The Efficacy and Safety of Vitamin D Supplementation during Pregnancy on the Incidence Rate of Pre-Eclampsia: a Systematic Review of Maternal and Infant Health Outcomes

Abstract

Background: The aetiology of pre-eclampsia (PE) remains poorly understood, yet recent research suggests that an increase in inflammatory mediators produced by the placenta may be a potential causative mechanism. To date, studies published on vitamin D (Vit D) emphasise the association between its deficiency and the development of PE. However, data regarding the efficacy of Vit D supplementation in reducing PE risk are inconclusive. Objective: This systematic review aimed to evaluate the effect of Vit D supplementation on the incidence of PE, preterm delivery, Caesarean section (C- section), and 25(OH)-D serum levels, assess the safety of supplements for pregnant women, and determine the optimal supplementation strategy. Methodology: A systematic search of four databases (PubMed, Web of Science, Embase via Ovid, and Scopus) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) of full-text English- language papers published from 2013 to 2023. Eligible studies were randomised controlled trials (RCTs) that examined the effects of Vit D supplementation on the incidence of PE and maternal and infant outcomes referring to birth weight, preterm delivery, C-section and 25(OH)-D levels. An independent t-test was performed to compare the mean difference between groups. Results: In total, six RCTs with a total sample size of 762 pregnant women were included and showed that prenatal Vit D supplementation was associated with a non- significant decrease in PE risk (8.47± 8.070 vs 15.59±9.522, P=0.193) and birth weight (BW) (2957.75±296.679 vs. 2819.47±313.248g, P= 0.545), preterm delivery (7.07 % vs 15.92 %, P=0.165) C-section (37.55 vs 42.80 %, P=0.464) and 25(OH)-D levels (46.11±7421 nmol/l vs 80±51.53 nmol/l. P=0.143). Moreover, no major side effects were reported. Conclusion: Vit D supplementation during pregnancy is a potential safe intervention strategy for preventing preeclampsia in pregnancy. However, the impact of the supplementation was not significant on PE odds, birth weight, preterm delivery C- section and 25(OH)-D levels; thus, more RCTs are needed to determine the optimal strategy in terms of population-specific dose recommendations and ideal timing.