The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre‐eclampsia. Outcome for children at 18 months

Abstract

Objective To assess the long-term effects of in utero exposure to magnesium sulphate for children whose mothers had pre-eclampsia.Design Assessment at 18 months of age for children whose mothers were recruited to the Magpie Trial (recruitment 1998(recruitment -2001, which compared magnesium sulphate with placebo.Setting Follow-up of children born at 125 centres in 19 countries across five continents.Population A total of 6922 children were born to women randomised before delivery at follow-up centres. Of these, 2271 were not included for logistic reasons and 168 were excluded (101 at a centre where <20% were contacted, 40 whose death or disability was due to a problem at conception or embryogenesis and 27 whose parent/s opted out). Therefore, 4483 children were included in follow-up, of whom 3283 (73%) were contacted.Methods Assessment by questionnaire, with interview and neurodevelopmental testing of selected children.Main outcome measures Death or neurosensory disability at age of 18 months.Results Of those allocated magnesium sulphate, 245/1635 (15.0%) were dead or had neurosensory disability at 18 months compared with 233/1648 (14.1%) allocated placebo (relative risk [RR] 1.06, 95% CI 0.90-1.25), and of survivors, 19/1409 (1.3%) had neurosensory disability at 18 months compared with 27/1442 (1.9%) (RR 0.72, 95% CI 0.40-1.29). There were no substantial differences in causes of death or in the risk of individual impairments or disabilities.Conclusions The lower risk of eclampsia following prophylaxis with magnesium sulphate was not associated with a clear difference in the risk of death or disability for children at 18 months.

Magnesium Decreases Inflammatory Cytokine Production: A Novel Innate Immunomodulatory Mechanism

“…MgSO 4 has been demonstrated to have a neonatal neuroprotective effect when given to women at risk for preterm delivery (3–7). We observed that MgSO 4 supplementation decreases baseline and LPS-stimulated TNF-α and IL-6 production within CBMCs from preterm neonates who were not exposed to MgSO 4 intrapartum (Fig.…”

“…Despite widespread use, the mechanism by which MgSO 4 exerts its action is poorly understood. Retrospective, clinical studies associated antepartum MgSO 4 exposure with reduced risk of adverse neurologic outcome in premature newborns (1, 2), leading to randomized clinical trials (3–7); additionally, a recent review concluded that antenatal MgSO 4 therapy significantly reduces the risk of cerebral palsy and substantial gross motor dysfunction (8). These findings raise a critical question, “How does MgSO 4 mediate neuroprotection?”…”

Antenatal Magnesium Sulphate (Mgso4) for Fetal NeuroProtection Prior to Preterm Labor: Mini-Review

“…Recently; Doyle et al, meta-analysis reported that the antenatal MgSO4 infusion before 37 gestational weeks` to women at risk of PTL associated with reduced CP risk (RR 0.68, CI; 0.54-0.87), and gross motor disabilities (RR 0.61, CI; 0.44-0.85) in their children without affecting the pediatric mortality (RR 1.04, CI; 0.92-1.17) [3] . In the Magpie trial, which concluded that the lower risk of eclampsia following prophylaxis with MgSO4 was not associated with a clear decrease in the risk of death or disability for infants at 18 months [6] , the time of MgSO4 infusion was unclear, and the assessment of CP done at 18 months of age. However; preterm infants, have a lot of neurologic manifestations in the first months of age, which resolve later, and diagnosed wrongly as CP [1,14] .…”

“…Although; Magpie trial, concluded that the lower risk of eclampsia following prophylaxis with MgSO4 was not associated with a clear decrease in the risk of death or disability for infants at 18 months [6] . A Cochrane metaanalysis reported that the antenatal MgSO4 infusion before 37 gestational weeks to women at risk of PTL associated with reduced CP risk in their children (RR 0.68, CI; 0.54-0.87) [3] .…”

Impact of Common Treatments Given in the Perinatal Period on the Developing Brain

“…While none of these 4 trials individually has reported any statistical differences in the rates of their primary composite outcome (death/CP), secondary analyses demonstrated a reduction in the rate of neonatal CP among infants exposed to MgSO 4 . The Doyle Cochrane meta-analysis included a fifth trial aimed at comparing MgSO 4 with placebo in women with pre-eclampsia [12] and demonstrated a significant reduction in CP in infants exposed to antenatal MgSO 4 (RR 0.68; 95% CI 0.54-0.87), confirmed within the neuroprotective-intent subgroup (RR 0.71; 95% CI 0.55-0.91). In addition, substantial gross motor dysfunction, measured in four trials, was lower (RR 0.61; 95% CI 0.44-0.85), and there was a significant reduction in the combined rate of death and CP in the neuroprotective-intent groups (RR 0.85; 95% CI 0.74-0.98).…”