Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways

Abstract Prenatal exposure to metals has been associated with impaired neurodevelopment in children, but the detailed molecular mechanisms remain largely unknown. Based on the Wuhan Healthy Baby Cohort, China (N = 1088), eleven metals were measured in maternal urine during early pregnancy (13.1 ± 1....

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Main Authors: Ya Xie, Han Xiao, Dejuan Zheng, Gaga Mahai, Yuanyuan Li, Wei Xia, Shunqing Xu, Aifen Zhou
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-57253-3
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author Ya Xie
Han Xiao
Dejuan Zheng
Gaga Mahai
Yuanyuan Li
Wei Xia
Shunqing Xu
Aifen Zhou
author_facet Ya Xie
Han Xiao
Dejuan Zheng
Gaga Mahai
Yuanyuan Li
Wei Xia
Shunqing Xu
Aifen Zhou
author_sort Ya Xie
collection DOAJ
description Abstract Prenatal exposure to metals has been associated with impaired neurodevelopment in children, but the detailed molecular mechanisms remain largely unknown. Based on the Wuhan Healthy Baby Cohort, China (N = 1088), eleven metals were measured in maternal urine during early pregnancy (13.1 ± 1.1 weeks) and metabolomics profiling was conducted in cord blood. Neurodevelopment was evaluated using the Bayley Scales of Infant Development in 2-year-old children to obtain the mental development index (MDI) and psychomotor development index (PDI). After false discovery rate correction, higher maternal urinary levels of manganese, nickel, aluminum, rubidium, gallium, and the summary score of metals were only significantly associated with lower MDI scores. The weighted quantile sum index of the metal mixture showed a significant inverse association with MDI and PDI scores, with aluminum contributing the most to the associations. Histidine, beta-alanine, purine, and pyrimidine metabolism significantly mediated the above associations, suggesting that disturbances in amino acids, neurotransmitter and neuroendocrine metabolism may be important mediators in contributing to impaired neurodevelopment of children.
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record_format Article
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spelling doaj-art-cfbc6483446849029affdb03e95fdc932025-08-20T02:16:40ZengNature PortfolioNature Communications2041-17232025-03-0116111710.1038/s41467-025-57253-3Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathwaysYa Xie0Han Xiao1Dejuan Zheng2Gaga Mahai3Yuanyuan Li4Wei Xia5Shunqing Xu6Aifen Zhou7Department of Obstetrics, Wuhan Children’s Hospital (Wuhan Maternal and Child Health care Hospital), Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics, Wuhan Children’s Hospital (Wuhan Maternal and Child Health care Hospital), Tongji Medical College, Huazhong University of Science and TechnologySchool of Public Health, Tongji Medical College, Huazhong University of Science and Technology / Key Laboratory of Environment and Health, Ministry of Education / Key Laboratory of Environmental Pollution and Health Effects of the Ministry of Ecology and EnvironmentSchool of Environmental Science and Engineering, Hainan UniversityDepartment of Obstetrics, Wuhan Children’s Hospital (Wuhan Maternal and Child Health care Hospital), Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics, Wuhan Children’s Hospital (Wuhan Maternal and Child Health care Hospital), Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics, Wuhan Children’s Hospital (Wuhan Maternal and Child Health care Hospital), Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics, Wuhan Children’s Hospital (Wuhan Maternal and Child Health care Hospital), Tongji Medical College, Huazhong University of Science and TechnologyAbstract Prenatal exposure to metals has been associated with impaired neurodevelopment in children, but the detailed molecular mechanisms remain largely unknown. Based on the Wuhan Healthy Baby Cohort, China (N = 1088), eleven metals were measured in maternal urine during early pregnancy (13.1 ± 1.1 weeks) and metabolomics profiling was conducted in cord blood. Neurodevelopment was evaluated using the Bayley Scales of Infant Development in 2-year-old children to obtain the mental development index (MDI) and psychomotor development index (PDI). After false discovery rate correction, higher maternal urinary levels of manganese, nickel, aluminum, rubidium, gallium, and the summary score of metals were only significantly associated with lower MDI scores. The weighted quantile sum index of the metal mixture showed a significant inverse association with MDI and PDI scores, with aluminum contributing the most to the associations. Histidine, beta-alanine, purine, and pyrimidine metabolism significantly mediated the above associations, suggesting that disturbances in amino acids, neurotransmitter and neuroendocrine metabolism may be important mediators in contributing to impaired neurodevelopment of children.https://doi.org/10.1038/s41467-025-57253-3
spellingShingle Ya Xie
Han Xiao
Dejuan Zheng
Gaga Mahai
Yuanyuan Li
Wei Xia
Shunqing Xu
Aifen Zhou
Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways
Nature Communications
title Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways
title_full Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways
title_fullStr Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways
title_full_unstemmed Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways
title_short Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways
title_sort associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways
url https://doi.org/10.1038/s41467-025-57253-3
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