BACKGROUND:Epidemiological and basic science evidence suggests that magnesium sulphate before birth may be neuroprotective for the fetus. OBJECTIVES:To assess the effectiveness and safety of magnesium sulphate as a neuroprotective agent when given to women considered at risk of preterm birth. SEARCH STRATEGY:We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (October 2006), CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE (1966 to October 2006), EMBASE (1980 to October 2006), Current Contents (1992 to October 2006), references of retrieved articles, and abstracts submitted to the Society for Pediatric Research (1996 to 2006). SELECTION CRITERIA:Randomised controlled trials of antenatal magnesium sulphate therapy given to women threatening or likely to give birth at less than 37 weeks' gestational age. DATA COLLECTION AND ANALYSIS:We independently extracted data regarding clinical outcomes including paediatric mortality, neurologic outcome of survivors (including blindness, deafness, cerebral palsy and major neurosensory disability), and maternal complications and side-effects. At least two authors assessed trial eligibility and quality, and extracted data. MAIN RESULTS:Four trials (3701 babies) were eligible for this review. No statistically significant effect of antenatal magnesium sulphate therapy was detected on any major paediatric outcome, including mortality (e.g., paediatric mortality relative risk (RR) 0.97; 95% confidence interval (CI) 0.74 to 1.28; four trials; 3701 infants), and neurological outcomes in the first few years of life, including cerebral palsy (RR 0.77; 95% CI 0.56 to 1.06; four trials; 3701 infants), neurological impairments or disabilities. There were also no significant effects of antenatal magnesium therapy on combined rates of mortality with neurologic outcomes. There was a significant reduction in the rate of substantial gross motor dysfunction (RR 0.56; 95% CI 0.33 to 0.97; two trials; 2848 infants). There were higher rates of minor maternal side-effects in the magnesium groups, but no significant effects on major maternal complications. AUTHORS' CONCLUSIONS:The role for antenatal magnesium sulphate therapy as a neuroprotective agent for the preterm fetus is not yet established. Given the possible beneficial effects of magnesium sulphate on gross motor function in early childhood, outcomes later in childhood should be evaluated to determine the presence or absence of later potentially important neurologic effects, particularly on motor or cognitive function. Further information will be available from one of the studies where outcomes are being evaluated again at eight to nine years of age, and from another trial currently in progress.