In utero PFAS exposure, inflammation, and behavioral problems in childhood.

BACKGROUND

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been posited to be harmful for neurodevelopment; however, researchers have not yet examined its influence on behavioral problems longitudinally across childhood or the immunological underpinnings of these links.

METHODS

This birth-cohort study followed 264 Singaporean mother-infant dyads from the prenatal period to 10.5 years post-delivery. Concentrations of 9 PFAS and 3 inflammatory markers were assayed from umbilical cord blood. Internalizing and externalizing problems were assessed using the Child Behavior Checklist when children were ages 2, 3, 4, 7, and 10.5 years. Linear mixed effect models estimated the associations of PFAS with children's internalizing and externalizing problems as children aged. For the PFAS that were significantly associated with children's behavioral problems, we tested whether levels of inflammatory cytokines statistically mediated the associations.

RESULTS

Higher cord blood concentrations of PFNA, PFDA and PFUnDA were associated with more severe internalizing problems at 2 years of age (PFNA: B = 1.65 [0.60, 2.71]; PFDA: B = 1.85 [0.81, 2.89]; PFUnDA: B = 1.26 [0.27, 2.25]). Two of these associations (PFNA, PFDA) weakened significantly as children aged (PFNA: B = -0.26 [-0.44, -0.08]; PFDA: B = -0.35 [-0.52, -0.17]). Higher levels of cord blood interleukin (IL)-6 mediated the association of PFNA with internalizing problems (B = 0.25 [0.01, 0.58]).

CONCLUSION

Greater in utero exposure to three types of PFAS was related to more severe internalizing problems from two to four years of age, with associations attenuated after 7 years of age. Inflammation may be one pathway through which PFAS influence development, although replication is warranted.