PMID- 32069748 OWN - NLM STAT- MEDLINE DCOM- 20200909 LR - 20200909 IS - 1096-0953 (Electronic) IS - 0013-9351 (Linking) VI - 182 DP - 2020 Mar TI - Metabolomics study and meta-analysis on the association between maternal pesticide exposome and birth outcomes. PG - 109087 LID - S0013-9351(19)30883-7 [pii] LID - 10.1016/j.envres.2019.109087 [doi] AB - BACKGROUND: Pregnant women are exposed to a number of pesticides which are widely used in China. Their potential risks on reproduction and infants are still unknown. OBJECTIVE: We aimed to investigate whether infant's birth weight and length of gestation were associated with levels of various pesticides in maternal blood based on Nanjing Medical University (NMU) affiliated hospitals data and meta-analysis, and also to explore the possible intermediate metabolomics pathways. METHODS: Eligible subjects (n = 102) were included in this study from the affiliated hospitals of NMU. Gas chromatography tandem mass spectrometry (GC/MS) and Q-Exactive mass spectrometer (QE) were used to detect 37 pesticides (9 organophosphorus pesticides, 7 organochlorine pesticides, 5 carbamate pesticides, and 16 others) and 161 metabolites (53 in animo acid metabolism 47 in lipid metabolism, 18 in carbohydrate metabolism, 14 in nucleotide metabolism and 29 in other metabolisms) in maternal blood, respectively. Multi-linear regression and Bayesian kernel machine regression (BKMR) were performed to identify the association of single/mixed pesticide exposure in maternal blood with birth weight and length of gestation. Moreover, we conducted a meta-analysis including additional 2497 subjects to evaluate whether exposure to key pesticide, beta-hexachlorocyclohexane (beta-HCH) was associated with decreased birth weight globally. Mediation analysis was used to explore the metabolic alteration mediating the association between key pesticide exposure and birth outcomes. RESULTS: We found that decreased birth weight was significantly associated with increasing levels of mecarbam and beta-HCH. We did not find any association between length of gestation and these pesticides. Among pesticides with detection rate more than 50%, BKMR analysis found an overall negative association of mixed pesticides exposure with birth weight, and verified that beta-HCH was the key pesticide for such effect. Meta-analysis revealed a significantly negative association between exposure to beta-HCH and birth weight. Metabolomics identified three metabolites and five metabolites as significant mediators for the effect of mecarbam and beta-HCH, respectively, among which glyceraldehyde and its related glycerolipid metabolism and thyroxine and its related thyroid hormone metabolism were found to be the mostly enriched mediating metabolic pathway. CONCLUSIONS: Based on the comprehensive pesticide exposome and metabolome wide associational study combined with meta-analysis, we found that prenatal exposure to beta-HCH and mecarbam decreased birth weight via disrupting thyroid hormone metabolism and glyceraldehyde metabolism, providing new insights into the toxic effects of exposure to pesticides on birth outcomes. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Yang, Xu AU - Yang X AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Zhang, Mingzhi AU - Zhang M AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Lu, Ting AU - Lu T AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Chen, Shiyao AU - Chen S AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Sun, Xian AU - Sun X AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Guan, Yusheng AU - Guan Y AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Zhang, Yiyun AU - Zhang Y AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Zhang, Ting AU - Zhang T AD - Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, 214002, China. FAU - Sun, Rongli AU - Sun R AD - Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China. FAU - Hang, Bo AU - Hang B AD - Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. FAU - Wang, Xinru AU - Wang X AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Chen, Minjian AU - Chen M AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. Electronic address: minjianchen@njmu.edu.cn. FAU - Chen, Ying AU - Chen Y AD - Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, 214002, China. Electronic address: yingchen8@163.com. FAU - Xia, Yankai AU - Xia Y AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. Electronic address: yankaixia@njmu.edu.cn. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20191231 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 0 (Pesticides) RN - 0 (Thyroid Hormones) SB - IM MH - Bayes Theorem MH - *Birth Weight MH - China MH - *Exposome MH - Female MH - Gas Chromatography-Mass Spectrometry MH - Humans MH - *Maternal Exposure MH - *Metabolomics MH - *Pesticides/toxicity MH - Pregnancy MH - *Pregnancy Outcome MH - Thyroid Hormones/metabolism OTO - NOTNLM OT - Birth outcomes OT - Hexachlorocyclohexane OT - Mecarbam OT - Metabolomics OT - Pesticides COIS- Declaration of competing interest None of the authors have a conflict of interest pertaining to this work. EDAT- 2020/02/20 06:00 MHDA- 2020/09/10 06:00 CRDT- 2020/02/20 06:00 PHST- 2019/10/10 00:00 [received] PHST- 2019/12/22 00:00 [revised] PHST- 2019/12/23 00:00 [accepted] PHST- 2020/02/20 06:00 [entrez] PHST- 2020/02/20 06:00 [pubmed] PHST- 2020/09/10 06:00 [medline] AID - S0013-9351(19)30883-7 [pii] AID - 10.1016/j.envres.2019.109087 [doi] PST - ppublish SO - Environ Res. 2020 Mar;182:109087. doi: 10.1016/j.envres.2019.109087. Epub 2019 Dec 31.