Department of Maternal, Child and Adolescent Health, School of Public Health Anhui Medical University Hefei China.
Key Laboratory of Population Health Across Life Cycle (AHMU), MOE Hefei China.
J Am Heart Assoc. 2024 Sep 3;13(17):e035754. doi: 10.1161/JAHA.124.035754. Epub 2024 Aug 29.
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.
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.
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.
母体宫内免疫环境可能会影响后代的长期健康。我们旨在研究宫内胎盘免疫环境与儿童糖脂代谢健康之间的关系。
本研究纳入了 1803 对来自马鞍山出生队列（2013-2014 年）的母婴对子。采用实时定量聚合酶链反应定量检测胎盘炎症细胞因子（白细胞介素-1β[IL-1β]、IL-10、单核细胞趋化蛋白-1、肿瘤坏死因子-α、IL-4、IL-6、IL-8、C 反应蛋白和干扰素-γ）和氧化应激生物标志物（血红素加氧酶-1、缺氧诱导因子-1α和葡萄糖相关蛋白 78）的 mRNA 表达。在 5 至 6 岁时检测空腹血糖、胰岛素、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和总胆固醇。统计分析包括多元线性回归、二元逻辑回归、限制立方样条模型和贝叶斯核机器回归模型。胎盘炎症细胞因子（IL-1β、单核细胞趋化蛋白-1、C 反应蛋白、IL-6、IL-8、IL-10）和氧化应激生物标志物（血红素加氧酶-1、缺氧诱导因子-1α、葡萄糖相关蛋白 78）与儿童空腹血糖水平呈正相关。血红素加氧酶-1 和葡萄糖相关蛋白 78 与儿童空腹胰岛素水平呈负相关。IL-6、血红素加氧酶-1、缺氧诱导因子-1α 和葡萄糖相关蛋白 78 水平升高与儿童发生糖尿病前期的风险增加相关。胎盘促炎细胞因子和氧化应激因子 mRNA 表达整体上调与儿童发生糖尿病前期的风险增加相关。贝叶斯核机器回归分析表明，12 种胎盘炎症和氧化应激混合物对儿童空腹高血糖风险具有联合正效应。
这项探索性研究强调了母体宫内胎盘炎症、氧化应激标志物与后代空腹血糖和胰岛素水平之间存在显著相关性。这些发现突出了宫内整体免疫在塑造后代葡萄糖代谢健康方面的潜在作用。
