HFOV reduces BPD risk in preterm infants

Research published in JAMA Network Open has identified a reduced risk of bronchopulmonary dysplasia (BPD) among preterm infants receiving high-frequency oscillatory ventilation (HFOV) vs conventional mechanical ventilation (CMV) for neonatal acute respiratory distress syndrome (NARDS).¹

NARDS has an in-hospital mortality rate between 12.6% and 23.8%, with a reported mean gestational age among NARDS patients of 32.3 to 36.4 weeks.² Additionally, key clinical features of NARDS do not significantly differ from those observed in adult ARDS patients.¹

“However, despite extensive research in adult and pediatric populations, evidence remains insufficient to recommend [HFOV] or [CMV] as the preferred first-line therapy,” wrote investigators.

Comparing HFOV and CMV

The randomized clinical trial was conducted to compare the impact of HFOV vs CMV toward reducing BPD incidence among preterm infants born from 25 weeks 0 days’ to 34 weeks 6 days’ gestation. These infants were admitted to the neonatal care unit within 12 hours after birth, diagnosed with NARDS, and stable for 2 hours before randomization.

Exclusion criteria included major congenital abnormalities or chromosomal abnormalities, upper respiratory tract abnormalities, need for surgery before randomization, and more than grade 2 intraventricular hemorrhage (IVH). Participants were randomly assigned to receive HFOV or CMV.

HFOV was provided only with an active expiratory phase. Chest radiography or lung ultrasonography was performed to evaluate lung volume. Participants in the CMV group received the treatment from time-cycled, pressure-limited ventilators. Ventilator settings could be adjusted at the attending clinician’s discretion.

Infants not responding to their assigned ventilation could undergo a trial of the alternate mode. The first successful weaning from invasive intervention marked the end of the intervention. Continued monitoring for oxygen saturation as measured by pulse oximetry, electrocardiographic signals, heart rate, and respiratory rate was performed.

BPD assessment and secondary outcomes

The overall BPD incidence was reported as the primary outcome. Mild BPD was defined as no oxygen needed at 36 weeks’ gestational age, moderate BPD as less than 30% oxygen needed, and severe BPD as 30% or more oxygen needed. Alternatively, BPD severity could be defined by respiratory support administered at discharge.

Based on the latter definition, infants who were not given supplemental respiratory support were categorized as no BPD. In comparison, grade 1 BPD was defined as those treated with nasal cannula of 2 L/min or less, grade 2 BPD as nasal cannula over 2 L/min, and grade 3 BPD as invasive mechanical ventilation.

Major adverse neonatal outcomes were also reported. These included total ventilation duration, air leak, death, greater than grade 2 IVH, greater than stage 2 retinopathy of prematurity, stage 2 or higher necrotizing enterocolitis, and hemodynamically significant patent ductus arteriosus.

BPD risk reduction

There were 386 preterm infants included in the final analysis, 181 of whom initially received HFOV and 205 CMV. Twenty-four in the former group switched to CMV during the trial, vs 20 in the latter group switching to HFOV. BPD was reported in 39.9% of patients overall, with rates of 34.3% in the HFOV group and 44.9% in the CMV group.

A significant difference in oxygenation index was not reported between groups, at 8.30 in the HFOV group and 8.00 in the CMV group. However, the risk of BPD was 8% lower in the former group vs the latter based on oxygen needed at 36 weeks’ gestational age and 32% lower based on respiratory support administered at discharge.

Secondary outcomes did not significantly differ between groups. However, the difference in BPD rates highlighted significant improvements from HFOV vs BPD.

“These findings suggest that elective HFOV may be a promising strategy for preventing BPD in this high-risk population, especially the more severe forms linked to increased long-term morbidity and mortality,” wrote investigators.

References

1. Li J, Liu K, Yang Q, et al. High-frequency oscillation vs mechanical ventilation for neonatal acute respiratory distress syndrome: a randomized clinical trial. JAMA Netw Open. 2026;9(3):e260268. doi:10.1001/jamanetworkopen.2026.0268
2. Chen L, Li J, Shi Y; Chinese Neonatal ARDS (ChiNARDS) Study Group. Clinical characteristics and outcomes in neonates with perinatal acute respiratory distress syndrome in China: national, multicentre, cross-sectional study. EClinicalMedicine. 2022;55:101739. doi:10.1016/j.eclinm.2022.101739