Long-term effects of prenatal exposure to perfluoroalkyl substances on female reproduction

Does prenatal exposure to perfluoroalkyl substances (PFASs) have long-term effects on female reproductive function?. Our results suggest an association between in utero exposure to perfluorooctanoic acid (PFOA) and delay in age of menarche. Previous cross-sectional studies have reported possible effects of PFASs on female reproduction including reduced fecundity, delayed puberty and accelerated age at menopause. Only limited data exist from follow-up studies on long-term implications of prenatal exposure to PFASs. In this study we used data from a Danish population-based cohort established in 19881989. Of 1212 eligible pregnant women, 965 participated. Follow-up was initiated in 2008 on the female offspring at 20 years of age. Three hundred and sixty seven (84) daughters answered a questionnaire and 267 (61) daughters furthermore attended clinical examinations which were conducted in 20082009. The final study population consisted of 343 daughters of which 254 had attended the clinical examinations and 89 had answered the questionnaire only. Levels of PFASs in maternal serum from pregnancy week 30 were used as a measure of prenatal exposure and related to age of menarche, menstrual cycle length, levels of reproductive hormones and follicle number of the daughters. Data were divided into three groups according to tertiles of maternal concentrations of PFASs (low, medium, high). In adjusted regression analyses, daughters exposed to higher levels of PFOA in utero had a 5.3 (95 confidence interval: 1.3; 9.3) months later age of menarche compared with the reference group of lower PFOA. Crude (P 0.05) and adjusted (P 0.01) trend tests also indicated a relationship between higher prenatal PFOA exposure and delay of menarche. We did not measure the exact amount of PFASs to which the daughters had been exposed prenatally. Instead we used PFAS concentrations in maternal serum as surrogates. However, PFASs are efficiently transferred to the fetus via placenta. Information on age of menarche was collected retrospectively but the time interval for recall in our study was relatively short (210 years). The remaining outcome measures depended on participation in clinical examination which reduced the number of observations leading to limited statistical power and risk of selection bias. Since PFASs can be detected in humans all over the world, effects of prenatal exposure on female reproductive function later in life may have wide health implications.