To explore the timing of drug therapy for patent ductus arteriosus (PDA) in preterm infants.

A total of 151 premature infants (gestational age <32 weeks) who were admitted to the Neonatology Department of Sichuan Jinxin Women and Children's Hospital from January 2016 to December 2018 and met the inclusion criteria were retrospectively analyzed. According to the use of ibuprofen, the patients were divided into three groups: symptomatic treatment group (n=43), pre-symptomatic treatment group (n=32), and control group (n=76). According to whether hemodynamically significant PDA (hsPDA) was diagnosed or not, the patients were divided into either an hsPDA group or a non-hspda group. The symptomatic treatment group belonged to the hsPDA group, while the pre-symptomatic treatment group and control group belonged to the non-hspda group. Routine blood tests, blood biochemistry, and blood gas analysis were performed on the first day of birth. Echocardiography was performed 3 days after birth, and pulse pressure difference and urine output were recorded. The two treatment groups were initially given ibuprofen orally at 10 mg/kg, followed by 5 mg/kg at 24 h and 48 h, respectively. Echocardiography was reexamined 72 hours after treatment. The control group was not treated with ibuprofen and echocardiography was reviewed 7 days after birth. Echocardiography was reexamined 30 days after birth in patients with unclosed ductus arteriosus. The chi-square test was used to compare gender, proportion of pregnant mothers who used hormone, rate of premature rupture of membranes >18 h, cesarean section rate, proportion of neonates less than gestational age, closure rates of ductus arteriosus at 7 d and 30 d, and the incidences of sepsis, respiratory distress syndrome, intraventricular hemorrhage, bronchial pulmonary hypoplasia, and necrotizing enterocolitis between the symptomatic treatment group, pre-symptomatic treatment group, and control group. Univariate analysis was used to compare the differences in gestational age, birth weight, urine volume, pulse pressure, and blood pH. Kruskal-Wallis H method was used to compare the difference of 5 min Apgar score, positive pressure ventilation time, and oxygen absorption time.

Gender, gestational age, proportion of pregnant mothers who used hormone, rate of premature rupture of membranes >18 h, cesarean section rate, birth weight, proportion of neonates less than gestational age, 5 min Apgar score, blood pH, urine output, the incidence of respiratory distress syndrome, closure rate of ductus arteriosus at 30 d, positive pressure ventilation time, oxygen time, intraventricular hemorrhage, bronchial pulmonary hypoplasia, and necrotizing enterocolitis did not differ significantly among the three groups (P>0.05). The pulse pressure differences in the symptomatic treatment group, pre-symptomatic treatment group, and control group were (22.13±13.83) mmHg (1 mmH=0.133 kPa), (24.24-9.72) mmHg, and (16.22-8.81) mmHg, respectively; although there was no significant difference between the pre-symptomatic treatment group and control group (t=0.732, P=0.639), the pulse pressure difference in the symptomatic treatment group was significantly higher than those of the pre-symptomatic treatment group and control group (t=3.25 and 4.710, P=0.002 and <0.001, respectively). The incidence of sepsis in the symptomatic treatment group, pre-symptomatic treatment group, and control group was 9.38% (3/32), 27.91% (12/43), and 10.53% (8/76), respectively; although there was no significant difference between the pre-symptomatic treatment group and control group (χ²=0.033, P=0.856), the incidence of sepsis in the symptomatic treatment group was significantly higher than that of the pre-symptomatic treatment group and control group (χ²=5.933 and 4.230, P=0.015 and 0.040, respectively). The closure rate of ductus arteriosus at 7 d was signficantly higher in both the symptomatic treatment group and pre-symptomatic treatment group than in the control group [(65.63% (21/32) vs 60.47% (26/43) and 32.89% (25/76), χ²=8.524 and 9.866, P=0.004 and 0.002, respectively].

Oral ibuprofen can promote the early closure of ductus arteriosus, but has no significant advantage in terms of long-term closure rate. For premature infants with PDA, preventive ibuprofen intervention could not shorten positive pressure ventilation and oxygen absorption time or reduce the incidence of intraventricular hemorrhage, bronchial pulmonary dysplasia, and necrotizing enterocolitis. However, for premature infants with hsPDA, whether ibuprofen intervention can reduce respiratory support dependence and the occurrence of complications remains to be further studied.