Maternal plasma concentrations of perfluoroalkyl and polyfluoroalkyl substances during pregnancy and anogenital distance in male infants

STUDY QUESTION Are maternal plasma concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFASs) during pregnancy associated with anogenital distance (AGD) in male infants at birth, 6, and 12 months of age? SUMMARY ANSWER Higher maternal plasma concentrations of some PFASs were associated with shorter AGD in male infants at birth and 6 months of age. WHAT IS KNOWN ALREADY Two animal studies have found that exposure to PFASs was associated with shorter AGD in male rat fetuses and wild male minks. There is only one human study on the topic that did not identify consistent patterns between maternal serum concentrations of PFASs during pregnancy and AGD in male infants. STUDY DESIGN, SIZE, DURATION In the prospective cohort study, a total of 1292 eligible pregnant women were recruited at 12–16 weeks of gestation between April and December 2012 at the Maternal and Child Health Hospital of Minhang district in Shanghai, China. At delivery, 667 male singletons were born. They were then followed up at birth (n = 439) and at 6 (n = 411) and 12 months (n = 376) of age when anopenile distance (AGDAP) and anoscrotal distance (AGDAS) were measured. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 500 male infants who had both maternal plasma concentrations of PFASs and at least one AGD measurement of at three time points were included in the present study. Multiple linear regression models were used to evaluate the potential linear associations between maternal concentrations of PFASs and AGD. MAIN RESULTS AND THE ROLE OF CHANCE Maternal plasma concentrations (ln-transformed) of perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA) were inversely associated with AGDAS or AGDAP at birth (AGDAS: per ln unit increase in PFAS concentrations: β (95% CI): −0.65 (−1.27 to −0.02) mm for PFOS; −0.58 (−1.11 to −0.06) mm for PFDA; and −0.57 (−1.09 to −0.06) mm for PFUdA; AGDAP: per ln unit increase in PFAS concentrations: β (95% CI): −0.63 (−1.24 to −0.01) mm for PFDA and − 0.76 (−1.36 to −0.16) mm for PFUdA). At 6 months of age, per unit increase in maternal ln concentrations of PFOS and perfluorotridecanoic acid (PFTrDA), AGDAS decreased on average by −2.21 (95% CI: −4.28 to −0.14) and −1.11 (95% CI: −2.17 to −0.06) mm, respectively. Additionally, ln-transformed perfluorooctanoic acid (PFOA) showed nonsignificant but inverse associations with both AGDAS and AGDAP at 6 months of age. We found no significant associations between ln-transformed maternal concentrations of PFASs and either AGDAS or AGDAP at 12 months of age. However, significantly inverse association of ln-transformed PFOA with AGDAP was observed in male infants who never or shortly breastfed (<3 months) at 12 months of age. LIMITATIONS, REASONS FOR CAUTION AGD measurements were performed by different examiners at each follow-up visit, and the intra-examiner variation was not assessed, which might cause intra-rater and inter-rater measurement errors. Additionally, our study may have selection bias since a considerable number of participants withdrew from the cohort although the differences in demographic characteristics were not statistically significant between included mother–infant pairs and those excluded. No statistical correction was made for multiple comparisons. WIDER IMPLICATIONS OF THE FINDINGS Our findings may have important implications for the early development of genital health in male infants since PFASs can be detected in almost all pregnant women and infants worldwide. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the National Key Research and Development program of China (2018YFC1002801 and 2016YFC1000505), the Science and Technology Commission of Shanghai Municipality (16ZR1430100), the National Natural Science Foundation of China (81428011), and the Innovation-Oriented Science and Technology Grant from National Health Commission Key Laboratory of Reproduction Regulation (CX2017-06). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.