Prenatal exposure to perfluoroalkyl substances and behavioral difficulties in childhood at 7 and 11 years

Abstract

Background: Perfluoroalkyl substances (PFAS) are suggested to interfere with thyroid hormone during pregnancy and influence fetal neurodevelopment. Epidemiological evidence regarding behavioral difficulties in childhood associated with prenatal PFAS exposure has been inconclusive. Objective: The study aimed to assess the association between prenatal PFAS exposure and behavioral difficulties at 7 and 11 years, and evaluated the potential mediating role of maternal thyroid hormones in these associations. Methods: Using pooled samples in the Danish National Birth Cohort, we evaluated the associations between concentrations of six types of PFAS in maternal plasma collected in early pregnancy (median, 8 gestational weeks) and child behavioral assessments from the Strength and Difficulties Questionnaire (SDQ), reported by parents at 7 years (n=2,421), and by parents (n=2,070) and children at 11 years (n=2,071). Behavioral difficulties were defined as having composite SDQ scores of the total, externalizing and internalizing behaviors above the 90th percentile. We used logistic regression to estimate the adjusted Odds Ratio (OR) by doubling increase of prenatal PFAS exposure. The possible mediating effect of maternal TSH and fT4 level in the association between prenatal PFAS and SDQ scores were also evaluated. Results: Prenatal perfluorononanoic acid (PFNA) was consistently associated with total and externalizing behavioral difficulties in all three SDQ measures reported by parents (OR=1.40, 95% CI: 1.14-1.73 for age 7; OR=1.27, 95% CI: 1.05-1.53 for age 11) or children (OR=1.32, 95% CI: 1.11-1.58) while no consistent associations were observed for other types of PFAS. A small magnitude of indirect effects via maternal TSH and fT4 level were observed for total and externalizing behaviors at 7 years reported by parents only. Discussion: Prenatal PFNA exposure was associated with externalizing behavioral difficulties in childhood in repeated SDQ measures at 7 and 11 years. The slight mediating effects of maternal thyroid hormones in early gestation warrant further evaluation.