The association between circulating 25-hydroxyvitamin D levels and preeclampsia: a systematic review and dose-response meta-analysis of epidemiologic studies with GRADE assessment

Context Although some studies have examined the connection between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and preeclampsia (PE) risk, the results were inconsistent. Objective A dose-response meta-analysis on epidemiologic investigations was conducted to evaluate the relation of 25(OH)D concentration and PE. Data Source Electronic databases, including Scopus, MEDLINE (PubMed), the Institute for Scientific Information, Embase, and Google Scholar, were comprehensively search until July 2021. Data Extraction A total of 65 observational studies evaluating the link between circulating 25(OH)D concentrations and PE were included. The body of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Data Analysis Combining 32 effect sizes from 32 prospective studies with 76 394 participants revealed that highest vs lowest circulating 25(OH)D concentrations was significantly related to a 33% reduced risk of PE (relative risk [RR], 0.67; 95%CI, 0.54-0.83). Subgroup analysis by study design revealed that PE risk has significantly decreased in cohort and case-cohort studies (RR, 0.72; 95%CI, 0.61-0.85), and a slight decline was found in nested case-control studies (RR, 0.62; 95%CI, 0.38-1.02). Dose-response analysis in 27 prospective studies with 73 626 participants illustrated that each 10 ng/mL increment in circulating 25(OH)D concentration led to a 14% reduced incidence of PE (RR, 0.86; 95%CI, 0.83-0.90). A U-shaped significant association in nonlinear dose-response analysis was found between 25(OH)D and PE. A significant inverse association was also found between highest vs lowest circulating 25(OH)D concentration and PE in 32 nonprospective studies with 37 477 participants (odd ratio, 0.37; 95%CI, 0.27-0.52). This inverse association was significant in almost all subgroups, based on different covariates. Conclusion This meta-analysis of observational investigations showed blood 25(OH)D levels were negatively related to PE risk, in a dose-response manner. Systematic Review Registration PROSPERO registration no. CRD42021267486.

Automated summary

A dose-response meta-analysis of observational studies found a negative association between blood 25(OH)D levels and the risk of preeclampsia (PE). This suggests that adequate levels of 25(OH)D may reduce the risk of PE.