A prospective twin cohort investigates placental transfer efficiency as a potential determinant of fetal growth across a 300-xenobiotic maternal-fetal exposure landscape.

Prenatal exposure to environmental chemicals poses risks to fetal growth, yet most epidemiological studies have examined single chemical classes in isolation, leaving the broader multi-class maternal-fetal exposure landscape inadequately characterized. In addition, fetal exposure is typically inferred from cord blood concentrations, which conflates maternal body burden with transplacental transfer (TPT), obscuring the independent contribution of placental transport. We conducted a prospective cohort study screening 300 xenobiotics spanning multiple chemical classes, including PFAS, phthalate metabolites, environmental phenols/parabens, and pesticide- or industrial-related chemicals, across maternal serum and paired cord blood to define the core maternal-fetal exposome. Nineteen priority pollutants were detected at frequencies of ≥ 70% across all three biological matrices, including maternal serum, larger-twin cord blood, and smaller-twin cord blood, with PFAS representing the predominant chemical class. TPT varied substantially across compounds and differed nominally between co-twins for MBP. In linear mixed-effects models, higher TPT indices of MMP (β =  - 15.14; 95% CI: -27.66 to - 2.62), MBP (β =  - 11.61; 95% CI: -22.17 to - 1.05), and PFTrDA (β =  - 34.60; 95% CI: -67.91 to - 1.30) were nominally associated with lower birth weight. For PFTrDA, these associations were detected only when exposure was characterized by TPT, whereas corresponding cord blood concentrations were not significantly associated with fetal growth outcomes. These findings characterize a multi-class maternal-fetal exposome in twin pregnancies and provide exploratory evidence that TPT may constitute a complementary dimension of prenatal chemical exposure relevant to fetal growth.