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Magnesium Sulfate Before Preterm Birth for Neuroprotection: An Updated Cochrane Systematic Review
Emily S Shepherd1, Shona Goldsmith, Lex W Doyle
1SAHMRI Women and Kids, South Australian Health and Medical Research Institute (SAHMRI), and Adelaide Medical School, University of Adelaide, Adelaide, the Cerebral Palsy Alliance Research Institute, Specialty of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, and the Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, Australia; INSERM Unit 1245, Team 4, Rouen School of Medicine, Normandy University, and the Department of Neonatal Pediatrics, Intensive Care, and Neuropediatrics, Rouen University Hospital, Rouen, France; Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, Rhode Island; the Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; the Department of Gynaecology and Obstetrics, Hvidovre University Hospital, Hvidovre, Denmark; and the Liggins Institute, University of Auckland, Auckland, New Zealand.
Objective:
To systematically review the evidence for the effectiveness and safety of magnesium sulfate as a fetal neuroprotective agent when given to individuals at risk of preterm birth.
Data Sources:
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov , the World Health Organization International Clinical Trials Registry Platform (through March 17, 2023), and reference lists of relevant studies.
Methods Of Study Selection:
Randomized controlled trials (RCTs) assessing magnesium sulfate for fetal neuroprotection in pregnant participants at risk of imminent preterm birth were eligible. Two authors assessed RCTs for inclusion, extracted data, and evaluated risk of bias, trustworthiness, and evidence certainty (GRADE [Grading of Recommendations Assessment, Development and Evaluation]).
Tabulation, Integration, And Results:
We included six RCTs (5,917 pregnant participants and 6,759 fetuses at less than 34 weeks of gestation at randomization). They were conducted in high-income countries (two in the United States, two across Australia and New Zealand, and one each in Denmark and France) and commenced between 1995 and 2018. Primary outcomes: up to 2 years of corrected age, magnesium sulfate compared with placebo reduced the risk of cerebral palsy (risk ratio [RR] 0.71, 95% CI, 0.57-0.89; six RCTs, 6,107 children) and death or cerebral palsy (RR 0.87, 95% CI, 0.77-0.98; six RCTs, 6,481 children) (high-certainty evidence). Magnesium sulfate had little or no effect on death up to 2 years of corrected age (moderate-certainty evidence) or these outcomes at school age (low-certainty evidence). Although there was little or no effect on death or cardiac or respiratory arrest for pregnant individuals (low-certainty evidence), magnesium sulfate increased adverse effects severe enough to stop treatment (RR 3.21, 95% CI, 1.88-5.48; three RCTs, 4,736 participants; moderate-certainty evidence). Secondary outcome: magnesium sulfate reduced the risk of severe neonatal intraventricular hemorrhage (moderate-certainty evidence).
Conclusion:
Magnesium sulfate for preterm fetal neuroprotection reduces cerebral palsy and death or cerebral palsy for children. Further research is required on longer-term benefits and harms for children, effect variation by participant and treatment characteristics, and the generalizability of findings to low- and middle-income countries.
Systematic Review Registration:
The review protocol was based on a standard Cochrane Pregnancy and Childbirth template and our previous Cochrane Systematic Review (doi: 10.1002/14651858.CD004661.pub3 ; published before the introduction of PROSPERO).
