Early pharmacologic treatment of a common congenital heart defect did not improve survival outcomes compared to expectant management in preterm infants, according to a recent clinical trial published in JAMA.
The study found no significant difference in survival in preterm infants that received active treatment versus expectant management (regular monitoring without immediate treatment) to close the patent ductus arteriosus (PDA), a fetal blood vessel that connects the pulmonary artery and aorta.
“Despite closing the ductus more often, medications did not improve the studied outcomes,” said Cassandra Montoya, MD, assistant professor of Pediatrics in the Division of Neonatology and a co-author of the study. “The results contribute to evidence that routine early pharmacologic PDA closure does not improve outcomes and may, in fact, cause harm.”
The PDA is necessary to support fetal life but typically closes shortly after birth in full-term infants. In premature infants, however, the blood vessel can remain open and may lead to complications, including chronic respiratory difficulties or bronchopulmonary dysplasia (BPD), a complication of other breathing conditions.
Medications including indomethacin, ibuprofen, and acetaminophen can close the PDA, but prior research has not shown improved survival or reduced key morbidities of prematurity in patients that receive this treatment, Montoya said.
“Despite this, practice varies widely in NICUs across the U.S.,” Montoya said. “Our motivation for this study was to provide rigorous evidence to help guide PDA management.”
In the current clinical trial, Montoya and her colleagues aimed to determine if early pharmacologic PDA treatment with acetaminophen, ibuprofen or indomethacin in infants born between 22 and 28 weeks gestation with a detected PDA improved survival compared to expectant management.
A total of 482 infants at an average age 25 weeks from 33 hospitals across the U.S. were randomized to receive active treatment or expectant management. The primary outcome was death or BPD at 36 weeks postmenstrual age.
Unexpectedly, the scientists found no difference in mortality or BPD between both groups; 80.9 percent in the expectant management group versus 79.6 percent in the active treatment group, respectively.
Particularly, they found infants who received early active treatment demonstrated more than double the mortality of those who received expectant management, as well as more infection‑related deaths in the active treatment group. The incidence of death by 36 weeks’ postmenstrual age was 4.1 percent in the expectant management group versus 9.6 percent in the active treatment group.
Montoya said the findings reinforce the future direction of precision PDA management in infants.
“We need to identify a more specific subset of infants that may truly benefit from active closure of the PDA. Not all PDAs have equal hemodynamic impact, and the sickest infants (those with cardiopulmonary compromise) were intentionally excluded from this trial,” Montoya said.
Going forward, Montoya said her team will perform neurodevelopmental follow-up exams of participants at 2 years to collect more data on long-term outcomes. She added that her team is also in the process of establishing a neonatal hemodynamics and targeted neonatal echocardiography (TNE) program to better characterize PDA physiology and guide individualized, data‑driven treatment decisions.
This study was supported by grants UG1 HD872293, UG1 HD112093, UG1 HD87226, UG1 HD68244, UG1 HD40689, UG1 HD40492, UG1 HD34216, UG1 HD68244, UG1 HD21364, UG1 HD112100, UG1 HD68278, UG1 HD68263, UG1 HD27851, UG1 HD27853, UG1 HD27880, UG1 HD112097, UG1 HD27853, UG1 HD40492, UG1 HD27904, UG1 HD68244, UG1 HD53089, UG1 HD27851, UG1 HD40492, UG1 HD53109, UG1 HD68263, UG1 HD40689, UG1 HD53109, UG1 HD112079, UG1 HD40492, and U24 HD95254 from the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by grants UL1 TR1067, UL1 TR2489, UL1 TR454, UL1 TR1425, UL1 TR1085, UL1 TR1425, UL1 TR1449, UL1 TR454, UL1 TR442, and UL1 TR1117 from the National Center for Advancing Translational Sciences.
