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Meta-Analysis
. 2014 Apr 3;2014(4):CD000937.
doi: 10.1002/14651858.CD000937.pub2.

Magnesium supplementation in pregnancy

Maria Makrides  1 , Danielle D Crosby, Emily Bain, Caroline A Crowther
Affiliations
Meta-Analysis

Magnesium supplementation in pregnancy

Maria Makrides et al. Cochrane Database Syst Rev. .

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.

PubMed Disclaimer

Conflict of interest statement

Maria Makrides ‐ has received advisory board payments from Nestle Nutrition Insitute, Fonterra,and Nutricia/Danone. These advisory boards were related to clinical nutrition in paediatric settings (and therefore not related to the topic under review). The Nestle Nutrition Institute advisory board was only focused on education and training aspects and there were no discussions relating to products. All the honoraria associated with these boards were paid to Maria Makrides' institution and used to fund continuing education and travel for students, early and mid‐career researchers.

Danielle Crosby ‐ none known

Emily Shepherd ‐ none known

Caroline Crowther ‐ none known

Figures

1
1
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 1 Perinatal mortality.
1.2
1.2. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 2 Small‐for‐gestational age (< 10th percentile).
1.3
1.3. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 3 Pre‐eclampsia.
1.4
1.4. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 4 Stillbirth.
1.5
1.5. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 5 Neonatal death prior to hospital discharge.
1.6
1.6. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 6 Miscarriage (< 20 weeks' gestation).
1.7
1.7. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 7 Gestational age at birth (weeks).
1.8
1.8. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 8 Preterm birth < 37 weeks' gestation.
1.9
1.9. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 9 Low birthweight.
1.10
1.10. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 10 Birthweight (g).
1.11
1.11. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 11 Baby admitted to the neonatal unit.
1.12
1.12. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 12 Apgar score.
1.13
1.13. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 13 Late fetal heart rate decelerations.
1.14
1.14. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 14 Meconium‐stained liquor.
1.15
1.15. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 15 Meconium aspiration.
1.16
1.16. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 16 Breech presentation.
1.17
1.17. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 17 Placental abruption.
1.18
1.18. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 18 Placental weight (g).
1.19
1.19. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 19 Hypoxic‐ischaemic encephalopathy.
1.20
1.20. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 20 Significant congenital abnormality.
1.21
1.21. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 21 Maternal side effects.
1.22
1.22. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 22 Systolic blood pressure near birth (mm Hg).
1.23
1.23. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 23 Diastolic blood pressure near birth (mm Hg).
1.24
1.24. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 24 Pregnancy‐induced hypertension.
1.25
1.25. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 25 Eclampsia.
1.26
1.26. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 26 Need for maternal hospitalisation.
1.27
1.27. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 27 Antepartum haemorrhage.
1.28
1.28. Analysis
Comparison 1 Magnesium supplementation versus no magnesium, Outcome 28 Length of labour (hours).
2.1
2.1. Analysis
Comparison 2 Subgroup analysis based on study design, Outcome 1 Perinatal mortality.
2.2
2.2. Analysis
Comparison 2 Subgroup analysis based on study design, Outcome 2 Small‐for‐gestational age (< 10th percentile).
3.1
3.1. Analysis
Comparison 3 Sensitivity analysis based on the ICC, Outcome 1 Perinatal mortality.
3.2
3.2. Analysis
Comparison 3 Sensitivity analysis based on the ICC, Outcome 2 Stillbirth.
3.3
3.3. Analysis
Comparison 3 Sensitivity analysis based on the ICC, Outcome 3 Neonatal death prior to hospital discharge.
4.1
4.1. Analysis
Comparison 4 Sensitivity analysis by quality rating, Outcome 1 Perinatal mortality.
4.2
4.2. Analysis
Comparison 4 Sensitivity analysis by quality rating, Outcome 2 Small‐for‐gestational age (< 10th percentile).
4.3
4.3. Analysis
Comparison 4 Sensitivity analysis by quality rating, Outcome 3 Pre‐eclampsia.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Austria 1997 {published data only}
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References to studies excluded from this review

Denmark 1990 {published data only}
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Denmark 1991 {published data only}
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Detroit 1999 {published data only}
    1. Hallak M, Martinez‐Poyer J, Brish L, Poole‐Bryant K, Mammen EF, Sorokin Y. Magnesium sulfate impairs platelet function in normal pregnant women. American Journal of Obstetrics and Gynecology 1999;180(1 Pt 2):S142.
    1. Hallak M, Martinez‐Poyer J, Kruger M, Hassan S, Blackwell S, Sorokin Y. The effect of magnesium sulfate on fetal heart rate parameters: A randomized, placebo‐controlled trial. American Journal of Obstetrics and Gynecology 1999;181(5):1122‐7. - PubMed
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India 2012 {published data only}
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ISRCTN03989660 {published data only}
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NCT01709968 {published data only}
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Norway 2008 {published data only}
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Sweden 1987 {published data only}
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References to ongoing studies

ISRCTN98365455 {published data only}
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NCT01510665 {published data only}
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References to other published versions of this review

Keirse 1995
    1. Keirse MJNC. Routine magnesium supplementation in pregnancy. Pregnancy and Childbirth Module; The Cochrane Pregnancy and Childbirth Database [database on disk and CDROM]. The Cochrane Collaboration; Oxford, 1995 [revised 16 June 1993], issue 2.
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