Magnesium sulfate for women at risk of preterm birth for neuroprotection of the fetus
Antenatal magnesium sulfate therapy given to women at risk of preterm birth reduces the risk of neurological disorders in their infants. Although magnesium sulfate is a safe drug, its safe dosage range is narrow. Hence, women receiving magnesium sulfate for neuroprotection of their infants should be closely monitored during treatment.
RHL Commentary by Lumbiganon P
Preterm birth and low birth weight are important public health problems, especially in low- and middle-income countries. Infants who survive preterm birth have a higher risk of developing neurological problems such as cerebral palsy and impairment of cognitive function compared with term infants. The risk of neurological problems increases with decreasing gestational age at birth, especially among very-low-birth-weight (VLBW) infants (1). In 1993, Ho et. al. (2) evaluated the prevalence and patterns of neurodevelopment handicap at 2 years of age among VLBW infants admitted to three Malaysian nurseries. Among 150 VLBW babies included in this study, 82 were found to have survived up to 2 years of age, of whom 77 were evaluated for neurodevelopment. Functionally, 24 (31%) children were found to have mild to severe handicap (2). Another study involving 2036 children in South Africa found the prevalence of overall disabilities among VLBW infants to be 60 per 1000 [95% confidence interval (CI) 50–71]. The most common disabilities were mild perceptual or learning disability (17 per 1000), cerebral palsy (10 per 1000) and hearing loss (10 per 1000) (3). A prospective cohort study conducted in Malaysia to evaluate morbidities in VLBW infants found that VLBW infants had significantly higher risk of cerebral palsy [odds ratio (OR) 8.6; 95% CI 2.0–77.6] and neurosensory hearing loss (OR 12.0; 95% CI 1.7–513.6) (4).
In developing countries, owing to a lack of facilities for the care of disabled children, even mild disability can have serious consequences for the health and welfare of children. The present Cochrane (5) review sought to assess the effects of magnesium sulfate as a neuroprotective agent when given to women considered at risk of preterm birth.
A total of five trials were found to be eligible for inclusion in the review. They involved 6145 infants born to women at risk of preterm birth due to preterm labour, premature rupture of membranes, pre-eclampsia or eclampsia. The comparison groups in these trials were women who had received magnesium sulfate versus placebo or no treatment. In four of the five trials, the primary intent behind maternal magnesium sulfate treatment was to protect the infant from possible adverse neurological effects of preterm birth. In one trial (the Magpie trial) (6), magnesium sulfate was given to the mother for prevention of eclampsia, but outcomes for the infant were also examined.
The review authors chose appropriate outcomes and employed the standard Cochrane Pregnancy and Childbirth Review Group search strategy. Their assessment of methodological quality and methods of data analyses of trials were appropriate.
Antenatal magnesium sulfate therapy given to women at risk of preterm birth substantially reduced the risk of cerebral palsy in their infants [relative risk (RR) 0.68; 95% CI 0.54–0.87; five trials; 6145 infants). There was also a significant reduction in the rate of substantial gross motor dysfunction (RR 0.61; 95% CI 0.44–0.85; four trials; 5980 infants). In all five studies, infants born to women who were recruited at less than 34 weeks of gestation and who received magnesium sulfate experienced a reduced risk of cerebral palsy (RR 0.69; 95% CI 0.54–0.88; five trials; 5357 infants) compared with those who received no treatment or received placebo.
Four studies reported corticosteroid use in more than 50% of women at risk for preterm birth. Analysis of those four studies separately did not change the conclusions (RR 0.67; 95% CI 0.53–0.86; four trials; 4493 infants). No statistically significant effect of magnesium sulfate therapy for women at risk for preterm birth was observed on neonatal mortality or other neurological outcomes.
There were higher rates of minor maternal side-effects in the magnesium sulfate groups, but no significant increase in maternal complications was observed.
4.1. APPLICABILITY OF THE RESULTS
Four of the five included trials were conducted in high-income countries. Although it is unlikely that there would be pathophysiological differences among infants born in low- and middle-income countries compared with those born in high-income countries, co-interventions in infants after delivery are likely to be different. These include availability and quality of a neonatal intensive care unit and availability of surfactant. These factors are likely to have an impact on infant outcomes.
Magnesium sulfate is safe only within a narrow dosage range and overdose can cause serious complications, including respiratory depression and cardiac arrest in the mother. One large study (6) has reported that administration of magnesium sulfate using a strict protocol did not lead to a greater frequency of complications compared with placebo, even in under-resourced settings. It is likely that in some under-resourced settings there may not be resources available (human and facility) to administer magnesium sulfate with rigorous monitoring of the patient. In such settings, if serious complications occur, they may prove difficult to manage. On the other hand, given that in under-resourced settings even mild disability can have serious consequences for the welfare of children, use of magnesium sulfate for neuroprotection of infants can potentially yield significant benefits overall despite the risk of complications in the mother.
4.2. IMPLEMENTATION OF THE INTERVENTION
Magnesium sulfate is a safe and relatively inexpensive drug and as such it would not be too difficult for health services in under-resourced settings to make it available for this indication. Health-care facilities in under-resourced settings considering introducing magnesium sulfate for neuroprotection of infants in women at risk of preterm birth will need to ensure that women given this drug are closely monitored during the treatment in order to avoid overdose in the mother. This requirement, and the fact that more women than before will become candidates for magnesium sulfate treatment, will likely increase demands on the resources of health-care facilities.
4.3. IMPLICATIONS FOR RESEARCH
High-quality randomized controlled trials with adequate sample size should be conducted in under-resourced settings to evaluate the effectiveness of magnesium sulfate for neuroprotection of the fetus as well as side-effects for women at risk of preterm birth.
Acknowledgements: The author is grateful to Doris Chou and Guillermo Carroli for their technical advice.
- Paneth N, Hong T, Korzeniewski S. The descriptive epidemiology of cerebral palsy. Clinics in Perinatology 2006; 33:251-67.
- Ho JJ, Amar HSS, Mohan AJ, Hon TH. Neurodevelopment outcome of very low birth weight babies admitted to a Malaysia nursery. Journal of Paediatrics and Child Health 1999; 35:175-80.
- Couper J. Prevalence of childhood disability in rural KwaZulu-Natal. South African Medical Journal 2002; 92:549-52.
- Boo NY, Ong LC, Lye MS, Chandran V, Teoh SL, Zamratol S, et. al. Comparison of morbidities in very low birthweight and normal birthweight infants during the first year of life in a developing country. Journal of Paediatrics and Child Health 1996; 32:439-44.
- Doyle LW, Crowther CA, Middleton P, Marret S. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database of Systematic Reviews 2007;Issue 3. Art. No.:CD004661; DOI: 10.1002/14651858.CD004661.pub2.
- Altman D, Carroli G, Duley L, Farrell B, Moodley J, Neilson J, Smith D; Magpie Trial Collaboration Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. The Lancet 2002;359:1877-1890.
This document should be cited as: Lumbiganon P. Magnesium sulfate for women at risk of preterm birth for neuroprotection of the fetus: RHL commentary (last revised: 1 July 2009). The WHO Reproductive Health Library; Geneva: World Health Organization.