Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Magnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial*. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy.
Prenatal magnesium sulfate may reduce the risk of cerebral palsy or death in very preterm infants.
                To determine the effectiveness of magnesium sulfate given for neuroprotection to women at risk of preterm birth before 30 weeks' gestation in preventing pediatric mortality and cerebral palsy.
                Randomized controlled trial at 16 tertiary hospitals in Australia and New Zealand with stratification by center and multiple pregnancy. A total of 1062 women with fetuses younger than 30 weeks' gestation for whom birth was planned or expected within 24 hours were enrolled from February 1996 to September 2000 with follow-up of surviving children at a corrected age of 2 years.
                Women were randomly assigned to receive a loading infusion of 8 mL (4 g [16 mmol] of 0.5 g/mL of magnesium sulfate solution or isotonic sodium chloride solution [0.9%]) for 20 minutes followed by a maintenance infusion of 2 mL/h for up to 24 hours.
                Rates of total pediatric mortality, cerebral palsy, and the combined outcome of death or cerebral palsy at a corrected age of 2 years.
                Data were analyzed for 1047 (99%) 2-year survivors. Total pediatric mortality (13.8% vs 17.1%; relative risk [RR], 0.83; 95% confidence interval [CI], 0.64-1.09), cerebral palsy in survivors (6.8% vs 8.2%; RR, 0.83; 95% CI, 0.54-1.27), and combined death or cerebral palsy (19.8% vs 24.0%; RR, 0.83; 95% CI, 0.66-1.03) were less frequent for infants exposed to magnesium sulfate, but none of the differences were statistically significant. Substantial gross motor dysfunction (3.4% vs 6.6%; RR, 0.51; 95% CI, 0.29-0.91) and combined death or substantial gross motor dysfunction (17.0% vs 22.7%; RR, 0.75; 95% CI, 0.59-0.96) were significantly reduced in the magnesium group.
                Magnesium sulfate given to women immediately before very preterm birth may improve important pediatric outcomes. No serious harmful effects were seen. Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate.
                Eligible women (n=10141) had not given birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty about magnesium sulphate. Women were randomised in 33 countries to either magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia and, for women randomised before delivery, death of the baby. Follow up was until discharge from hospital after delivery. Analyses were by intention to treat.
                Follow-up data were available for 10,110 (99.7%) women, 9992 (99%) of whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71) than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with eclampsia per 1000 women). Maternal mortality was also lower among women allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women randomised before delivery, there was no clear difference in the risk of the baby dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only notable difference in maternal or neonatal morbidity was for placental abruption (relative risk 0.67, 99% CI 0.45-0.89).
                Magnesium sulphate halves the risk of eclampsia, and probably reduces the risk of maternal death. There do not appear to be substantive harmful effects to mother or baby in the short term. To evaluate whether magnesium sulphate (MgSO(4)) given to women at risk of very-preterm birth would be neuroprotective in preterm newborns and would prevent neonatal mortality and severe white-matter injury (WMI).
                A randomised study.
                Eighteen French tertiary hospitals. Population Women with fetuses of gestational age < 33 weeks whose birth was planned or expected within 24 hours were enrolled from July 1997 to July 2003 with follow up of infants until hospital discharge. METHODS Five hundred and seventy-three mothers were randomly assigned to receive a single 40-ml infusion of 0.1 g/ml of MgSO(4) (4 g) solution or isotonic 0.9% saline (placebo) over 30 minutes. This study is registered as an International Standard Randomised Controlled Trial, number 00120588.
                The primary endpoints were rates of severe WMI or total mortality before hospital discharge, and their combined outcome. Analyses were based on intention to treat.
                After 6 years of enrolment, the trial was stopped. Data from 688 infants were analysed. Comparing infants who received MgSO(4) or placebo, respectively, total mortality (9.4 versus 10.4%; OR: 0.79, 95% CI 0.44-1.44), severe WMI (10.0 versus 11.7%; OR: 0.78, 95% CI 0.47-1.31) and their combined outcomes (16.5 versus 17.9%; OR: 0.86, 95% CI 0.55-1.34) were less frequent for the former, but these differences were not statistically significant. No major maternal adverse effects were observed in the MgSO(4) group.
                Although our results are inconclusive, improvements of neonatal outcome obtained with MgSO(4) are of potential clinical significance. More research is needed to assess the protective effect of MgSO(4) alone or in combination with other neuroprotective molecules. Research suggests that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of cerebral palsy.
                In this multicenter, placebo-controlled, double-blind trial, we randomly assigned women at imminent risk for delivery between 24 and 31 weeks of gestation to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour, or matching placebo. The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age.
                A total of 2241 women underwent randomization. The baseline characteristics were similar in the two groups. Follow-up was achieved for 95.6% of the children. The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group (11.3% and 11.7%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.77 to 1.23). However, in a prespecified secondary analysis, moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group (1.9% vs. 3.5%; relative risk, 0.55; 95% CI, 0.32 to 0.95). The risk of death did not differ significantly between the groups (9.5% vs. 8.5%; relative risk, 1.12; 95% CI, 0.85 to 1.47). No woman had a life-threatening event.
                Fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate or severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. (ClinicalTrials.gov number, NCT00014989.)
                2008 Massachusetts Medical Society
The neuroprotective role for antenatal magnesium sulphate therapy given to women at risk of preterm birth for the preterm fetus is now established. The number of women needed to be treated to benefit one baby by avoiding cerebral palsy is 63 (95% confidence interval 43 to 155). Given the beneficial effects of magnesium sulphate on substantial gross motor function in early childhood, outcomes later in childhood should be evaluated to determine the presence or absence of later potentially important neurological effects, particularly on motor or cognitive function.