Magnesium not associated with neuroprotection in preterm chorioamnionitis

1. Rates of severe neonatal and childhood morbidity were similar between preterm infants whose mothers received magnesium sulfate compared to placebo.

2. The proportion of infants with low mental developmental scores was lower in the magnesium group but failed to achieve significance.

Evidence Rating Level: 1 (Excellent)     

Study Rundown: Cerebral palsy (CP) is a common, heterogeneous non-progressive neuromuscular clinical syndrome. It is characterized by a combination of motor and postural dysfunction and other neurologic signs that can result in lifelong disability. Risk factors include prematurity, intrauterine growth restriction, and intrauterine infection. While there is no definitive treatment for CP, administration of antenatal magnesium sulfate during preterm labor has been shown to decrease the incidence and severity of CP. The mechanism by which magnesium sulfate acts is unknown, but evidence suggests it modifies inflammatory cytokines that may play a role in the development of CP. A landmark trial defined the benefit of magnesium sulfate administration to women in preterm labor up to 32 weeks gestation in decreasing the incidence of CP (see relevant reading). In the present work, authors assessed whether magnesium confers neuroprotection among a subset of preterm infants exposed to chorioamnionitis. They found that outcomes were similar among infants who received magnesium sulfate and placebo.

Strengths of the investigation included randomized controlled trial design, prospective data collection and evaluation of long-term outcomes. Limitations included post hoc analysis and small sample size which increases the risk of Type II error (erroneous failure to reject the null hypothesis). Additional investigation to better characterize which patients benefit most from this treatment is merited.

Click to read the study in BJOG

Relevant Reading: The BEAM trial (Beneficial Effects of Antenatal Magnesium Sulfate)

In-Depth [randomized controlled trial]: This secondary analysis of a randomized clinical trial evaluated the neuroprotective effects of magnesium sulfate in preterm infants of women diagnosed with chorioamnionitis. Women at risk of delivery between 24 and 0/7 and 31 and 6/7 weeks gestation with a clinical diagnosis of chorioamnionitis and temperature >37.8°C or receiving antibiotics for chorioamnionitis were randomized to receive magnesium sulfate (n = 192) or placebo (n = 204). The primary outcome was a composite of severe childhood morbidity encompassing stillbirth or death before age 1 and moderate or severe CP at or after age 2. Secondary outcomes included neonatal morbidities such as sepsis, intraventricular hemorrhage, necrotizing enterocolitis, and developmental delay.

There were no differences in severe composite childhood morbidity (p = 0.42), composite neonatal morbidity (p = 0.27) or developmental delay. Similarly, there were no differences in the composite primary outcome in a subgroup of very preterm infants <28 weeks gestational age. Infants born to women who received antenatal magnesium experienced an insignificantly lower risk of low mental developmental score (RR: 0.67, p = 0.10).

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