Magnesium supplementation in pregnancy.

The Cochrane database of systematic reviews

Apr 2014

DOI: 10.1002/14651858.CD000937.pub2

Citations:180

Influential Citations:10

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Randomised and quasi-randomised trials; one cluster-randomised trial; total 9090 pregnant women and babies; included women with normal or high-risk pregnancies; primiparous and multiparous; started magnesium at various stages of pregnancy; all interventions were oral magnesium (no intravenous/intramuscular magnesium).

Intervention

Oral magnesium supplements with varied salts/formulations and dosing across trials. Examples include magnesium oxide 1000 mg/day started by four months post-conception or earlier; magnesium citrate 340–365 mg/day started before 9–18 weeks and continued to birth or hospitalization; magnesium gluconate regimens include 2–4 g/day starting around 23–30 weeks to birth; magnesium aspartate regimens include 15 mmol/day or six tablets daily from about 6–16/21 weeks to birth; magnesium stearate 64 mg elemental Mg per tablet taken as two tablets daily from enrollment (10–35 weeks) to birth; some trials used 2 g/day then 3 g/day magnesium gluconate from 28 weeks onward; overall regimens varied and no single standard dose emerged.

Results

Across 10 trials (9090 participants), oral magnesium during pregnancy did not significantly reduce perinatal mortality, small-for-gestational-age, or preeclampsia. Maternal death was not reported. Some infant outcomes favored magnesium in individual trials (e.g., lower risk of Apgar <7 at 5 minutes, meconium-stained liquor, late fetal heart decelerations, mild hypoxic-ischaemic encephalopathy) and maternal hospitalization during pregnancy was reduced, but overall evidence quality was low and primary outcomes showed no clear benefit. The conclusion: there is not enough high-quality evidence to show magnesium supplementation during pregnancy is beneficial; routine use cannot be recommended; more large, well-designed trials are needed.

Limitations

Most trials had unclear or variable risk of bias; substantial heterogeneity in dosing, timing, and outcome definitions; many trials were small; one large trial (South Africa 2007) dominated several outcomes; long-term infant outcomes were not reported; several outcomes were not prespecified and reporting varied across studies.

Abstract

BACKGROUND Magnesium is an essential mineral required for regulation of body temperature, nucleic acid and protein synthesis and in maintaining nerve and muscle cell electrical potentials. Many women, especially those from disadvantaged backgrounds, have low intakes of magnesium. Magnesium supplementation during pregnancy may be able to reduce fetal growth restriction and pre-eclampsia, and increase birthweight. OBJECTIVES To assess the effects of magnesium supplementation during pregnancy on maternal, neonatal/infant and paediatric outcomes. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2013). SELECTION CRITERIA Randomised and quasi-randomised trials assessing the effects of dietary magnesium supplementation during pregnancy were included. The primary outcomes were perinatal mortality (including stillbirth and neonatal death prior to hospital discharge), small-for-gestational age, maternal mortality and pre-eclampsia. DATA COLLECTION AND ANALYSIS Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. MAIN RESULTS Ten trials involving 9090 women and their babies were included; one trial had a cluster design (with randomisation by study centre). All 10 trials randomly allocated women to either an oral magnesium supplement or a control group; in eight trials a placebo was used, and in two trials no treatment was given to the control group. In the 10 included trials, the compositions of the magnesium supplements, gestational ages at commencement, and doses administered varied, including: magnesium oxide, 1000 mg daily from ≤ four months post-conception (one trial); magnesium citrate, 365 mg daily from ≤ 18 weeks until hospitalisation after 38 weeks (one trial), and 340 mg daily from nine to 27 weeks' gestation (one trial); magnesium gluconate, 2 to 3 g from 28 weeks' gestation until birth (one trial), and 4 g daily from 23 weeks' gestation (one trial); magnesium aspartate, 15 mmol daily (three trials, commencing from either six to 21 weeks' gestation until birth, ≤ 16 weeks' gestation until birth, or < 12 weeks until birth), or 365 mg daily from 13 to 24 weeks until birth (one trial); and magnesium stearate, 128 mg elemental magnesium from 10 to 35 weeks until birth (one trial).In the analysis of all trials, oral magnesium supplementation compared to no magnesium was associated with no significant difference in perinatal mortality (stillbirth and neonatal death prior to discharge) (risk ratio (RR) 1.10; 95% confidence interval (CI) 0.72 to 1.67; five trials, 5903 infants), small-for-gestational age (RR 0.76; 95% CI 0.54 to 1.07; three trials, 1291 infants), or pre-eclampsia (RR 0.87; 95% CI 0.58 to 1.32; three trials, 1042 women). None of the included trials reported on maternal mortality.Considering secondary outcomes, while no increased risk of stillbirth was observed, a possible increased risk of neonatal death prior to hospital discharge was shown for infants born to mothers who had received magnesium (RR 2.21; 95% CI 1.02 to 4.75; four trials, 5373 infants). One trial contributed over 70% of the participants to the analysis for this outcome; the trial authors suggested that the large number of severe congenital anomalies in the supplemented group (unlikely attributable to magnesium) and the deaths of two sets of twins (with birthweights < 750 g) in the supplemented group likely accounted for the increased risk of death observed, and thus this result should be interpreted with caution. Furthermore, when the deaths due to severe congenital abnormalities in this trial were excluded from the meta-analysis, no increased risk of neonatal death was seen for the magnesium supplemented group. Magnesium supplementation was associated with significantly fewer babies with an Apgar score less than seven at five minutes (RR 0.34; 95% CI 0.15 to 0.80; four trials, 1083 infants), with meconium-stained liquor (RR 0.79; 95% CI 0.63 to 0.99; one trial, 4082 infants), late fetal heart decelerations (RR 0.68; 95% CI 0.53 to 0.88; one trial, 4082 infants), and mild hypoxic-ischaemic encephalopathy (RR 0.38; 95% CI 0.15 to 0.98; one trial, 4082 infants). Women receiving magnesium were significantly less likely to require hospitalisation during pregnancy (RR 0.65, 95% CI 0.48 to 0.86; three trials, 1158 women).Of the 10 trials included in the review, only two were judged to be of high quality overall. When an analysis was restricted to these two trials none of the review's primary outcomes (perinatal mortality, small-for-gestational age, pre-eclampsia) were significantly different between the magnesium supplemented and control groups. AUTHORS' CONCLUSIONS There is not enough high-quality evidence to show that dietary magnesium supplementation during pregnancy is beneficial. show less