434 - Impact of Surgical Ligation of Patent Ductus Arteriosus in Extremely Preterm Infants: A Multicenter Cohort Study

Publication Number: 3419.434

Hsin-Chung Huang, National Taiwan University Children's Hospital, Taipei, Taipei, Taiwan (Republic of China); Mei-Hung Pan, Academia Sicina / Genomics Research Center, Taipei city, Taipei, Taiwan (Republic of China); Po-Nien Tsao, National Taiwan Univsersity Hospital, TAIPEI, Taipei, Taiwan (Republic of China); Hwai-I Yang, Academia Sinica, Taipei, Taipei, Taiwan (Republic of China)

Background: Patent ductus arteriosus affects more than 70% of preterm infants born before the gestational age of 28 weeks and is a critical aspect of neonatal care, impacting mortality and long-term outcomes. Observational studies on surgical ligation for hemodynamically significant patent ductus arteriosus have shown variable outcomes, often attributed to inadequate adjustment for confounding factors and inconsistent handling of survival bias.

Objective: This study aimed to assess the impact of surgical ligation on mortality and neurodevelopmental outcomes in extremely preterm infants.

Design/Methods: Data from the Taiwan Premature Infant Follow-up Network were analyzed for infants born before 28 weeks of gestation (1997-2017), excluding those with congenital anomalies or early mortality. Propensity score matching based on perinatal characteristics compared surgical ligation with medical treatment only. Multivariable analyses adjusted for confounders, and mediation analyses assessed the effects of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) requiring treatment on treatment-outcome associations.

Results: Among 4,071 extremely preterm infants, 1,211 matched pairs were analyzed. Compared with medical treatment alone, surgical ligation was associated with higher risk of neurodevelopmental impairment (NDI) (adjusted risk ratio [ARR] 1.38; 95% CI, 1.20-1.60) and lower mortality before discharge (ARR 0.53; 95% CI, 0.43-0.64). In infants surviving beyond 36 weeks postmenstrual age, ligation remained associated with increased risks of NDI (ARR 1.19; 95% CI, 1.01-1.40) and the composite of NDI or death (ARR 1.17; 95% CI, 1.01-1.37), while the reduction in mortality was not significant (ARR 1.08; 95% CI, 0.68-1.74). Mediation analyses indicated that part of the adverse effect on outcomes was transmitted via BPD and ROP requiring treatment: direct effects on NDI were ARR 1.13 (95% CI, 0.96-1.33) and ARR 1.17 (95% CI, 0.99-1.38), and on the composite outcome were ARR 1.11 (95% CI, 0.95-1.30) and ARR 1.15 (95% CI, 0.99-1.35), respectively.

Conclusion(s): Compared with medical treatment alone, surgical ligation of hemodynamically significant patent ductus arteriosus in extremely preterm infants was associated with an increased risk of NDI at two years of corrected age and higher rates of the composite outcome of NDI or death before discharge. Part of the adverse effect of surgical ligation on NDI and the composite outcome of NDI or death before discharge may be transmitted through an increased risk of BPD and ROP requiring treatment.

Table 1. Postnatal Characteristics and Morbidities of Infants Receiving Medical and Surgical Treatment for Patent Ductus Arteriosus After Propensity Score Matching.


Table 2. Outcomes in Infants with Patent Ductus Arteriosus Who Received Surgical Ligation vs Medical Treatment Only


Table 3.
Mediation Analysis of the Association Between Surgical Ligation and Outcomes by Prespecified Mediators.