Background/Aims: Vitamin D may protect from pre-eclampsia through influences on immune modulation and vascular function. To evaluate the role of vitamin D in the development of pre-eclampsia, we conducted a systematic review and meta-analysis including novel data from 2 large-scale epidemiological studies. Methods: PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched for prospective observational studies of association between vitamin D supplementation or status (measured by maternal 25-hydroxyvitamin D, 25(OH)D) with a subsequent risk of pre-eclampsia, or randomised controlled trials using vitamin D supplementation to prevent pre-eclampsia. The Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) and the Avon Longitudinal Study of Parents and Children (ALSPAC) were included in meta-analyses with published studies. Results: Mothers receiving vitamin D supplementation earlier in pregnancy had lower odds of pre-eclampsia [pooled odds ratios (OR) 0.81 and 95% confidence interval (CI) 0.75-0.87, p = 2.4 × 10^-8, 2 studies] in the meta-analysis of published studies with HCCSCA. The meta-analysis of published studies with ALSPAC suggested an association between higher serum 25(OH)D levels and a reduced risk of pre-eclampsia (pooled OR 0.52 and 95% CI 0.30-0.89, p = 0.02, 6 studies). Randomised trials of supplementation were suggestive of protective association (pooled OR 0.66 and 95% CI 0.52-0.83, p = 0.001, 4 studies). Conclusions: This study suggests that low maternal serum 25(OH)D concentrations increase pre-eclampsia risk and that vitamin D supplementation lowers this risk. The quality of evidence is insufficient to determine a causal association, which highlights the need for adequately powered clinical trials.

Vitamin D deficiency was common in this contemporary U.K. cohort. Despite some overlap, there are differences in potential confounding structures for associations of 25(OH)D₃ and 25(OH)D₂ with health outcomes. These should be accounted for in future studies.

SummaryBackgroundMaternal vitamin D status in pregnancy is a suggested determinant of bone-mineral content (BMC) in offspring, but has been assessed in small studies. We investigated this association in a large prospective study.MethodsEligible participants were mother-and-singleton-offspring pairs who had participated in the Avon Longitudinal Study of Parents and Children, and in which the mother had recorded measurements of 25(OH)D concentration in pregnancy and the offspring had undergone dual-energy x-ray absorptiometry at age 9–10 years. 25(OH)D concentrations in pregnancy were assessed per 10·0 nmol/L and classified as sufficient (more than 50·00 nmol/L), insufficient (49·99–27·50 nmol/L), or deficient (lower than 27·50 nmol/L). Associations between maternal serum 25(OH)D concentrations and offspring total body less head (TBLH) and spinal BMC were assessed by trimester.Results3960 mother-and-offspring pairs, mainly of white European origin, were assessed (TBLH BMC n=3960, spinal BMC n=3196). Mean offspring age was 9·9 years. 2644 (67%) mothers had sufficient, 1096 (28%) insufficient, and 220 (6%) deficient 25(OH)D concentrations in pregnancy, but TBLH and spinal BMC did not differ between offspring of mothers in the lower two groups versus sufficient 25(OH)D concentration. No associations with offspring BMC were found for any trimester, including the third trimester, which is thought to be most relevant (TBLH BMC confounder-adjusted mean difference −0·03 g per 10·0 nmol/L, 95% CI −1·71 to 1·65; spinal BMC 0·04 g per 10·0 nmol/L, 95% CI −0·12 to 0·21).ConclusionsWe found no relevant association between maternal vitamin D status in pregnancy and offspring BMC in late childhood.FundingUK Medical Research Council, Wellcome Trust, and University of Bristol.

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