Expectant management for patent ductus arteriosus (PDA) in preterm infants did not lower risk of death or lung disease compared with active treatment. However, more infants survived in the expectant management group, according to results from the PDA trial published Dec. 9 in JAMA.

The multicenter trial randomized 482 infants between 48 hours and 21 days old born at 22-28 weeks' gestation with symptomatic PDA (median gestation, 25.6 weeks; median birth weight, 760 g.; 49% female) 1:1 to either expectant management, defined as no treatment aimed at PDA closure unless the infant developed cardiopulmonary compromise or reached 36 weeks' postmenstrual age (n=241), or active treatment with medication (acetaminophen, ibuprofen or indomethacin; n=240).

Results at 36 weeks' postmenstrual age showed that 80.9% (195/241) of infants in the expectant management group experienced the primary outcome of death or bronchopulmonary dysplasia compared with 79.6% (191/240) in the active treatment group (adjusted risk difference, 1.2%; p=0.73). While rates of moderate to severe bronchopulmonary dysplasia were similar between the two groups, 4.1% (10/241) of infants died in the expectant management group compared to 9.6% (23/240) in active treatment (adjusted risk difference, –5.6%; p=0.01). Additionally, 0.8% (2/241) of infants in the expectant management arm experienced infections resulting in death compared to 3.8% (9/240) in active treatment.

The study was stopped early for futility and safety following the 50% interim analysis.

Addressing the increased risk of mortality and the higher incidence of infection in the active treatment group, study authors Matthew M. Laughon, MD, MPH, et al., write that "One possible mechanism is that pharmacological treatment ... is often accompanied by the withholding or delaying of enteral feedings or increasing the use of parenteral nutrition, both of which may increase the risk of sepsis."

"Alternatively," they add, "the medications themselves may alter the immune system or contribute directly to infection risk through reduced mesenteric blood flow or gastrointestinal mucosal injury, potentially facilitating bacterial translocation and sepsis."

In an accompanying editorial comment, Tim Hundscheid, MD, PhD, and Willem P. de Boode, MD, PhD, note that two major strengths of the trial were the large proportion of infants (56.8%) born before 26 weeks' gestation and the inclusion of infants between the postnatal age of 48 hours and 21 days. While they call for additional trials focused on high-risk infants with large transductal shunt volume, they write that the study "adds to the growing evidence that expectant management is safe in the majority of extremely preterm infants."