For decades, clinicians have debated whether inhaled nitric oxide is truly effective in treating pulmonary hypertension in newborns with congenital diaphragmatic hernia (CDH). Now, Children’s Hospital Los Angeles is participating in a landmark national trial designed to answer this longstanding question.

CHLA is one of 19 centers in the study, which will compare outcomes as sites care for infants with or without inhaled nitric oxide. As part of this national effort, CHLA’s experience with some of the most complex CDH cases will help shape the evidence base guiding future care.

“Large, collaborative studies like this are essential for improving care in rare conditions,” says James E. Stein, MD, MSc, FACS, FAAP, Senior Vice President and Chief Medical Officer at CHLA and a site co-principal investigator. “Working together allows us to generate the robust evidence that will finally answer this critical question.”

CHLA treats 10 to 20 infants a year with CDH, a rare condition in which the diaphragm doesn’t fully form before birth. The defect allows abdominal organs to move into the chest, limiting space for lung growth. In addition, the lungs and pulmonary blood vessels often develop abnormally from the outset as a result of the underlying developmental process.

“One major challenge with congenital diaphragmatic hernia is that these abnormalities can vary widely in severity,” says Philippe Friedlich, MD, MSEpi, MBA, Chief of Neonatology and Co-Director of the Fetal and Neonatal Institute at CHLA, and the Teresa and Byron Pollitt Family Chair in Fetal and Neonatal Medicine. “Some babies with CDH have relatively mild respiratory distress, while others have life-threatening complications. It’s not one uniform disease.”

That variability has contributed to differing treatment approaches across centers. Inhaled nitric oxide is one example. Some centers use it routinely for infants with CDH, others rarely use it, and some—including CHLA—reserve it for select patients.

“This study gives us an important opportunity to answer that question,” Rachel Chapman, MD, Associate Chief of Neonatology at CHLA.

Funded by the National Institutes of Health, the trial is being led by UTHealth Houston and the University of Tennessee Health Science Center and Le Bonheur Children’s Hospital. It is being conducted through the CDH Study Group, an international collaborative network of high-volume centers—including CHLA—dedicated to improving outcomes for infants with CDH.

Under the study’s innovative stepped-wedge design, participating sites will initially follow their usual care with inhaled nitric oxide. Over the next several years, centers will be randomized on a preset schedule to treat infants with CDH without this therapy. This will allow researchers to determine whether using inhaled nitric oxide leads to better, worse, or equivalent outcomes.

The study’s primary endpoint is a composite of mortality and the need for extracorporeal membrane oxygenation (ECMO). Secondary measures include oxygenation, duration of respiratory support, and other indicators of early heart-lung stability.

This design enables investigators to evaluate real-world practice across institutions while maintaining each site’s standard approaches to ventilation, stabilization, and ECMO decision-making.

“By contributing to this landmark effort, CHLA is helping generate the evidence needed to guide future CDH care,” says Caroline Noh, MD, MSEpi, Associate Director of Neonatal Hemodynamics and Point-of-Care Ultrasound Program at CHLA and a site co-principal investigator. “We want to ensure that therapies used in the critical first days of life are grounded in the strongest possible data and achieve the best possible outcomes for the critically ill babies with CDH.”

(Newswise/HG)