Expectant management improves survival for preterm infants with PDA, major U.S. trial finds

UNC-led study coordinated by RTI shows less aggressive approach reduces mortality without increasing complications

RESEARCH TRIANGLE PARK, N.C. — A large U.S. clinical trial led by the NICHD Neonatal Research Network (NRN) and coordinated by RTI International has found that expectant management of patent ductus arteriosus (PDA), a common heart condition in extremely premature infants, results in higher survival compared to early medication treatment. Expectant management refers to the treatment plan of monitoring and treating only if symptoms worsen.

The randomized trial, published in JAMA and presented at the Hot Topics in Neonatology conference, enrolled 482 infants born between 22 and 28 weeks’ gestation across 33 hospitals. Researchers compared expectant management with active pharmacologic treatment using acetaminophen, ibuprofen or indomethacin.

While rates of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age were similar between groups (80.9% vs. 79.6%), mortality was more than twice as high among infants receiving early medication (9.6% vs. 4.1%).

“This trial provides the strongest evidence to date that routine early drug treatment for PDA does not improve outcomes and may increase risk,” said Dr. Matt Laughon, lead investigator for the trial at the University of North Carolina, Chapel Hill. “Expectant management should be considered the safer approach for most extremely preterm infants without cardiopulmonary compromise.”

PDA occurs when a fetal blood vessel connecting the pulmonary artery and aorta fails to close after birth. While medications and surgery can close the ductus, prior studies have not shown clear benefits for survival or long-term health. The new trial reinforces emerging data suggesting harm from early treatment for pharmacologic closure.

Researchers noted that infections leading to death were significantly more common in the active treatment group (3.8% vs. 0.8%). One possible explanation is that drug therapy often delays feeding and increases reliance on intravenous nutrition, which may raise infection risk.

“Our team ensured rigorous data oversight and statistical analysis across the 33 participating hospitals in the NRN,” said Abhik Das, Ph.D., a Distinguished Fellow in Biostatistics and principal investigator for the NRN Data Coordinating Center at RTI. “This collaboration demonstrates the power of rigorous and pragmatic large-scale, multicenter trials to answer critical questions in neonatal care.”

The study’s implications are profound: PDA affects thousands of preterm infants annually, and nearly one-quarter of U.S. babies born at 22–28 weeks currently receive medication for PDA closure.

The trial was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Neurodevelopmental follow-up at two years is ongoing.

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