Abstract:
Background: Bronchopulmonary dysplasia (BPD) remains a common and serious complication among preterm neonates. Oxidative stress is believed to play a central role in its development. N-acetylcysteine (NAC), an antioxidant and glutathione precursor, has been explored as a potential therapy, but its clinical benefit in this population remains unclear.
Objective: To evaluate the effects of postnatal NAC on BPD and other neonatal respiratory outcomes in preterm neonates requiring respiratory support.
Methods: A systematic review and meta-analysis of randomized controlled trials was conducted following PRISMA guidelines. Electronic databases and trial registries were searched from inception without language restrictions. Searches were conducted in March 2026. Eligible studies included preterm neonates receiving postnatal NAC compared with placebo or standard care. Outcomes included BPD, mortality, duration of mechanical ventilation, and adverse events. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE approach. Two independent reviewers performed screening, extraction, and appraisal.
Result: Three randomized controlled trials involving 461 participants were included. Bronchopulmonary dysplasia, duration of mechanical ventilation, and other reported respiratory outcomes were synthesized narratively, while mortality and adverse events were pooled using meta-analysis. Postnatal NAC did not reduce BPD at 36 weeks’ postmenstrual age compared with control (64/160 [40.0%] vs 68/168 [40.5%]; OR 1.0, 95% CI 0.6–1.5). Pooled analysis showed no clear difference in mortality (RR 1.02, 95% CI 0.41–2.53) or adverse events (RR 1.64, 95% CI 0.19–14.03). The wide confidence intervals indicate substantial imprecision. Therefore, the findings remain inconclusive.
Conclusion: Current evidence does not demonstrate a clinically meaningful benefit of postnatal NAC in preterm neonates. Meta-analysis of mortality and adverse events yielded inconclusive findings with imprecise estimates. Given the low to very low certainty of evidence, the current findings are insufficient to support routine postnatal NAC use in this population. Further well-designed trials are needed to better define its role in this population.
Keywords: Bronchopulmonary dysplasia, N-acetylcysteine, preterm neonates
