Effect of prophylactic phenylephrine versus norepinephrine on foeto-maternal outcomes in caesarean delivery under neuraxial anaesthesia: A systematic review and meta-analysis with trial sequential analysis.

Abstract

Background and aims: The prevention of hypotension in parturients scheduled for caesarean section is of utmost importance for improving foeto-maternal outcomes. We compared the prophylactic use of phenylephrine (PE) and norepinephrine (NE) on foeto-maternal outcomes in women undergoing caesarean delivery under neuraxial anaesthesia. Umbilical artery (UA) pH was the primary objective, and umbilical vein (UV) pH, APGAR scores, incidence of bradycardia, hypotension, and hypertension were secondary objectives.

Methods: PubMed, EMBASE, Web of Science, Google Scholar, and CENTRAL databases were searched to identify all relevant randomised controlled trials (RCTs) published up to April 2023, further updated till May 2025. Our review was prospectively registered with PROSPERO (ID: CRD42023429328). The effect of PE and NE on UA pH was our primary outcome. The quality of evidence of outcomes was graded using the GRADE methodology. Only RCTs involving term pregnant females undergoing caesarean section under neuraxial anaesthesia were included.

Results: Seventeen trials (2138 patients) were included in the final analysis. NE and PE were comparable in terms of UA and UV pH, with standardised mean difference (SMD) of 0.18 [95% confidence interval (CI): -0.09; 0.45] (I² = 81%, P < 0.01) and -0.39 (95% CI: -0.82; 0.04) (I² = 91%, P < 0.01), respectively. NE group had significantly lesser episodes of bradycardia [Relative Risk (RR): 0.44 (95% CI: 0.34; 0.56) (I² = 28%, P = 0.15)] and hypertension [RR: 0.54 (95% CI: 0.33; 0.90) (I² = 0%, P = 0.62)], but incidence of hypotension was comparable between groups [RR: 0.99 (95% CI: 0.82; 1.18) (I² = 18%, P = 0.25)]. Trial sequential analysis revealed that the required information size was reached for the outcome of bradycardia only.

Conclusion: There is insufficient evidence to recommend using NE preemptively to improve foetal outcomes. Further studies are recommended to validate its effect.