Maternal oxidative stress throughout pregnancy and early childhood neurodevelopment at different stages: insights from a prospective cohort study

Abstract Background Maternal oxidative stress during pregnancy plays a role as a hazardous factor of offspring neurodevelopment in animal models. However, epidemiological evidence remains limited. In this prospective cohort, we aimed to investigate the associations between maternal oxidative stress...

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Main Authors: Sen He, Jingyu Wang, Shuting Cao, Aizhen Wang, Yuyan Wang, Pei Li, Xiuli Cao, Rongrong Cheng, Ruixin Chen, Yin Wang, Fei Yang, Yuehao Fu, Yang Peng, Han Li, Wei Xia, Zhiqiang Zhu, Hongxiu Liu, Shunqing Xu
Format: Article
Language:English
Published: BMC 2025-08-01
Series:BMC Medicine
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Online Access:https://doi.org/10.1186/s12916-025-04297-3
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author Sen He
Jingyu Wang
Shuting Cao
Aizhen Wang
Yuyan Wang
Pei Li
Xiuli Cao
Rongrong Cheng
Ruixin Chen
Yin Wang
Fei Yang
Yuehao Fu
Yang Peng
Han Li
Wei Xia
Zhiqiang Zhu
Hongxiu Liu
Shunqing Xu
author_facet Sen He
Jingyu Wang
Shuting Cao
Aizhen Wang
Yuyan Wang
Pei Li
Xiuli Cao
Rongrong Cheng
Ruixin Chen
Yin Wang
Fei Yang
Yuehao Fu
Yang Peng
Han Li
Wei Xia
Zhiqiang Zhu
Hongxiu Liu
Shunqing Xu
author_sort Sen He
collection DOAJ
description Abstract Background Maternal oxidative stress during pregnancy plays a role as a hazardous factor of offspring neurodevelopment in animal models. However, epidemiological evidence remains limited. In this prospective cohort, we aimed to investigate the associations between maternal oxidative stress biomarkers (OSBs) across pregnancy and neurodevelopmental outcomes in different stages across early childhood. Methods This was a prospective cohort study conducted in 1791 mother–child pairs from Wuhan, China. Three OSBs, including DNA oxidative damage marker (8-hydroxy-2′-deoxyguanosine, 8-OHdG), RNA oxidative damage marker (8-hydroxyguanosine, 8-OHG) and lipid oxidative damage marker (4-hydroxy nonenal mercapturic acid, HNE-MA), were measured in repeatedly collected urine samples in three trimesters across pregnancy. We followed children at age 2, age 3, and age 6 years. At age 2 years, the Bayley Scales of Infant Development of China Revision (BSID-CR) was employed to assess children’s mental and psychomotor development. Brain-derived neurotrophic factor (BDNF) levels were measured in children’s plasma at age 3 years. The Wechsler Preschool and Primary Scale—Fourth Edition (WPPSI-IV) was used to assess children’s intelligence quotients at ages 6 years. Generalized estimating equation models were applied to estimate the associations between OSBs and neurodevelopmental outcomes. Results Higher maternal HNE-MA levels in late pregnancy were associated with lower mental development index at age 2 years (β =  − 0.95, 95% confidence interval (CI): − 1.78, − 0.11). Elevated early pregnancy HNE-MA levels were associated with decreased BDNF levels at age 3 years (β =  − 0.07, 95% CI: − 0.13, − 0.01). Each one-unit increase in natural log-transformed concentrations of 8-OHdG and 8-OHG in mid pregnancy was associated with a decrease in full-scale intelligence quotient at age 6 years by 1.55 points (95% CI: − 2.84, − 0.26) and 1.89 points (95% CI: − 3.30, − 0.49), respectively. Conclusions This study suggested that higher levels of OSBs in each trimester of pregnancy might be a risk factor of consistently suboptimal neurodevelopment across early childhood. This finding provides new epidemiological data on the linkages of oxidative stress across pregnancy to child neurodevelopment and gives clues to the possible sensitive windows.
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spelling doaj-art-5c809f17711d4a59a53249adfbdecb8f2025-08-20T03:42:53ZengBMCBMC Medicine1741-70152025-08-0123111310.1186/s12916-025-04297-3Maternal oxidative stress throughout pregnancy and early childhood neurodevelopment at different stages: insights from a prospective cohort studySen He0Jingyu Wang1Shuting Cao2Aizhen Wang3Yuyan Wang4Pei Li5Xiuli Cao6Rongrong Cheng7Ruixin Chen8Yin Wang9Fei Yang10Yuehao Fu11Yang Peng12Han Li13Wei Xia14Zhiqiang Zhu15Hongxiu Liu16Shunqing Xu17Department of Environmental Health, School of Environmental Science and Engineering, Hainan UniversityKey Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyKey Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyKey Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Population Health, New York University Grossman School of MedicineDepartment of Physiology and Biophysics, University of New York at BuffaloKey Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyKey Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyKey Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyKey Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyThe Key Laboratory of Typical Environmental Pollution and Health Hazards of Hunan Province, School of Public Health, Hengyang Medical School, University of South ChinaKey Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Environmental and Occupational Health, School of Public Health, Guangxi Medical UniversityDepartment of Sanitary Chemistry, School of Public Health, Guangxi Medical UniversityKey Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Environmental Health, School of Environmental Science and Engineering, Hainan UniversityDepartment of Environmental Health, School of Environmental Science and Engineering, Hainan UniversityDepartment of Environmental Health, School of Environmental Science and Engineering, Hainan UniversityAbstract Background Maternal oxidative stress during pregnancy plays a role as a hazardous factor of offspring neurodevelopment in animal models. However, epidemiological evidence remains limited. In this prospective cohort, we aimed to investigate the associations between maternal oxidative stress biomarkers (OSBs) across pregnancy and neurodevelopmental outcomes in different stages across early childhood. Methods This was a prospective cohort study conducted in 1791 mother–child pairs from Wuhan, China. Three OSBs, including DNA oxidative damage marker (8-hydroxy-2′-deoxyguanosine, 8-OHdG), RNA oxidative damage marker (8-hydroxyguanosine, 8-OHG) and lipid oxidative damage marker (4-hydroxy nonenal mercapturic acid, HNE-MA), were measured in repeatedly collected urine samples in three trimesters across pregnancy. We followed children at age 2, age 3, and age 6 years. At age 2 years, the Bayley Scales of Infant Development of China Revision (BSID-CR) was employed to assess children’s mental and psychomotor development. Brain-derived neurotrophic factor (BDNF) levels were measured in children’s plasma at age 3 years. The Wechsler Preschool and Primary Scale—Fourth Edition (WPPSI-IV) was used to assess children’s intelligence quotients at ages 6 years. Generalized estimating equation models were applied to estimate the associations between OSBs and neurodevelopmental outcomes. Results Higher maternal HNE-MA levels in late pregnancy were associated with lower mental development index at age 2 years (β =  − 0.95, 95% confidence interval (CI): − 1.78, − 0.11). Elevated early pregnancy HNE-MA levels were associated with decreased BDNF levels at age 3 years (β =  − 0.07, 95% CI: − 0.13, − 0.01). Each one-unit increase in natural log-transformed concentrations of 8-OHdG and 8-OHG in mid pregnancy was associated with a decrease in full-scale intelligence quotient at age 6 years by 1.55 points (95% CI: − 2.84, − 0.26) and 1.89 points (95% CI: − 3.30, − 0.49), respectively. Conclusions This study suggested that higher levels of OSBs in each trimester of pregnancy might be a risk factor of consistently suboptimal neurodevelopment across early childhood. This finding provides new epidemiological data on the linkages of oxidative stress across pregnancy to child neurodevelopment and gives clues to the possible sensitive windows.https://doi.org/10.1186/s12916-025-04297-3Birth cohortOxidative stressNeurodevelopmentIntelligence quotientChildren
spellingShingle Sen He
Jingyu Wang
Shuting Cao
Aizhen Wang
Yuyan Wang
Pei Li
Xiuli Cao
Rongrong Cheng
Ruixin Chen
Yin Wang
Fei Yang
Yuehao Fu
Yang Peng
Han Li
Wei Xia
Zhiqiang Zhu
Hongxiu Liu
Shunqing Xu
Maternal oxidative stress throughout pregnancy and early childhood neurodevelopment at different stages: insights from a prospective cohort study
BMC Medicine
Birth cohort
Oxidative stress
Neurodevelopment
Intelligence quotient
Children
title Maternal oxidative stress throughout pregnancy and early childhood neurodevelopment at different stages: insights from a prospective cohort study
title_full Maternal oxidative stress throughout pregnancy and early childhood neurodevelopment at different stages: insights from a prospective cohort study
title_fullStr Maternal oxidative stress throughout pregnancy and early childhood neurodevelopment at different stages: insights from a prospective cohort study
title_full_unstemmed Maternal oxidative stress throughout pregnancy and early childhood neurodevelopment at different stages: insights from a prospective cohort study
title_short Maternal oxidative stress throughout pregnancy and early childhood neurodevelopment at different stages: insights from a prospective cohort study
title_sort maternal oxidative stress throughout pregnancy and early childhood neurodevelopment at different stages insights from a prospective cohort study
topic Birth cohort
Oxidative stress
Neurodevelopment
Intelligence quotient
Children
url https://doi.org/10.1186/s12916-025-04297-3
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