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Maternal oxidative stress throughout pregnancy and early childhood neurodevelopment at different stages: insights
Sen He1, Jingyu Wang2, Shuting Cao2
1Department of Environmental Health, School of Environmental Science and Engineering, Hainan University, Haikou, 570228, China.
Insights
Maternal oxidative stress biomarkers (OSBs) during pregnancy are linked to lower child neurodevelopment. Elevated levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 4-hydroxy nonenal mercapturic acid (HNE-MA) may negatively impact cognitive and psychomotor development.
Area of Science:
- Environmental Health
- Neuroscience
- Reproductive Biology
Background:
- Maternal oxidative stress is a suspected risk factor for offspring neurodevelopmental issues, primarily based on animal models.
- Limited epidemiological data exists on the association between maternal oxidative stress biomarkers (OSBs) and child neurodevelopment.
- This study investigates the link between OSBs during pregnancy and neurodevelopmental outcomes in early childhood.
Purpose of the Study:
- To examine the association between maternal oxidative stress biomarkers (OSBs) measured across pregnancy and neurodevelopmental outcomes in children.
- To identify potential sensitive windows during pregnancy where oxidative stress may impact child neurodevelopment.
- To provide epidemiological evidence on the role of maternal oxidative stress in child neurodevelopment.
Main Methods:
- A prospective cohort study of 1791 mother-child pairs in Wuhan, China.
- Measurement of three OSBs (8-hydroxy-2 -deoxyguanosine, 8-hydroxyguanosine, 4-hydroxy nonenal mercapturic acid) in maternal urine across three trimesters.
- Neurodevelopmental assessments of children at ages 2, 3, and 6 years, including the Bayley Scales of Infant Development, plasma BDNF levels, and Wechsler Preschool and Primary Scale of Intelligence.
Main Results:
- Higher maternal 4-hydroxy nonenal mercapturic acid (HNE-MA) in late pregnancy correlated with lower mental development index at age 2.
- Elevated early pregnancy HNE-MA was associated with decreased brain-derived neurotrophic factor (BDNF) levels at age 3.
- Increased mid-pregnancy levels of 8-hydroxy-2 -deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG) were linked to reduced full-scale intelligence quotient at age 6.
Conclusions:
- Elevated maternal oxidative stress biomarkers (OSBs) during any trimester of pregnancy may pose a risk for sustained suboptimal neurodevelopment in children.
- Findings suggest specific trimesters might be sensitive windows for oxidative stress impact on neurodevelopment.
- This research contributes epidemiological data linking pregnancy oxidative stress to child neurodevelopmental trajectories.
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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