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Perinatal & Pediatric

Paternal and Maternal Prenatal Exposures to Per- And Polyfluoroalkyl Substances (PFAS) and Child Behavioral Difficulties at Ages 5 to 9 Years Pengfei Guo* Pengfei Guo Jiajun Luo Onyebuchi A Arah Gunnar Toft Zeyan Liew

Background Per- and polyfluoroalkyl substances (PFAS) are widespread environmental pollutants with potential developmental neurotoxicity. Prior research of prenatal PFAS exposure and offspring neurodevelopment have focused on maternal exposure with no study considering paternal PFAS exposure. Studying PFAS exposures in both parents may offer insights into the intrauterine effect from maternal exposure and the influence from unmeasured confounding. We evaluated the parent-specific associations of prenatal PFAS exposures and offspring behavioral difficulties in mid-childhood.

Methods We studied 334 father-mother-singleton triads from the INUENDO birth cohort in Greenland, Poland, and Ukraine. We measured five PFAS in matched parental serum samples collected during pregnancy (median weeks of gestation: 31). We assessed child behavioral difficulties at ages 5-9 years using the parent-rated Strength and Difficulties Questionnaire (SDQ). We conducted logistic regression analyses to estimate the parent-specific associations between log2-PFAS (ng/ml) and offspring SDQ outcomes defined using country- and sex-specific cut-offs (≥90th percentile), adjusting for spousal PFAS exposure and other confounders. We used quantile g-computation model to estimate mixture effects per quartile increase in all paternal and/or maternal PFAS.

Results Multiple maternal PFAS were associated with the total (mixture OR=2.58, 95% CI: 1.29, 5.16) and externalizing behavioral difficulties (mixture OR=2.57, 95% CI: 1.30, 5.07) in male children. Some associations between maternal individual PFAS and internalizing behaviors in female children were also noted (OR=2.18, 95% CI: 1.04, 4.58 for perfluorononanoic acid (PFNA)). In contrast, paternal exposure to each PFAS or PFAS mixture was not associated with the SDQ behavioral outcome measures in male and female children.

Discussion Prenatal exposure to maternal PFAS, but not paternal PFAS, was associated with offspring childhood behavioral difficulties in a sex-specific manner. Paternal PFAS exposure may act as a negative control indicating unmeasured confounding shared between parents is unlikely to explain the findings concerning maternal and intrauterine programming effect of PFAS exposure on offspring neurodevelopment.