PMID- 36894112 OWN - NLM STAT- MEDLINE DCOM- 20230417 LR - 20230417 IS - 1096-0953 (Electronic) IS - 0013-9351 (Linking) VI - 226 DP - 2023 Jun 1 TI - Mediating effect of endocrine hormones on association between per- and polyfluoroalkyl substances exposure and birth size: Findings from sheyang mini birth cohort study. PG - 115658 LID - S0013-9351(23)00450-4 [pii] LID - 10.1016/j.envres.2023.115658 [doi] AB - BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to affect fetus growth, but current results were inconsistent and their mechanism remained unclear. OBJECTIVES: We aimed to evaluate the associations of prenatal exposure to single and/or multiple PFAS with birth size and to elucidate whether thyroid hormones and reproductive hormones mediate these associations. METHODS: A total of 1087 mother-newborn pairs from Sheyang Mini Birth Cohort Study were included in the present cross-sectional analysis. 12 PFAS, 5 thyroid hormones and 2 reproductive hormones were measured in cord serum. Multiple linear regression models and Bayesian kernel machine regression (BKMR) models were used to examine the associations of PFAS with either birth size or endocrine hormones. One-at-a-time pairwise mediating effect analysis was applied to estimate the mediating effect of single hormone in the association between individual chemical and birth size. High-dimensional mediation approach including elastic net regularization and Bayesian shrinkage estimation were further performed to reduce exposure dimension and figure out the global mediation effects of joint endocrine hormones. RESULTS: Perfluorononanoic acid (PFNA) exposure was positively associated to weight for length z score [WLZ, per log10-unit: regression coefficient (beta) = 0.26, 95% confidence intervals (CI): 0.04, 0.47] and ponderal index (PI, beta = 0.56, 95% CI: 0.09, 1.02), and PFAS mixture results fit by BKMR model showed consistent consequences. High-dimensional mediating analyses revealed that thyroid stimulating hormone (TSH) explained 6.7% of the positive association between PFAS mixtures exposure and PI [Total effect (TE) = 1.499 (0.565, 2.405); Indirect effect (IE) = 0.105 (0.015, 0.231)]. Besides, 7.3% of the PI variance was indirectly explained by 7 endocrine hormones jointly [TE = 0.810 (0.802, 0.819); IE = 0.040 (0.038, 0.041)]. CONCLUSIONS: Prenatal PFAS mixtures exposure, especially PFNA, was positively associated to birth size. Such associations were partly mediated by cord serum TSH. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Wang, Zheng AU - Wang Z AD - School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China. FAU - Zhang, Jiming AU - Zhang J AD - School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China. FAU - Dai, Yiming AU - Dai Y AD - School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China. FAU - Zhang, Lei AU - Zhang L AD - School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China. FAU - Guo, Jianqiu AU - Guo J AD - School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China. FAU - Xu, Sinan AU - Xu S AD - School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China. FAU - Chang, Xiuli AU - Chang X AD - School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China. FAU - Wu, Chunhua AU - Wu C AD - School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China. Electronic address: chwu@shmu.edu.cn. FAU - Zhou, Zhijun AU - Zhou Z AD - School of Public Health/ MOE Key Laboratory of Public Health Safety/ NHC Key Lab of Health Technology Assessment, Fudan University, No.130 Dong'an Road, Shanghai, 200032, China. Electronic address: zjzhou@fudan.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230308 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 0 (Environmental Pollutants) RN - 0 (Thyroid Hormones) RN - 9002-71-5 (Thyrotropin) RN - 375-95-1 (perfluoro-n-nonanoic acid) RN - 0 (Fluorocarbons) RN - 0 (Alkanesulfonic Acids) SB - IM MH - Pregnancy MH - Infant, Newborn MH - Female MH - Humans MH - Cohort Studies MH - *Prenatal Exposure Delayed Effects MH - Bayes Theorem MH - Cross-Sectional Studies MH - *Environmental Pollutants/toxicity MH - Thyroid Hormones MH - Thyrotropin MH - *Fluorocarbons/toxicity MH - *Alkanesulfonic Acids OTO - NOTNLM OT - Birth size OT - Mediating effect OT - Per- and polyfluoroalkyl substances (PFAS) OT - Reproductive hormone OT - Thyroid hormone OT - Umbilical cord serum COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/03/10 06:00 MHDA- 2023/04/17 06:41 CRDT- 2023/03/09 19:35 PHST- 2023/01/09 00:00 [received] PHST- 2023/03/05 00:00 [revised] PHST- 2023/03/07 00:00 [accepted] PHST- 2023/04/17 06:41 [medline] PHST- 2023/03/10 06:00 [pubmed] PHST- 2023/03/09 19:35 [entrez] AID - S0013-9351(23)00450-4 [pii] AID - 10.1016/j.envres.2023.115658 [doi] PST - ppublish SO - Environ Res. 2023 Jun 1;226:115658. doi: 10.1016/j.envres.2023.115658. Epub 2023 Mar 8.