[Correlation of per- and polyfluoroalkyl substances exposure with gestational age acceleration and birth outcomes in...

Objective: To investigate the associations between in utero per- and polyfluoroalkyl substances exposure and gestational age acceleration, as well as the relationship of this acceleration with birth outcomes, using a small sample of monozygotic (MZ) twins. Methods: We studied 20 MZ twin pairs and their mothers from the Wuhan Twin Birth Cohort. Cord blood DNA methylation was measured using Illumina Infinium Methylation EPIC 935K array. Gestational age acceleration was calculated using three established clocks (Knight, Bohlin, and Haftorn), yielding the metrics ageAcc.Knight, ageAcc.Bohlin, and ageAcc.Haftorn. Birth outcomes included weight, length, and head circumference. Data were analyzed using Spearman and Pearson correlation analyses and linear mixed models. Results: In individual-level analyses, positive correlations were observed between perfluorooctanesulfonic acid (PFOS) and all three gestational age acceleration (Spearman ρ=0.55, 0.35, and 0.36, respectively). 6∶2 chlorinated polyfluoroalkyl ether sulfonic acid (6∶2 Cl-PFESA) were also positively correlated with ageAcc.Knight (ρ=0.33). After covariate adjustment, the positive associations of PFOS, perfluorodecanoic acid (PFDA), and 6∶2 Cl-PFESA with ageAcc.Knight remained significant in linear mixed models. In within-twin-pair analyses, higher maternal PFOS concentrations in mid- and late pregnancy were associated with a greater intra-twin difference in ageAcc.Bohlin (mid-pregnancy: ρ=0.46, P=0.040; late pregnancy: ρ=0.53, P=0.018). ageAcc.Bohlin was inversely correlated with head circumference at the individual level (r=-0.33, P=0.035). The within-pair difference in ageAcc.Bohlin showed a positive correlation with the head circumference difference (r=0.48, P=0.032). Conclusion: In-utero PFOS exposure may have an association with gestational age acceleration, which may influence neonatal head circumference development.