Vitamin D treatment during pregnancy and maternal and cord blood metal concentrations at delivery; results of a randomized controlled trial in Bangladesh

Abstract

Background: Vitamin D facilitates calcium absorption, but also other essential elements such as magnesium and iron. In animal studies, vitamin D treatment also increases toxic metal absorption such as lead and cadmium. We examined maternal blood and infant cord blood levels of toxic metals in response to vitamin D supplementation. Methods: The Maternal Vitamin D for Infant Growth (MDIG) trial was a randomized, placebo-controlled, multi-arm study of maternal vitamin D supplementation during pregnancy in Dhaka, Bangladesh. Women were randomized during their second trimester to blinded weekly doses of placebo or 4,200, 16,800, or 28,000IU of vitamin D3 throughout pregnancy. Each group had 118, 141, 121, and 239 maternal blood specimens analyzed, respectively, and 100, 104, 111, and 201 infant cord blood samples. Cadmium, lead, mercury, and manganese were measured using inductively-coupled plasma mass spectrometry. We used linear regression models to calculate percent differences. Detectable versus undetectable cord blood cadmium was analyzed with log-binomial regression. Results: Maternal blood metal concentrations did not differ between treatment and placebo groups. However, compared with placebo, the 4,200, 16,800, and 28,000IU groups had infant cord blood lead levels that were 8.5% (-3.5, 22), 16% (3.3, 30), and 11% (0.4, 23) higher, respectively, and higher risk of having detectable cadmium levels, relative risk (95% confidence interval): 2.2(1.3, 3.7), 1.4(0.8, 2.5), 1.7(1.0, 2.9). Inferences were unchanged when excluding women with sufficient baseline 25OHD or excluding women who completed less than 95% of their treatment visits. Conclusions: Vitamin D supplementation from the second trimester of pregnancy did not affect maternal blood metal levels at delivery. However, higher lead and cadmium levels in cord blood were observed in some vitamin D groups. As there are no safe levels of metal exposures in infants, the observed increases in cord blood lead and cadmium concentrations require further exploration.