Prenatal Exposure to Perfluoroalkyl Substances and Child Behavior at Age 12: A PELAGIE Mother-Child Cohort Study

Abstract

Background: Per- and polyfluoroalkyl substances (PFAS) are chemical substances spread throughout the environment worldwide. Exposure during pregnancy represents a specific window of vulnerability for child health.

Objective: Our objective was to assess the impact of prenatal exposure to multiple PFAS on emotional and behavioral functions in 12-y-old children.

Method: In the PELAGIE mother-child cohort (France), prenatal exposure to nine PFAS was measured from concentrations in cord serum samples. Behavior was assessed at age 12 y using the parent-reported Strengths and Difficulties Questionnaire (SDQ) and the self-reported Dominic Interactive for Adolescents (DIA) for 444 children. Associations were estimated using negative binomial models for each PFAS. Bayesian kernel machine regression (BKMR) models were performed to assess the exposure mixture effect on children's behavior.

Results: In our study population, 73% of mothers had spent more than 12 y in education. Higher scores on SDQ externalizing subscale were observed with increasing cord-serum concentration of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) [adjusted mean ratio $\left(\text{aMR}\right)=1.18$, 95% confidence interval (CI): 1.03, 1.34, and $\text{aMR}=1.14$ (95% CI: 1.00, 1.29) for every doubling of concentration, respectively]. Results for the hyperactivity score were similar [$\text{aMR}=1.20$ (95% CI: 1.04, 1.40) and $\text{aMR}=1.18$ (95% CI: 1.02, 1.36), respectively]. With regard to major depressive disorder and internalizing subscales, perfluorodecanoic acid (PFDA) was associated with higher self-reported DIA scores [$\text{aMR}=1.14$ (95% CI: 1.01, 1.27) and $\text{aMR}=1.11$ (95% CI: 1.02, 1.21), respectively]. In terms of the anxiety subscale, PFDA and PFNA were associated with higher scores [$\text{aMR}=1.11$ (95% CI: 1.02, 1.21) and $\text{aMR}=1.10$ (95% CI: 1.01, 1.19), respectively]. Concurrent increases in the PFAS concentrations included in the BKMR models showed no change in the SDQ externalizing and DIA internalizing subscales scores.

Conclusion: Prenatal exposure to PFNA and PFOA were associated with increasing scores for measures of externalizing behaviors, specifically hyperactivity. We also identified associations between PFNA and PFDA prenatal exposure levels and increasing scores related to internalizing behaviors (general anxiety and major depressive disorder), which adds to the as yet sparse literature examining the links between prenatal exposure to PFAS and internalizing disorders. https://doi.org/10.1289/EHP12540.

Figure 1.

Overall PFAS mixture effect for SDQ Externalizing subscale (A) and DIA internalizing subscale (B) from BKMR models ($n=378$), PELAGIE mother–child cohort, Brittany, France. Change in estimate are spotted as blue and orange dots and 95% CIs as blue and orange bars (for externalizing and internalizing subscales, respectively) for concurrent increase of exposures in comparison with the 25th percentile. PIP are provided on the figure. Mixture was composed of PFOA, PFNA, PFDA, PFUnDA, PFHxS, and PFOS. Models were adjusted for maternal age at the beginning of pregnancy (in years), maternal prepregnancy BMI (in three categories: $<18.5\mathrm{kg}/\mathrm{m}²$, $18.5–25\mathrm{kg}/\mathrm{m}²$, $\ge 25\mathrm{kg}/\mathrm{m}²$), maternal education (in three groups: $<12$ y, 12 y, $>12$ y), parity (nulliparous vs. multiparous), maternal prepregnancy fish intake ($<1$ once/month, at least once a month, at least twice a week), smoking status at inclusion (smoker vs. nonsmoker) and child sex. Numeric data can be found in Table S13. Note: BKMR, Bayesian kernel machine regression; BMI, body mass index; CI, confidence interval; DIA, Dominic Interactive for Adolescents; PFAS, per- and polyfluoroalkyl substances; PFDA, perfluorodecanoic acid; PFHxS, perfluorohexanesulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; PFUnDA, perfluoroundecanoic acid; PIP, posterior inclusion probabilities; SDQ, Strengths and Difficulties Questionnaire.