Introduction: Perfluorinated alkylated substances (PFAS) are persistent industrial chemicals that have resulted in global environmental exposures. Previous epidemiological studies have reported possible effects on the immune system after developmental PFAS exposure, but the possible impact on childhood infectious disease is unclear.Objectives: To investigate the association between prenatal exposure to PFAS and symptoms of infections at age 1-4 years. Methods:The Odense Child Cohort is an on-going prospective study on children's health, where serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA) were measured in 649 pregnant women before gestational week 16. Of these women, 359 reported on symptoms of infection in their child every two weeks for a one-year period. The association between prenatal exposure to PFAS and the symptoms was estimated using a logistic regression model and a negative binomial regression model. For the latter, the outcome was reported as an incidence rate-ratio (IRR), and all models were adjusted for maternal age, educational level, parity and child age.Results: On average, and accounting for incomplete reporting, the children experienced symptoms of infection 23% of the time during one year. PFOS exposure in the high tertile compared to the low tertile was associated with a statistically significant increased proportion of days with fever (IRR: 1.65 (95% CI: 1.24, 2.18), p-trend<0.001) and an increased odds of experiencing days with fever above the median (OR: 2.35 (95%CI: 1.31, 4.11). The latter tendency was also apparent for PFOA (OR: 1.97 (95%CI: 1.07, 3.62). Further, higher concentrations of PFOS and PFOA tended to increase the number of episodes of cooccurrence of fever and coughing and fever and nasal discharge during the one-year study period. 4 Conclusion:We found a positive association between prenatal exposure to PFOS and PFOA and the prevalence of fever, which may be a sensitive marker of infection. This finding is in agreement with an immunotoxic effect of prenatal exposure to PFAS. The wider implications for childhood infectious disease deserve attention.

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Our findings are notable, as adverse associations were suggested even in this low-level exposed population, with only one spot urine sample for exposure assessment and control for confounders. Lower scores in early language development are of relevance to health as this test predicts later educational success.

In Odense Child Cohort (OCC), concentrations of the pesticide metabolites 3-phenoxybenzoic acid (3-PBA), 3,5,6-trichloro-2-pyridinol (TCPY), 2,4-Dichlorophenoxyacetic acid (2,4-D) and dialkyl phosphates (DAPs) were measured in urine samples collected in gestational week 28 in up to 858 women. Gestational length, birth weight, head and abdominal circumference were obtained from birth records and anogenital distance (AGD) was measured at age three month. We did not find consistent dose-related associations between pesticide metabolite concentrations and birth outcomes or AGD. However, females tended to have shorter abdominal circumference with higher maternal 3-PBA concentrations (β: -0.3 (95% CI: -0.5, -0.003) cm). Further, a non-significant dose-related elongation of AGD in females was seen for 3-PBA (p-trend: 0.14) and diethyl phosphates (p-trend: 0.08). In males, exposure to 2,4-D in the second compared to the first tertile showed a statistically significant shorter AGD (β: -1.55 (-2.81, -0.28) mm). These findings may suggest a weak disturbance of sex-hormone action.

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