# Multiple-element exposure in early pregnancy and birth defects: a nested case–control study based on the China birth cohort study

## TL;DR

This study explores how exposure to multiple elements during early pregnancy is linked to a reduced risk of birth defects, particularly highlighting nickel and zinc.

## Contribution

The novel contribution is the investigation of multiple-element exposure during early pregnancy and its association with birth defects using a nested case–control design.

## Key findings

- High levels of Al, Cr, Mn, Fe, Ni, and Zn in urine during early pregnancy were associated with reduced total birth defects.
- Nickel and zinc showed a dose–response relationship with birth defects, with a trend of slight increase followed by rapid decrease.
- Interactions between nickel and other elements suggest complex relationships in element mixtures affecting birth defect risk.

## Abstract

Birth defects have become the leading cause of death among children, placing a heavy burden on society and families. Various elements from the environment may be associated with birth defects in the fetus, but few prospective studies have investigated the relationship between multiple-element exposure in the first trimester and birth defects.

In this study, 271 cases were matched to 542 controls for age (±2 years) and gestational age (±2 weeks). We measured the concentrations of 17 elements in urine samples collected from pregnant women during the first trimester and used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). The BKMR model was used to evaluate the correlation between element mixed exposure and birth defects.

In the single-metal multivariate model, aluminum (Al), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), and zinc (Zn) were negatively associated with total birth defects. Restricted cubic splines revealed linear or nonlinear dose-responsive relationships between either Ni or Zn and the risk of birth defects. BKMR results showed that birth defects showed a trend of first slightly rising and then declining; when the element mixture was above the 50th percentile, it was significantly negatively associated with total birth defects. Ni and Zn showed an obvious trend of slight increase and then rapid decrease, indicating that there was a dose–response relationship between these elements and birth defects. There were interactions between Ni and the other five elements.

The mixture of high levels of Al, Cr, Mn, Fe, Ni, and Zn in urine during the first trimester of pregnancy was related to a reduction in total birth defects. In particular, the influence of Ni and Zn on total birth defects should be considered.