Abstract
BACKGROUND: Transient tachypnoea of the newborn (TTN) is a common cause of early respiratory distress, especially after caesarean delivery. Salbutamol, a β(2)-agonist, may enhance alveolar fluid clearance and improve outcomes. The objective of the present study was to evaluate the benefits and harms of nebulised salbutamol compared with placebo or standard care in neonates with TTN, through a systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS: We conducted a systematic search of five electronic databases and trial registries up to April 2025. Risk of bias was assessed with the Cochrane Risk of Bias 1 tool, and certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analyses were performed when appropriate. RESULTS: 21 RCTs (n=1223) were included. Repeated doses of salbutamol probably reduce hospital stay by 2.3 days (mean difference (MD) -2.3 days, 95% CI -3.2 to -1.4 days; moderate certainty) and a single dose may reduce oxygen therapy duration by 19.4 h (MD -19.4 h, 95% CI -26.0 to -12.9 h; low certainty) and duration of assisted ventilation by 12.7 h (MD -12.7 h, 95% CI -19.6 to -5.7 h; low certainty). Effects on need for mechanical ventilation (risk ratio 0.37, 95% CI 0.07-1.96; very low certainty) and continuous positive airway pressure (risk ratio 0.84, 95% CI 0.59-1.19; very low certainty) were very uncertain. In addition, single dose of salbutamol may reduce tachypnoea duration by 6.6 h (MD -6.6 h, 95% CI -12.6 to -0.7 h; low certainty) and clinical severity scores at 4 and 8 h (MD -3.0 and -3.4 points, respectively; low certainty). CONCLUSION: Salbutamol shows modest benefits in TTN, particularly in reducing oxygen therapy duration and hospital stay with repeated doses. However, given the low certainty of the evidence for most outcomes, its use should be carefully weighed within each healthcare context. Further high-quality trials are needed.