Associations of Placental Inflammation and Oxidative Stress Biomarkers with Glucolipid Metabolism in Children: A Birth Cohort Study in China
Open accessAbstract
Background: The maternal intrauterine immune environment may affect offspring long‐term health. We aimed to investigate the association between the intrauterine placental immunological milieu and glycolipid metabolic health in children. Methods and Results: This study enrolled 1803 mother–child pairs from the Ma'anshan birth cohort (2013–2014). Placental mRNA expression of inflammatory cytokines (interleukin‐1β [IL‐1β], IL‐10, monocyte chemoattractant protein‐1, tumor necrosis factor‐α, IL‐4, IL‐6, IL‐8, C‐reactive protein, and interferon‐γ) and oxidative stress biomarkers (heme oxygenase‐1, hypoxia‐inducible factor‐1alpha, and glucose‐related protein 78) was quantified using real‐time quantitative polymerase chain reaction. Fasting blood glucose, insulin, triglycerides, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and total cholesterol were assessed at 5 to 6 years old. Statistical analyses included multiple linear regression, binary logistic regression, restricted cubic spline model, and the Bayesian kernel machine regression model. Placental inflammatory cytokines (IL‐1β, monocyte chemoattractant protein‐1, C‐reactive protein, IL‐6, IL‐8, IL‐10) and oxidative stress biomarkers (heme oxygenase‐1, hypoxia‐inducible factor‐1alpha, glucose‐related protein 78) showed positive associations with children's fasting blood glucose levels. Heme oxygenase‐1 and glucose‐related protein 78 exhibited negative correlations with children's fasting insulin levels. Elevated IL‐6, heme oxygenase‐1, hypoxia‐inducible factor‐1alpha, and glucose‐related protein 78 were associated with increased risk of prediabetes in children. Overall upregulation of placental proinflammatory cytokines and oxidative stress factors mRNA expression correlated with higher prediabetes risk in children. Bayesian kernel machine regression analysis indicated a joint positive effect of the 12 placental inflammation and oxidative stress mixtures on children's risk of high fasting blood glucose. Conclusions: This exploratory study underscores significant correlations between maternal intrauterine placental inflammation, oxidative stress markers, and offspring fasting blood glucose and insulin levels. These findings highlight the potential role of intrauterine holistic immunity in shaping offspring glucose metabolism health.
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In a birth cohort of 1803 mother-child pairs, placental inflammatory and oxidative-stress mRNA markers were associated with fasting glucose, insulin and prediabetes risk at 5-6 years.
“A birth cohort of 1803 mother–child pairs extended the placental link beyond birth: placental inflammatory and oxidative-stress mRNA markers were associated with fasting glucose, insulin and prediabetes risk at 5–6 years [139].”
From Placental Pathophysiology and Developmental Programming of Adult Cardiometabolic Risk: A Narrative Review of Pregnancy Exposures (2026) · cites this paper as [139]
This placenta-to-child evidence does not include a single defined maternal exposure and does not establish adult disease.
“This is comparatively integrated placenta-to-child evidence, but it does not include a single defined maternal exposure and does not establish adult disease.”
From Placental Pathophysiology and Developmental Programming of Adult Cardiometabolic Risk: A Narrative Review of Pregnancy Exposures (2026) · cites this paper as [139]
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- Authors
- Zhou, J., Teng, Y., Ouyang, J., Wu, P., Tong, J., Gao, G., Yan, S., Tao, F., & Huang, K.
- Affiliations
- Anhui Medical University (CN)
- Anhui Medical University
- Maternal and Child Health Care Center of Ma’anshan
- Corresponding author
- Huang, Kun
- Venue
- Journal of the American Heart Association
- Published
- 2024-09-03
- Volume
- 13
- Issue
- 17
- Pages
- e035754-e035754
- ISSN
- 2047-9980 (ISSN-L)
- PMC
- PMC11646502
- OpenAlex
- W4402006463
- Cited by
- 7
- References
- 56
- Citations by year
- 2026: 4 · 2025: 3
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China
- Anhui Medical University
- National Key Research and Development Program of China
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- placental inflammation, oxidative stress, heme oxygenase-1, hypoxia-inducible factor-1α, prediabetes, fasting blood glucose, insulin, children, maternal-fetal immune interaction, glycolipid metabolism
- MeSH terms
- Adult, Blood Glucose, Child, Child, Preschool, China, Female, Humans, Inflammation, Lipids, Male, Placenta, Pregnancy, Biomarkers, Cytokines, Oxidative Stress, Inflammation Mediators
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