{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:16:01Z","timestamp":1789791361590,"version":"4.0.1"},"reference-count":67,"publisher":"American Chemical Society (ACS)","issue":"31","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473641"],"award-info":[{"award-number":["82473641"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20361"],"award-info":[{"award-number":["U22A20361"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although neurotoxic, prenatal exposure to organophosphate esters (OPEs) and phthalic acid esters (PAEs) and their effects on preschoolers\u2019 autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) cotrajectories and underlying metabolic mechanisms remain unclear, we aimed to elucidate these links. Maternal urinary OPEs\/PAEs were measured in 3040 dyads from the Ma\u2019anshan Birth Cohort across three trimesters. Child ADHD\/ASD symptom scale scores were assessed at ages 3, 5, and 6, and cotrajectories were identified using group-based multitrajectory modeling. Single-pollutant models revealed that bis(2-ethylhexyl) phosphate (BEHP) across pregnancy was positively associated with high-score trajectories (HST) (OR = 1.20, 95% CI: 1.06, 1.37), whereas bis(2-butoxyethyl) phosphate (BBOEP) exhibited U-shaped associations. Second-trimester diphenyl phosphate (DPHP) (OR = 1.13, 95% CI: 1.01, 1.26), BEHP (OR = 1.14, 95% CI: 1.04, 1.24), and monobutyl phthalate (OR = 1.15, 95% CI: 1.00, 1.32) were positively associated with HST. First-trimester DPHP exhibited a positive correlation with moderate-score trajectories and HST in girls, while bis(1-chloro-2-propyl) phosphate across pregnancy was inversely associated with HST in boys (psex-int &amp;lt; 0.05). No mixed effects were detected. BBOEP across pregnancy was negatively associated with ADHD symptoms, whereas BEHP was positively associated. BEHP, monomethyl phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate were positively associated with ASD symptoms, whereas dibutyl phosphate and monoethyl phthalate were negatively associated (p &amp;lt; 0.05). Cord blood metabolomics identified pyrimidine, biotin, lysine, cysteine, and methionine metabolism as key mediators of OPE-induced cotrajectories, and purine metabolism mediated PAEs\u2019 effects (p &amp;lt; 0.05). This study highlights OPE\/PAE neurotoxicity and reveals novel cord metabolomic insights.<\/jats:p>","DOI":"10.1021\/acs.est.6c01402","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:20:19Z","timestamp":1785849619000},"page":"21465-21479","source":"Crossref","is-referenced-by-count":2,"title":["Sex- and Trimester-Specific\nAssociations of Prenatal\nCo-Exposure to Organophosphate Esters and Phthalates with Preschoolers\u2019\nTrajectories of Co-Occurring ADHD and ASD Symptoms: Cord Blood Metabolomic\nStudy in the Ma\u2019anshan Birth Cohort"],"prefix":"10.1021","volume":"60","author":[{"given":"Xing","family":"Wang","sequence":"first","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Tong","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Luo","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qizheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lv","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Gan","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglong","family":"Geng","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuman","family":"Tao","sequence":"additional","affiliation":[{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyong","family":"Tao","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangqin","family":"Yan","sequence":"additional","affiliation":[{"name":"Ma\u2019anshan Maternal and Child Health Care Hospital , , ,","place":["Ma\u2019anshan, Anhui, China, 243011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guopeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Ma\u2019anshan Maternal and Child Health Care Hospital , , ,","place":["Ma\u2019anshan, Anhui, China, 243011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Wu","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Huang","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Cao","sequence":"additional","affiliation":[{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gao","sequence":"additional","affiliation":[{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"The First Affiliated Hospital of Anhui Medical University , , ,","place":["Hefei, China, 230022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3039-6961","authenticated-orcid":true,"given":"Fangbiao","family":"Tao","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Ministry of Education of the People's Republic of China , , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course , ,","place":["Hefei, Anhui, China, 230032"]},{"name":"National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract , No 81 Meishan Road , , ,","place":["Hefei, Anhui, China, 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Biobehav.\nRev."},{"key":"2026081110092477900_cit5","doi-asserted-by":"publisher","first-page":"110731","DOI":"10.1016\/j.pnpbp.2023.110731","article-title":"The shared\nwhite matter developmental trajectory anomalies of attention-deficit\/hyperactivity\ndisorder and autism spectrum disorders: A meta-analysis of diffusion\ntensor imaging studies","volume":"124","author":"Zhang","year":"2023","journal-title":"Prog. Neuropsychopharmacol.\nBiol. Psychiatry"},{"issue":"1","key":"2026081110092477900_cit6","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1177\/1087054717713638","article-title":"The Co-Occurrence of Autism Spectrum\nDisorder in Children With ADHD","volume":"24","author":"Zablotsky","year":"2020","journal-title":"J. Atten. Disord"},{"issue":"1","key":"2026081110092477900_cit7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s12402-014-0142-1","article-title":"Comorbid mental disorders in children and adolescents\nwith attention-deficit\/hyperactivity disorder in a large nationwide\nstudy","volume":"7","author":"Jensen","year":"2015","journal-title":"Atten. Defic. Hyperact. 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Autism."},{"key":"2026081110092477900_cit10","first-page":"1233","article-title":"Comorbidity\nand differential diagnosis of autism spectrum disorder and attention\ndeficit hyperactivity disorder","volume":"33","author":"Duan","year":"2025","journal-title":"Chin. J. Child.\nHealth Care"},{"issue":"2","key":"2026081110092477900_cit11","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S2215-0366(17)30167-0","article-title":"ADHD in children\nand young people: prevalence, care pathways, and service provision","volume":"5","author":"Sayal","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"2026081110092477900_cit12","doi-asserted-by":"publisher","first-page":"105349","DOI":"10.1016\/j.envint.2019.105349","article-title":"Worker\nexposure to flame retardants in manufacturing, construction and service\nindustries","volume":"135","author":"Estill","year":"2020","journal-title":"Environ. 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Total Environ."},{"issue":"11","key":"2026081110092477900_cit17","doi-asserted-by":"publisher","first-page":"6489","DOI":"10.1021\/acs.est.7b01122","article-title":"Organophosphorus\nFlame Retardants in Pregnant Women and Their Transfer to Chorionic\nVilli","volume":"51","author":"Zhao","year":"2017","journal-title":"Environ. Sci. Technol."},{"issue":"6","key":"2026081110092477900_cit18","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1289\/ehp.1104522","article-title":"Phthalates\nand perfluorooctanesulfonic acid in human amniotic fluid: temporal\ntrends and timing of amniocentesis in pregnancy","volume":"120","author":"Jensen","year":"2012","journal-title":"Environ. 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Int."},{"key":"2026081110092477900_cit23","doi-asserted-by":"publisher","first-page":"114078","DOI":"10.1016\/j.ijheh.2022.114078","article-title":"Gestational\norganophosphate ester exposure and preschool attention-deficit\/hyperactivity\ndisorder in the Norwegian Mother, Father, and Child cohort study","volume":"248","author":"Hall","year":"2023","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"2026081110092477900_cit24","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.neuro.2019.03.007","article-title":"Prenatal\nexposure\nto organophosphate esters and behavioral development in young children\nin the Pregnancy, Infection, and Nutrition Study","volume":"73","author":"Doherty","year":"2019","journal-title":"Neurotoxicology"},{"issue":"1","key":"2026081110092477900_cit25","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1038\/s41467-025-57273-z","article-title":"Impact of prenatal phthalate\nexposure on newborn metabolome\nand infant neurodevelopment","volume":"16","author":"Hoffman","year":"2025","journal-title":"Nat. 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Technol."},{"issue":"8","key":"2026081110092477900_cit28","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1016\/j.cell.2024.02.035","article-title":"Infant microbes and metabolites point\nto childhood neurodevelopmental disorders","volume":"187","author":"Ahrens","year":"2024","journal-title":"Cell"},{"issue":"7","key":"2026081110092477900_cit29","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1111\/jcpp.13332","article-title":"Maternal and cord plasma branched-chain\namino acids and child risk\nof attention-deficit hyperactivity disorder: a prospective birth cohort\nstudy","volume":"62","author":"Anand","year":"2021","journal-title":"J. Child Psychol Psychiatry"},{"issue":"1","key":"2026081110092477900_cit30","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41398-022-01992-0","article-title":"Association between\ncord blood metabolites in tryptophan pathway and childhood risk of\nautism spectrum disorder and attention-deficit hyperactivity disorder","volume":"12","author":"Raghavan","year":"2022","journal-title":"Transl. Psychiatry"},{"issue":"6","key":"2026081110092477900_cit31","doi-asserted-by":"publisher","first-page":"dyae142","DOI":"10.1093\/ije\/dyae142","article-title":"Cohort profile: The Ma\u2019anshan birth\ncohort (MABC) study","volume":"53","author":"Huang","year":"2024","journal-title":"Int. J. Epidemiol."},{"key":"2026081110092477900_cit32","doi-asserted-by":"publisher","first-page":"138309","DOI":"10.1016\/j.jhazmat.2025.138309","article-title":"Sex-and stage-specific\neffect of prenatal exposure to organophosphate esters with children\u2019s\nphysical growth patterns and adiposity rebound timing: Modification\nby breastfeeding","volume":"493","author":"Wang","year":"2025","journal-title":"J. Hazard. Mater."},{"issue":"4","key":"2026081110092477900_cit33","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.eehl.2024.01.007","article-title":"Associating prenatal phthalate exposure\nwith childhood autistic traits:\nInvestigating potential adverse outcome pathways and the modifying\neffects of maternal vitamin D","volume":"3","author":"Gao","year":"2024","journal-title":"Eco Environ.\nHealth"},{"key":"2026081110092477900_cit34","doi-asserted-by":"publisher","first-page":"135541","DOI":"10.1016\/j.jhazmat.2024.135541","article-title":"Associations of prenatal exposure to individual and\nmixed organophosphate esters with ADHD symptom trajectories in preschool\nchildren: The modifying effects of maternal Vitamin D","volume":"478","author":"Li","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"2026081110092477900_cit35","doi-asserted-by":"publisher","first-page":"785","DOI":"10.2147\/NDT.S126100","article-title":"Attention-deficit hyperactivity\ndisorder in elementary school students in Shantou, China: prevalence,\nsubtypes, and influencing factors","volume":"13","author":"Huang","year":"2017","journal-title":"Neuropsychiatr.\nDis. Treat."},{"issue":"1","key":"2026081110092477900_cit36","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1080\/1047322X.1990.10389587","article-title":"Estimation of Average Concentration in the Presence\nof Nondetectable Values","volume":"5","author":"Hornung","year":"1990","journal-title":"Appl. Occup. 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