Associations of gestational perfluoroalkyl substances exposure with early childhood BMI Z-scores and risk of overweight/obesity: results from the ECHO cohorts

BACKGROUND AND AIM: Gestational per- and polyfluoroalkyl substances (PFAS) exposure may be associated with adiposity and increased risk of obesity among children and adolescents. However, results from prospective cohort studies evaluating associations between gestational PFAS and child adiposity are inconsistent. We estimated the associations of PFAS concentrations in pregnancy with child BMI z-scores and risk of overweight/obesity. METHODS: We used data from 1,391 mother-child pairs that enrolled in eight Environmental Influences on Child Health Outcomes (ECHO) cohort studies. We quantified concentrations of seven PFAS in maternal plasma or serum in pregnancy. We measured child weight and height between ages 2-5 years and calculated age- and sex-specific body mass index (BMI) z-scores. We estimated associations of individual PFAS and their mixture with repeated child BMI z-scores and risk of overweight/obesity using linear mixed models, modified Poisson regression models, and two Bayesian approaches for mixtures. We explored whether child sex modified these associations. RESULTS: Overall, gestational PFAS were associated with slightly higher BMI z-scores and risk of overweight/obesity. For instance, adjusting for covariates, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI z-scores at age 2-5 years (β=0.06, 95%CI: 0.01, 0.11). Each doubling in perfluroundecanoic acid (RR=1.10, 95%CI: 1.04, 1.16) and N-methyl perfluorooctane sulfonamido acetic acid (RR=1.06, 95%CI: 1.00, 1.10) were associated with increased risk of overweight/obesity, with some evidence of a monotonic dose-response relation. We found no mixture effect of PFAS on child BMI z-scores or the risk of being overweight/obese. These associations did not differ by child sex. CONCLUSIONS: In eight US-based prospective cohorts, higher gestational concentrations of PFAS were associated with subtly higher childhood BMI z-score and risk of overweight or obesity. Future ECHO studies should evaluate the associations between PFAS concentrations in pregnancy and related cardiometabolic health outcomes in children. KEYWORDS: PFAS; pregnancy; BMI; ECHO