Magnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial*. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. [Magnesium sulfate in prevention of preterm labor]. Randomized investigation of magnesium sulfate for prevention of preterm birth. Comparison of magnesium sulfate, terbutaline and a placebo for inhibition of preterm labor. A randomized study. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Prevention of preterm delivery: nifedipine or magnesium sulfate. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy.
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. 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. 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. To observe the efficacy of magnesium sulfate in the treatment of preterm labor, 65 uncomplicated cases of preterm labor between 28 and 36 weeks of gestation were studied prospectively during Sep. 1988-May 1991. They were divided into two groups randomly. 30 cases were treated with magnesium sulfate and 35 cases with barbiturates or bed rest. The prevention of delivery for at least 48 hours after the initiation of therapy was achieved in 23 of the 30 cases (76.67%) of the magnesium sulfate group and in 3 of the 35 cases (8.57%) in the control group. Delay of more than 7 days was achieved in 17 of the 30 cases (56.67%) and in 2 of the 35 cases (5.71%). The postponement of delivery between the two groups. There was highly significantly difference (P less than 0.01). There was a significant correlation of cervical dilation at the onset of treatment to success of controlling preterm labor. In the magnesium sulfate group, the mean magnesium level to achieve tocolysis was 2.8 +/- 0.35 mmol/L (mean +/- s). The side effects to the mothers, fetus, and the neonates were mild and not prominent.(ABSTRACT TRUNCATED AT 250 WORDS) One hundred fifty-six women with preterm labor between 24 and 34 weeks' gestation were randomized to receive either intravenous magnesium sulfate or no tocolytic therapy. Magnesuim sulfate infusions of up to 3 gm/hr were used in 76 pregnancies and resulted in a mean serum magnesium concentration of 5.5 +/- 1.4 mEq/L (mean +/- SEM). Compared with 80 control pregnancies, magnesium sulfate tocolysis had no significant effect on duration of gestation, birth weight, neonatal morbidity, and perinatal mortality. We conclude that clinically safe infusions of magnesium sulfate are ineffective when used to prevent preterm birth. Magnesium sulfate has been recommended as a safe and effective agent for inhibiting preterm labor. Its reported adequacy as a tocolytic agent, however, has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated a prospective, randomized study comparing the capabilities of magnesium sulfate, terbutaline and a placebo (5% dextrose in lactated Ringer's solution) for labor inhibition. The study population consisted of 54 patients between 26 and 34 weeks of gestation and in preterm labor. The diagnosis of labor was made if, following hydration, persistent uterine contractions occurred at a frequency of at least three in a ten-minute period and cervical examination suggested active labor. Success was defined as postponement of delivery for at least 48 hours after initiation of therapy. Despite a trend toward increased efficacy in the terbutaline group there were no significant differences between the three treatment groups with regard to capability of delaying delivery at least 48 hours. Also, there were no significant differences between the groups with regard to gestational age at delivery, birth weight and neonatal survival. The fact that delivery occurred in less than 48 hours of approximately one-half the patients under the best of circumstances emphasizes the need for more effective techniques for the inhibition of preterm labor and the need for a better understanding of the mechanisms involved in the initiation of preterm labor. The purpose of this study was to determine whether the use of antenatal magnesium sulfate prevents adverse outcomes (neonatal intraventricular hemorrhage, periventricular leucomalacia, death, and cerebral palsy).
                In a controlled trial, we randomized mothers in preterm labor to magnesium sulfate, "other" tocolytic, or placebo. At delivery, umbilical cord blood was collected for the later determination of serum ionized magnesium levels. Neonatal cranial ultrasound scans were obtained periodically for the diagnosis of intraventricular hemorrhage and periventricular leucomalacia. Among survivors, the diagnosis of cerebral palsy was made at age 18 months.
                Children with adverse outcomes had higher umbilical cord magnesium levels at delivery. In regression models that controlled for confounders, which included very low birth weight, magnesium remained a significant risk factor (adjusted odds ratio, 3.7; 95% CI, 1.1-11.9; P =.03).
                Contrary to original hypotheses, this randomized trial found that the use of antenatal magnesium sulfate was associated with worse, not better, perinatal outcome in a dose-response fashion. to establish the efficacy and safety of nifedipine and magnesium sulfate in arresting preterm labor.
                seventy-four patients with singleton pregnancies at 23-36 weeks in preterm labor, were selected randomly to receive either oral nifedipine or intravenous magnesium sulfate.
                both drugs had similar tocolytic efficacy and side effects while nifedipine was faster than magnesium sulfate in arresting uterine contractions (4.8 +/- 4.23 vs. 2.98 +/- 3.03 h) P = 0.04.
                this data suggests that oral nifedipine with the same efficacy, side effects and faster action could be a suitable and more convenient alternative to intravenous magnesium sulfate in arresting preterm labor. 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
Magnesium sulphate is ineffective at delaying birth or preventing preterm birth, and its use is associated with an increased mortality for the infant. Any further trials should be of high quality, large enough to assess serious morbidity and mortality, compare different dose regimens, and provide neurodevelopmental status of the child.