Neuroprotective effects of in utero exposure to magnesium sulfate
- Hyagriv N Simhan, MD, MS
Hyagriv N Simhan, MD, MS
- Professor & Chief, Division of Maternal-Fetal Medicine
- Executive Vice Chair, Obstetrical Services Department of Ob/Gyn/RS
- University of Pittsburgh School of Medicine
- Medical Director of Obstetrical Services
- Magee-Womens Hospital of UPMC
- Katherine P Himes, MD, MSCR
Katherine P Himes, MD, MSCR
- Assistant Professor of Obstetrics, Gynecology and Reproductive Sciences
- University of Pittsburgh School of Medicine
Cerebral palsy is the leading cause of neurologic impairment in young children, and prematurity and low birth weight are the most important risk factors for developing the disease. (See "Epidemiology, etiology, and prevention of cerebral palsy".)
In utero exposure to magnesium sulfate before early preterm birth appears to decrease the incidence and severity of cerebral palsy. The use of magnesium sulfate for neuroprotection will be reviewed here. Use of magnesium sulfate for tocolysis or for seizure prevention in women with preeclampsia/eclampsia is discussed separately. (See "Inhibition of acute preterm labor", section on 'Magnesium sulfate' and "Preeclampsia: Management and prognosis", section on 'Regimen'.)
The mechanism for the neuroprotective effects of magnesium sulfate in preterm infants is not well understood. The following mechanisms have been proposed [1,2]:
●Stabilization of cerebral circulation by stabilizing blood pressure and normalizing cerebral blood flow
●Prevention of excitatory injury by stabilization of neuronal membranes and blockade of excitatory neurotransmitters, such as glutamate
- Marret S, Doyle LW, Crowther CA, Middleton P. Antenatal magnesium sulphate neuroprotection in the preterm infant. Semin Fetal Neonatal Med 2007; 12:311.
- Costantine MM, Drever N. Antenatal exposure to magnesium sulfate and neuroprotection in preterm infants. Obstet Gynecol Clin North Am 2011; 38:351.
- Crowther CA, Hiller JE, Doyle LW, et al. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. JAMA 2003; 290:2669.
- Rouse DJ, Hirtz DG, Thom E, et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008; 359:895.
- Marret S, Marpeau L, Zupan-Simunek V, et al. Magnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial*. BJOG 2007; 114:310.
- Mittendorf R, Dambrosia J, Pryde PG, et al. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Am J Obstet Gynecol 2002; 186:1111.
- Gano D, Ho ML, Partridge JC, et al. Antenatal Exposure to Magnesium Sulfate Is Associated with Reduced Cerebellar Hemorrhage in Preterm Newborns. J Pediatr 2016; 178:68.
- Marret S, Marpeau L, Follet-Bouhamed C, 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]. Gynecol Obstet Fertil 2008; 36:278.
- Costantine MM, Weiner SJ, Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a meta-analysis. Obstet Gynecol 2009; 114:354.
- Doyle LW, Crowther CA, Middleton P, Marret S. Antenatal magnesium sulfate and neurologic outcome in preterm infants: a systematic review. Obstet Gynecol 2009; 113:1327.
- Doyle LW, Crowther CA, Middleton P, et al. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2009; :CD004661.
- Zeng X, Xue Y, Tian Q, et al. Effects and Safety of Magnesium Sulfate on Neuroprotection: A Meta-analysis Based on PRISMA Guidelines. Medicine (Baltimore) 2016; 95:e2451.
- Altman D, Carroli G, Duley L, et al. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 2002; 359:1877.
- Doyle LW, Anderson PJ, Haslam R, et al. School-age outcomes of very preterm infants after antenatal treatment with magnesium sulfate vs placebo. JAMA 2014; 312:1105.
- American College of Obstetricians and Gynecologists Committee on Obstetric Practice, Society for Maternal-Fetal Medicine. Committee Opinion No. 455: Magnesium sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol 2010; 115:669. Reaffirmed February 2017.
- Benshushan A, Rojansky N, Weinstein D. Myasthenia gravis and preeclampsia. Isr J Med Sci 1994; 30:229.
- Piura B. The association of preeclampsia and myasthenia gravis: double trouble. Isr J Med Sci 1994; 30:243.
- Nguyen TM, Crowther CA, Wilkinson D, Bain E. Magnesium sulphate for women at term for neuroprotection of the fetus. Cochrane Database Syst Rev 2013; :CD009395.
- Pryde PG, Mittendorf R. Contemporary usage of obstetric magnesium sulfate: indication, contraindication, and relevance of dose. Obstet Gynecol 2009; 114:669.
- McPherson JA, Rouse DJ, Grobman WA, et al. Association of duration of neuroprotective magnesium sulfate infusion with neonatal and maternal outcomes. Obstet Gynecol 2014; 124:749.
- Turitz AL, Too GT, Gyamfi-Bannerman C. Proximity of magnesium exposure to delivery and neonatal outcomes. Am J Obstet Gynecol 2016; 215:508.e1.
- Reeves SA, Gibbs RS, Clark SL. Magnesium for fetal neuroprotection. Am J Obstet Gynecol 2011; 204:202.e1.
- Raju TN, Mercer BM, Burchfield DJ, Joseph GF Jr. Periviable birth: executive summary of a joint workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists. Am J Obstet Gynecol 2014; 210:406.
- The Antenatal Magnesium Sulphate for Neuroprotection Guideline Development Panel. Antenatal magnesium sulphate prior to preterm birth for neuroprotection of the fetus, infant, and child: National clinical practice guidelines. www.adelaide.edu.au/arch (Accessed on June 20, 2016).
- Magee L, Sawchuck D, Synnes A, von Dadelszen P. SOGC Clinical Practice Guideline. Magnesium sulphate for fetal neuroprotection. J Obstet Gynaecol Can 2011; 33:516.
- EVIDENCE OF EFFICACY FROM RANDOMIZED TRIALS AND META-ANALYSES
- Death and/or cerebral palsy
- Other short-term outcomes
- Outcomes at school-age
- CLINICAL APPROACH
- Candidates for treatment
- - Contraindications
- Gestational age
- - Lower limit
- - Upper limit
- Side effects
- Choice of tocolytic for women in preterm labor
- GUIDELINES FROM SELECTED ORGANIZATIONS
- SUMMARY AND RECOMMENDATIONS