Antenatal Magnesium Sulfate and Neurologic Outcome in Preterm Infants: A Systematic Review

OBJECTIVE: To systematically review rates of neurologic outcomes reported in childhood for the preterm fetus exposed to antenatal magnesium sulfate. DATA SOURCES: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register, CENTRAL (The Cochrane Library 2008, Issue 3), relevant references from retrieved articles, and abstracts submitted to major congresses. METHODS OF STUDY SELECTION: We sought all randomized controlled trials (RCTs) of antenatal magnesium sulfate with neurologic outcomes reported for the fetus. TABULATION, INTEGRATION, AND RESULTS: Five eligible RCTs with 6,145 fetuses were identified; in four studies (4,446 fetuses) the primary intent was neuroprotection of the fetus. Methods of the Cochrane Collaboration were used to analyze the data. Antenatal magnesium sulfate therapy given to women at risk of preterm birth substantially reduced the risk of cerebral palsy in their children (relative risk [RR] 0.69; 95% confidence interval [CI] 0.54–0.87; five trials; 6,145 infants). The number needed to treat to prevent one case of cerebral palsy was 63 (95% CI 43–155). Moreover, there was a significant reduction in the rate of substantial gross motor dysfunction (RR 0.61; 95% CI 0.44–0.85; four trials; 5,980 infants). No statistically significant effect of antenatal magnesium sulfate therapy was detected on pediatric mortality (RR 1.01; 95% CI 0.82–1.23; five trials; 6,145 infants), or on other neurologic impairments or disabilities in the first few years of life. There were no significant effects of antenatal magnesium sulfate on combined rates of mortality with neurologic outcomes, except in the studies where the primary intent was neuroprotection, where there was a reduction in death or cerebral palsy (RR 0.85; 95% CI 0.74–0.98; four trials; 4,446 infants). CONCLUSION: Antenatal magnesium sulfate therapy given to women at risk of preterm birth is neuroprotective against motor disorders in childhood for the preterm fetus.

[1]  Michele Tarsilla Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[2]  L. Doyle,et al.  Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. , 2009, The Cochrane database of systematic reviews.

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

[4]  B. Delaporte,et al.  Effet du sulfate de magnésium sur la mortalité et la morbidité neurologique chez le prématuré de moins de 33 semaines, avec recul à deux ans : résultats de l’essai prospectif multicentrique contre placebo PREMAG , 2008 .

[5]  S. Marret,et al.  Benefit of Magnesium Sulfate Given Before Very Preterm Birth to Protect Infant Brain , 2008, Pediatrics.

[6]  J. Dungan Magnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial , 2008 .

[7]  S. Marret,et al.  [Effect of magnesium sulphate on mortality and neurologic morbidity of the very-preterm newborn (of less than 33 weeks) with two-year neurological outcome: results of the prospective PREMAG trial]. , 2008, Gynecologie, obstetrique & fertilite.

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

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

[10]  M. Kaminski,et al.  Neonatal and 5-Year Outcomes After Birth at 30–34 Weeks of Gestation , 2007, Obstetrics and gynecology.

[11]  D. Altman,et al.  The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months , 2006, BJOG : an international journal of obstetrics and gynaecology.

[12]  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.

[13]  Gérard Bréart,et al.  Cerebral Palsy Among Very Preterm Children in Relation to Gestational Age and Neonatal Ultrasound Abnormalities: The EPIPAGE Cohort Study , 2006, Pediatrics.

[14]  N. Marlow,et al.  Neurologic and developmental disability at six years of age after extremely preterm birth. , 2005, The New England journal of medicine.

[15]  L. Doyle Evaluation of neonatal intensive care for extremely low birth weight infants in Victoria over two decades: II. Efficiency. , 2004, Pediatrics.

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

[17]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[18]  T. McElrath Association between use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. , 2003, American journal of obstetrics and gynecology.

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

[20]  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.

[21]  D. Schendel,et al.  Tocolytic magnesium sulfate exposure and risk of cerebral palsy among children with birth weights less than 1,750 grams. , 2000, American journal of epidemiology.

[22]  N. Bayley Bayley Scales of Infant Development , 1999 .

[23]  T. O'Shea,et al.  Prenatal events and the risk of cerebral palsy in very low birth weight infants. , 1998, American journal of epidemiology.

[24]  B. Khoshnood,et al.  Is tocolytic magnesium sulphate associated with increased total paediatric mortality? , 1997, The Lancet.

[25]  J. Pinto-Martin,et al.  Magnesium sulfate in labor and risk of neonatal brain lesions and cerebral palsy in low birth weight infants. The Neonatal Brain Hemorrhage Study Analysis Group. , 1997, Pediatrics.

[26]  R. Palisano,et al.  Development and reliability of a system to classify gross motor function in children with cerebral palsy , 1997, Developmental medicine and child neurology.

[27]  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. , 1997, JAMA.

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

[29]  D. Sackett,et al.  Cochrane Collaboration , 1994, BMJ.

[30]  F. Stanley Using Cerebral Palsy Data in the Evaluation of Neonatal Intensive Care: a Warning , 1982, Developmental medicine and child neurology.