Micronutrient supplementation interventions in preconception and pregnant women at increased risk of developing pre-eclampsia: a systematic review and meta-analysis

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

FIGO Preconception Checklist: Preconception care for mother and baby

“…For instance, 77% of women aged 18-25 years were found to have insufficient daily dietary intakes of iodine and 96% of women of reproductive age had daily intakes of iron and folate below the recommended levels for pregnancy. 19 Preconception supplementation of certain micronutrients is associated with a reduction in several adverse obstetric outcomes, for example calcium and vitamin D supplementation reduce the risk of pre-eclampsia 36 ; myoinositol, probiotics, and micronutrient supplementation decrease the risk of preterm births (aRR 0.43; 95% CI, 0.22-0.82). 37 Moreover, preconceptional micronutrient supplementation may influence intellectual development in offspring.…”

“…Preconception supplementation of certain micronutrients is associated with a reduction in several adverse obstetric outcomes, for example calcium and vitamin D supplementation reduce the risk of pre‐eclampsia 36 ; myoinositol, probiotics, and micronutrient supplementation decrease the risk of preterm births (aRR 0.43; 95% CI, 0.22–0.82) 37 . Moreover, preconceptional micronutrient supplementation may influence intellectual development in offspring.…”

Vitamin D may alleviate pre‐eclampsia by modulating the ferroptosis signalling pathway: A hypothesis based on recent literature

“…In a case–control study, disrupted vitamin D homeostasis and calcium transport was found in the placenta of PE cases 18 . A systematic review and meta‐analysis found that micronutrient supplementation (calcium and vitamin D) interventions reduced the risk of developing PE 19 . Vitamin D is known to promote calcium absorption.…”

“… 18 A systematic review and meta‐analysis found that micronutrient supplementation (calcium and vitamin D) interventions reduced the risk of developing PE. 19 Vitamin D is known to promote calcium absorption. Can calcium supplementation also reduce the risk of PE?…”

Dietary supplements and vascular function in hypertensive disorders of pregnancy

“…A recent systematic review and meta-analysis have shown the positive correlation between lower rate of preeclampsia and calcium and vitamin D intake [ 207 ]. Vitamin D is a pre-hormone, that can also be endogenously produced by the skin when exposed to UV-B.…”