Prenatal exposure to PFAS, associations with child cognitive ability and modification by maternal Vitamin D status: The MABC study.

BACKGROUND

Prenatal per- and polyfluoroalkyl substances (PFAS) exposure may adversely influence neurodevelopment. However, few studies have considered whether cumulative PFAS exposure over the entire course of pregnancy impacts child cognitive development and whether nutritional factors modify these associations.

OBJECTIVES

To investigate whether Vitamin D status modifies the association between maternal PFAS exposure during pregnancy and child cognitive ability.

METHODS

This analysis used 728 mother-child pairs in the Ma'anshan Birth Cohort (MABC), a population-based Chinese birth cohort enrolled from 2013 to 2014. We measured and averaged serum PFAS and Vitamin D concentrations during the first, second, and third trimesters of pregnancy. Child cognitive ability was assessed at age 2.7-6.0 years using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition. We used linear regression, Bayesian kernel machine regression, and quantile g-computation to estimate covariate-adjusted associations of individual PFAS concentrations and their mixture with child cognitive scores. Analyses were stratified by sex to examine sex-specific associations between PFAS and child cognitive scores, with further stratification by categorizing maternal Vitamin D levels into deficient (<20 ng/mL, n = 636) and non-deficient (≥ 20 ng/mL, n = 92) groups.

RESULTS

Overall, the pregnancy average of br-PFOA concentrations was inversely associated with VCI scores (β = -1.72, 95 %CI: -3.43, -0.02), 8:2 Cl-PFESA was inversely associated with VSI scores (β = -1.21, 95 %CI: -2.30, -0.11), and n-PFHxS was inversely associated with WMI scores (β = -2.19, 95 %CI: -4.35, -0.03). Generally, PFAS were associated with lower cognitive scores in boys, but not girls. Further, the PFAS mixture was negatively associated with boys' total cognitive scores (β = -1.94, 95 %CI: -3.69, -0.19), with br-PFOA and n-PFHxS having the greatest weights; in contrast, PFHpS was the major contributor to the positive association of the PFAS mixture with cognitive scores in girls. After stratifying by maternal Vitamin D status, adverse associations were primarily observed in the deficient group among boys, whereas positive associations were present only in the deficient group among girls. Specifically, associations of cognitive scores with n-PFOA, br-PFOA, PFNA, n-PFHxS, and br-PFHxS were significantly stronger among boys born to women with Vitamin D deficiency (Range of betas=-4.73 to -2.04, P < 0.05) than those with sufficient levels of Vitamin D (Range of betas=-3.81-1.52, P > 0.05). The PFAS mixture was negatively related to child cognitive ability in boys, where each quartile increase in the mixture was associated with boys' VCI, VSI, WMI, and FSIQ scores decreased by 2.77, 2.21, 2.57, and 1.94 scores, respectively (all p-FDR < 0.05).

CONCLUSION

We observed sex-specific adverse associations between prenatal PFAS and cognitive ability. Our findings suggest that prenatal Vitamin D may modify these associations, potentially mitigating the neurotoxic effects of prenatal PFAS exposure.