Elementomics of 32 elements in cord serum depicts the risk of orofacial clefts: A case-control study in Shanxi, China

Maternal exposure to various metallic and non-metallic elements has been linked to the occurrence of orofacial clefts (OFCs), yet there remains a dearth of comprehensive research on the potential ramifications of simultaneous exposure to multiple elements. In this study, we investigated the individual and combined effects of element exposure on OFCs in a cohort of 168 pregnant women (49 cases and 119 controls) in the Shanxi province of northern China from 2010 to 2015. Cord serum samples were obtained from all participants to analyze the levels of 32 elements using inductively coupled plasma-mass spectrometry. The study examined the independent correlation between element concentrations and OFCs using two machine screening models, Boruta and Least Absolute Shrinkage and Selection Operator. Bayesian kernel machine regression (BKMR) was utilized to determine the combined effects of key exposure elements on OFCs and to clarify the interaction between exposed elements through the generalized additive model (GAM). The screening models identified lead (Pb), tin (Sn), iron (Fe), and cesium (Cs) as the most significant risk factors for OFC development in offspring. In the BKMR model, the probability of OFCs increased with higher overall levels of these risk elements, with Pb emerging as the primary contributor to the combined effect of the mixture. The findings of the GAM indicated that the combined exposure to Pb and Sn had a synergistic effect on the risk of developing OFCs. Analysis of elemental exposure in umbilical cord serum suggested that Pb exposure may have detrimental effects on OFC development in offspring, which may be further intensified by a synergistic interaction between Sn and Pb in the occurrence of OFCs.