Vitamin D Treatment during Pregnancy and Maternal and Neonatal Cord Blood Metal Concentrations at Delivery: Results of a Randomized Controlled Trial in Bangladesh

Abstract

Background: Vitamin D improves absorption of calcium; however, in animal studies vitamin D also increases the absorption of toxic metals, such as lead and cadmium.

Objectives: We examined maternal and neonatal cord blood levels of lead, cadmium, manganese, and mercury after supplementation with vitamin D during pregnancy.

Methods: The Maternal Vitamin D for Infant Growth trial was a randomized, placebo-controlled, multi-arm study of maternal vitamin D supplementation during pregnancy in Dhaka, Bangladesh (NCT01924013). Women were randomized during their second trimester to blinded weekly doses of placebo or 4,200, 16,800, or 28,000 IU of vitamin D3 throughout pregnancy. Each group had 118-239 maternal blood specimens and 100-201 cord blood samples analyzed. Metals were measured using inductively coupled plasma mass spectrometry. Unadjusted estimates from linear regression models were expressed as percentage differences. Cord blood cadmium was analyzed as detectable or undetectable with log-binomial regression.

Results: Maternal cadmium, mercury, and manganese levels were nearly identical across groups. Maternal lead levels were 6.3%, 7.4%, and 6.0% higher in the treatment groups (4,200, 16,800, and 28,000 IU, respectively) vs. placebo; however, 95% confidence intervals (CIs) showed that differences from 4.1% lower to 20% higher were compatible with the data. In treatment groups (4,200, 16,800, 28,000 IU) vs. placebo, neonatal cord blood lead levels were 8.5% (95% CI: $-3.5$, 22), 16% (95% CI: 3.3, 30), and 11% (95% CI: 0.4, 23) higher and had higher risk of detectable cadmium, relative risk $\left(\text{RR}\right)=2.2$ (95% CI: 1.3, 3.7), $\text{RR}=1.4$ (95% CI: 0.8, 2.5), $\text{RR}=1.7$ (95% CI: 1.0, 2.9).

Discussion: Vitamin D supplementation from the second trimester of pregnancy did not influence maternal cadmium, mercury, or manganese levels at delivery. Vitamin D was associated with nonsignificant increases in maternal lead and with significant increases in cord blood lead and cadmium. These associations were not dose dependent. Given that there are no safe levels of metals in infants, the observed increases in cord blood lead and cadmium require further exploration. https://doi.org/10.1289/EHP7265.

Figure 1.

CONSORT diagram showing the maternal and cord samples from the MDIG trial that were analyzed for metal levels at the CDC. Note: CDC, Centers for Disease Control and Prevention; CONSORT, Consolidated Standards of Reporting Trials; MDIG, Maternal Vitamin D for Infant Growth.