Patent ductus arteriosus (PDA) ligation has been variably associated with neonatal morbidities and neurodevelopmental impairment (NDI). The objective was to systematically review and meta-analyze the impact of PDA ligation in preterm infants at <32 weeks’ gestation on the risk of mortality, severe neonatal morbidities, and NDI in early childhood.


Medline, Embase, Cochrane Central Register of Controlled Trials, Education Resources Information Centre (ERIC), Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Dissertation database were searched (1947 through August 2013). Risk of bias was assessed by using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. Meta-analyses were performed by using a random-effects model. Unadjusted and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were pooled when appropriate.


Thirty-nine cohort studies and 1 randomized controlled trial were included. Nearly all cohort studies had at least moderate risk of bias mainly due to failure to adjust for survival bias and important postnatal preligation confounders such as ventilator dependence, intraventricular hemorrhage, and sepsis. Compared with medical treatment, surgical ligation was associated with increases in NDI (aOR: 1.54; 95% CI: 1.01–2.33), chronic lung disease (aOR: 2.51; 95% CI: 1.98–3.18), and severe retinopathy of prematurity (aOR: 2.23; 95% CI: 1.62–3.08) but with a reduction in mortality (aOR: 0.54; 95% CI: 0.38–0.77). There was no difference in the composite outcome of death or NDI in early childhood (aOR: 0.95; 95% CI: 0.58–1.57).


Surgical ligation of PDA is associated with reduced mortality, but surviving infants are at increased risk of NDI. However, there is a lack of studies addressing survival bias and confounding by indication.

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