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.

Magnesium for newborns with hypoxic-ischemic encephalopathy: a systematic review and meta-analysis.

OBJECTIVE: Magnesium may have a role in neuroprotection in neonatal hypoxic-ischemic encephalopathy (HIE). The objective of this study was to systematically review the efficacy and safety of postnatal magnesium therapy in newborns with HIE. STUDY DESIGN: MEDLINE, EMBASE, CINAHL and CCRCT were searched for studies of magnesium for HIE. Randomized controlled trials that compared magnesium to control in newborns with HIE were selected. The primary outcome was a composite outcome of death or moderate-to-severe neurodevelopmental disability at 18 months. When appropriate, meta-analyses were conducted using random effects model and risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. RESULT: Five studies with sufficient quality were included. There was no difference in the primary outcome between the magnesium and the control groups (RR 0.81, 95% CI 0.36 to 1.84). There was significant reduction in the unfavorable short-term composite outcome (RR 0.48, 95% CI 0.30 to 0.77) but no difference in mortality (RR 1.39, 95% CI 0.85 to 2.27), seizures (RR 0.84, 95% CI 0.59 to 1.19) or hypotension (RR 1.28, 95% CI 0.69 to 2.38) between the magnesium and the control groups. CONCLUSION: The improvement in short-term outcomes without significant increase in side effects indicate the need for further trials to determine if there are long-term benefits of magnesium and to confirm its safety. Mortality was statistically insignificant between the magnesium and the control groups. However, the trend toward increase in mortality in the magnesium group is a major clinical concern and should be monitored closely in future trials.