Early ibuprofen treatment may not lower risk of death, bronchopulmonary dysplasia in preterm infants with PDA

According to the study, published in The New England Journal of Medicine, Ibuprofen again failed to improve short-term outcomes when used to close PDA in newborns. The researchers argued that they at least found no evidence that ibuprofen caused serious complications.

Ibuprofen, administered parenterally a few days after infants were born prematurely, did not reduce the trial's combined primary endpoint nor its components at 36 weeks of postmenstrual age: Mortality and moderate or severe bronchopulmonary dysplasia: 69.2% vs 63.5% with placebo; mortality: 13.6% vs 10.3%; and moderate or severe bronchopulmonary dysplasia: 64.2% vs 59.3%.

The cyclooxygenase inhibitor ibuprofen ibuprofen may be used for treating PDA in preterm infants. However, it is unknown whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes. Samir Gupta, Sidra Medicine in Doha, Qatar, and colleagues aimed to evaluate early ibuprofen treatment (≤72 hours after birth) for a large patent ductus arteriosus (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days and 28 weeks 6 days’ gestation).

The study's primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia assessed at 36 weeks of postmenstrual age. A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses.

The study led to the following findings:

· A primary outcome event occurred in 69.2% of infants in the ibuprofen group and 63.5% of infants in the placebo group (adjusted risk ratio, 1.09).

· 13.6% of infants in the ibuprofen group and 10.3% of infants in the placebo group died (adjusted risk ratio, 1.32).

· Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 64.2% in the ibuprofen group and 59.3% in the placebo group (adjusted risk ratio, 1.09).

· Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen.

"We did not find a significantly lower risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age among infants who received early treatment with ibuprofen than among those who received a placebo," the researchers wrote.

Reference:

Gupta S, Subhedar NV, Bell JL, Field D, Bowler U, Hutchison E, Johnson S, Kelsall W, Pepperell J, Roberts T, Sinha S, Stanbury K, Wyllie J, Hardy P, Juszczak E; Baby-OSCAR Collaborative Group. Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen. N Engl J Med. 2024 Jan 25;390(4):314-325. doi: 10.1056/NEJMoa2305582. PMID: 38265644.