fig3
Figure 3. Regulatory role of primary conjugated BAs in the association between prenatal PFAS exposure and neurodevelopmental trajectories (n = 225). (A) Identification of key primary conjugated BAs predictive of neurodevelopment. RF analysis ranked BAs by their importance in predicting children’s neurodevelopmental trajectories (%IncMSE). Six of these eight top-ranked BAs were primary conjugated BAs (TCA, GHCA, TCDCA, GCDCA, GCA, and THCA); (B-D) Logistic regression models were employed to estimate the associations (ORs and 95%CIs) between maternal serum PFAS concentrations during pregnancy and children’s neurodevelopmental trajectories, stratified by child TCA, TCDCA, and GCA levels (high vs. low, median split). Interaction P-values reflect effect modification. For interaction terms, we considered P < 0.1 as nominally significant. The ORs indicate the likelihood of a child being in the persistently low neurodevelopmental trajectory group, with the persistently high group as the reference. All models were controlled for maternal age, pre-pregnancy BMI, parity, maternal education, family income, maternal passive smoking before pregnancy, alcohol drinking, folic acid or vitamin supplementation during pregnancy, child sex, and gestational age. Detailed estimates are presented in Supplementary Tables 17-22. BAs: Bile acids; PFAS: per- and polyfluoroalkyl substances; RF: random forest; %IncMSE: percentage increase in mean squared error; TCA: taurocholic acid; GHCA: glycohyocholic acid; TCDCA: taurochenodeoxycholic acid; GCDCA: glycochenodeoxycholic acid; GCA: glycocholic acid; THCA: taurohyocholic acid; ORs: odds ratios; CIs: confidence intervals; BMI: body mass index; GUDCA: glycoursodeoxycholilc acid; DCA: deoxycholic acid; GDCA: glycodeoxycholic acid; TDCA: taurodeoxycholic acid; CA: cholic acid; CDCA: chenodeoxycholic acid; GLCA: glycolithocholic acid; HCA: hyocholic acid; UDCA: ursodeoxycholic acid; PFOS: perfluorooctane sulfonate; PFDA: perfluoro-n-decanoic acid; PFDoDA: perfluoro-n-dodecanoic acid; PFUnDA: perfluoro-n-undecanoic acid.
