Inconsistent evidence exists on the association between maternal essential metals exposure and birth outcomes. We aim to investigate these associations and explore potential effect modification by maternal thyroid hormones (THs). We collected data from the Ma'anshan birth cohort, including 953 mother-infant pairs. Metals and THs were measured in early pregnancy. Multiple regression and restricted cubic spline (RCS) models were used to evaluate associations between individual metals and outcomes. Bayesian Kernel Machine Regression (BKMR) was applied to assess mixture effects. Stratified analyses with interaction tests were performed to evaluate effect modification by THs. Multiple regression models showed that higher manganese (Mn) and zinc (Zn) concentrations were associated with higher birth weight z-score (BWZ) (Mn: β = 0.44, 95% CI: 0.17, 0.72; Zn: β = 0.38, 95% CI: 0.09, 0.68) and increased large for gestational age (LGA) risk (Mn: OR = 2.82, 95% CI: 1.28, 6.21; Zn: OR = 2.50, 95% CI: 1.08, 5.80). Copper (Cu) was inversely associated with small for gestational age (SGA) risk (OR = 0.27, 95% CI: 0.08, 0.97). RCS analyses revealed significant non-linear associations with LGA for both Se and Zn, with a more clearly inverted U-shaped pattern for Se. BKMR showed a monotonic increasing association of the metal mixture with both BWZ and LGA, with the trend significant at lower-to-moderate concentrations. Mn was the primary contributor for both outcomes, whereas no significant associations were observed for SGA. Interaction and stratified analyses showed that Cu was positively associated with BWZ and LGA in the overall population, with stronger effects in the high FT4 subgroup (BWZ: β = 0.35, 95% CI: 0.05, 0.80; LGA: OR = 2.14, 95% CI: 1.01, 8.20), whereas no associations were found in the low FT4 subgroup, indicating a potential modifying role of FT4. Other stratified findings lacked interaction evidence and were considered exploratory.
Xiao-yu Zhao, Zhen-Hua Li, Kai Huang et al.· Environmental Pollution· 0 citations
BACKGROUND
Prenatal exposure to metal mixtures may influence newborn birth size, but the underlying metabolic mechanisms remain unclear. This study aimed to evaluate the associations of 19 individual maternal metals and metal mixtures during pregnancy with birth size indicators, specifically birth weight z score (BWZ) and birth length z score (BLZ), and to identify potential metabolic pathways and mediating metabolites based on cord blood metabolomics.
METHODS
A total of 1059 mother-infant pairs were included in the full cohort. We applied ExWAS, ENET/DSA, WQS, qgcomp, and BKMR to assess both single-metal and joint exposure effects. Exploratory MWAS, pathway enrichment, and mediation analyses were conducted using cord blood metabolomics data.
RESULTS
In single-metal analyses, Zn, Se, and Mn showed positive associations with BWZ and BLZ, whereas Cu was positively associated with BWZ only; As, Pb, and Cd generally showed inverse associations. In mixture analyses, the negative-direction WQS index was associated with lower BLZ (β = -0.039, P = 0.042). Exploratory metabolomics analyses highlighted lipid-related metabolites, organic acid derivatives, and nucleotide-related metabolites, with enrichment in caffeine metabolism and steroid hormone biosynthesis pathways. Mediation analyses suggested potential indirect effect signals, including As-BWZ via 10-hydroxystearic acid (19.6%), Cu-BWZ via 2-ethyl-2-hydroxybutyric acid (30.8%), and Se-BLZ via 2-ethyl-2-hydroxybutyric acid (21.1%).
CONCLUSION
In this industrial city cohort, our findings provide evidence linking prenatal metal exposure to newborn birth size and suggest that cord blood metabolic profiles may offer exploratory mechanistic clues for understanding metal-related fetal growth patterns.
Hai-Yang Weng, Zhen-Hua Li, Chun-Yong Wang et al.· Ecotoxicology and Environmen...· 0 citations
It is suggested that prenatal PFAS exposure is associated with reduced BW-z, particularly among female infants, and that altered fasting glucose may represent one possible, but not primary, pathway linking selected PFAS to fetal growth.
