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AJP Rep 2016; 06(01): e148-e154
DOI: 10.1055/s-0036-1581059
Case Report
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Antenatal Magnesium Sulfate, Necrotizing Enterocolitis, and Death among Neonates < 28 Weeks Gestation

Manijeh Kamyar
1   Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah
,
Erin A. S. Clark
1   Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah
,
Bradley A. Yoder
2   Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah
,
Michael W. Varner
1   Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah
,
Tracy A. Manuck
1   Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah
3   Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina
› Author Affiliations
Further Information

Publication History

11 November 2015

19 February 2016

Publication Date:
31 March 2016 (online)

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Abstract

Objective This study aims to examine the relationship between antenatal magnesium sulfate (MgSO4) and neonatal death and/or severe necrotizing enterocolitis (NEC) among infants < 28 weeks.

Methods Secondary analysis of a multicenter randomized trial of antenatal MgSO4 versus placebo administered to women to prevent death and cerebral palsy. Neonates < 28 weeks were included. The primary outcome was neonatal death before NICU discharge, and/or severe NEC (Bell criteria stage II/III). Neonates with and without death/severe NEC were compared.

Results A total of 697 neonates met the criteria. Out of which 150 (21.5%) died and/or were diagnosed with severe NEC. Antenatal MgSO4 exposure was not associated with death/severe NEC in infants < 28 weeks. In a subgroup analysis of neonates < 26 weeks, treatment group assignment to antenatal MgSO4 was associated with an increased odds of death/severe NEC (adjusted odds ratio: 1.90, 95% confidence interval: 1.12–3.22, p = 0.017).

Conclusions Among neonates < 26 weeks, antenatal MgSO4 was associated with death and severe NEC. Further prospective study in larger populations is needed.

Keywords

magnesium sulfate - preterm delivery - necrotizing enterocolitis
 

  • References

  • 1 Marret S, Marpeau L, Zupan-Simunek V , et al; PREMAG trial group. Magnesium sulphate given before very-preterm birth to protect infant brain: the andomized controlled PREMAG trial. BJOG 2007; 114 (3) 310-318
    PubMedGoogle Scholar
  • 2 Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a andomized trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months. BJOG 2007; 114 (3) 289-299
    PubMedGoogle Scholar
  • 3 Crowther CA, Hiller JE, Doyle LW, Haslam RR ; Australasian Collaborative Trial of Magnesium Sulphate (ACTOMg SO4) Collaborative Group. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. JAMA 2003; 290 (20) 2669-2676
    CrossrefPubMedGoogle Scholar
  • 4 Rouse DJ, Hirtz DG, Thom E , et al; Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008; 359 (9) 895-905
    CrossrefPubMedGoogle Scholar
  • 5 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 (2 Pt 1) 354-364
    CrossrefPubMedGoogle Scholar
  • 6 Nguyen TMN, Crowther CA, Wilkinson D, Bain E. Magnesium sulphate for women at term for neuroprotection of the fetus. Cochrane Database Syst Rev 2013; 2: CD009395
    PubMedGoogle Scholar
  • 7 Pryde PG, Mittendorf R. Using prophylactic, but not tocolytic, magnesium sulfate to reduce cerebral palsy related to prematurity: what dose, and what about infant mortality?. J Perinat Med 2011; 39 (4) 375-378
    PubMedGoogle Scholar
  • 8 Rattray BN, Kraus DM, Drinker LR, Goldberg RN, Tanaka DT, Cotten CM. Antenatal magnesium sulfate and spontaneous intestinal perforation in infants less than 25 weeks gestation. J Perinatol 2014; 34 (11) 819-822
    CrossrefPubMedGoogle Scholar
  • 9 Wadhawan R, Oh W, Hintz SR , et al; NICHD Neonatal Research Network. Neurodevelopmental outcomes of extremely low birth weight infants with spontaneous intestinal perforation or surgical necrotizing enterocolitis. J Perinatol 2014; 34 (1) 64-70
    CrossrefPubMedGoogle Scholar
  • 10 Blakely ML, Tyson JE, Lally KP , et al; NICHD Neonatal Research Network. Laparotomy versus peritoneal drainage for necrotizing enterocolitis or isolated intestinal perforation in extremely low birth weight infants: outcomes through 18 months adjusted age. Pediatrics 2006; 117 (4) e680-e687
    CrossrefPubMedGoogle Scholar
  • 11 Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med 2011; 364 (3) 255-264
    CrossrefPubMedGoogle Scholar
  • 12 Neu J. Necrotizing enterocolitis: the mystery goes on. Neonatology 2014; 106 (4) 289-295
    CrossrefPubMedGoogle Scholar
  • 13 Gordon PV, Herman AC, Marcinkiewicz M, Gaston BM, Laubach VE, Aschner JL. A neonatal mouse model of intestinal perforation: investigating the harmful synergism between glucocorticoids and indomethacin. J Pediatr Gastroenterol Nutr 2007; 45 (5) 509-519
    CrossrefPubMedGoogle Scholar
  • 14 Carey JC, Klebanoff MA, Hauth JC , et al; National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. N Engl J Med 2000; 342 (8) 534-540
    CrossrefPubMedGoogle Scholar
  • 15 Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics 2010; 125 (2) e214-e224
    CrossrefPubMedGoogle Scholar
  • 16 Bell MJ, Ternberg JL, Feigin RD , et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187 (1) 1-7
    CrossrefPubMedGoogle Scholar
  • 17 Hallak M, Berry SM, Madincea F, Romero R, Evans MI, Cotton DB. Fetal serum and amniotic fluid magnesium concentrations with maternal treatment. Obstet Gynecol 1993; 81 (2) 185-188
    PubMedGoogle Scholar
  • 18 Lu JF, Nightingale CH. Magnesium sulfate in eclampsia and pre-eclampsia: pharmacokinetic principles. Clin Pharmacokinet 2000; 38 (4) 305-314
    CrossrefPubMedGoogle Scholar
  • 19 Tanner SM, Berryhill TF, Ellenburg JL , et al. Pathogenesis of necrotizing enterocolitis: modeling the innate immune response. Am J Pathol 2015; 185 (1) 4-16
    CrossrefPubMedGoogle Scholar
  • 20 Kemp PA, Gardiner SM, March JE, Rubin PC, Bennett T. Assessment of the effects of endothelin-1 and magnesium sulphate on regional blood flows in conscious rats, by the coloured microsphere reference technique. Br J Pharmacol 1999; 126 (3) 621-626
    CrossrefPubMedGoogle Scholar
  • 21 Kemp PA, Gardiner SM, March JE, Bennett T, Rubin PC. Effects of NG-nitro-L-arginine methyl ester on regional haemodynamic responses to MgSO4 in conscious rats. Br J Pharmacol 1994; 111 (1) 325-331
    CrossrefPubMedGoogle Scholar
  • 22 Rees CM, Eaton S, Pierro A. National prospective surveillance study of necrotizing enterocolitis in neonatal intensive care units. J Pediatr Surg 2010; 45 (7) 1391-1397
    CrossrefPubMedGoogle Scholar
  • 23 Ghidini A, Espada RA, Spong CY. Does exposure to magnesium sulfate in utero decrease the risk of necrotizing enterocolitis in premature infants?. Acta Obstet Gynecol Scand 2001; 80 (2) 126-129
    CrossrefPubMedGoogle Scholar
  • 24 Hammers AL, Sanchez-Ramos L, Kaunitz AM. Antenatal exposure to indomethacin increases the risk of severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia: a systematic review with metaanalysis. Am J Obstet Gynecol 2015; 212 (4) 505.e1-505.e13
    CrossrefPubMedGoogle Scholar
  • 25 Sharma R, Hudak ML, Tepas III JJ , et al. Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis. J Perinatol 2010; 30 (12) 786-793
    CrossrefPubMedGoogle Scholar
  • 26 Yee WH, Soraisham AS, Shah VS, Aziz K, Yoon W, Lee SK ; Canadian Neonatal Network. Incidence and timing of presentation of necrotizing enterocolitis in preterm infants. Pediatrics 2012; 129 (2) e298-e304
    CrossrefPubMedGoogle Scholar
  • 27 Elimian A, Verma R, Ogburn P, Wiencek V, Spitzer A, Quirk JG. Magnesium sulfate and neonatal outcomes of preterm neonates. J Matern Fetal Neonatal Med 2002; 12 (2) 118-122
    CrossrefPubMedGoogle Scholar
  • 28 Kimberlin DF, Hauth JC, Owen J , et al. Indicated versus spontaneous preterm delivery: An evaluation of neonatal morbidity among infants weighing </=1000 grams at birth. Am J Obstet Gynecol 1999; 180 (3 Pt 1) 683-689
    CrossrefPubMedGoogle Scholar
  • 29 Bottoms SF, Paul RH, Mercer BM , et al. Obstetric determinants of neonatal survival: antenatal predictors of neonatal survival and morbidity in extremely low birth weight infants. Am J Obstet Gynecol 1999; 180 (3 Pt 1) 665-669
    CrossrefPubMedGoogle Scholar
  • 30 Stoll BJ, Hansen NI, Bell EF , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 (3) 443-456
    CrossrefPubMedGoogle Scholar
  • 31 Su BH, Hsieh WS, Hsu CH, Chang JH, Lien R, Lin CH ; Premature Baby Foundation of Taiwan (PBFT). Neonatal outcomes of extremely low birth weight infants from Taiwan: comparison with Canada, Japan and the USA. Pediatr Neonatol 2015; 56 (1) 46-52
    Google Scholar