Investigating Bidirectional Associations of Blood Metals and Vitamin D levels throughout Pregnancy: The MIREC Cohort Study

Abstract

BACKGROUND AND AIM: The standard biomarker of vitamin D status is plasma 25-hydroxyvitamin D (25OHD). Low 25OHD is associated with reduced immune function and adverse pregnancy outcomes including preterm birth. There is evidence that high exposure to lead (Pb) and cadmium (Cd) is associated with lower vitamin D status. However, the directionality of these associations is uncertain, particularly for low-level Pb and Cd exposure. In this study we explore the bidirectional relationship of heavy metal biomarkers (Pb and Cd) with 25OHD. METHODS: In the longitudinal MIREC Study, we measured maternal blood 25OHD and metals in the 1st (n=1905) and 3rd (n=1649) trimester and 25OHD at delivery (n=1542). We used multivariable linear regressions and latent growth curve models (LGCMs) to explore the impact of Cd and Pb on 25OHD levels throughout pregnancy. Using Cross Lag Panel Models we examined the bidirectional relationship of metals and 25OHD. RESULTS:The majority of women (~85%) had 25OHD levels 50 nmol/L at each visit. We found weak inverse associations between Cd and 25OHD concentrations cross-sectionally and longitudinally, with stronger estimates in smokers. LGCMs suggested 1st trimester Cd and Pb concentrations more strongly affect a woman’s 25OHD baseline value (1st trimester) than her 25OHD trajectory in pregnancy; however, confidence intervals crossed the null. In contrast, the bidirectional analysis showed that for each doubling in 1st trimester 25OHD there was a 12% reduction in Cd (95% CI: -20%, -4%) and 5% reduction in Pb (95% CI: -9.42, 0.2%) concentrations in the 3rd trimester. CONCLUSIONS:Our results suggest higher early pregnancy 25OHD values are associated with a lowering of 3rd trimester metal concentrations. There was no evidence for an effect of early pregnancy metals on later 25OHD. To our knowledge, this is the first study to investigate the bidirectional relationship between vitamin D status and metals in pregnancy. KEYWORDS: Vitamin D metals, Cross Lag Panel Model, Pregnancy, Biomarkers