High Levels of Magnesium in Cord Blood May Adversely Affect Non-Neurologic Outcomes in Infants

Infants with higher levels of magnesium in cord blood at birth may be at an increased risk of adverse non-neurologic outcomes, according to the results of a new subgroup analysis from the Beneficial Effects of Antenatal Magnesium Sulfate (BEAM) trial. These findings call into question the optimal dosing of magnesium sulfate supplements during pregnancy.

James M. Edwards, MD, a fellow in the Division of Maternal Fetal Medicine in the Department of Obstetrics and Gynecology at Duke University, presented results from the study at the 37th Annual Pregnancy Meeting of the Society for Maternal Fetal Medicine held January 23 to 28, 2017, in Las Vegas, NV.

“Antenatal magnesium sulfate is intended to improve neonatal neurologic outcomes but not at the expense of other non-neurologic outcomes,” commented Edwards. “Our goal with this analysis was to clarify the full spectrum of effects of antenatal magnesium sulfate exposure,” he said.

Magnesium sulfate is used in the setting of preterm birth to protect against cerebral palsy and other adverse neurologic outcomes. The primary analysis of the BEAM trial, which was published in 2008, supported the use of magnesium (6-g bolus followed by 2 g/hour for 12 hours) in pregnant women at imminent risk of delivery between 24 and 31 weeks of gestation. Compared with placebo, antenatal exposure to magnesium significantly reduced the risk of moderate or severe cerebral palsy by 45% at 2 years of age (relative risk 0.55; 95% confidence interval [CI], 0.32-0.95).

However, despite the increased use of magnesium sulfate for neuroprotection, little is known about the non-neurologic effects of magnesium exposure during pregnancy. Thus, the current analysis was designed to evaluate the relationship between levels of magnesium in cord blood at birth and non-neurologic outcomes in the original BEAM study cohort.

The BEAM trial included 2,444 pregnant women at imminent risk for delivery between 24 and 31 weeks of gestation. Of these, 1,254 pregnancies with complete data on magnesium levels in cord blood were included in the current analysis. The study focused on infants born with the highest and lowest magnesium levels in cord blood at birth.

In total, 259 infants were in the highest quintile group (magnesium level ≥ 2.9 mg/mL) and 389 were in the lowest quintile group (magnesium level ≤ 1.5 mg/mL). Infants with levels of magnesium in cord blood between 1.6 and 2.8 mg/mL at birth were not included.

Gestational age at birth, birth weight, and BEAM treatment group were significantly different between the higher- and lower-level magnesium groups (Table 1). Infants with higher levels of magnesium were more likely to be born prematurely, have lower birth weights, and have been assigned to the magnesium-exposure group in the BEAM trial.

Table 1. Baseline Characteristics

Characteristic Magnesium Level
≥ 2.9 mg/mL
(n = 259)
Magnesium Level
≤ 1.5 mg/mL
(n = 389)
P Value
Maternal age, y 25.2 25.4 .70
Race/ethnicity, % .13
African American 44.8 39.6
Caucasian 38.2 37.8
Hispanic 14.3 21.1
Maternal education, y 11.6 11.9 .27
Antenatal corticosteroid use, % 97.3 97.2 .92
Gestational age at birth, d 209 217 < .0001
Birth weight, g 1422 1683 < .0001
Male neonate, % 41.3 46.0 .24
Magnesium-exposed group, % 96.1 25.2 < .0001

Neurologic outcomes were similar regardless of magnesium levels in cord blood. In particular, no difference was observed in the rate of death or moderate/severe cerebral palsy between the higher- and lower-level magnesium groups (5.1% vs 8.8%, respectively; P = .07).

Shifting focus to non-neurologic outcomes, the unadjusted analysis showed a significant link between level of magnesium in cord blood and adverse outcomes (Table 2).

Table 2. Unadjusted Analysis of Non-Neurologic Outcomes by Magnesium Level

Outcome Magnesium Level
≥ 2.9 mg/mL
(n = 259), %
Magnesium Level
≤ 1.5 mg/mL
(n = 389), %
P Value
Any necrotizing enterocolitis 9.7 5.9 .08
Severe (grade 2/3) necrotizing enterocolitis 6.6 2.8 .02
Bronchopulmonary dysplasia 15.1 9.5 .03
Retinopathy of prematurity 17.4 11.3 .03
Respiratory distress syndrome 45.6 40.6 .18
Hypotension in delivery room 1.2 2.3 .29
Definite sepsis 13.1 10.8 .37

Infants with higher levels of magnesium in cord blood were more likely to have severe necrotizing enterocolitis (odds ratio [OR] 2.41; 95% CI, 1.11-5.24), bronchopulmonary dysplasia (OR 1.70; 95% CI, 1.04-2.73), and retinopathy of prematurity (OR 1.65; 95% CI, 1.05-2.59).

However, after adjusting for gestational age at birth, birth weight, and BEAM treatment group, the links between magnesium level and adverse non-neurologic outcomes were no longer statistically significant. Conversely, in the adjusted analysis, higher levels of magnesium predicted a decreased rate of hypotension in the delivery room (OR 0.16; 95% CI, 0.03-0.68).

“We need further studies to tailor magnesium dosing and administration in order to avoid adverse effects while maintaining improved neurologic outcomes,” Edwards said. Factors that may influence future approaches to magnesium sulfate use include maternal body mass index, maternal kidney function, fetal growth restriction, and umbilical artery function.

Source: Edwards J, Edwards LE, Swamy G, Grotegut CA. Effect of cord blood magnesium level at birth on non-neurologic neonatal outcomes. Presented at: Society for Maternal-Fetal Medicine 37th Annual Pregnancy Meeting; January 23-28, 2017; Las Vegas, NV. Abstract 100.