In Reply We thank Razak for the comments on our randomized clinical trial comparing nonintervention and oral ibuprofen treatment for patent ductus arteriosus (PDA).1
First, because the PDA might close spontaneously,2 we could avoid unnecessary treatment exposure in 37% (143 of 383) of patients by delaying their enrollment for approximately 1 week.1 In contrast with other trials showing 21% pulmonary hemorrhage, 12.5% of intraventricular hemorrhage, and 40% of backup treatments,3 6% of intraventricular hemorrhage and no pulmonary hemorrhage nor backup treatment were observed in the nonintervention arm of our trial.1 Therefore, nonintervention alone is not enough, but meticulous neonatal intensive care including judicious fluid restriction starting at 67 mL/kg per day is essential for the success of this approach.1,2,4,5 Considering no significantly higher odds of PDA closure (1.63; 95% CI, 0.83-3.25) with high vs standard dose of oral ibuprofen and lowest incidence of bronchopulmonary dysplasia (BPD)/death with standard dose observed in a meta-analysis,6 our data showing significant PDA closure only in infants at the gestational age of 27 to 30 weeks but not at the gestational age of 23 to 26 weeks might thus reflect that it is gestational age rather than dose-dependent variation for PDA closure.1,2 Because only patients with symptomatic PDA requiring respiratory support, with the average PDA size of 2.5 mm and left atrium/aorta ratio of 1.69 and 1.61 in the ibuprofen and nonintervention arm, respectively, were enrolled, our study population was homogenous with moderate to severe clinical and echocardiographic severity in both arms.