Magnesium sulphate for women at term for neuroprotection of the fetus.

BACKGROUND Magnesium sulphate is extensively used in obstetrics for the treatment and prevention of eclampsia. A recent meta-analysis has shown that magnesium sulphate is an effective fetal neuroprotective agent when given antenatally to women at risk of very preterm birth. Term infants account for more than half of all cases of cerebral palsy, and the incidence has remained fairly constant. It is important to assess if antenatal administration of magnesium sulphate to women at term protects the fetus from brain injury, and associated neurosensory disabilities including cerebral palsy. OBJECTIVES To assess the effectiveness of magnesium sulphate given to women at term as a neuroprotective agent for the fetus. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trial Register (31 July 2012) and the reference lists of other Cochrane reviews assessing magnesium sulphate in pregnancy. SELECTION CRITERIA Randomised controlled trials comparing antenatally administered magnesium sulphate to women at term with placebo, no treatment or a different fetal neuroprotective agent. We also planned to include cluster-randomised trials, and exclude cross-over trials and quasi-randomised trials. We planned to exclude studies reported as abstracts only. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for eligibility and for risk of bias. Two authors independently extracted data. Data were checked for accuracy. MAIN RESULTS We included one trial (involving 135 women with mild pre-eclampsia at term). An additional six studies are awaiting further assessment.The included trial compared magnesium sulphate with a placebo and was at a low risk of bias. The trial did not report any of this review's prespecified primary outcomes. There was no significant difference between magnesium sulphate and placebo in Apgar score less than seven at five minutes (risk ratio (RR) 0.51; 95% confidence interval (CI) 0.05 to 5.46; 135 infants), nor gestational age at birth (mean difference (MD) -0.20 weeks; 95% CI -0.62 to 0.22; 135 infants).There were significantly more maternal side effects (feeling warm and flushed) in the magnesium sulphate group than in the placebo group (RR 3.81; 95% CI 2.22 to 6.53; 135 women). However, no significant difference in adverse effects severe enough to cease treatment was observed (RR 3.04; 95% CI 0.13 to 73.42; 135 women). There were no significant differences seen between groups in the rates of postpartum haemorrhage (RR 4.06; 95% CI 0.47 to 35.38; 135 women) and caesarean section (RR 0.80; 95% CI 0.39 to 1.63; 135 women). AUTHORS' CONCLUSIONS There is currently insufficient evidence to assess the efficacy and safety of magnesium sulphate when administered to women for neuroprotection of the term fetus. As there has been recent evidence for the use of magnesium sulphate for neuroprotection of the preterm fetus, high-quality randomised controlled trials are needed to determine the safety profile and neurological outcomes for the term fetus. Strategies to reduce maternal side effects during treatment also require evaluation.

[1]  Julie Brown,et al.  Magnesium sulphate for preventing preterm birth in threatened preterm labour. , 2014, The Cochrane database of systematic reviews.

[2]  J. Higgins,et al.  Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The Cochrane Collaboration , 2013 .

[3]  S. Brophy,et al.  Interventions for latent autoimmune diabetes (LADA) in adults. , 2011, The Cochrane database of systematic reviews.

[4]  M. Costantine,et al.  Antenatal exposure to magnesium sulfate and neuroprotection in preterm infants. , 2011, Obstetrics and gynecology clinics of North America.

[5]  A. Synnes,et al.  SOGC Clinical Practice Guideline. Magnesium sulphate for fetal neuroprotection. , 2011, Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC.

[6]  D. Chou,et al.  Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. , 2010, The Cochrane database of systematic reviews.

[7]  M. Gladstone A review of the incidence and prevalence, types and aetiology of childhood cerebral palsy in resource-poor settings , 2010, Annals of tropical paediatrics.

[8]  Robert N. Taylor,et al.  Chorioamnionitis--a complex pathophysiologic syndrome. , 2010, Placenta.

[9]  J. Olsen,et al.  Health of children born to mothers who had preeclampsia: a population-based cohort study. , 2009, American journal of obstetrics and gynecology.

[10]  R. Romero,et al.  Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis. , 2009, American journal of obstetrics and gynecology.

[11]  B. Jacobsson,et al.  Cerebral palsy and restricted growth status at birth: population‐based case–control study , 2008, BJOG : an international journal of obstetrics and gynaecology.

[12]  F. Malone,et al.  A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. , 2008, The New England journal of medicine.

[13]  L. Doyle,et al.  Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus ( Review ) , 2022 .

[14]  L. Doyle,et al.  Antenatal magnesium sulphate neuroprotection in the preterm infant. , 2007, Seminars in fetal & neonatal medicine.

[15]  C. Levêque,et al.  Magnesium sulphate given before very‐preterm birth to protect infant brain: the randomised controlled PREMAG trial * , 2006, BJOG : an international journal of obstetrics and gynaecology.

[16]  Roger M Harbord,et al.  A modified test for small‐study effects in meta‐analyses of controlled trials with binary endpoints , 2006, Statistics in medicine.

[17]  S. Glinianaia,et al.  Cerebral palsy and intrauterine growth. , 2006, Clinics in perinatology.

[18]  D. Silberberg,et al.  The Burden of Brain Disorders , 2006, Science.

[19]  Eve Blair,et al.  Epidemiology of cerebral palsy. , 2006, Seminars in fetal & neonatal medicine.

[20]  M. Delivoria-Papadopoulos,et al.  Effect of post-hypoxic MgSO4 administration in utero on Ca2+-influx and Ca2+/calmodulin kinase IV activity in cortical neuronal nuclei , 2005, Neuroscience Letters.

[21]  L. Doyle,et al.  Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. , 2003, JAMA.

[22]  Gabriel J Escobar,et al.  Chorioamnionitis and cerebral palsy in term and near-term infants. , 2003, JAMA.

[23]  R. Mittendorf,et al.  Association between use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. , 2003, American journal of obstetrics and gynecology.

[24]  B. Sibai,et al.  Magnesium Sulfate in Women With Mild Preeclampsia: A Randomized Controlled Trial , 2003, Obstetrics and gynecology.

[25]  G. Buonocore,et al.  Chorioamnionitis: A Risk Factor for Fetal and Neonatal Morbidity , 2003, Neonatology.

[26]  D. Altman,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[27]  L. Doyle,et al.  Magnesium sulphate for preventing preterm birth in threatened preterm labour. , 2002, The Cochrane database of systematic reviews.

[28]  P. Heywood,et al.  259 Mechanisms of mortality in the magnesium and neurologic endpoints trial (magnet trial): Fetal Inflammatory Response Syndrome (FIRS) , 2001 .

[29]  A. Majnemer,et al.  Topical Review: Long-Term Developmental Outcome of Asphyxiated Term Neonates , 2001, Journal of child neurology.

[30]  S. Blackwell,et al.  The effects of intrapartum magnesium sulfate therapy on fetal serum interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha at delivery: a randomized, placebo-controlled trial. , 2001, American journal of obstetrics and gynecology.

[31]  Ann Johnson,et al.  Cerebral palsies: epidemiology and causal pathways , 2000, Archives of disease in childhood.

[32]  K. Nelson,et al.  Magnesium sulfate for tocolysis and risk of spastic cerebral palsy in premature children born to women without preeclampsia. , 2000, American journal of obstetrics and gynecology.

[33]  F. Stanley,et al.  Cerebral Palsies: Epidemiology and Causal Pathways , 2000 .

[34]  A. Maclennan A template for defining a causal relation between acute intrapartum events and cerebral palsy: international consensus statement , 1999, BMJ.

[35]  J. Canterino,et al.  Maternal magnesium sulfate and the development of neonatal periventricular leucomalacia and intraventricular hemorrhage. , 1999, Obstetrics and gynecology.

[36]  E. Coetzee,et al.  A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre‐eclampsia , 1998, British journal of obstetrics and gynaecology.

[37]  S. Selvin,et al.  Magnesium sulfate tocolysis and risk of neonatal death. , 1998, American journal of obstetrics and gynecology.

[38]  G. Thurnau,et al.  The effect of maternal magnesium sulfate treatment on neonatal morbidity in < or = 1000-gram infants. , 1998, American journal of perinatology.

[39]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[40]  C. Shen,et al.  Effect of magnesium sulfate on the development of cystic periventricular leukomalacia in preterm infants. , 1997, American journal of perinatology.

[41]  A. Witlin,et al.  The effect of magnesium sulfate therapy on the duration of labor in women with mild preeclampsia at term: a randomized, double-blind, placebo-controlled trial. , 1997, American journal of obstetrics and gynecology.

[42]  C. Berg,et al.  Prenatal Magnesium Sulfate Exposure and the Risk for Cerebral Palsy or Mental Retardation Among Very Low-Birth-Weight Children Aged 3 to 5 Years , 1996 .

[43]  D. Rouse,et al.  The feasibility of a randomized clinical perinatal trial: maternal magnesium sulfate for the prevention of cerebral palsy. , 1996, American journal of obstetrics and gynecology.

[44]  J. N. Martin,et al.  Acute tocolysis for suspected intrapartum fetal distress: maternal effects of terbutaline versus magnesium sulfate. , 1995, International journal of obstetric anesthesia.

[45]  Shuenn-Dyh Chang,et al.  Expectant management in severe preeclampsia: does magnesium sulfate prevent the development of eclampsia? , 1995, Acta obstetricia et gynecologica Scandinavica.

[46]  K. Nelson,et al.  Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants? , 1995, Pediatrics.

[47]  R. Ehrenkranz,et al.  Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants. , 1995, Pediatrics.

[48]  J. Moodley,et al.  Prophylactic Anticonvulsant Therapy in Hypertensive Crises of Pregnancy—The Need for a Large, Randomized Trial , 1994 .

[49]  P. Lipsitz The clinical and biochemical effects of excess magnesium in the newborn. , 1971, Pediatrics.