Research In Practice Blog
Achieving lung aeration is the most critical task for preterm neonates during the transition to life outside the womb. Nearly all extremely preterm neonates require help breathing after birth through continuous positive airway pressure (CPAP) or positive pressure ventilation (PPV). Researchers from the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP), including lead investigators Elizabeth Foglia, MD, MSCE, and Clinical Futures’ fellow, David M. Rub, MD, aimed to investigate which respiratory targets are associated with successful lung aeration in preterm infants receiving PPV in the delivery room.
Study Design and Findings
Researchers designed a 5-year prospective, observational, international, multicenter cohort study titled, "Infant Lung Aeration During Transition Events" (INFLATE), that was conducted from March 2016 to April 2021 at the University of Pennsylvania, Leiden University (Leiden, Netherlands), and the Royal Women’s Hospital (Melbourne, Australia). The primary study population consisted of 132 preterm neonates, specifically those born between 22 weeks and 31 weeks and 6 days of gestation, who experienced bradycardia at birth (defined as a heart rate of less than 100 beats per minute) and received positive pressure ventilation during their resuscitation. Results were validated in an independent cohort.
The primary outcome of the study, published in JAMA Pediatrics on August 11, 2025, was an increase in the neonate's heart rate above 100 beats per minute, which is considered the best clinical indicator of lung aeration during neonatal resuscitation. Respiratory parameters were measured using a Respiratory Function Monitor (RFM), an innovative tool used to gather real-time, breath-to-breath data. The study assessed the association between various RFM parameters and an increase in heart rate.
Surprisingly, expiratory tidal volume was the only respiratory parameter measured associated with successful lung aeration during PPV. Peak pressure- the current recommended target- was not associated with lung aeration. Results from both the primary and confirmatory cohorts study suggest that a minimum expiratory tidal volume of 4 mL/kg is an appropriate evidence-based target for effective lung aeration during delivery room resuscitation of preterm neonates.
Implications and Insights
“These findings will enhance our understanding of effective ventilation strategies during neonatal resuscitation and ultimately help improve outcomes for preterm infants,” said David M. Rub, MD, lead author of the study.
Related Research and Additional Information
Clinical Futures author(s): David M. Rub, MD
CHOP Authors: David M. Rub, MD; Jesse Y. Hsu, PhD; Danielle D. Weinberg, MPH; Matthew Felix, RRT; Vinay M. Nadkarni, MD, MS; Arjan B. te Pas, MD, PhD; Kristel L. A. M> Kuypers, PhD; Peter G. David, MD; Sarah J. Ratcliffe, PhD; Haresh M. Kirpalani, MD; Elizabeth E. Foglia, MD, MSCE