Background: The effectiveness of repeated drug course to close or constrict a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants has not been studied extensively. Our aim was to assess the effectiveness of a second or third course of treatment with ibuprofen and/or paracetamol in 107 infants with gestational age < 29 weeks.

Methods: Infants with echocardiographic diagnosis of hsPDA were treated with ibuprofen, paracetamol, or with ibuprofen plus paracetamol between 24 and 72 h of life. Echocardiography was repeated at the end of each pharmacological course.

Results: The failure rate of the first, second and third course of drug treatment was 38% (41/107), 76% (31/41), and 92% (24/26), respectively. Among 24 infants who failed treatment, 8 (31%) had closure or constriction of the hsPDA after >3 drug courses, 15 (57%) received surgical closure, and 3 (12%) died with hsPDA. Logistic regression analyses did not show independent risk factors for the failure of the second and third course of treatment.

Conclusions: We found a higher failure rate of the second and third courses of drug treatment than previously reported. Planning the third and additional pharmacological courses at centers where the failure rate is very high may prolong the exposure of very preterm infants to the adverse effects of hsPDA.