Micronutrient supplementation interventions in preconception and pregnant women at increased risk of developing pre-eclampsia: a systematic review and meta-analysis
What this study found
Calcium and vitamin D supplementation were associated with a lower rate of preeclampsia in high-risk women, while other micronutrient regimens did not show consistent benefit. Pooled effects were risk difference -0.15 for calcium (95% CI -0.27, -0.03; I2 = 83.41%) and -0.09 for vitamin D (95% CI -0.17, -0.02; I2 = 0.00%). Vitamin C plus vitamin E showed only a small, non-significant trend overall (risk difference -0.04, 95% CI -0.09, 0.00; I2 = 65.76%), and there was no demonstrated effect on severe preeclampsia. One trial also reported more low-birthweight infants with vitamin C and E (387…
- Study & population
- Systematic review and meta-analysis of 20 randomized controlled trials in women aged 18 to 50 who were at high risk for preeclampsia and were either planning pregnancy or already pregnant.
- Intervention
- This systematic review evaluated preconception and pregnancy micronutrient supplementation regimens aimed at preventing preeclampsia in high-risk women.
- Key limitation
- The evidence base was limited by small sample sizes, heterogeneity across trials, and variable methods, doses, timing of initiation, and co-formulations.
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Open PDFOriginal abstract
Pre-eclampsia can lead to maternal and neonatal complications and is a common cause of maternal mortality worldwide. This review has examined the effect of micronutrient supplementation interventions in women identified as having a greater risk of developing pre-eclampsia. A systematic review was performed using the PRISMA guidelines. The electronic databases MEDLINE, EMBASE and the Cochrane Central Register of Controlled trials were searched for relevant literature and eligible studies identified according to a pre-specified criteria. A meta-analysis of randomised controlled trials (RCTs) was conducted to examine the effect of micronutrient supplementation on pre-eclampsia in high-risk women. Twenty RCTs were identified and supplementation included vitamin C and E (n = 7), calcium (n = 5), vitamin D (n = 3), folic acid (n = 2), magnesium (n = 1) and multiple micronutrients (n = 2). Sample size and recruitment time point varied across studies and a variety of predictive factors were used to identify participants, with a previous history of pre-eclampsia being the most common. No studies utilised a validated prediction model. There was a reduction in pre-eclampsia with calcium (risk difference, −0.15 (−0.27, −0.03, I2 = 83.4%)), and vitamin D (risk difference, −0.09 (−0.17, −0.02, I2 = 0.0%)) supplementation. Our findings show a lower rate of pre-eclampsia with calcium and vitamin D, however, conclusions were limited by small sample sizes, methodological variability and heterogeneity between studies. Further higher quality, large-scale RCTs of calcium and vitamin D are warranted. Exploration of interventions at different time points before and during pregnancy as well as those which utilise prediction modelling methodology, would provide greater insight into the efficacy of micronutrient supplementation intervention in the prevention of pre-eclampsia in high-risk women.