Association of adverse birth outcomes with prenatal exposure to vanadium: a population-based cohort study

Background: Vanadium, an important pollutant produced from anthropogenic activities, has been suggested to be embryotoxic and fetotoxic in animal studies. However, little is known about its effects on humans. We aimed to assess the association of prenatal exposure to vanadium with the risk of adverse birth outcomes in babies born to women in China.

Methods: For this population-based cohort study, the Healthy Baby Cohort, women were recruited from three cities in Hubei Province, China. Women included in this analysis were recruited from Wuhan Women and Children Medical Care Center, Wuhan. We measured urinary concentrations of vanadium and other metals simultaneously using inductively coupled plasma mass spectrometry. We used multivariable logistic regressions, with adjustment for potential confounders, to estimate the associations of natural logarithm transformed creatinine-corrected urinary vanadium (Ln-vanadium) concentrations as continuous variables and categorised into quartiles (Q; Q1: ≤0·84 μg/g creatinine, Q2: 0·84-1·40 μg/g creatinine, Q3: 1·40-2·96 μg/g creatinine, Q4: >2·96 μg/g creatinine, with the lowest quartile set as reference) with preterm delivery, early-term delivery, low birthweight, and being small for gestational age. We applied restricted cubic spline models to evaluate the dose-response relationships.

Findings: Data from 7297 women recruited between Sept 22, 2012, and Oct 22, 2014, were included in this study. Urinary Ln-vanadium concentrations showed non-linear dose-response relationships with risk of preterm delivery (S-shaped, p<0·0001) and low birthweight (J-shaped, p=0·0001); the adjusted odds ratios (ORs) for increasing quartiles of urinary vanadium were 1·76 (95% CI 1·05-2·95) for Q2, 3·17 (1·96-5·14) for Q3, and 8·86 (5·66-13·86) for Q4 for preterm delivery, and 2·29 (95% CI 1·08-4·84) for Q2, 3·22 (1·58-6·58) for Q3, and 3·56 (1·79-7·10) for Q4 for low birthweight. Ln-vanadium concentrations were linearly associated with the risk of early-term delivery (linear, p<0·0001) and being small for gestational age (linear, p=0·0027), with adjusted ORs of 1·15 (95% CI 1·10-1·21) for early-term delivery and 1·12 (1·04-1·21) for being small for gestational age per unit increase in Ln-vanadium concentrations.

Interpretation: Our findings reveal a relationship between prenatal exposure to higher levels of vanadium and increased risk of adverse birth outcomes, suggesting that vanadium might be a potential toxic metal for human beings. Further studies are needed to replicate the observed associations and investigate the interaction effects of prenatal exposure to different metals on adverse birth outcomes.

Funding: National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Key Laboratory of Environment and Health.