Pre-symptomatic targeted treatment of patent ductus arteriosus in preterm newborns: A systematic review and meta-analysis.

BACKGROUND: A clinically significant patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in premature newborns. Symptomatic PDAs are often treated with prostaglandin synthesis inhibitors (PSI), but controversy remains if PSIs should also be used to manage early, asymptomatic PDAs.

OBJECTIVE: To systematically identify, critically appraise, and evaluate the efficacy and safety of pharmacological management of pre-symptomatic PDA in preterm newborns after confirmed patency by echocardiography.

STUDY DESIGN: Systematic review and meta-analysis.

SEARCH METHODS: We searched MEDLINE (Ovid), EMBASE (Ovid), Cochrane Central Register of Controlled Trials (Wiley), from date of inception to February 2017. Supplemental searching was performed in Scopus and Web of Science to identify additional relevant citations. We also searched conference proceedings, reference lists of relevant articles and the WHO International Clinical Trials Registry Platform (ICTRP).

SELECTION CRITERIA: We included only randomized controlled trials (RCTs) that compared the use of indomethacin or ibuprofen to placebo for treatment of pre-symptomatic PDA in preterm newborns (<32 weeks gestational age and <1500gms).

DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials, assessed risk of bias and extracted trial-level data. Outcomes are reported as risk ratios from random-effects models. Absolute risk reduction (ARR) is additionally reported for significant outcomes.We included seven trials (466 newborns). Targeted medical treatment did not significantly reduce mortality rates (RR 0.85, 95% CI 0.50 to 1.43; ARR -2.38%, 95% CI -8.04% to 3.29%; I2 0% 6 studies; 442 newborns), but it did significantly reduce the overall incidence of developing symptomatic PDA (RR 0.39, 95% CI 0.21 to 0.73; ARR -34.3%, 95% CI -50.8% to -17.8%; I2 0%; 3 studies; 97 newborns) compared to placebo. Other efficacy or safety outcomes were not significantly different.

CONCLUSIONS: Targeted medical treatment of pre-symptomatic PDA decreases the incidence of developing symptomatic PDA, but not neonatal mortality. Further studies are essential to confirm these results.