Antenatal Magnesium Sulfate for Neuroprotective Effects In Preterm Infants

Young lim Oh

doi:10.7180/kmj.2014.29.2.99

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Oh: Antenatal Magnesium Sulfate for Neuroprotective Effects In Preterm Infants

Review Article

Kosin Medical Journal 2014;29(2):99-106.

Published online: 18 December 2014

DOI: https://doi.org/10.7180/kmj.2014.29.2.99

Antenatal Magnesium Sulfate for Neuroprotective Effects In Preterm Infants

Young lim Oh

¹Department of Obstetrics and Gynecology, College of Medicine, Kosin University, Busan, Korea

Corresponding Author : Young Lim Oh, Department of Obstetrics and Gynecology, College of Medicine, Kosin University, 262, Kamcheon-ro, Seo-gu, Busan, 602-702, Korea TEL: +82-51-990-6359 FAX: +82-51-244-6939 E-mail: marianna1113@naver.com

Received 10 October 201410 October 2014 Accepted 15 October 2014

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

Fetal or neonatal brain injury can result in lifelong neurologic disability. Although survival rates for preterm infants have increased dramatically with the advent of modern perinatal and neonatal intensive care, but the rates of neurologic abnormalities in survivors, particularly motor disorders such as cerebral palsy, have not diminished. Antenatal magnesium sulfate may reduce the rates of cerebral palsy in survivors of preterm birth. There are five randomized controlled trials of magnesium sulfate administered to women at risk of preterm delivery before 34 weeks of gestation which have reported neurological outcomes for the child. From meta-analysis of these randomized trials, the rate of cerebral palsy was reduced by magnesium sulfate (RR, ᄋ·69; 95% CI, ᄋ·54-ᄋ·87; five trials; 6,145 infants) as did the moderate/severe cerebral palsy incidence (RR, 0.64; 95% CI, ᄋ·44-ᄋ·92; three trials; 4387 infants). There was no statistically significant difference between the rates of neonatal adverse outcomes of the magnesium administration group and the control group. In most prospective randomized studies, no significant difference in the severe mother-side side effects between the magnesium sul- fate administration group and the control group.

Antenataᅵ magnesium sulfate therapy is neuroprotective against motor dysfunction in offspring for the preterm infant; however the possibility of an increase in the fetal or neonatal death rate was not completely excluded.

Keywords: Cerebral Palsy, Magnesium Sulfate, Mortality, Neroprotection, preterm birth

REFERENCES

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Table 1.

Characteristics of Included Studies

Study	Centers	NumbeT of participants	Gestational age	Magnesium regimen	Neuroprotective outcomes
MagNET	1	149 mothers	25-33 weeks	4 gm bolus	Antenatal MgSO₄ was associated with worse perinatal
Mittendorff et al	(United States)	165 fetus		(neuroprotective arm)	outcome
ACTOMgSO₄	16	1,062 mothers	<30 weeks	4 gm bolus, 1 gm/h	CP RR:0.83; 95% CI: 0,54-1.27
Crowther et al	(Austrailia and New Zealand)	1,255 fetuses		maintenance
PreMAG trial + folllow up trial	18 (France)	573 mothers 6S8 fetuses	<33 weeks	4 gm bolus, no maintenance	Original trial: Nonsignificant decrease in risk of short-term severe white matter injury, mortality before hospital discharge
Marret et al		(original trial)
		472 children			Follow-up trial (2 years): Combined death or cerebral palsy
		(follow-up trial)			OR, 0.65; 95% CI: 0.42-1.03

					Combined death or gross motor dysfunction OR: 0.62; 95%
					CI: 0.41-0,95 (siatisiicatly significant)
BEAM. Rouse et al	20 (United States)	2.241 mothers 2,444 fetuses	24-31 weeks	6 gm bolus. 2gm/h maintenance	Significant dcciease in the risk of moderate or severe CP (RR: 0,55; 95% CI: 0,32-0.92) among survival children in the MgSO₄ group
					Death and CP RR: 0.97; 95% CI:
Magpie trial	125	3.283 children	<37 weeks c	4 gm bolus, 1 gm/h IV	Combined death or neuroseasory disability RR: 1.06; 95% CI:
Duley et al	(International)		preeclampsia	matnieaance or, 4 gm	0.40-1.29
				bolus combined wilh 10
				gm IM, then 5 gm/4 hrs
				IM maintenance

CI: Confidence Interval; CP: Cerebral Palsy; OR: Odds ratio; RR: Relative risk

Table 2.

Meta-Analysis of Mortality, Cerebral Palsy, Substantial Gross Motor Dysfonction an Combined Outcome by Subcategory of Intent²³

Outcome and Subcategory	No. of Studies	Magnesium n/N (%)	Control n/N (%)	RR^∗	95% CI^∗	Statistical Significance	Heterogeneity [I²(%)]
Mortality
Neuroprotective intent	4	226/2,199(10.3)	242/2,247 (10.8)	0.94	0.77-1.15	Z=0.58,P=.56	19.6
Other intent	2	217/853 (25.4)	188/846 (22.2)	2.86	0.23-35.8	Z=0.81,P=.42	71.2
Total	5^†	443/3,052 (145)	430/3,093 (13.9)	1.01	0.82-1.23	Z=0.08,P=.94	44.9
Cerebral palsy
Neuroprotective intent	4	102/2,199(4.6)	146/2,247 (6.5)	0.71	0.55-0.91	Z=2.74,P=006	25.2
Other intent	1	2/853 (0.2)	8/846 (0.9)	0.29	0.07-1.16	Z=I.75,P=.08	0
Total	5^†	104/3,052 (3.4)	154/3,093(5.0)	0.69	0.54-0,87	Z=3.07,P=.002	11.7
Mortality or cerebral palsy
Neuroprotective intent	4	528/2,199(14.9)	387/2,247 (172)	0.85	0.74-0.98	Z=2.21,P=.03	5.3
Other intent	2	219/853 (25.7)	196/846 (23.2)	1.28	0,68-1.12	Z=0.75,P=.45	36.5
Total	5^†	547/3,052(17.9)	583/3,095 (18.8)	0.94	0.78-1.12	z=0.70,p=.48	51.3
Substantial gross motordysfunction
Neuroprotective intent	3	56/2,169 (2.6)	94/2.218(4.2)	0.60	0.43-0.83	z=3.08,p=.002	0
Other intent	1	1/798(0.1)	0/795 (0)	199	0.12-73.3	z=0.67,p=.50	NA
Total	4	57/2,967(1,9)	94/3,013(3.1)	0.61	0.44-0.85	z=2.98,p=.003	0
Mortality or substantial gross motor dysfunction
Netiroprotective intent	3	280/2,169 (12.9)	335/2,218 (15.1)	0,84	0,71-1.00	z=1.95p=.05	25.2
Other intent	1	210/798 (26.3)	188/795 (23.6)	1.11	0,94-1.32	z=1.23,p=.22	NA
Total	4	490/2,967 (16.5)	523/3,013(17.4)	0.92	0.75-1.12	z=0.87, p=.39	65.0

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

^∗ Values obtained from meta-analysis, which is not obtained simply by comparing pooled rates of events.

^† One study4 represented in both subgroups; hence, there are only five studies overall.

Table 3.

Effect of magnesium sulfate on cerebral palsy and pediatric mortality²⁴

Outcome	No. of trials	No. of events/total number		Relative risk (95% O)	I²(°/o)
Outcome	No. of trials	Mngnesium	No magnesium	Relative risk (95% O)	I²(°/o)
Cerebral palsy	6	104/2658	152/2699	0.69 (0.55-0,88)	4.4
Moderate/severe cerebral palsy	3	45/2169	72/2218	0.64 (0.44-0,92)	0,0
Mild cerebral palsy	3	54/2169	74/2218	0.74 (0.52-1.04)	0.0
Tolal pediatric mortality	6	401/2658	400/2699	1.01 (0.89-1 J4)	38.9
Fetal mortality	5	17/2254	22/2298	0,78 (0,42-1.46)	0,0
Under 2 y of corrected age mortality	5	217/2254	220/2298	1.00 (0.84-1.19)	47.3
Death or cerebral palsy	6	505/2658	551/2699	0.92 (0.83-1.02)	43.3

CI, confidence interval.

Table 4.

Meta-Analysis of Other Neurologic Outcomes²³

Outcome	No. of studies	Magnesium [n/N(%)]	Control [n/N(%)]	RR(95% CI)^∗	Statistical 11 Significance	Heterogeneity [I²(%)]
Newborn period
Apgar less than 7 at 5 minutes	3	351/2469(16.2)	351/2,218(15.8)	1.03 (0.90-1.18)	Z=0.42,P=.68	7
Ongoing respiratory support	3	980/2,169(45,2)	1,069/2,218(48.2)	0,94 (0.89 L00)	Z=1.91, P=.06	24
Any imraventricular heinontiage	4	467/2,254(20,7)	493/2,298 (21,5)	0,96(0.86 1.08)	Z=0.65,P=.51	20
Periventricular Icukomalacia	4	71/2,254(3.1)	76/2,298 (3.3)	0.93 (0.68 1.28)	Z=0.43,P=.67	0
Neonatal convulsions	3	55/2,169(2.5)	70/2,218(3.2)	0.80(0.56-1.13)	Z=1.28,P=.20	0
Follow-up
Blindness	3	3/1,779 (0,2)	4/1,757(0.2)	0.74(0.17 3.30)	2=0.40, p=m	0
Deafness	3	9/1,779 (0.5)	12/1,757(0.7)	0.79 (0.24-2.56)	z=0.40, p=.69	17
Devctopmcnlal delay	4	647/2,967(21.8)	670/3,013 (22.2)	0.99(0.91 1.09)	z=0.11, p=.91	0

RR, relative risk; CI, confidence interval.

^∗ Values obtained from meta-analysis, which is not obtained simply by comparing pooled rates of events.

Table 5.

Effect of magnesium sulfate on neonatal outcomes²⁴

Outcome	No. of trials	No, of events/total number		Relative risk (95% CI)	I²/(%)
Outcome	No. of trials	Magnesium	No magnesium	Relative risk (95% CI)	I²/(%)
Intraventricular hemorrhage (ala grades)	5	467/2254	493/2298	0,96 (0.86-1.08)	20.1
Grade III/IV intraventricular hemorrhage	4	74/1902	91/1962	0.83(0.61-1.11)	0.0
Periventricular leukomalacia	5	71/2254	76/2298	0.93 (0.68-1,28)	0.0
Apgar score < 7 at 5 min	3	351/2169	351/2218	1.03 (0.90-1.18)	7.3
Neonatal seizures	3	55/2169	70/2218	0.80(0.56-1.13)	0
Respiratory distress syndrome	2	730/1540	779/1592	1.01 (0.85-1,19)	65.8
Need for supplemental oxygen at 36wk	2	220/981	195/962	1.12(0.95-132)	23.1
Bronchopulmonary dysplasia	1	213/188	218/1256	1.03(0.87-1.23)	NA
Mechanical ventilation	3	1381/2169	1446/2218	0,99 (0.89-1.09)	82.1
Necrotizing enterocolitis	3	155/2169	131/2218	1.23 (0.98-1.54)	0.0

CI, confidence interval; NA, not applicable.

Table 6.

Effect of magnesium sulfate on maternal outcomes²⁴

Outcome	No. of trials	No. of events/total number		Relative risk (95% CI)	I² (%)
Outcome	No. of trials	Magnesium	No magnesium	Relative risk (95% CI)	I² (%)
Death	3	0/1917	1/1950	0.32 (0.01-7.92)	0.0
Cardiac or respiratory arrest	3	0/1917	35 0/1950	Not estimable	NA
Fulmonary edema	1	8/1096	3/1145	2.79(0.74-10.47)	NA
Respiratory depression	2	41/1631	31/1672	1.31 (0.83-2.07)	0.0
Hypotension	2	80/821	52/S05	1.51 (1,09-2.09)	3.6
Tachycardia	1	56/535	36/527	1.53 (1.03-2.29)	NA
Severe postpartum hemorrhage	2	28/821	26/805	1.06(0,63-1.79)	0.0
Cesarean section	3	822/1917	BM/1950	1.00 (0.93-1.07)	21.6
Clinical and self-assessed maternal side effects of the infusion
Flushing	3	1119/1917	162/1950	7.56(339-16.88)	93,8
Nausea or vomiting	3	312/1917	76/1950	4.60(1.54-13,75)	91.5
Sweating	2	411/1631	57/1672	6.37(1.96-20.68)	94,6
Problems at injection site	2	614/1631	68/1672	9.12 (7J9-11.57)	0.0
Stopping of infusion because of adverse effects	2	125/J631	44/1672	2.81 (2.01-3.93)	0.0
Any side effect	3	1356/1917	343/1950	105 (2.06-12.39)	983

CI, confidence interval; NA, not applicable.

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