Exposure to perfluoroalkyl substances during fetal life and pubertal development in boys and girls from the Danish national birth cohort

Abstract

BACKGROUND: It remains unsettled whether prenatal exposure to perfluoroalkyl substances (PFASs) affects human reproductive health through potential endocrine disruption. OBJECTIVES: We aimed to explore the associations between prenatal exposure to several PFASs and various aspects of pubertal development in boys and girls. METHODS: We studied two samples (n=722 and 445) from the Puberty Cohort, nested within the Danish National Birth Cohort (DNBC), measuring PFAS in maternal plasma from early gestation. Data on pubertal development were collected biannually from the age of 11 y until full maturation, using web-based questionnaires. Outcomes were age at menarche, voice break, first ejaculation, and Tanner stages 2 to 5 for pubic hair, breast, genital development, and a combined puberty indicator. A regression model for censored data was used to estimate mean difference (months) in age at achieving the pubertal outcomes across tertiles of PFAS concentrations and with a doubling of PFAS concentrations (continuous). For perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), a meta-analysis was used to provide a weighted average of the point estimates from samples 1 and 2. RESULTS: Overall, prenatal exposure to PFOS, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PDFA) (girls) and PFHxS and PFHpS (boys) was associated with lower mean age at puberty marker onset. PFDA and PFNA exposure was associated with higher mean age at onset of puberty in boys. Nonmonotonic associations in girls (PFOS, PFHpS, PFDA) and boys (PFDA, PFNA) were observed, showing larger mean age differences for the combined puberty indicator in the middle tertile [girls: PFOS: -3:73 mo, 95% confidence interval (CI): -6:59, -0:87; PFHpS: -4:92 mo, 95% CI: -11:68, 1.85; PFDA: -3:60 mo, 95% CI: -9:03, 1.83; and boys: PFNA: 4.45 mo, 95% CI: -1:30, 10.21; PFDA: 4.59 mo, 95% CI: -0:93, 10.11] than in the highest tertile with the lowest as reference. CONCLUSIONS: Our population-based cohort study suggests sex-specific associations of altered pubertal development with prenatal exposure to PFASs. These findings are novel, and replication is needed.