional hazards regression were applied for outcome risk assessment where applicable.

Results  A total of 386 preterm infants (230 male [59.6%]; mean [SD] maternal age, 29.9 [4.8] years) were randomized: 181 to elective HFOV and 205 to CMV. Overall, 154 (39.9%) and 83 (21.5%) developed BPD according definitions 1 and 2, respectively. Elective HFOV reduced the risk of BPD by 8.0% (34.3% vs 44.9%; relative risk, 0.92; 95% CI, 0.86-0.99) according to definition 1 and by 32.0% (17.1% vs 25.4%; relative risk 0.68; 95% CI, 0.45-1.00) according to definition 2 compared with CMV. No significant between-group differences were observed for death, higher than stage 2 retinopathy of prematurity, stage 2 or higher necrotizing enterocolitis, grade 3 or higher intraventricular hemorrhage, air leak, or hemodynamically significant patent ductus arteriosus. Sensitivity analysis excluding 44 participants who crossed over between treatment groups did not significantly attenuate the estimates.

Conclusions and Relevance  This randomized clinical trial found that elective HFOV reduced the incidence of BPD in preterm infants born at 34 weeks’ gestation or earlier with NARDS compared with CMV. The results of this study suggest that elective HFOV is a promising strategy for preventing BPD in this high-risk population, especially the more severe forms linked to increased long-term morbidity and mortality.

Trial Registration  ClinicalTrials.gov Identifier: NCT03591796.