Association between prenatal exposure to per- and polyfluoroalkyl substances and pubertal development in boys and
Sara Lopez de Calle1, Aitana Lertxundi1, Oihane Alvarez2
1Public Health and Environmental Epidemiology Group, BIOGIPUZKOA Health Research Institute, Donostia-San Sebastian, Spain; Preventive Medicine and Public Health Department, Faculty of Medicine and Nursing, University of the Basque Country, Leioa, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Abstract:
Exposure to endocrine-disrupting chemicals (EDCs), including per- and polyfluoroalkyl substances (PFAS), has been linked to altered pubertal timing, though epidemiological findings remain inconsistent. This study examined associations between prenatal PFAS exposure and pubertal development in children. Concentrations of perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) and perfluorononanoic acid (PFNA) were quantified in maternal plasma collected during the first trimester of pregnancy in the Spanish INMA (Infancia y Medio Ambiente) cohort. Children's pubertal development was assessed longitudinally between ages 7 and 13 using the parent-reported Pubertal Development Scale (PDS), with specific scales for gonadal and adrenal development. Data were available for 492 mother-girls pairs at the 7-9-year follow up and 475 mother-boys pairs at the 11-13-year follow up based on the typical sex-specific timing of puberty. Poisson regression and Bayesian Kernel Machine Regression (BKMR) were used to estimate associations between PFAS (individually and as mixtures, respectively) and the risk of earlier puberty development (PDS stage 1 vs. 2+), adjusting for confounders. Among girls, PFHxS was associated with an increased risk of early adrenarche (Relative Risk [RR] = 1.85; 95% confidence interval [CI]: 1.05-3.25), while PFOS was inversely associated with early gonadarche RR = 0.61; 95% CI: 0.37-1.00). In boys, PFOS showed a marginal trend toward an increased risk of early overall pubertal onset (RR = 1.47; 95% CI: 0.99-2.19). Stratified analyses mainly revealed stronger associations among overweight/obese children. The mixture analysis suggested a positive trend for early adrenal development in both sexes, with significant associations in boys. Although our findings do not provide definitive evidence of a relationship between prenatal PFAS exposure and pubertal timing, they are compatible with the endocrine-disrupting potential of PFAS. The observed patterns, including possible modification by weight status and mixture signals, warrant further research.
