Magnesium for the prevention of cerebral palsy [Classics Series] |  Medicine in 2 Minutes

Magnesium for the prevention of cerebral palsy [Classics Series] | Medicine in 2 Minutes

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials

1. Among women with imminent preterm birth, babies of women randomized to magnesium were less likely to be diagnosed with moderate or severe cerebral palsy.

Original publication date: August 2008

Summary of the study: Cerebral palsy, the leading cause of childhood disability, is a group of syndromes characterized by motor and postural dysfunction. A major risk factor for cerebral palsy is premature birth, which is associated with up to a third of cerebral palsy cases. In the early 2000s, research identified an increased prevalence of cerebral palsy in very preterm infants (28 to 32 weeks gestation). Survival of preterm (< 37 weeks gestation) and very preterm infants born in the United States has improved dramatically in recent decades, resulting in more preterm infants surviving to infancy. As part of improving survival, researchers have worked to prevent, mitigate, and treat morbidities associated with prematurity, including cerebral palsy. A retrospective survey identified a lower odds ratio of cerebral palsy in preterm infants whose mothers received magnesium. However, previous studies have recruited women in preterm labor, who are often recommended to receive magnesium for uterine tocolysis. The present study achieves greater parsimony by recruiting women with no other indications for magnesium treatment to specifically assess the benefit of intrapartum magnesium for fetal neuroprotection in preterm infants born between 24 and 31 weeks.

This randomized, placebo-controlled trial evaluated the benefit of intrapartum administration of magnesium sulfate for fetal neuroprotection in women at risk of imminent preterm birth between 24 and 31 weeks of gestation. Follow-up examinations at age 2 showed an almost 50% decrease in the diagnosis of moderate or severe cerebral palsy in infants whose mothers received magnesium. Along with other studies, this landmark investigation indicated that magnesium may significantly reduce the risk of cerebral palsy in the group of infants most at risk of developing this debilitating condition. Strengths included an elegant study design and a high follow-up rate of 96%. The inclusion of women with singleton and twin pregnancies receiving care at 20 birthing centers across the United States yields broadly applicable results. Limitations included potential selection bias, with 40% of eligible participants (1602/3843) declining to participate.

Click to read the study in the NEJM

In depth [randomized controlled trial]: Multicenter trial of 2241 women at risk of imminent delivery between 24 and 31 weeks of gestation were randomized to receive magnesium sulphate (loading dose of 6 g followed by an infusion of 2 g/hour) or a placebo. Women with hypertension, pre-eclampsia or those requiring magnesium for tocolysis were excluded. The outcomes assessed included the composite primary endpoint of stillbirth or infant death within one year. The secondary endpoints evaluated were moderate or severe cerebral palsy beyond 2 years. The diagnosis of cerebral palsy has been rigorously determined by an annually certified pediatrician or pediatric neurologist. The diagnosis was made if the children met at least 2 strictly defined criteria, including motor delay, abnormal muscle tone or reflexes, persistence of primitive reflexes and movement abnormality.

Among women with imminent delivery between 24 and 31 weeks of gestation, those randomized to receive magnesium sulfate were 45% less likely to be diagnosed with moderate or severe cerebral palsy at 2 years of life (1.9% versus 3.5%, RR 0.55; p = 0.03). The risk of fetal death did not differ between the groups (9.5 versus 8.5%, p = 0.4). Obstetric outcomes and a range of other neonatal outcomes including respiratory distress, intraventricular haemorrhage, necrotizing enterocolitis and retinopathy of prematurity were similar between groups (all p > 0.5).

Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY, Mercer BM, et al. A randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy. The New England Journal of Medicine. 2008;359(9):895-905.

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