Korean J Perinatol.  2013 Sep;24(3):133-141. 10.14734/kjp.2013.24.3.133.

Effects of Antenatal Exposure to Magnesium Sulfate on Neuroprotection in Preterm Infants

• Oh MJ

• KMID: 2280931
• DOI: http://doi.org/10.14734/kjp.2013.24.3.133

Abstract

Although the survival of preterm infants has improved with advances in perinatal care, the occurrence of cerebral palsy has increased further, because infants who would previously have died now survive with their cerebral pathology. In several observational studies, preterm infants whose mothers received magnesium sulfate were reported to have marked reductions in cerebral palsy, as compared with infants of untreated mothers. From meta-analyses of 5 randomized controlled trials of magnesium sulfate therapy given to the mother prior to very preterm birth, magnesium sulfate reduced the rate of cerebral palsy by approximately 30% (relative risk [RR] 0.68, 95% confidence interval [CI] 0.54-0.87) and moderate to severe cerebral palsy (by 40-45%) without increasing the rate of death in 6,145 infants (RR 10.4, 95% CI 0.92-1.17). Given the relative safety of magnesium sulfate for the mother and the lack of evident risk regarding infant mortality, magnesium sulfate should be considered for use as a neuroprotectant in the setting of anticipated preterm birth.

Keyword

Cerebral palsy; Magnesium sulfate; Preterm

MeSH Terms

Cerebral Palsy
Humans
Infant
Infant Mortality
Infant, Newborn
Infant, Premature*
Magnesium Sulfate*
Magnesium*
Mothers
Pathology
Perinatal Care
Premature Birth
Magnesium
Magnesium Sulfate

Reference

1). Paneth N., Hong T., Korzeniewski S. The descriptive epidemiology of cerebral palsy. Clin Perinatol. 2006. 33:251–67.

2). Himpens E., Van den Broeck C., Oostra A., Calders P., Vanhae-sebrouck P. Prevalence, type, distribution, and severity of cerebral palsy in relation to gestational age: a meta-analytic review. Dev Med Child Neurol. 2008. 50:334–40.

3). Moster D., Lie RT., Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008. 359:262–73.

4). Himmelmann K., Hagberg G., Beckung E., Hagberg B., Uve-brant P. The changing panorama of cerebral palsy in Sweden: IX, prevalence and origin in the birth-year period 1995-1998. Acta Paediatr. 2005. 94:287–94.

5). Honeycutt A., Dunlap L., Chen H., al Homsi G. Economic costs associated with mental retardation, cerebral palsy, hearing loss, and vision impairment-United States 2003. MMWR Morb Mortal Wkly Rep. 2004. 53:57–9.

6). Nelson KB., Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low bithweight infants? Pediatrics. 1995. 95:263–9.

7). Schendel DE., Berg CJ., Yeargin-Allsopp M., Boyle CA., De-coufle P. Prenatal magnesium sulfate exposure and the risk for cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years. JAMA. 1996. 276:1805–10.

8). Matsuda Y., Kouno S., Hiroyama Y., Kuraya K., Kamitomo M., Ibara S, et al. Intrauterine infection, magnesium sulfate exposure and cerebral palsy in infants born between 26 and 30 weeks of gestation. Eur J Obstet Gynecol Reprod Biol. 2000. 91:159–64.

9). Boyle CA., Yeargin-Allsopp M., Schendel DE., Holmgreen P., Oakley GP. Tocolytic magnesium sulfate exposure and risk of cerebral palsy among children with birth weights less than 1,750 grams. Am J Epidemiol. 2000. 152:120–4.

10). Grether JK., Hoogstrate J., Walsh-Greene E., Nelson KB. Magnesium sulfate for tocolysis and risk of spastic cerebral palsy in premature children born to women without preeclampsia. Am J Obstet Gynecol. 2000. 183:717–25.

11). Costantine MM., How HY., Coppage K., Maxwell RA., Sibai BM. Does peripartum infection increase the incidence of cerebral palsy in extremely low birthweight infants? Am J Obstet Gynecol. 2007. 196:e6–8.

12). Marret S., Gressens P., Gadisseux JF., Evrard P. Prevention by magnesium of excitotoxic neuronal death in the developing brain: an animal model for clinical intervention studies. Dev Med Child Neurol. 1995. 37:473–84.

13). Marret S., Doyle LW., Crowther CA., Middleton P. Antenatal magnesium sulphate neuroprotection in the preterm infant. Semin Fetal Neonatal Med. 2007. 2:311–7.

14). Turkyilmaz C., Turkyilmaz Z., Atalay Y., Soylemezoglu F., Celasun B. Magnesium pre-treatment reduces neuronal apoptosis in newborn rats in hypoxiaeischemia. Brain Res. 2002. 955:133–7.

15). Mami AG., Ballesteros J., Mishra OP., Delivoria-Papadopoulos M. Effects of magnesium sulfate administration during hypoxia on Ca(2þ) influx and IP(3) receptor modification in cerebral cortical neuronal nuclei of newborn piglets. Neurochem Res. 2006. 31:63–70.

16). Shogi T., Miyamoto A., Ishiguro S., Nishio A. Enhanced release of IL-1beta and TNF-alpha following endotoxin challenge from rat alveolar macrophages cultured in low-Mg(2þ) medium. Magnes Res. 2003. 16:111–9.

17). Ovbiagele B., Kidwell CS., Starkman S., Saver JL. Neuroprotective agents for the treatment of acute ischemic stroke. Curr Neurol Neurosci Rep. 2003. 3:9–20.

18). MacDonald RL., Curry DJ., Aihara Y., Zhang ZD., Jahromi BS., Yassari R. Magnesium and experimental vasospasm. J Neurosurg. 2004. 100:106–10.

19). Mittendorf R., Dambrosia J., Pryde PG., Lee KS., Gianopoulos JG., Besinger RE, et al. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Am J Obstet Gynecol. 2002. 186:1111–8.

20). Mittendorf R., Covert R., Boman J., Khoshnood B., Lee KS., Siegler M. Is tocolytic magnesium sulphate associated with increased total paediatric mortality? Lancet. 1997. 350:1517–8.

21). Crowther CA., Hiller JE., Doyle LW., Haslam RR. Australasian Collaborative Trial of Magnesium Sulphate (ACTOMgSO4) Collaborative Group. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. JAMA. 2003. 290:2669–76.

22). Marret S., Marpeau L., Zupan-Simunek V., Eurin D., Lévêque C., Hellot MF, et al. PREMAG Trial Group. Magnesium sulphate given before very-preterm birth to protect infant brain: the randomized controlled PREMAG trial. BJOG. 2007. 114:310–8.

23). Marret S., Marpeau L., Follet-Bouhamed C., Cambonie G., Astruc D., Delaporte B, et al. PREMAG Trial Group. Effect of magnesium sulphate on mortality and neurologic morbidity of the very-preterm newborn with two-year neurologic outcome: results of the prospective PREMAG trial. Gynecol Obstet Fertil. 2008. 36:278–88.

24). Rouse DJ., Hirtz DG., Thom E., Varner MW., Spong CY., Mercer BM, et al. Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med. 2008. 359:895–905.

25). Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a randomized trial comparing magnesium sulphate with placebo for preeclampsia. Outcome for children at 18 months. BJOG. 2007. 114:289–99.

26). Doyle LW., Crowther CA., Middleton P., Marret S. Antenatal magnesium sulfate and neurologic outcome in preterm infants. Obstet Gynecol. 2009. 113:1327–33.

27). Doyle LW., Crowther CA., Middleton P., Marret S., Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009. 1:CD004661.

28). Doyle LW. Antenatal magnesium sulfate and neuroprotection. Curr Opin Pediatr. 2012. 24:154–9.

29). Costantine MM., Weiner SJ. Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants. Obstet Gynecol. 2009. 114:354–64.

30). Conde-Agudelo A., Romero R. Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis. Am J Obstet Gynecol. 2009. 200:595–609.

31). Constantine MM., Drever N. Antenatal exposure to magnesium sulfate and neuroprotection in preterm infants. Obstet Gynecol Clin N Am. 2011. 38:351–66.

32). Food and Drug Administration. FDA recommends against prolonged use of magnesium sulfate to stop preterm labor due to bone changes in exposed babies. FDA Drug Safety Communication. Silver Spring (MD): FDA;2013. Available from:. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM353335.pdf.

33). Committee opinion no. 573: Magnesium sulfate use in obstetrics. Obstet Gynecol. 2013. 122:727–8.

34). Committee Opinion No. 455: Magnesium sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol. 2010. 115:669–71.

35). The University of Adelaide. 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 (2010). Available from:. http://www.nhmrc.gov.au/guidelines/publications/cp128.

36). Magee L., Sawchuck D., Synnes A., von Dadelszen P. SOGC Clinical Practice Guideline. Magnesium sulphate for fetal neuroprotection. J Obstet Gynaecol Can. 2011. 33:516–29.