The optimal timing of surgical ligation of patent ductus arteriosus in preterm or very-low-birth-weight infants A systematic review and meta-analysis

Background: Patent ductus arteriosus (PDA) is a particularly common problem in preterm infants. Although surgical ligation is rarely performed in many contemporary neonatal intensive care units, it remains a necessary treatment option for preterm infants with a large hemodynamically significant PDA under strict clinical criteria, and it can reduce mortality in preterm infants. However, the optimal timing of surgical ligation is still controversial. We conducted this systematic review and meta-analysis to compare the mortality and morbidity of early and late surgical ligation of FDA in preterm or very-low-birth-weight (VLBW) infants. Methods: This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42019133686). We searched the databases of PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the World Health Organization International Clinical Trials Registry Platform up to May 2019. Results: This review included 6 retrospective studies involving 397 premature or VLBW infants with PDA. Pooled analysis showed that compared with the late ligation group, the early ligation group had a lower fraction of inspired oxygen (F1O2) at 24 hours postoperatively (mean difference [MD] -6.34, 95% confidence interval [CI] -945 to -3.22). fewer intubation days (MD -19.69, 95% CI -29.31 to -10.07), earlier date of full oral feeding (MD -22.98, 95% CI -28.63 to -17.34) and heavier body weight at 36 weeks of conceptional age (MD 232.08, 95% CI 57.28 to 406.88). No significant difference in mortality or other complications was found between the early and late groups. Conclusion: Our meta-analysis implies that compared with late surgical ligation, early ligation might have a better respiratory outcome and nutritional status for PDA in preterm or VLBW infants. There was no difference in mortality or postoperative complications between early and late ligation. A randomized prospective clinical trial with a possible large sample size is urgently needed to reinvestigate this conclusion.