Correct answer
d Observation
The presence of a large (>1.5mm) hemodynamically significant PDA, especially in extreme preterm infants, has been associated with increased mortality and morbidity such as bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH). Its optimal management, however, has been a source of debate since PDA closure does not appear to impact overall clinical outcome. Furthermore, expectant management strategies have become more widely employed due to a lack of causality between PDA closure and neonatal mortality and morbidity. It is also important to note that >80% of PDAs will spontaneously close, again supporting a non-interventional philosophy with respect to PDA management.
Supporting the above approach, the results of two recent randomized controlled trials have demonstrated the non-inferiority of expectant management vs ibuprofen therapy in premature infants with large PDAs (>1.5mm). In the BeNeDuctus trial, Hundscheid et al. randomized 273 neonates born at less than 28 weeks GA to receive ibuprofen 24-72h postnatally or expectant management. The risk of the composite outcome of moderate to severe BPD, NEC and death measured at 36 weeks post-menstrual age was 0.72 (CI 0.57-0.90) indicating the harm related to ibuprofen. While the relative numbers were low, the strength of this trial related to its restriction of off-label ibuprofen use. Gupta et al., for the Baby-OSCAR Collaborative Group, randomized 326 extreme preterm infants with large PDAs to either ibuprofen or placebo. The adjusted risk ratio for death (1.32; CI 0.96-1.90) or moderate to severe BPD (1.09; CI 0.98-1.20) measured at 36 weeks post-menstrual age was not significantly lower in the ibuprofen group. These studies further support expectant management of large PDAs in extreme premature infants.
Invasive techniques, either through PDA ligation or percutaneous catheter closure, are usually considered after a second course of ibuprofen for persistent PDAs since the risk and complication profiles for invasive techniques are higher. Indomethacin has also been used to medically close PDAs. However, the risk profile of indomethacin compared to ibuprofen is worse and includes intestinal perforation, acute kidney injury, fluid retention and cerebral vasoconstriction.
