{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:59:51Z","timestamp":1791950391155,"version":"4.3.4"},"reference-count":131,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"crossref","award":["HRZZ-IP-2016-06-1998"],"award-info":[{"award-number":["HRZZ-IP-2016-06-1998"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["533-03-23-0006"],"award-info":[{"award-number":["533-03-23-0006"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Developmental programming, shaped by environmental and lifestyle stressors during prenatal life, is increasingly recognized as a major contributor to non-communicable diseases (NCDs) later in life. Oxidative stress, one of key mechanisms linking these stressors to fetal metabolomic reprogramming and disease pathogenesis, leaves measurable metabolomic signatures that reflect disrupted redox balance. Alterations in glucose, lipid, and amino acid metabolism and antioxidant response could reveal the main pathways driving NCD development. This review summarizes epidemiological studies that have investigated biochemical responses of the prenatal exposure to metals, air pollution, and tobacco smoke and e-cigarette vapor in maternal\u2013placental\u2013fetal compartments using a metabolomic approach. Summarized studies indicate that maternal exposure to metals primarily disrupts amino acid pathways related to one-carbon metabolism, glutathione synthesis, and oxidative stress defense, while air pollution, particularly fine particulate matter, mainly affects lipid oxidation, fatty acid \u03b2-oxidation, and amino acid and carbohydrate metabolism. Tobacco smoke and e-cigarette vapor induce widespread disturbances involving reduced citric acid cycle intermediates, altered acylcarnitines and phospholipids, and impaired antioxidant capacity, collectively promoting oxidative damage and inflammatory signaling. The identification of these metabolome alterations might contribute to a deeper understanding of the toxicity and biological impact of environmental stressors on offspring health. These results may eventually lead to the identification of early biomarkers and to the development of therapeutic strategies aimed at reducing NCD risk.<\/jats:p>","DOI":"10.3390\/antiox14121442","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T09:34:37Z","timestamp":1764581677000},"page":"1442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Oxidative Stress-Related Metabolomic Alterations in Pregnancy: Evidence from Exposure to Air Pollution, Metals\/Metalloid, and Tobacco Smoke"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0216-0166","authenticated-orcid":false,"given":"Alica","family":"Pizent","sequence":"first","affiliation":[{"name":"Division of Occupational and Environmental Health, Institute for Medical Research and Occupational Health, Ksaverska Cesta 2, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.clnesp.2024.10.155","article-title":"Nutritional requirements in pregnancy and lactation","volume":"64","author":"Talebi","year":"2024","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1002\/oby.23224","article-title":"Maternal adaptations to food intake across pregnancy: Central and peripheral mechanisms","volume":"29","author":"Clarke","year":"2021","journal-title":"Obesity"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Morrison, J.L., and Regnault, T.R. (2016). Nutrition in pregnancy: Optimising maternal diet and fetal adaptations to altered nutrient supply. Nutrients, 8.","DOI":"10.3390\/nu8060342"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tain, Y.L., and Hsu, C.N. (2024). Amino acids during pregnancy and offspring cardiovascular-kidney-metabolic health. Nutrients, 16.","DOI":"10.3390\/nu16091263"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Agarwal, A., Aponte-Mellado, A., Premkumar, B.J., Shaman, A., and Gupta, S. (2012). The effects of oxidative stress on female reproduction: A review. Reprod. Biol. Endocrinol., 10.","DOI":"10.1186\/1477-7827-10-49"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00418-004-0677-x","article-title":"Oxidative stress in the placenta","volume":"122","author":"Myatt","year":"2004","journal-title":"Histochem. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vornic, I., Buciu, V., Furau, C.G., Gaje, P.N., Ceausu, R.A., Dumitru, C.S., Barb, A.C., Novacescu, D., Cumpanas, A.A., and Latcu, S.C. (2024). Oxidative stress and placental pathogenesis: A contemporary overview of potential biomarkers and emerging therapeutics. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202410.0912.v1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/aji.12454","article-title":"Oxidative stress: Placenta function and dysfunction","volume":"76","author":"Wu","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ruano, C.S.M., Miralles, F., M\u00e9hats, C., and Vaiman, D. (2022). The impact of oxidative stress of environmental origin on the onset of placental diseases. Antioxidants, 11.","DOI":"10.3390\/antiox11010106"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Rodr\u00edguez, P., Ramiro-Cortijo, D., Reyes-Hern\u00e1ndez, C.G., L\u00f3pez de Pablo, A.L., Gonz\u00e1lez, M.C., and Arribas, S.M. (2018). Implication of oxidative stress in fetal programming of cardiovascular disease. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00602"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/10937404.2013.775048","article-title":"Environmental contaminant exposures and preterm birth: A comprehensive review","volume":"16","author":"Ferguson","year":"2013","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/bdrc.21137","article-title":"The effect of maternal exposure to endocrine disrupting chemicals on fetal and neonatal development: A review on the major concerns","volume":"108","author":"Mallozzi","year":"2016","journal-title":"Birth Defects Res. Part C Embryo Today"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Street, M.E., and Bernasconi, S. (2020). Endocrine-disrupting chemicals in human fetal growth. Int. J. Mol. Sci., 21.","DOI":"10.37247\/PAMB.1.2020.42"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s12978-021-01257-x","article-title":"The role of oxidative stress in patients with recurrent pregnancy loss: A review","volume":"18","author":"Zejnullahu","year":"2021","journal-title":"Reprod. Health"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Grzeszczak, K., \u0141anocha-Arendarczyk, N., Malinowski, W., Zi\u0119tek, P., and Kosik-Bogacka, D. (2023). Oxidative stress in pregnancy. Biomolecules, 13.","DOI":"10.20944\/preprints202310.1578.v1"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.placenta.2024.11.005","article-title":"Understanding the impact of placental oxidative and nitrative stress in pregnancies complicated by fetal growth restriction","volume":"158","author":"Brooker","year":"2024","journal-title":"Placenta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.reprotox.2010.12.055","article-title":"Prenatal environmental exposures, epigenetics, and disease","volume":"31","author":"Perera","year":"2011","journal-title":"Reprod. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"582748","DOI":"10.1155\/2012\/582748","article-title":"Impact of oxidative stress in fetal programming","volume":"2012","author":"Thompson","year":"2012","journal-title":"J. Pregnancy"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"59819","DOI":"10.1007\/s11356-024-35016-9","article-title":"Effect of environmental air pollutants on placental function and pregnancy outcomes: A molecular insight","volume":"31","author":"Singh","year":"2024","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sun, C., Shen, J., Fang, R., Huang, H., Lai, Y., Hu, Y., and Zheng, J. (2025). The impact of environmental and dietary exposure on gestational diabetes mellitus: A comprehensive review emphasizing the role of oxidative stress. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1393883"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/bs.acc.2017.12.006","article-title":"Distribution of fatty acids and lipids during pregnancy","volume":"84","author":"Rani","year":"2018","journal-title":"Adv. Clin. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Duttaroy, A.K., and Basak, S. (2022). Maternal fatty acid metabolism in pregnancy and its consequences in the feto-placental development. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.787848"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"139626","DOI":"10.1016\/j.scitotenv.2020.139626","article-title":"Early-life exposure to widespread environmental toxicants and maternal-fetal health risk: A focus on metabolomic biomarkers","volume":"739","author":"Dai","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12940-025-01162-x","article-title":"Maternal metabolomics linking prenatal exposure to fine particulate matter and birth weight: A cross-sectional analysis of the MADRES cohort","volume":"24","author":"Chen","year":"2025","journal-title":"Environ. Health"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"134717","DOI":"10.1016\/j.jhazmat.2024.134717","article-title":"Metabolic signatures of prenatal exposure to \u2018cocktails\u2019 of benzotriazoles and benzothiazoles and its health implications","volume":"473","author":"Zhou","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ore\u0161i\u010d, M., McGlinchey, A., Wheelock, C.E., and Hy\u00f6tyl\u00e4inen, T. (2020). Metabolic signatures of the exposome\u2014Quantifying the impact of exposure to environmental chemicals on human health. Metabolites, 10.","DOI":"10.3390\/metabo10110454"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s40572-020-00284-3","article-title":"Air pollution and adverse pregnancy and birth outcomes: Mediation analysis using metabolomic profiles","volume":"7","author":"Inoue","year":"2020","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.3390\/ijms12106469","article-title":"Metabolomics of oxidative stress in recent studies of endogenous and exogenously administered intermediate metabolites","volume":"12","author":"Liu","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12953-025-00241-8","article-title":"Mass-spectrometry based metabolomics: An overview of workflows, strategies, data analysis and applications","volume":"23","author":"Hajnajafi","year":"2025","journal-title":"Proteome Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.redox.2017.08.009","article-title":"Short overview on metabolomics approach to study pathophysiology of oxidative stress in cancer","volume":"14","author":"Andrisic","year":"2018","journal-title":"Redox Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"DeFreitas, M.J., Katsoufis, C.P., Benny, M., Young, K., Kulandavelu, S., Ahn, H., Sfakianaki, A., and Abitbol, C.L. (2022). Educational review: The impact of perinatal oxidative stress on the developing kidney. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.853722"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9962860","DOI":"10.1155\/2021\/9962860","article-title":"The role of oxidative stress and antioxidant balance in pregnancy","volume":"2021","author":"Hussain","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9174521","DOI":"10.1155\/2019\/9174521","article-title":"New insights into the process of placentation and the role of oxidative uterine microenvironment","volume":"2019","author":"Mendes","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/1440-1681.13172","article-title":"Placental mitochondria and reactive oxygen species in the physiology and pathophysiology of pregnancy","volume":"47","author":"Fisher","year":"2020","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"454","DOI":"10.3906\/sag-1311-72","article-title":"Malondialdehyde and nitric oxide levels and catalase, superoxide dismutase, and glutathione peroxidase levels in maternal blood during different trimesters of pregnancy and in the cord blood of newborns","volume":"45","year":"2015","journal-title":"Turk. J. Med. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhang, C., Guo, Y., Yang, Y., Du, Z., Fan, Y., Zhao, Y., and Yuan, S. (2023). Oxidative stress on vessels at the maternal-fetal interface for female reproductive system disorders: Update. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1118121"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.siny.2008.09.004","article-title":"Normal and abnormal maternal metabolism during pregnancy","volume":"14","author":"Hadden","year":"2009","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Parrettini, S., Caroli, A., and Torlone, E. (2020). Nutrition and metabolic adaptations in physiological and complicated pregnancy: Focus on obesity and gestational diabetes. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.611929"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1097\/GRF.0b013e31815a5494","article-title":"Metabolic changes in pregnancy","volume":"50","author":"Lain","year":"2007","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1256S","DOI":"10.1093\/ajcn\/71.5.1256s","article-title":"Carbohydrate and lipid metabolism in pregnancy: Normal compared with gestational diabetes mellitus","volume":"71","author":"Butte","year":"2000","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Li, S., Zhu, J., Zhao, Y., An, P., Zhao, H., and Xiong, Y. (2025). Metabolic disorder of nutrients\u2014An emerging field in the pathogenesis of preeclampsia. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1560610"},{"key":"ref_42","unstructured":"Feingold, K.R., Ahmed, S.F., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., and Dungan, K. (2025, October 09). Effect of pregnancy on lipid metabolism and lipoprotein levels, Endotext [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK498654\/."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6018","DOI":"10.7150\/ijbs.103404","article-title":"Fatty acid metabolism disruptions: A subtle yet critical factor in adverse pregnancy outcomes","volume":"20","author":"Cao","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2478\/aiht-2018-69-2966","article-title":"Glutathionylation: A regulatory role of glutathione in physiological processes","volume":"69","author":"Dominko","year":"2018","journal-title":"Arh. Hig. Rada Toksikol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Pizent, A., Lazarus, M., Kova\u010di\u0107, J., Tariba Lovakovi\u0107, B., Br\u010di\u0107 Kara\u010donji, I., \u017divkovi\u0107 Semren, T., Sekovani\u0107, A., Orct, T., Branovi\u0107-\u010cakani\u0107, K., and Brajenovi\u0107, N. (2020). Cigarette smoking during pregnancy: Effects on antioxidant enzymes, metallothionein and trace elements in mother-newborn pairs. Biomolecules, 10.","DOI":"10.3390\/biom10060892"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.toxrep.2023.04.010","article-title":"Disease-associated metabolic pathways affected by heavy metals and metalloid","volume":"10","author":"Haidar","year":"2023","journal-title":"Toxicol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2478\/10004-1254-63-2012-2151","article-title":"Reproductive toxicity of metals in men","volume":"63","author":"Pizent","year":"2012","journal-title":"Arh. Hig. Rada Toksikol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s10354-012-0074-3","article-title":"The role of the placenta in fetal exposure to heavy metals","volume":"162","author":"Gundacker","year":"2012","journal-title":"Wien. Med. Wochenschr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2478\/intox-2019-0001","article-title":"The pathway of lead through the mother\u2019s body to the child","volume":"12","year":"2019","journal-title":"Interdiscip. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Dack, K., Fell, M., Taylor, C.M., Havdahl, A., and Lewis, S.J. (2022). Prenatal mercury exposure and neurodevelopment up to the age of 5 years: A systematicrReview. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19041976"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.placenta.2024.12.019","article-title":"Arsenic and the placenta: A review with emphasis on the immune system","volume":"160","author":"Rychlik","year":"2025","journal-title":"Placenta"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"108854","DOI":"10.1016\/j.envres.2019.108854","article-title":"Exposure to 17 trace metals in pregnancy and associations with urinary oxidative stress biomarkers","volume":"179 Pt B","author":"Kim","year":"2019","journal-title":"Environ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Piasek, M., \u0160krgati\u0107, L., Sulimanec, A., Orct, T., Sekovani\u0107, A., Kova\u010di\u0107, J., Kati\u0107, A., Branovi\u0107 \u010cakani\u0107, K., Pizent, A., and Brajenovi\u0107, N. (2023). Effects of maternal cigarette smoking on trace element levels and steroidogenesis in the maternal-placental-fetal unit. Toxics, 11.","DOI":"10.3390\/toxics11080714"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3109\/15376516.2011.557878","article-title":"Epigenetic mechanisms in metal toxicity","volume":"21","author":"Fragou","year":"2011","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kurita, H., Ohuchi, K., and Inden, M. (2025). Effects of environmental non-essential toxic heavy metals on epigenetics during development. Toxics, 13.","DOI":"10.3390\/toxics13030167"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Dettwiler, M., Flynn, A.C., and Rigutto-Farebrother, J. (2023). Effects of non-essential \u201ctoxic\u201d trace elements on pregnancy outcomes: A narrative overview of recent literature syntheses. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20085536"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"168380","DOI":"10.1016\/j.scitotenv.2023.168380","article-title":"Exposure to metal mixtures and adverse pregnancy and birth outcomes: A systematic review","volume":"908","author":"Issah","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.ijheh.2019.02.007","article-title":"Environmental cadmium exposure induces alterations in the urinary metabolic profile of pregnant women","volume":"222","author":"Li","year":"2019","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"115611","DOI":"10.1016\/j.ecoenv.2023.115611","article-title":"Environmental concentrations of cadmium and zinc and associating metabolomics profile alternations in urine of pregnant women in the first trimester: A prospective cohort study in Taiyuan, North China","volume":"267","author":"Li","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s12940-021-00810-2","article-title":"Lead exposure and serum metabolite profiles in pregnant women in Mexico City","volume":"20","author":"Niedzwiecki","year":"2021","journal-title":"Environ. Health"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.chroma.2016.12.007","article-title":"Urinary metabolomics revealed arsenic exposure related to metabolic alterations in general Chinese pregnant women","volume":"1479","author":"Li","year":"2017","journal-title":"J. Chromatogr. A"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"164761","DOI":"10.1016\/j.scitotenv.2023.164761","article-title":"Metabolic biomarkers linking urinary arsenic species to gestational diabetes mellitus: A cross-sectional study in Chinese pregnant women","volume":"892","author":"Zhang","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7769","DOI":"10.1021\/cr300015c","article-title":"Arsenic binding to proteins","volume":"113","author":"Shen","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-nutr-082117-051757","article-title":"Nutritional influences on one-carbon metabolism: Effects on arsenic methylation and toxicity","volume":"38","author":"Saxena","year":"2018","journal-title":"Annu. Rev. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1021\/acs.est.6b04374","article-title":"Neonatal metabolomic profiles related to prenatal arsenic exposure","volume":"51","author":"Laine","year":"2017","journal-title":"Environ. Sci. Technol."},{"key":"ref_66","first-page":"459","article-title":"Interactions of essential and\/or toxic metals and metalloid regarding interindividual differences in susceptibility to various toxicants and chronic diseases in man","volume":"46","year":"1995","journal-title":"Arh. Hig. Rada Toksikol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"106373","DOI":"10.1016\/j.envint.2020.106373","article-title":"Prenatal exposure to multiple metals and birth outcomes: An observational study within the National Children\u2019s Study cohort","volume":"147","author":"Shih","year":"2021","journal-title":"Environ. Int."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"106976","DOI":"10.1016\/j.envint.2021.106976","article-title":"A metabolome-wide association study of in utero metal and trace element exposures with cord blood metabolome profile: Findings from the Boston Birth Cohort","volume":"158","author":"Zhang","year":"2022","journal-title":"Environ. Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/978-3-319-41334-1_8","article-title":"Piperine and its role in chronic diseases","volume":"928","author":"Derosa","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/j.1751-7176.2011.00489.x","article-title":"Role of mercury toxicity in hypertension, cardiovascular disease, and stroke","volume":"13","author":"Houston","year":"2011","journal-title":"J. Clin. Hypertens."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s12012-025-09966-6","article-title":"Mercury-mediated cardiovascular toxicity: Mechanisms and remedies","volume":"25","author":"Amin","year":"2025","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Kim, C., Ashrap, P., Watkins, D.J., Mukherjee, B., Rosario-Pab\u00f3n, Z.Y., V\u00e9lez-Vega, C.M., Alshawabkeh, A.N., Cordero, J.F., and Meeker, J.D. (2022). Maternal metals\/metalloid blood levels are associated with lipidomic profiles among pregnant women in Puerto Rico. Front. Public Health, 9.","DOI":"10.3389\/fpubh.2021.754706"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"108183","DOI":"10.1016\/j.envint.2023.108183","article-title":"Association of maternal metals exposure, metabolites and birth outcomes in newborns: A prospective cohort study","volume":"179","author":"Zhao","year":"2023","journal-title":"Environ. Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1038\/s41467-025-57253-3","article-title":"Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways","volume":"16","author":"Xie","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Anesti, O., Papaioannou, N., Gabriel, C., Karakoltzidis, A., Dzhedzheia, V., Petridis, I., Stratidakis, A., Dickinson, M., Horvat, M., and Snoj Tratnik, J. (2023). An exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopment. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.871218"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1039\/C8TX00042E","article-title":"Urinary metabolomics reveals novel interactions between metal exposure and amino acid metabolic stress during pregnancy","volume":"7","author":"Wang","year":"2018","journal-title":"Toxicol. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"138107","DOI":"10.1016\/j.scitotenv.2020.138107","article-title":"A metabolomic study on the association of exposure to heavy metals in the first trimester with primary tooth eruption","volume":"723","author":"Wu","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_78","first-page":"1","article-title":"Particle characteristics responsible for effects on human lung epithelial cells","volume":"110","author":"Aust","year":"2002","journal-title":"Res. Rep. Health Eff. Inst."},{"key":"ref_79","first-page":"5","article-title":"A global perspective of fine particulate matter pollution and its health effects","volume":"244","author":"Mukherjee","year":"2018","journal-title":"Rev. Environ. Contam. Toxicol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1039\/D2EA00043A","article-title":"The oxidative potential of particulate matter (PM) in different regions around the world and its relation to air pollution sources","volume":"2","author":"Farahani","year":"2022","journal-title":"Environ. Sci. Atmos."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"175542","DOI":"10.1016\/j.scitotenv.2024.175542","article-title":"Associations of air pollutants and related metabolites with preterm birth during pregnancy","volume":"951","author":"Zheng","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10905","DOI":"10.1021\/acs.est.5c02071","article-title":"Unraveling the molecular links between fine particulate matter exposure and early birth risks in African American mothers: A metabolomics study in the Atlanta African American Maternal-Child Cohort","volume":"59","author":"Li","year":"2025","journal-title":"Environ. Sci. Technol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Parthasarathy, A., Cross, P.J., Dobson, R.C.J., Adams, L.E., Savka, M.A., and Hudson, A.O. (2018). A three-ring circus: Metabolism of the three proteogenic aromatic amino acids and their role in the health of plants and animals. Front. Mol. Biosci., 5.","DOI":"10.3389\/fmolb.2018.00029"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"117891","DOI":"10.1016\/j.ecoenv.2025.117891","article-title":"The effect of PM2.5 exposure on placenta and its associated metabolites: A birth cohort study","volume":"292","author":"Wang","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"104872","DOI":"10.1016\/j.envint.2019.05.066","article-title":"Maternal serum metabolome and traffic-related air pollution exposure in pregnancy","volume":"130","author":"Yan","year":"2019","journal-title":"Environ. Int."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"110823","DOI":"10.1016\/j.envres.2021.110823","article-title":"Metabolomics analysis of maternal serum exposed to high air pollution during pregnancy and risk of autism spectrum disorder in offspring","volume":"196","author":"Kim","year":"2021","journal-title":"Environ. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.bbadis.2013.02.001","article-title":"Branched-chain amino acids influence the immune properties of microglial cells and their responsiveness to pro-inflammatory signals","volume":"1832","author":"Vissicchio","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00726-016-2332-y","article-title":"Body fluid levels of neuroactive amino acids in autism spectrum disorders: A review of the literature","volume":"49","author":"Zheng","year":"2017","journal-title":"Amino Acids"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6400","DOI":"10.1021\/acs.est.4c10717","article-title":"Pregnancy as a susceptible period to ambient air pollution exposure on the maternal postpartum metabolome","volume":"59","author":"Petrick","year":"2025","journal-title":"Environ. Sci. Technol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"147604","DOI":"10.1016\/j.scitotenv.2021.147604","article-title":"PM2.5 exposure exaggerates the risk of adverse birth outcomes in pregnant women with pre-existing hyperlipidemia: Modulation role of adipokines and lipidome","volume":"787","author":"Zhang","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"111907","DOI":"10.1016\/j.envres.2021.111907","article-title":"Child serum metabolome and traffic-related air pollution exposure in pregnancy","volume":"203","author":"Ritz","year":"2022","journal-title":"Environ. Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Szczuko, M., Kikut, J., Komorniak, N., Bilicki, J., Celewicz, Z., and Zi\u0119tek, M. (2020). The role of arachidonic and linoleic acid derivatives in pathological pregnancies and the human reproduction process. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249628"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"14121","DOI":"10.1021\/acs.est.4c02929","article-title":"Prenatal and early life exposure to ambient air pollutants is associated with the fecal metabolome in the first two years of life","volume":"58","author":"Holzhausen","year":"2024","journal-title":"Environ. Sci. Technol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"19131","DOI":"10.1021\/acs.est.5c04955","article-title":"Prenatal nitrogen oxide (NOx) and its potential impact on infant metabolism during the first month of life: Evidence from two distinct cohorts\u2014The Atlanta African American Maternal-Child Cohort and the Southern California Mother\u2019s Milk Study","volume":"59","author":"Holzhausen","year":"2025","journal-title":"Environ. Sci. Technol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"613","DOI":"10.3390\/ijerph8020613","article-title":"Hazardous compounds in tobacco smoke","volume":"8","author":"Talhout","year":"2011","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"113179","DOI":"10.1016\/j.fct.2022.113179","article-title":"Carcinogenic components of tobacco and tobacco smoke: A 2022 update","volume":"165","author":"Li","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"6485","DOI":"10.3390\/ijerph10126485","article-title":"Smoking and pregnancy\u2014A review on the first major environmental risk factor of the unborn","volume":"10","author":"Mund","year":"2013","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_98","first-page":"27","article-title":"Pulmonary effects of maternal smoking on the fetus and child: Effects on lung development, respiratory morbidities, and lifelong lung health","volume":"21","author":"McEvoy","year":"2017","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1146\/annurev-pharmtox-042921-084202","article-title":"E-Cigarette Toxicology","volume":"62","author":"Gordon","year":"2022","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Patanavanich, R., Thatasawakul, C., Youngcharoen, K., Soponvashira, V., and Pichetsin, P. (2025). Health Effects from Secondhand Exposure to E-Cigarettes: A Systematic Review of Peer-Reviewed Articles from 2004\u20132024. Int. J. Environ. Res. Public Health, 22.","DOI":"10.3390\/ijerph22091408"},{"key":"ref_101","first-page":"211","article-title":"Urine Levels of Nicotine and Its Metabolites in Young Population Exposed to Second-Hand Smoke in Nightclubs: A Pilot Study","volume":"75","author":"Vazdar","year":"2024","journal-title":"Arh. Hig. Rada Toksikol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Rodriguez, J., Silverstein, D., Mutic, A., Liang, D., Peterson, S., and Yang, I. (2025). Passive electronic cigarette vapor exposure in children: A systematic review. Biol. Res. Nurs.","DOI":"10.1177\/10998004251357832"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Cajachagua-Torres, K.N., Blaauwendraad, S.M., El Marroun, H., Demmelmair, H., Koletzko, B., Gaillard, R., and Jaddoe, V.W.V. (2022). Fetal exposure to maternal smoking and neonatal metabolite profiles. Metabolites, 12.","DOI":"10.3390\/metabo12111101"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Snyder, B.M., Nian, H., Miller, A.M., Ryckman, K.K., Li, Y., Tindle, H.A., Ammar, L., Ramesh, A., Liu, Z., and Hartert, T.V. (2023). Associations between smoking and smoking cessation during pregnancy and newborn metabolite concentrations: Findings from PRAMS and INSPIRE birth cohorts. Metabolites, 13.","DOI":"10.3390\/metabo13111163"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s11306-016-0983-z","article-title":"Metabolomics reveals effects of maternal smoking on endogenous metabolites from lipid metabolism in cord blood of newborns","volume":"12","author":"Krumsiek","year":"2016","journal-title":"Metabolomics"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.envint.2017.07.019","article-title":"Low-level maternal exposure to nicotine associates with significant metabolic perturbations in second-trimester amniotic fluid","volume":"107","author":"Fischer","year":"2017","journal-title":"Environ. Int."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"118361","DOI":"10.1016\/j.envpol.2021.118361","article-title":"High-resolution metabolomics of exposure to tobacco smoke during pregnancy and adverse birth outcomes in the Atlanta African American maternal-child cohort","volume":"292 Pt A","author":"Tan","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_108","first-page":"293","article-title":"Role of taurine in the vasculature: An overview of experimental and human studies","volume":"1","author":"Abebe","year":"2011","journal-title":"Am. J. Cardiovasc. Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1089\/met.2014.0113","article-title":"Plasma levels of lysine, tyrosine, and valine during pregnancy are independent risk factors of insulin resistance and gestational diabetes","volume":"13","author":"Park","year":"2015","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.placenta.2017.03.019","article-title":"Maternal choline supplementation during murine pregnancy modulates placental markers of inflammation, apoptosis and vascularization in a fetal sex-dependent manner","volume":"53","author":"Kwan","year":"2017","journal-title":"Placenta"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1093\/aje\/kwh068","article-title":"The dietary glycemic index during pregnancy: Influence on infant birth weight, fetal growth, and biomarkers of carbohydrate metabolism","volume":"159","author":"Scholl","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s11306-025-02225-3","article-title":"An untargeted metabolome-wide association study of maternal perinatal tobacco smoking in newborn blood spots","volume":"21","author":"He","year":"2025","journal-title":"Metabolomics"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Xue, Y., Harris, E., Wang, W., and Baybutt, R.C. (2015). Vitamin A depletion induced by cigarette smoke is associated with an increase in lung cancer-related markers in rats. J. Biomed. Sci., 22.","DOI":"10.1186\/s12929-015-0189-0"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.neuropharm.2016.03.024","article-title":"Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases","volume":"112 Pt B","author":"Lovelace","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s11306-025-02280-w","article-title":"Exploratory Untargeted Metabolomics Analysis Reveals Differences in Metabolite Profiles in Pregnant People Exposed vs. Unexposed to E-Cigarettes Secondhand in the NYU Children\u2019s Health and Environment Study","volume":"21","author":"Cavalier","year":"2025","journal-title":"Metabolomics"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tox.2011.03.001","article-title":"Advances in metal-induced oxidative stress and human disease","volume":"283","author":"Jomova","year":"2011","journal-title":"Toxicology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00204-024-03903-2","article-title":"Heavy metals: Toxicity and human health effects","volume":"99","author":"Jomova","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"56002","DOI":"10.1289\/EHP11851","article-title":"A state-of-the-science review on high-resolution metabolomics application in air pollution health research: Current progress, analytical challenges, and recommendations for future direction","volume":"131","author":"Liang","year":"2023","journal-title":"Environ. Health Perspect."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"178999","DOI":"10.1016\/j.scitotenv.2025.178999","article-title":"Maternal mechanisms in air pollution exposure-related adverse pregnancy outcomes: A systematic review","volume":"970","author":"Syama","year":"2025","journal-title":"Sci. Total Environ."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1007\/s40726-024-00313-x","article-title":"Metabolomics application in understanding the link between air pollution and infant health outcomes: A narrative review","volume":"10","author":"Hood","year":"2024","journal-title":"Curr. Pollut. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e00161","DOI":"10.1016\/j.teac.2022.e00161","article-title":"Metabolomics in environmental toxicology: Applications and challenges","volume":"34","author":"Bedia","year":"2022","journal-title":"Trends Environ. Anal. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1080\/15287394.2014.915779","article-title":"Cadmium in placenta\u2014A valuable biomarker of exposure during pregnancy in biomedical research","volume":"77","author":"Piasek","year":"2014","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1080\/15287394.2016.1165640","article-title":"Placental cadmium as an additional noninvasive bioindicator of active maternal tobacco smoking","volume":"79","author":"Piasek","year":"2016","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Lovri\u0107, M., Gajski, G., Fern\u00e1ndez-Ag\u00fcera, J., P\u00f6hlker, M., Gursch, H., EDIAQI Consortium, Borg, A., Switters, J., and Mureddu, F. (2025). Evidence driven indoor air quality improvement: An innovative and interdisciplinary approach to improving indoor air quality. Biofactors, 51.","DOI":"10.1002\/biof.2126"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Soni, V., and Hartman, T.E. (2023). Future Perspectives of Metabolomics: Gaps, Planning, and Recommendations. Metabolomics, Springer.","DOI":"10.1007\/978-3-031-39094-4"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Hsu, C.N., Lin, Y.J., Hou, C.Y., Chen, Y.W., Chang-Chien, G.P., Lin, S.F., and Tain, Y.L. (2025). Antioxidants, gut microbiota, and cardiovascular programming: Unraveling a triad of early-life interactions. Antioxidants, 14.","DOI":"10.3390\/antiox14091049"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/nutrit\/nuz101","article-title":"Safety and efficacy of supplements in pregnancy","volume":"78","author":"Brown","year":"2020","journal-title":"Nutr. Rev."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"116670","DOI":"10.1016\/j.taap.2023.116670","article-title":"Toxic element contaminations of prenatal vitamins","volume":"477","author":"Zhang","year":"2023","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1158\/1055-9965.EPI-07-0457","article-title":"Molecular epidemiology and biomarkers in etiologic cancer research: The new in light of the old","volume":"16","author":"Vineis","year":"2007","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.1021\/pr8005099","article-title":"The metabolome-wide association study: A new look at human disease risk factors","volume":"7","author":"Nicholson","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.tibs.2017.01.004","article-title":"Metabolomics: A primer","volume":"42","author":"Liu","year":"2017","journal-title":"Trends Biochem. Sci."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/12\/1442\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:20:38Z","timestamp":1764652838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/12\/1442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,30]]},"references-count":131,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["antiox14121442"],"URL":"https:\/\/doi.org\/10.3390\/antiox14121442","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,30]]}}}