To explore and compare the efficacy and safety of oral ibuprofen and paracetamol in treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in extreme premature neonates (gestational age < 28 weeks).

A total of 96 extreme premature neonates with hsPDA who met the inclusion and exclusion criteria of this study from November 2012 to October 2019 in Shanghai First Maternity and Infant Hospital were selected as research subjects. They were classified into two groups according to oral medication regimen for treatment of hsPDA in extreme premature neonates: ibuprofen group (n=53) and paracetamol group (n=43). The time to full enteral feeding, duration of invasive mechanical ventilation and inner diameter of ductus arteriosus before and after medication between two groups were compared by independent-samples t tests. The rate of closure of ductus arteriosus, incidence of complications, rate of failure of oral medication and transfer to surgery and mortality of neonates after medication between two groups were compared by chi-square test or Fisher′s exact test. There were no statistical differences between two groups in general clinical data, such as gender ratio, gestational age, birth weight, 1 and 5 min Apgar scores, rate of surfactant administration, the age of commencement of oral medication, and rates of administration of dexamethasone for promoting fetal lung maturity before labor, cesarean section and the duration of premature rupture of membranes more than 18 h of pregnant mother (P>0.05). This study was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013.

①The rate of closure of ductus arteriosus was 56.6% (30/53) in extreme premature neonates of ibuprofen group, which was statistically higher than that of paracetamol group 30.2% (13/43), and the difference was statistically significant (χ²=6.676, P=0.009). After oral medication, the inner diameter of ductus arteriosus in ibuprofen group was (0.14±0.26) cm, which was significantly shorter than that of paracetamol group (0.30±0.14) cm, and the difference was also statistically significant (t=-5.406, P=0.007). ②There were no differences between two groups in time to full enteral feeding and duration of invasive mechanical ventilation (P>0.05). ③There were no differences between two groups in incidence of liver injury, kidney injury, hyperbilirubinemia, thrombocytopenia, anemia, gastrointestinal bleeding, pulmonary hemorrhage, intraventricular hemorrhage (IVH), early-onset sepsis (EOS), late-onset sepsis (LOS), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), failure of oral medication and transfer to surgery or mortality of neonates (P>0.05).

The safety of oral treatment by ibuprofen in extreme premature neonates with hsPDA is similar to that of paracetamol. The efficacy of oral treatment by ibuprofen is superior to that of paracetamol. Since this study is just a single-center study and sample size is relatively small, efficacy and safety of oral treatment by ibuprofen and paracetamol in extreme premature neonates with hsPDA still needs to be further confirmed by large-sample size, multi-center and randomized controlled trials.