Not enough evidence that magnesium supplementation in pregnancy is beneficial…

small_3367833777An updated Cochrane review has concluded that there is no evidence to show that dietary magnesium supplementation during pregnancy is beneficial.

In the previous review (Makrides and Crowther 2001), magnesium supplementation appeared to be associated with a lower frequency of preterm birth, low birthweight and babies who were deemed small-for-gestational age. But only one of the seven trials included in that review was of high methodological quality, and the authors concluded that ‘Poor quality trials are likely to have resulted in a bias favouring magnesium supplementation.’

A few papers and studies have considered this issue in the meantime, including one published in the BJOG (Harrison et al 2007) which showed that babies might benefit during labour if their mothers had taken magnesium supplements during pregnancy.  This and a related paper led to an RCOG press release debating the possible benefits of supplementation.

Ten trials were included in the most recent Cochrane review, and two of these were judged to be of high quality.  Although, as before, some of the poorer quality trials appear to show a benefit, the authors conclude that, overall, and despite the fact that many women have been shown to have magnesium intakes that are below recommended levels, we do not have enough high-quality evidence that magnesium supplementation during pregnancy is beneficial.

The Research

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.

Harrison, S Fawcus, E Jordaan (2007).  Magnesium supplementation and perinatal hypoxia: outcome of a parallel group randomised trial in pregnancy BJOG 114(8):994-1002. Epub 2007 Jun 18.

Makrides M, Crosby DD, Bain E, Crowther CA. Magnesium supplementation in pregnancy. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD000937. DOI: 10.1002/14651858.CD000937.pub2.

Makrides M, Crowther CA. Magnesium supplementation in pregnancy. Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD000937. DOI: 10.1002/14651858.CD000937.

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