Research Article: Natural evolution of ductus arteriosus with noninterventional conservative management in extremely preterm infants born at 23-28 weeks of gestation

Date Published: February 13, 2019

Publisher: Public Library of Science

Author(s): Se In Sung, Yun Sil Chang, Jisook Kim, Jin Hwa Choi, So Yoon Ahn, Won Soon Park, Umberto Simeoni.


This study aimed to determine the natural course of patent ductus arteriosus (PDA) with noninterventional conservative management and whether the presence and/or prolonged duration of hemodynamically significant (HS) PDA increased the risk of mortality and morbidities in extremely preterm (EPT) infants. We retrospectively reviewed the medical records of EPT infants born at 23–28 weeks of gestation (n = 195) from January 2011 to June 2014, when PDA was managed with noninterventional conservative treatment. We stratified infants into three subgroups of 23–24, 25–26, and 27–28 weeks and analyzed the prevalence and natural evolution of HS PDA, defined as ventilator dependency and PDA size ≥2 mm. Multivariate regression analyses determined if the presence and/or prolonged duration of HS PDA increased the risk for mortality and/or morbidities. The overall incidence of HS PDA was 57% (111/195) at the end of the first postnatal week. In subgroup analyses, infants with 23–24 weeks of gestation had the highest incidence (93%, 50/54), with 64% (47/74) for 25–26 weeks and 21% (14/67) for 27–28 weeks. Six (5%) of 111 infants with HS PDA were discharged without ductus closure, 4 had spontaneous PDA closure on follow up, and device closure was performed for 2 infants. In the multivariate analyses, the presence or prolonged duration (per week) of HS PDA was not associated with the risk of mortality and/or morbidities. Spontaneous closure of HS PDA was mostly achieved, even in EPT infants, with a noninterventional conservative approach. In conclusion, our data showed the incidence and natural course of HS PDA in EPT infants and suggested that the presence or prolonged duration of HS PDA might not increase the rate of mortality or morbidities.

Partial Text

Persistent patent ductus arteriosus (PDA) in premature infants is associated with increased mortality and morbidities including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH), but evidence supporting their causal relationships is lacking [1–4]. A deeply ingrained hypothesis is that left-to-right shunt is a direct cause of adverse outcomes in preterm infants with persistent PDA; thus, developing sequelae are a function of the magnitude and duration of left-to-right ductal shunting [1,6]. This hypothesis has suggested mandatory closure of PDA at the earliest time with medical and/or surgical therapy for persistent PDA in preterm infants [5,6]. However, compelling evidence is lacking on the therapeutic efficacy and safety of conventional medical or surgical therapy of PDA from meta-analyses and a few small prospective studies [7,8]. A high spontaneous closure rate for PDA, even in extremely low birth-weight (ELBW) infants, has caused a trend in PDA treatment toward more permissive and less aggressive conservative approaches [7–11].

Data collection was approved by the Institutional Review Board of Samsung Medical Center (SMC) with waiver of informed consent for the retrospective chart review (IRB No. SMC 2016-10-045). The medical records of 203 EPT infants born at 23–28 weeks of gestation who were admitted to the SMC NICU from January 2011 to June 2014 were reviewed retrospectively (Fig 1). After excluding infants who died before the first echocardiography and those who had congenital heart disease or multiple congenital anomalies, 195 EPT infants were included for analysis. We stratified the EPT infants into 23–24, 25–26, and 27–28 weeks of gestation and compared mortality and morbidities such as BPD, NEC, and IVH according to the presence or absence and duration of HS PDA. HS PDA was defined as ≥2 mm with predominant left-to-right shunt on echocardiography (ACUSON SeQuoia C512; Siemens Medical Solutions, Mountain View, California, USA) initially performed at the end of the first postnatal week and need for ventilator support with symptoms and signs suggestive of symptomatic PDA including cardiac murmur, hypotension, widened pulse pressure, or respiratory deterioration. The initial echocardiography was deferred until the end of the first week because early spontaneous ductal closure could occur during the first week even in EPT infants [10]. Non-HS PDA was defined as PDA <2 mm on echocardiography, or there was no requirement for ventilator support regardless of PDA size. Follow up echocardiography was conducted if any symptoms/signs suggestive of PDA occurred and regularly at 2- to 4-week intervals until PDA closure. The natural evolution of PDA, especially in EPT infants, has not been studied well because PDA is often treated. Our data illustrated the natural course of PDA using a retrospective cohort of EPT infants who all received noninterventional conservative management. HS PDA was observed only in 57% of patients at the end of the first postnatal week. Spontaneous closure of PDA was achieved in 97% (189/195) before hospital discharge and in an additional 2% (4/195) during follow up at the outpatient clinic. Device closure was conducted only in 1% (2/195) of EPT infants with 23–28 weeks of gestation. In concordance with our data, Semberova et al. reported spontaneous closure of PDA in 85% of VLBW infants who underwent conservative PDA management with no medical and/or surgical intervention [18]. Rolland et al. observed a spontaneous closure rate of 73% in EPT infants born before 28 weeks, without any specific treatment to close PDA [12]. Collectively, these findings suggest that spontaneous closure of PDA, even in EPT infants near the limit of viability, can be achieved with noninterventional conservative management. These findings thus suggest that exposure to the risks of therapeutic interventions for ductal closure, even in EPT infants, might not be warranted.   Source: