AUTHOR=Okulu Emel , Erdeve Omer , Arslan Zehra , Demirel Nihal , Kaya Huseyin , Gokce Ismail Kursad , Ertugrul Sabahattin , Cetinkaya Merih , Buyukkale Gokhan , Ozlu Ferda , Simsek Huseyin , Celik Yalcin , Ozkan Hilal , Köksal Nilgun , Akcan Baris , Turkmen Munevver , Celik Kiymet , Armangil Didem , Bulbul Ali , Tekgunduz Kadir Serafettin , Oncel Mehmet Yekta , Tuzun Funda , Ergenekon Ebru , Ergin Hacer , Arsan Saadet , Turkish Neonatal Society INTERPDA Study Group TITLE=An Observational, Prospective, Multicenter, Registry-Based Cohort Study Comparing Conservative and Medical Management for Patent Ductus Arteriosus JOURNAL=Frontiers in Pediatrics VOLUME=8 YEAR=2020 URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.00434 DOI=10.3389/fped.2020.00434 ISSN=2296-2360 ABSTRACT=

No consensus has been reached on which patent ductus arteriosus (PDAs) in preterm infants require treatment and if so, how, and when they should be treated. A prospective, multicenter, cohort study was conducted to compare the effects of conservative approaches and medical treatment options on ductal closure at discharge, surgical ligation, prematurity-related morbidities, and mortality. Infants between 240/7 and 286/7 weeks of gestation from 24 neonatal intensive care units were enrolled. Data on PDA management and patients' clinical characteristics were recorded prospectively. Patients with moderate-to-large PDA were compared. Among the 1,193 enrolled infants (26.7 ± 1.4 weeks and 926 ± 243 g), 649 (54%) had no or small PDA, whereas 544 (46%) had moderate-to-large PDA. One hundred thirty (24%) infants with moderate-to-large PDA were managed conservatively, in contrast to 414 (76%) who received medical treatment. Eighty (62%) of 130 infants who were managed conservatively did not receive any rescue treatment and the PDA closure rate was 53% at discharge. There were no differences in the rates of late-onset sepsis, necrotizing enterocolitis (NEC), retinopathy of prematurity, intraventricular hemorrhage (≥Grade 3), surgical ligation, and presence of PDA at discharge between conservatively-managed and medically-treated infants (p > 0.05). Multivariate analysis including perinatal factors showed that medical treatment was associated with increased risk for mortality (OR 1.68, 95% Cl 1.01–2.80, p = 0.046), but decreased risk for BPD or death (BPD/death) (OR 0.59, 95%Cl 0.37–0.92, p = 0.022). The preferred treatment options were ibuprofen (intravenous 36%, oral 31%), and paracetamol (intravenous 26%, oral 7%). Infants who were treated with oral paracetamol had higher rates of NEC and mortality in comparison to other treatment options. Infants treated before postnatal day 7 had higher rates of mortality and BPD/death than infants who were conservatively managed or treated beyond day 7 (p = 0.009 and 0.007, respectively). In preterm infants born at <29 weeks of gestation with moderate-to-large PDA, medical treatment did not show any reduction in the rates of open PDA at discharge, surgical or prematurity-related secondary outcomes. In addition to the high incidence of spontaneous closure of PDA in the first week of life, early treatment (<7 days) was associated with higher rates of mortality and BPD/death.