In this retrospective cohort study of VLBWIs with HSPDA that is unresponsive to pharmacological treatment, there was no statistically significant difference in mortality rate between the PDA ligation and Non-ligation groups. PDA ductal diameter > 2.0 mm, low GA, low Apgar score at 5 minutes, and histologic chorioamnionitis were related to the need for surgical ligation of HSPDA. Additionally, early surgical ligation was not significantly associated with increased mortality among VLBWIs with HSPDA. The LL group was significantly related to an increased risk of NEC (stage ≥ III), IVH (grade ≥ III), culture-proven sepsis and time on a mechanical ventilator > 4 weeks.
The role of HSPDA surgical ligation in VLBWIs is still controversial. Although surgical treatment can close HSPDA immediately, multiple postoperative comorbidities such as left recurrent laryngeal nerve injury, bleeding, chylothorax, development of coarctation and acute hemodynamic compromise, can be associated with in-hospital mortality . In addition, previous observational studies have demonstrated that surgical treatment is associated with an increased risk of chronic lung disease (CLD), ROP, and neurodevelopmental impairment (NDI) [5, 14–19]. In contrast, a recent observational study demonstrated that there was no significant difference in NDI between the PDA ligation and Non-ligation groups . Furthermore, another previous publication suggested that the preferred option for PDA after unsuccessful medical management should be surgical ligation to avoid prolonged low levels of cerebral saturation .
PDA surgical ligation is a viable option that is safe and effective , and it can be performed at the bedside in the NICU without transfer to the operating room [5, 22]. In our cohort, no infants died during their operations, and there was no statistically significant difference in mortality rate between the PDA ligation and Non-ligation groups, and between the EL and LL groups. Although this was a small retrospective study with only three infants who died and although its statistical power may be limited, this result was shown to be noninferior to those of previous publications [6, 9].
In this study, histologic chorioamnionitis, which is diagnosed by histologic biopsy of the maternal placenta, showed a significant association with factors related to PDA surgical ligation. The role of infection in maintaining the patency of PDA can be considered . Infection may induce the production of cyclooxygenase (COX) -2 and inducible nitric oxide synthetase (iNOS), and together, they increase the production of vasodilatory prostaglandins such as COX-1 and NOS . The infant born from a mother with chorioamnionitis can have PDA with a persistent opening due to increased levels of vasodilatory prostaglandins and nitric oxide. In addition, clinical factors such as the PDA ductal size and signs reflected in the Apgar score should be emphasized when considering surgical intervention to improve clinical outcomes.
In VLBWIs with HSPDA, it is important to determine the optimal timing of surgical ligation [21, 25]. Our results showed that the EL group was associated with lower odds of severe NEC and IVH than the LL group. This may be explained by the diastolic steal of systematic circulation through HSPDA, which can induce intestinal ischemia resulting in NEC, renal hypoperfusion, and a reduction in the blood flow rate in the middle cerebral artery  and increase the risk of IVH . In our previous publication, early surgical ligation had the benefit of reducing the incidence of NEC and improving feeding intolerance . The difference between this previous study and the current observational study is embodied, and there is a significant difference in severe NEC (stage ≥ III) between the EL and LL groups.
Additionally, sepsis with increased serum levels of inflammatory mediators or prostaglandins can be associated with smooth muscle relaxation of the ductus arteriosus . Thus, as previously mentioned, the role of infection in maintaining the patency of PDA can be considered . EL may reduce the duration of infection exposure and can be expected to minimize the risk of sepsis.
Prolonged patency of PDA increases pulmonary circulation that can be injurious to the capillary endothelium and stimulate an inflammatory cascade that results in pulmonary edema, CLD development, and increased ventilator support . EL may diminish the period of exposure to HSPDA , and can decrease pulmonary edema  and facilitate earlier endotracheal extubation .
This study has several limitations. First, this was a small retrospective study with only 233 patients, and a randomized and prospective trial could not be performed. Thus, the statistical power of population may be limited. Second, all operations were performed by one cardiac surgeon with a high level of experience in pediatric heart surgery. One goal of future research is to perform a large prospective multicenter study with long-term and close follow-up of VLBWIs with HSPDA that is refractory to pharmacological treatment.