Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a meta-analysis

Abstract

Objective: To review the evidence regarding neuroprotective effects of antenatal exposure to magnesium sulfate.

Data sources: We conducted database searches of MEDLINE, the Cochrane Library and Controlled Trials Register, as well as the ClinicalTrials.gov and International Clinical Trials Register websites. Bibliographies of all relevant articles were reviewed.

Methods of study selection: Randomized controlled trials comparing magnesium sulfate with placebo/other treatment in patients at risk of preterm delivery were evaluated for inclusion and methodological quality. The primary outcome was death or cerebral palsy by 18-24 months corrected age. Secondary outcomes were death, cerebral palsy, moderate-severe cerebral palsy, and death or moderate-severe cerebral palsy. Separate analyses were performed according to the gestational age (GA) at randomization (less than 32 to 34 weeks and less than 30 weeks) and for studies in which magnesium sulfate was used exclusively for fetal neuroprotection.

Tabulation, integration, and results: Five randomized controlled trials were included (5,235 fetuses/infants). When analyzed by GA at randomization, in utero exposure to magnesium sulfate at less than 32-34 weeks did not reduce the rate of death or cerebral palsy (relative risk [RR] 0.92, 95% confidence interval [CI] 0.83-1.03). However, cerebral palsy (RR 0.70, 95% CI 0.55-0.89), moderate-severe cerebral palsy (RR 0.60, 95% CI 0.43-0.84), and death or moderate-severe cerebral palsy were significantly reduced, without an evident increase in the risk of death (RR 1.01, 95% CI 0.89-1.14). Similar results were obtained when the GA at randomization was less than 30 weeks. When only neuroprotection trials (four trials, 4,324 fetuses/infants) are analyzed, in utero exposure to magnesium sulfate additionally reduced the primary outcome of death or cerebral palsy. The number needed to treat to prevent one case of cerebral palsy among those who survive until age 18-24 months is 46 (95% CI 26-187) in infants exposed to magnesium sulfate in utero before 30 weeks, and 56 (95% CI 34-164) in infants exposed to magnesium sulfate in utero before 32 to 34 weeks.

Conclusion: Fetal exposure to magnesium sulfate in women at risk of preterm delivery significantly reduces the risk of cerebral palsy without increasing the risk of death.

Figure 1

Summation of studies reporting the effect of antenatal exposure of magnesium sulfate at less than 32 to 34 weeks of gestation on death or cerebral palsy (A), cerebral palsy (B), death (C), moderate to severe cerebral palsy (D), and death or moderate-severe cerebral palsy (E). This is a Forest plot with the meta-analysis (fixed effects Mantel-Haenszel model) of the treatment/exposure effect expressed as pooled relative risk (RR) with its 95% confidence interval (CI).

Figure 2

Summation of randomized controlled trials reporting the effect of antenatal exposure of magnesium sulfate at less than 30 weeks on death or cerebral palsy (A), cerebral palsy (B), death (C), moderate-severe cerebral palsy (D), and death or moderate-severe cerebral palsy (E). This is a Forest plot with the meta-analysis (fixed effects Mantel-Haenszel model) of the treatment/exposure effect expressed as pooled relative risk (RR) with its 95% confidence interval (CI).

Figure 3

Summation of randomized controlled trials designed for neuroprotection summarizing the effect of antenatal exposure of magnesium sulfate on cerebral palsy or death (A), cerebral palsy (B), and death (C). This is a Forest plot with the meta-analysis (fixed effects Mantel-Haenszel model) of the treatment/exposure effect expressed as pooled relative risk (RR) with its 95% confidence interval (CI).