Impact of patent ductus arteriosus shunt size and duration on risk of death or severe respiratory morbidity in preterm infants born in China
Authors: Deng Yingping , Zhang Haiyan , Zhao Zhuoyu , Du Juan , Bai Ruimiao , McNamara Patrick J. 
Published: July 2022

The purpose of this study is to assess whether duration and size of the arterial duct were associated with severe respiratory morbidity and mortality in preterm infants. All echocardiography evaluations for patent ductus arteriosus (PDA) in a cohort of preterm infants, born at a gestational age less than 28 weeks, from birth up to 36 weeks of postconceptional age or final ductal closure were reviewed. Ductal size was measured at the pulmonary end. PDA was classified as small (E1: ductal diameter (DD) ≤ 1.5 mm), moderate (E2: 1.5 mm < DD ≤ 2.5 mm), or large (E3) (DD > 2.5 mm). The primary outcome was adverse outcome defined by the composite outcome of bronchopulmonary dysplasia (BPD) or death. Infants in whom the primary outcome occurred were classified as “high-risk” whereas patients who did not satisfy this outcome were classified as “low-risk”. Intergroup comparison (high vs. low risk) was performed using univariate and multivariate analyses. A total of 135 infants, born between 2010 and 2020, were evaluated. The primary outcome was satisfied in 46 (34.1%) patients. The high-risk group was characterized by increased duration of exposure to PDA of any (E1/E2/E3) grade (44 vs. 25.5 days, p = .0004), moderate or large (E2/E3) PDA (30.5 vs. 11.5 days, p < .0001), moderate (E2) PDA (10.8 vs.6 days, p = 0.05), and large (E3) PDA (11.5 vs.0 days, p < .0001) compared with low-risk group. Lower gestational age, prolonged duration of mechanical ventilation, higher rate of inotrope use, pharmacological therapy, and PDA ligation were also associated with development of BPD or death (high-risk group). After adjusting for confounders, the rate of inotrope use [OR 2.688, 95% CI (1.011–7.142), p = 0.047], duration of large (E3) PDA [OR 1.060, 95% CI (1.005–1.118), p = 0.03], and mechanical ventilation [OR 1.130, 95% CI (1.064–1.200), p = 0.0001] were independently associated with the composite of BPD or death. Among infants who developed BPD, 27 were classified as grade I and 18 as grade II BPD, respectively. Infants with grade II BPD had prolonged MV (20.0 vs. 9.0 days, p = 0.024), prolonged exposure to PDA of any grade (55.8 vs. 36.0 days, p = 0.03), and prolonged exposure to large (E3) PDA compared with infants with grade I BPD.

   Conclusion: Prolonged exposure to a large PDA was associated with severe respiratory morbidity and mortality in preterm infants. The modulator role of early intervention, in the most pathologic shunts, on severe respiratory morbidity in preterm infants should be tested in well-designed clinical trials.

What is Known:• Current guidelines recommended against accelerating PDA closure of preterm infants within 2 weeks of life, with low certainty evidence indicating improved long-term outcomes.• Recent studies suggest that conservative approach regarding PDA management has detrimental effects on the respiratory outcomes in a subgroup population.

What is New:• Persistent patency of significant PDA is associated with increased risk of BPD/death in extremely preterm infants.• Targeted intervention of PDA is beneficial for the at-risk preterm infants with increased PDA hemodynamic significance.