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

Min-Jeong Oh

doi:10.14734/kjp.2013.24.2.133

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

Case Report

Korean J Perinatol 2013;24(3):133-141.

Published online: 19 June 2013

DOI: https://doi.org/10.14734/kjp.2013.24.2.133

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

Min-Jeong Oh, M.D., Ph.D.

Department of Obstetrics and Gynecology College of Medicine, Korea University, Seoul, Korea

주관책임자 : 오민정, 152-703 서울특별시 구로구 구로동길 97 고려대학교 구로병원 산부인과 전화 : 02)2626-3141/1833, 전송 : 02)838-1560 E-mail : mjohmd@korea.ac.kr

Received 6 September 2013 Accepted 24 September 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Cerebral palsy, Magnesium sulfate, Preterm

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Table 1.

Characteristics of Included Studies²⁶

Study (First Author)	Inclusions	Women (n)	Fetuses (n)	Magnesium Dose
MagNET¹⁹ (Mittendorf et al.)	25-33 wk in preterm labor	149	165	Tocolytic arm; 4 g loading, 2-3 g/h maintenance. Neuroprotective arm; 4 g loading only
ACTOMgSO4²¹ (Crowther et al.)	<30 wk, likely to deliver within 24 h	1,062	1,255	4 g loading, 1 g/h maintenance
MAGPIE²⁵ (Duley et al.)	All gestations∗ with severe preeclampsia	1,544∗	1,593∗	4 g loading, 1 g/h IV maintenance, or 5 g every 4 h IM
PREMAG²² (Marret et al.)	<33 wk of gestation in labor	573	688	4 g loading only
BEAM²⁴ (Rouse et al.)	24031 wk at high risk of spontaneous birth	2,241	2,444	6 g loading, 2 g/h maintenance

MagNET, Magnesium and Neurologic endpoints Trials; ACTOMgSO4, Australasian Collaborative Trial of Magnesium Sulphate; MAGPIE, Magnesium Sulphate for Prevention of Eclampsia; IV, intravenously; IM, intramuscularly; BEAM, Beneficia Effects of Antenatal Magnesium Sulfate. ∗Only less than 37 weeks and undelivered at enrolment included in this analysis.

Table 2.

Meta-Analysis of Important Pediatric Outcomes Contrasted between Magnesium Sulfate and Control Groups, Both Overall and Also Limited to Trials Where the Primary Intent Was Neuroprotection of the Fetus²⁸

Outcome	Number of studies	s Magnesium n/N	Control n/N	Risk ratio^a	95%CI ^a
Pediatric mortality (fetal and later)	5	443/3,052	430/3,093	1.01^b	0.82-1.23
Neuroprotective intent only	4	226/2,199	242/2,247	0.95	0.80-1.12
Cerebral palsy	5	104/3,052	154/3,093	0.69	0.54-0.87
Neuroprotective intent only	4	102/2,199	146/2,247	0.71	0.55-0.91
Pediatric mortality or cerebral palsy	5	547/3,052	583/3,093^c	0.94 ^b	0.78-1.12
Neuroprotective intent only	4	328/2,199	387/2,247^c	0.86	0.75-0.98
Substantial motor dysfunction	4	57/2,967	94/3,013	0.61	0.44-0.85
Neuroprotective intent only	3	56/2,169	94/2,218	0.60	0.43-0.83
Pediatric mortality or substantial motor dysfunction	4	490/2,967	523/3,013	0.92^b	0.75-1.12
Neuroprotective intent only	3	280/2169	335/2218	0.85	0.73-0.98

CI, confidence interval. ^avalues obtained from meta-analysis.

^b random effects model because of significant heterogeneity.

^c one child with definite cerebral palsy died before 2 years of age

Table 3.

Meta-Analysis of Other Neurologic Outcomes²⁶

Outcome N	No. of Studies	Magnesium [n/N (%)]	Control [n/N (%)]	RR (95% CI)∗	I² (%)
Newborn period
Apgar less than 7 at 5 minutes	3	351/2,169 (16.2)	351/2,218 (15.8)	1.03 (0.90-1.18)	7
Ongoing respiratory support	3	980/2,169 (45.2)	1,069/2,218 (48.2)	0.94 (0.89-1.00)	24
Any intraventricular hemorrhage	4	467/2,254 (20.7)	493/2,298 (21.5)	0.96 (0.86-1.08)	20
Periventricular leukomalacia	4	71/2,254 (3.1)	76/2,298 (3.3)	0.93 (0.68-1.28)	0
Neonatal convulsion	3	55/2,169 (2.5)	70/2,218 (3.2)	0.80 (0.56-1.13)	0
Follow-up
Blindness	3	3/1,779 (0.2)	4/1,757 (0.2)	0.74 (0.17-3.30)	0
Deafness	3	9/1,779 (0.5)	12/1,757 (0.7)	0.79 (0.24-2.56)	17
Developmental delay	4	647/2,967 (21.8)	670/3,013 (22.2)	0.99 (0.91-1.09)	0

RR, relative risk; CI, confidence interval. ∗Values obtained from meta-analysis, which is not obtained by comparing pooled rates of events.

Table 4.

Effect of Magnesium Sulfate on Cerebral Palsy and Pediatric Mortality in Preterm Infants Less Than 34 Weeks’ Gestation³⁰

Outcome N	No. of trials	No. of events/total number		RR (95% CI)	I² (%)
Outcome N	No. of trials	Magnesium	No magnesium	RR (95% CI)	I² (%)
Cerebral palsy	6	104/2,658	152/2,699	0.69 (0.55-0.88)	4.4
Moderate/severe cerebral palsy	3	45/2,169	72/2,218	0.64 (0.44-0.92)	0.0
Mild cerebral palsy	3	54/2,169	74/2,218	0.74 (0.52-1.04)	0.0
Total pediatric mortality	6	401/2,658	400/2,699	1.01 (0.89-1.14)	38.9
Fetal mortality	5	17/2,254	22/2,298	0.78 (0.42-1.46)	0.0
Under 2 y of corrected age mortality	5	217/2,254	220/2,298	1.00 (0.84-1.19)	47.3
Death or cerebral palsy	6	505/2,658	551/2,699	0.92 (0.83-1.02)	43.3

RR, relative risk; CI, confidence interval.

Table 5.

Effect of Magnesium Sulfate on Neonatal Outcomes in Preterm Infants Less Than 34 Weeks’ Gestation³⁰

Outcome	No. of trials	No. of events/total number		RR (95% CI)	I² (%)
Outcome	No. of trials	Magnesium	No magnesium	RR (95% CI)	I² (%)
Intraventricular hemorrhage (all grades)	5	467/2,254	493/2,298	0.96 (0.86-1.08)	20.1
Grade III/IV intraventricular hemorrhage	4	74/1,902	91/1,962	0.83 (0.61-1.11)	0.0
Periventricular leukomalacia	5	71/2,254	76/2,298	0.93 (0.68-1.28)	0.0
Apgar score < 7 at 5 min	3	351/2,169	351/2,218	1.03 (0.90-1.18)	7.3
Neonatal seizures	3	55/2,169	70/2,218	0.80 (0.56-1.13)	0
Respiratory distress syndrome	2	730/1,540	779/1,592	1.01 (0.85-1.19)	65.8
Need for supplemental oxygen at 36 wk	2	220/981	195/962	1.12 (0.95-1.32)	23.1
Bronchopulmonary dysplasia	1	213/1,188	218/1,256	1.03 (0.87-1.23)	NA
Mechanical ventilation	3	1,381/2,169	1,446/2,218	0.99 (0.89-1.09)	82.1
Necrotizing enterocolitis	3	155/2,169	131/2,218	1.23 (0.98-1.54)	0.0

RR, relative risk; CI, confidence interval; NA, not applicable.

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