Conservative Treatment Without Any Intervention Compared With Other Therapeutic Strategies for Symptomatic Patent Ductus Arteriosus in Extremely Preterm Infants: A Nationwide Cohort Study in Korea

Abstract

Objective: Although symptomatic treatment is the most preferred treatment strategy for proven symptomatic patent ductus arteriosus (PDA), a considerable number of infants only received conservative treatment without any pharmacological or surgical interventions in the lower gestational age and lower birth weight group in Korea. We compared in-hospital outcomes of infants treated conservatively without any intervention and those of infants managed by other therapeutic strategies in extremely preterm infants with symptomatic PDA.Methods: A prospectively collected cohort study for 2,303 infants with gestational ages <28 weeks from the Korean Neonatal Network database. These infants were classified into four groups according to the presence of PDA-related symptoms and therapeutic treatment strategy: prophylactic treatment group, pre-symptomatic treatment (PST) group, symptomatic treatment (ST) group, and conservative treatment (CT) without any intervention group.Results: In multivariable logistic regression analysis, the risk of death was significantly decreased in the PST group (adjusted odds ratio [aOR] = 0.507; 95% confidence interval [CI] 0.311–0.826) and ST group (aOR = 0.349; 95% CI: 0.230–0.529) compared with the CT group. However, the risk of composite outcome of severe bronchopulmonary dysplasia or death had not increased in the PST group and ST group. Neonatal death due to pulmonary hemorrhage or neurological disease was significantly higher in the CT group than in the PST group or ST group.Conclusion: In extremely preterm infants, who are at highest risk of PDA-related morbidities and mortality, even less interventional approach for PDA can be allowed; the rescued pharmacological or surgical interventions are necessary if they met the criteria for hemodynamically significant PDA.

Treatment of patent ductus arteriosus and short-term outcomes among extremely preterm infants: a multicentre cohort study

“…This result remained significant following sensitivity analyses and subgroup analyses based on sex and GA. This finding is consistent with data from the Korean national cohort, 6 the EPIPAGE 2 national population-based cohort from France, 4 and the comparative study between Japan and Canada. 3 Pathophysiologically, the consequences of left-to-right shunting through the ductus arteriosus include pulmonary edema, congestive heart failure and reduced systemic blood flow leading to peripheral organ ischemia, which may compromise the survival for extremely preterm infants, and previous studies have shown that persistent PDA was associated with increased mortality in premature infants.…”

“… 1 , 2 Clinically, medical treatment has been widely used to close the ductus arteriosus, with data from several large national and international cohort studies showing that a large proportion (21–51%) of very low birth weight infants were medically treated for PDA. 3 , 4 , 5 , 6 , 7 , 8 However, several randomised clinical trials 9 , 10 , 11 , 12 and observational cohort studies 13 , 14 , 15 , 16 in recent years have shown that PDA treatment did not improve outcomes, prompting calls not to treat PDA in preterm infants actively. Nevertheless, these studies included relatively small proportions and absolute numbers of extremely preterm infants 10 , 13 , 14 , 15 , 16 who are the most vulnerable population to the harm of PDA, homogenised infants with different severity of disease, 12 , 13 , 14 , 15 , 16 focused mainly on composite outcomes, 10 , 12 , 13 , 15 and authorised rescue therapy in the non-treatment group.…”

Decreased plasma levels of PDGF-BB, VEGF-A, and HIF-2α in preterm infants after ibuprofen treatment

“…Color Doppler ultrasonography screening was routinely performed in all preterm infants who required respiratory support on the third day of life. Hemodynamically significant PDA (hsPDA) was diagnosed when a DA was present with predominantly left-to-right shunting across the DA associated with (1) left-atrium-to-aorta ratio (LA./Ao ratio) ≥ 1.5 and (2) PDA diameter (measured at its narrowest part, the end of pulmonary arterial) ≥ 1.5 mm, and when there were two out of the following clinical symptoms caused by PDA: (1) systolic or continuous murmur; (2) precordial pulsation distress; (3) hypotension; (4) respiratory distress; and (5) pulmonary edema or cardiomegaly (cardiothoracic ratio > 60%) on chest X-ray ( 23 , 24 ). Echocardiograms were performed by an experienced pediatric sonographer using a Mindray M9 ultrasound scanner (Mindray, China) with a 10-MHz probe.…”

“…(3) hypotension; (4) respiratory distress; and (5) pulmonary edema or cardiomegaly (cardiothoracic ratio > 60%) on chest X-ray (23,24). Echocardiograms were performed by an experienced pediatric sonographer using a Mindray M9 ultrasound scanner (Mindray, China) with a 10-MHz probe.…”

Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. A multicenter cohort study

“…As a result, divergent perspectives persist, with one faction asserting that PDA treatment plays a role in preventing adverse neonatal outcomes, while another contends that it does not offer such preventive benefits [ 9 , 10 ]. A conservative approach to managing PDA, encompassing strategies such as fluid restriction, diuretics, and higher positive airway end-expiratory pressure, has gained increasing favor [ 11 , 12 ].…”