Prenatal exposure to legacy PFAS and neurodevelopment in preschool-aged Canadian children: The MIREC cohort.

BACKGROUND: Exposure to perfluoroalkyl substances (PFAS) has been shown to be neurotoxic in experimental studies, but epidemiological evidence linking prenatal PFAS exposure to child neurodevelopment is equivocal and scarce. OBJECTIVE: To quantify associations between prenatal exposure to legacy PFAS and children's intelligence (IQ) and executive functioning (EF) in a Canadian pregnancy and birth cohort and to determine if these associations differ by child sex. METHODS: We measured first-trimester plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) in the Maternal-Infant Research on Environmental Chemicals (MIREC) study and assessed children's full-scale (n = 522), performance (n = 517), and verbal (n = 519) IQ using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Children's working memory (n = 513) and ability to plan and organize (n = 514) were assessed using a parent-reported questionnaire, the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P). We quantified associations between individual log2-transformed PFAS exposure and children's IQ and EF using multiple linear regression analyses and evaluated effect modification by child sex. We also used Repeated Holdout Weighted Quantile Sum (WQS) regression models with effect modification by child sex to quantify the effect of combined exposure to all three PFAS chemicals on IQ and EF. All models were adjusted for key sociodemographic characteristics. RESULTS: Geometric mean plasma concentrations (IQR) for PFOA, PFOS and PFHxS were 1.68 (1.10-2.50), 4.97 (3.20-6.20) and 1.09 (0.67-1.60) µg/L respectively. We found evidence of effect modification by child sex in all models examining performance IQ (p < .01). Specifically, every doubling of PFOA, PFOS, and or PFHxS was inversely associated with performance IQ, but only in males (PFOA: B = -2.80, 95% CI: -4.92, -0.68; PFOS: B = -2.64, 95% CI: -4.77, -0.52; PFHxS: B = -2.92, 95% CI: -4.72, -1.12). Similarly, every quartile increase in the WQS index was associated with poorer performance IQ in males (B = -3.16, 95% CI: -4.90, -1.43), with PFHxS contributing the largest weight to the index. In contrast, no significant association was found for females (B = 0.63, 95% CI: -0.99, 2.26). No significant associations were found for EF in either males or females. CONCLUSIONS: Higher prenatal PFAS exposure was associated with lower performance IQ in males, suggesting that this association may be sex- and domain-specific.

Effect of a new concussion substitute rule on medical assessment of head collision events in Premier League football.

OBJECTIVE: To investigate the utilisation of additional permanent concussion substitutes (APCSs) and its efficacy with regards to rate and duration of medical assessment of head collision events (HCEs) in the 2020-2021 Premier League season. The present APCS rule allows players with a suspected concussion to be removed from a match without counting towards a team's allocated substitutions. METHODS: Eighty Premier League matches, 40 prior to additional permanent concussion substitutes implementation (Pre-APCS) and 40 after (Post-APCS), were randomly selected and analysed by a team of trained reviewers for HCEs. Data on HCE incidence, rates of medical assessment, duration of medical assessment and return to play were collected for each match. Data for the Pre-APCS and Post-APCS groups were compared to analyse differences in assessment of HCEs. RESULTS: During the 2020-2021 Premier League season, three APCSs were used. There were 38 HCEs identified in the Pre-APCS group (0.95 per match, 28.79 per 1000 athlete-hours of exposure) and 42 in the Post-APCS group (1.05 per match, 31.82 per 1000 athlete-hours of exposure). Incidence of HCEs (p=0.657), rates of medical assessment (23.7% Pre-APCS vs 21.4% Post-APCS; p=0.545) and duration of medical assessment (median 81 s Pre-APCS vs 102 s Post-APCS; p=0.466) did not significantly differ between the two groups. CONCLUSIONS: The implementation of APCSs in the Premier League did not impact the rate or duration of medical assessement of HCEs. Despite the introduction of APCSs, the consensus protocols for HCE assessment were rarely followed. We recommend changes to APCS and its implementation that would be aimed at protecting player health.