Effect of maternal vitamin D status on risk of adverse birth outcomes: a systematic review and dose-response meta-analysis of observational studies.

Abstract

Accumulating evidence suggests that vitamin D deficiency increases the risk of adverse perinatal outcomes. However, the dose-response relationship between maternal vitamin D status and adverse birth outcomes remains unclear. Focusing on prospective observational studies, we aimed to explore the dose-response relationship of vitamin D status with the risk of low birth weight (LBW), macrosomia (MA), preterm birth (PTB), small for gestational age (SGA), and intrauterine growth restriction (IUGR). Databases including PubMed, Embase, Scopus, and Web of Science were used up to 19 January 2021 to search for observational studies that fulfilled criteria as follows: cohort studies, case-cohort studies, or nested case-control studies. Random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs) in the observational studies. A total of 72 publications were included in this systematic review and 71 in the meta-analysis. Maternal 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with the risk of LBW (RR: 0.65; 95% CI 0.48-0.86), PTB (RR: 0.67; 95% CI 0.57-0.79), and SGA (RR: 0.61; 95% CI 0.49-0.76) in the highest versus lowest meta-analysis, but not associated with MA and IUGR. Linear dose-response analysis showed that each 25nmol/L increase in 25(OH)D was associated with a 6% and 10% reduction in the risk of PTB (RR: 0.94; 95% CI 0.90-0.98) and SGA (RR: 0.90; 95% CI 0.84-0.97), respectively. Our study suggests that a sufficient vitamin D status during pregnancy is protective against the risk of LBW, PTB, and SGA.