Journal List > Korean J Perinatol > v.24(3) > 1013674

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

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.

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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 ratioa 95%CI a
Pediatric mortality (fetal and later) 5 443/3,052 430/3,093 1.01b 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 5 547/3,052 583/3,093c 0.94 b 0.78-1.12
  Neuroprotective intent only 4 328/2,199 387/2,247c 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 0.92b 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 (%)
Magnesium No magnesium
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 (%)
Magnesium No magnesium
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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