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Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Prenatal exposure to PFAS, associations with child cognitive ability and modification by maternal Vitamin D status:
Xiaoyan Wu1, Juan Tong2, George D Papandonatos3
1Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China; MOE Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, Anhui 230032, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, Anhui 230032, China; Anhui Provincial Key Laboratory of Environment and Population Health across the Life Course, Anhui Medical University, Hefei, Anhui 230032, China; Department of Epidemiology, Brown University, Providence, RI 02912, USA.
Insights
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is linked to lower child cognitive scores, especially in boys. Maternal Vitamin D levels may mitigate these neurotoxic effects, offering a potential protective factor.
Area of Science:
- Environmental Health
- Neuroscience
- Toxicology
Background:
- Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may negatively impact child neurodevelopment.
- Limited research exists on the effects of cumulative PFAS exposure throughout pregnancy on cognitive development and the role of nutritional factors.
Purpose of the Study:
- To examine if maternal Vitamin D status modifies the association between prenatal PFAS exposure and child cognitive ability.
- To investigate sex-specific associations between PFAS exposure and cognitive development.
Main Methods:
- Analysis of 728 mother-child pairs from the Ma'anshan Birth Cohort (2013-2014).
- Measurement of serum PFAS and Vitamin D levels across pregnancy trimesters.
- Assessment of child cognitive ability at ages 2.7-6.0 years using the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition.
- Application of linear regression, Bayesian kernel machine regression, and quantile g-computation, with stratification by sex and Vitamin D status.
Main Results:
- Specific PFAS (br-PFOA, 8:2 Cl-PFESA, n-PFHxS) were inversely associated with cognitive scores.
- PFAS exposure was generally linked to lower cognitive scores in boys, with no significant association in girls.
- Adverse associations were more pronounced in boys of mothers with Vitamin D deficiency.
- Maternal Vitamin D deficiency appeared to modify the neurotoxic effects of PFAS exposure, particularly in boys.
Conclusions:
- Prenatal PFAS exposure shows sex-specific adverse associations with child cognitive ability.
- Maternal Vitamin D status may play a modifying role, potentially mitigating the neurotoxic effects of prenatal PFAS exposure.
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.

