A new study published in the journal Neural Regeneration Research reports that magnesium sulfate, when administered before preterm delivery, significantly reduces the risk of cerebral palsy at two years.
Clement Chollat and Stephane Marret conducted a systematic review to summarize the evidence for the neuroprotective effects of MgSO4 on the immature brain obtained from the RCTs and meta-analyses.
A brief summary of the review is as follows:
- Strong evidence from randomized controlled trials and meta-analyses has demonstrated that magnesium sulfate, when administered before preterm delivery, significantly reduces the risk of cerebral palsy at two years.
- In a recent systematic review, maternal life-threatening side effects, such as death, cardiac or respiratory arrest, and intensive care admission were not associated with MgSO4 These data are consistent with the results of RCTs and meta-analyses.
- However, women receiving MgSO4 had an increased risk of developing minor side effects. Specifically, they had double the risk of hypotension, tachycardia, respiratory depression, discomfort at the injection site, drowsiness, headache, dizziness, mouth dryness or thirst, and blurred vision; five times the risk of nausea and/or vomiting, flushing and warmth, and sweating; and 15 times the risk of itching, tingling, and muscle weakness. These adverse effects are transient and disappear with treatment cessation.
- One trial has shown that a lower dose regimen (2 g/3 hours) significantly reduced treatment cessation due to side effects when compared with a higher dose regimen (5 g/4 hours). In addition, extending the duration of the loading dose from 20 to 60 minutes reduces flushing and warmth, but has no impact on other side effects.
- Low maternal body mass index (BMI) may also influence the occurrence of side effects. For example, more maternal adverse effects were observed in underweight women than in normal or overweight women.
- Results of the meta-analyses conducted on the RCTs did not show any adverse outcomes for neonates, including respiratory distress syndrome, need for mechanical ventilation, or necrotizing enterocolitis. However, one trial showed a higher incidence of spontaneous intestinal perforation after antenatal MgSO4administration among extremely low birthweight infants.
- Antenatal MgSO4administration did not influence neonatal vital parameters, such as heart and respiratory rates, temperature, oxygen saturation, and glycemia. The assessment of hemodynamic parameters by echocardiography one day after antenatal MgSO4 infusion showed lower systemic vascular resistance and higher myocardial function in preterm infants born before 29 weeks of gestation.
- A secondary analysis of the BEAM trial showed that MgSO4 significantly reduced CP, but only in non-obese women. This finding suggests that a dosage adjustment based on maternal weight is required. More studies are required to explore this association.
- Similarly, a retrospective study on 304 mother-baby dyads found a correlation between neurological outcomes and serum magnesium levels. Neonates with low (< 1.0 mM) or high (> 1.9 mM) serum magnesium levels had a higher OR for grade 3 or 4 intraventricular haemorrhage than neonates with magnesium levels between 1 and 1.9 mM. In this study, the neonatal magnesium levels were dependent on the maternal magnesium dose, maternal serum concentration, and duration of therapy.
- In a retrospective study with 88 infants exposed to MgSO4, elevated magnesium levels (> 1.5 mM) were associated with lower locomotor scores in the first year of life. Conversely, another retrospective cohort that included 75 preterm infants exposed to MgSO4revealed that higher levels of MgSO4 (> 1 mM) were associated with a significantly decreased risk of abnormal motor examination findings between 20 and 36 months of age.
- The duration of MgSO4 infusion does not affect its neuroprotective effects. A secondary analysis of the BEAM trial found no change in neurological outcomes when comparing the administration durations of < 12 hours, between 12 and 18 hours, or > 18 hours.
- A final MgSO4 exposure < 12 hours before delivery was associated with significantly reduced odds of CP compared with exposure > 12 hours before delivery.
- Two national surveys have shown heterogeneous clinical practices regarding the maintenance dose (1 or 2 g/h), duration of treatment (until delivery, or for a maximum of 12 or 24 hours), consideration of re-treatment, and a minimum interval between the two treatments.
The authors concluded that antenatal MgSO4 administration is a key intervention for preventing cerebral palsy in preterm neonates. MgSO4 infusion is associated with minor transient maternal side effects but is well tolerated by neonates. Maternal weight and preeclamptic status affect maternal and neonatal magnesium levels, which could in turn influence the neuroprotective effects of MgSO4.
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