Shepherd · The Cochrane database of systematic reviews 2024 · Systematic review and meta-analysis · n=6 RCTs (5,917 women and 6,759 fetuses)

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.

Cited 42 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials

PubMed 38726883 · doi:10.1002/14651858.CD004661.pub4 · record verified 2026-08-28

What was done

This Cochrane systematic review updated evidence on the neuroprotective efficacy and safety of magnesium sulphate compared with placebo or no treatment in women at risk of preterm birth prior to 34 weeks' gestation. Authors searched multiple trial registries through March 2023, assessed risk of bias and trustworthiness of eligible RCTs and cluster-RCTs, synthesized data into summary risk ratios (RR) with 95% confidence intervals, and evaluated evidence certainty using GRADE.

What was found

Six RCTs were included (5,917 women and 6,759 fetuses alive at randomisation). In children up to two years' corrected age, magnesium sulphate significantly reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6,107 children; NNTB 60; high-certainty evidence) and the composite outcome of death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6,481 children; NNTB 56; high-certainty evidence). It probably reduced severe intraventricular haemorrhage (RR 0.76, 95% CI 0.60 to 0.98; 5 RCTs, 5,885 infants; NNTB 92; moderate certainty) but showed little to no difference in death alone (RR 0.96, 95% CI 0.82 to 1.13; moderate certainty). At early school age, differences were not statistically significant for cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1,038 children; low certainty) or death (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1,758 children; low certainty). For mothers, magnesium sulphate probably increased adverse effects severe enough to stop treatment (RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4,736 women; moderate certainty), with no clear difference in severe maternal outcomes like death or arrest (RR 0.32, 95% CI 0.01 to 7.92; low certainty).

Why it matters

This review reinforces clinical guidelines supporting antenatal magnesium sulphate before 34 weeks' gestation to prevent cerebral palsy in surviving infants, while highlighting the substantial increase in maternal adverse events leading to therapy cessation.

Limits

All included RCTs were conducted in high-income countries, limiting applicability to low-resource settings. Treatment regimens and inclusion criteria varied across trials, follow-up to school age was available for only a small subset of children, and outcomes into adolescence/adulthood, breastfeeding rates, and maternal views of treatment were not reported.

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