2024: Prenatal exposure to per- and polyfluoroalkyl substances, genetic factors, and autistic traits

There are more than 7 million PFAS and over 21 million fluorinated compounds listed in PubChem (2023).
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2024: Prenatal exposure to per- and polyfluoroalkyl substances, genetic factors, and autistic traits

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Yun Huang, Weiran Chen, Yuexin Gan, Xin Liu, Ying Tian, Jun Zhang, Fei Li - "Prenatal exposure to per- and polyfluoroalkyl substances, genetic factors, and autistic traits: Evidence from the Shanghai Birth Cohort" Journal of Hazardous Materials, Available online 26 September 2024, 13585
https://www.sciencedirect.com/science/a ... 9424024361
Abstract

The epidemiological evidence regarding prenatal PFAS exposure and its interaction with genetic factors on the autistic traits risk is unclear. This study included 1,610 mother-child pairs from the Shanghai Birth Cohort (SBC). Ten PFAS were quantified in blood serum collected in the first trimester. Child autistic traits were evaluated at age 4 using a Chinese version of the social responsiveness scale-short form (SRS-SF). We calculated the polygenic risk score (PRS) to evaluate the cumulative genetic effects of autism. Additive interaction models were established to explore whether genetic susceptibility modified the effects of prenatal PFAS exposure. After adjusting for confounders, we found prenatal PFOA exposure was associated with an increased risk of autistic traits in children (OR, 3.05; 95% CI, 1.14-7.58), and the increased risk associated with PFOA was mitigated among women who reported pre-pregnancy folic acid supplementation. Additionally, an increased risk of autistic traits was observed in children with higher levels of prenatal PFHxS exposure and a high PRS (p for interaction = 0.021). Our findings suggest prenatal PFAS exposure may increase the risk of autistic traits in children, especially in those with a high genetic risk. Further research is warranted to confirm this association and explore the underlying mechanisms.
SEE:

Oh J, Bennett DH, Calafat AM, Tancredi D, Roa DL, Schmidt RJ, Hertz-Picciotto I, Shin HM - "Prenatal exposure to per- and polyfluoroalkyl substances in association with autism spectrum disorder in the MARBLES study" Environ Int 147:106328 (2021) doi: 10.1016/j.envint.2020.106328
https://www.sciencedirect.com/science/a ... 2020322832
Abstract

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has shown potential to adversely affect child brain development, but epidemiologic evidence remains inconsistent. We examined whether prenatal exposure to PFAS was associated with increased risk of autism spectrum disorder (ASD).

Methods: Participants were 173 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a high-risk ASD cohort. At 3 years old, children were clinically confirmed for ASD and classified into ASD (n = 57) and typical development (TD, n = 116). We quantified nine PFAS in maternal serum collected during pregnancy. We examined associations of ASD with individual PFAS as well as the combined effect of PFAS on ASD using scores of the first principal component (PC-1) accounting for the largest variance.

Results: Prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) showed positive associations (per 2 nanogram per milliliter increase: relative risk (RR) = 1.20, 95% CI: 0.90, 1.61 [PFOA]; RR = 1.24, 95% CI: 0.91, 1.69 [PFNA]), while perfluorohexane sulfonate (PFHxS) showed a negative association (RR = 0.88, 95% CI: 0.77, 1.01) with ASD risk. When examining associations of ASD with untransformed PFAS concentrations, PFOA, PFNA, and PC-1 were associated with increased ASD risk (per nanogram per milliliter increase: RR = 1.31, 95% CI: 1.04, 1.65; RR = 1.79, 95% CI: 1.13, 2.85; RR = 1.10, 95% CI: 0.97, 1.25, respectively), while the RR of PFHxS moved toward the null.

Conclusions: From this high-risk ASD cohort, we observed increased risk of ASD in children exposed to PFOA and PFNA. Further studies should be conducted in the general population because this population may have a larger fraction of cases resulting from genetic sources.
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