School of Basic Medicine, Clinical Medicine Department of Medical College, Qingdao University, Qingdao, Shandong, China.
Special Medicine Department, Medical College, Qingdao University, Qingdao, Shandong, China.
Front Immunol. 2023 May 30;14:1156039. doi: 10.3389/fimmu.2023.1156039. eCollection 2023.
Pre-eclampsia (PE) is a pregnancy complication associated with maternal and fetal morbidity and mortality. Among the potential pathogenesis discussed, inflammation is considered an essential initiator of PE. Previous studies have compared the levels of various inflammatory biomarkers that indicate the existence of PE; however, the relative levels of pro-inflammatory and anti-inflammatory biomarkers and their dynamic changes during PE progression remain unclear. This knowledge is essential to explain the occurrence and progression of the disease.
We aimed to identify the relationship between inflammatory status and PE using inflammatory biomarkers as indicators. We also discussed the underlying mechanism by which inflammatory imbalance contributes to PE by comparing the relative levels of pro-inflammatory and anti-inflammatory biomarkers. Furthermore, we identified additional risk factors for PE.
We reviewed PubMed, Embase, and the Cochrane Library for articles published until 15 September 2022. Original articles that investigated inflammatory biomarkers in PE and normal pregnancy were included. We selected healthy pregnant women as controls. The inflammatory biomarkers in the case and control groups were expressed as standardized mean differences and 95% confidence intervals using a random-effects model. Study quality was assessed using the Newcastle-Ottawa Scale. Publication bias was assessed using Egger's test.
Thirteen articles that investigated 2,549 participants were included in this meta-analysis. Patients with PE had significantly higher levels of C-reactive protein (CRP), interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) than the controls. CRP and pro-inflammatory cytokine levels were higher than those of anti-inflammatory cytokines. Patients with gestational age > 34 weeks had significantly higher IL-6 and TNF levels. Patients with higher systolic blood pressure had significantly higher IL-8, IL-10, and CRP levels.
Inflammatory imbalance is an independent risk factor for PE development. Impairment of the anti-inflammatory system is a crucial initiating factor for PE development. Failed autoregulation, manifested as prolonged exposure to pro-inflammatory cytokines, leads to PE progression. Higher levels of inflammatory biomarkers suggest more severe symptoms, and pregnant women after 34 weeks of gestation are more susceptible to PE.
子痫前期（PE）是一种与母婴发病率和死亡率相关的妊娠并发症。在讨论的潜在发病机制中，炎症被认为是 PE 的一个重要启动因素。先前的研究比较了各种炎症生物标志物的水平，以表明 PE 的存在；然而，促炎和抗炎生物标志物的相对水平及其在 PE 进展过程中的动态变化尚不清楚。这些知识对于解释疾病的发生和进展至关重要。
我们旨在使用炎症生物标志物作为指标，确定炎症状态与 PE 之间的关系。我们还通过比较促炎和抗炎生物标志物的相对水平，讨论了炎症失衡导致 PE 的潜在机制。此外，我们确定了 PE 的其他危险因素。
我们检索了 PubMed、Embase 和 Cochrane 图书馆截至 2022 年 9 月 15 日发表的文章。纳入了研究 PE 和正常妊娠中炎症生物标志物的原始文章。我们选择健康孕妇作为对照组。病例组和对照组的炎症生物标志物用标准化均数差值和 95%置信区间表示，采用随机效应模型。使用纽卡斯尔-渥太华量表评估研究质量。使用 Egger 检验评估发表偏倚。
这项荟萃分析纳入了 13 项研究共 2549 名参与者。PE 患者的 C 反应蛋白（CRP）、白细胞介素（IL）-4、IL-6、IL-8、IL-10 和肿瘤坏死因子（TNF）水平明显高于对照组。CRP 和促炎细胞因子水平高于抗炎细胞因子。胎龄>34 周的患者 IL-6 和 TNF 水平明显较高。收缩压较高的患者 IL-8、IL-10 和 CRP 水平明显较高。
炎症失衡是 PE 发生的独立危险因素。抗炎系统受损是 PE 发生的关键启动因素。抗炎系统失代偿，表现为促炎细胞因子持续暴露，导致 PE 进展。炎症生物标志物水平较高提示症状更严重，34 周后妊娠的孕妇更容易患 PE。
