Emerging plastic additives in umbilical cord serum, metabolomic profiles, and fetal growth restriction: A case-control study.

BACKGROUND

Fetal growth restriction (FGR) is associated with substantial perinatal and long-term health risks. As traditional plasticizers are being restricted, exposure to emerging plastic additives is increasing, yet their associations with FGR and related metabolic profiles remain poorly characterized.

METHODS

This case-control study included 90 FGR cases and 100 controls from the "Early Life Plan" cohort. A total of 117 plastic additives were measured in umbilical cord serum, and untargeted metabolomics was performed using UHPLC-HRMS. Multivariable logistic regression, restricted cubic splines, Bayesian kernel machine regression (BKMR), and quantile g-computation were used to evaluate the effects of single and mixed exposures of these chemicals on fetal growth outcomes. Meet-in-the-middle (MITM) analysis and pathway enrichment analysis were performed to identify associated metabolic features.

RESULTS

UV-360 was positively associated with FGR (OR = 1.35, 95% CI: 1.11-1.64), while 2,6-DtBEP was negatively associated with FGR (OR = 0.72, 95% CI: 0.61-0.84). Neither BKMR nor quantile g-computation provided clear evidence of an overall association between the 21-chemical mixture and FGR. Exploratory class-specific BKMR analyses suggested positive and negative associations for UV stabilizers and antioxidants, respectively. Differential metabolites were mainly enriched in amino acid, lipid, and one-carbon metabolism. MITM analyses suggested that six metabolites, including Valine, Proline, Palmitoylcarnitine, Ornithine, Xanthine, and (25 R)-Delta(4)-dafachronic acid, may be involved in the associations of UV-360 and DiBA/DnBA with FGR.

CONCLUSIONS

Concentrations of selected plastic additives in umbilical cord serum were associated with FGR, with UV-360 being consistently associated with higher odds of FGR. Metabolomic findings suggest that amino acid and lipid metabolism may be involved in these associations, warranting further validation in future studies.