Inflammatory and Angiogenic Factors at Mid-Pregnancy Are Associated with Spontaneous Preterm Birth in a Cohort of Tanzanian Women

Research Question
Preterm birth (PTB) is the leading cause of perinatal mortality worldwide, with the greatest burden occurring in resource-constrained settings. Based on the hypothesis that altered placental angiogenesis and inflammation early in pregnancy lead to PTB, we examined whether levels of inflammatory and angiogenic mediators, measured early in pregnancy, were predictive of spontaneous PTB (sPTB).
Study Design
Plasma samples were collected from a prospective cohort of primigravid Tanzanian women between 12–27 weeks gestation. A panel of 18 markers was screened on a training cohort of 426 women. Markers associated with sPTB in the training cohort were repeated in a test cohort of 628 women. All markers were measured by ELISA.
Findings
In both the training and test cohorts plasma levels of IL-18BP, sICAM-1, sEndoglin and CHI3L1 were elevated and Leptin was lower at enrollment in women who subsequently experienced sPTB. In multivariate analysis women with plasma levels of CHI3L1, C5a, sICAM-1, AngptL3, sEndgolin, sFlt-1 and IL-18BP in the highest quartile had an increased risk of sPTB compared with those in the lowest quartile. Women with Leptin and Ang2 in the highest quartile had a reduced risk of sPTB compared with women in the lowest quartile.
Implications
Levels of angiogenic and inflammatory mediators measured at mid-pregnancy were associated with subsequent sPTB. These findings provide insight into mechanisms underlying sPTB and suggest biomarkers that may have clinical utility in risk-stratifying pregnancies.

研究问题
早产（Preterm Birth, PTB）是全球围产期死亡的首要诱因，资源匮乏地区的疾病负担最为沉重。基于“妊娠早期胎盘血管生成异常与炎症反应异常可引发早产”这一假说，本研究探讨妊娠早期检测的炎症介质与血管生成介质水平是否可预测自发性早产（spontaneous PTB, sPTB）。

研究设计
本研究从坦桑尼亚初产妇的前瞻性队列中采集妊娠12~27周的血浆样本。针对由426名女性组成的训练队列，筛选18项标志物检测面板。将训练队列中与自发性早产相关的标志物，在包含628名女性的测试队列中进行重复验证。所有标志物均通过酶联免疫吸附试验（ELISA）完成检测。

研究结果
在训练队列与测试队列中，后续发生自发性早产的女性在入组时的血浆IL-18BP、sICAM-1、sEndoglin及CHI3L1水平均显著升高，而瘦素（Leptin）水平更低。多变量分析显示，血浆CHI3L1、C5a、sICAM-1、AngptL3、sEndoglin、sFlt-1及IL-18BP处于最高四分位数区间的女性，相较于最低四分位数区间的女性，自发性早产风险显著升高；而血浆瘦素与Ang2处于最高四分位数区间的女性，自发性早产风险则显著低于最低四分位数区间的女性。

研究意义
妊娠中期检测的血管生成与炎症介质水平与后续发生的自发性早产存在显著关联。本研究结果为自发性早产的潜在发病机制提供了新的研究视角，并提示部分标志物可应用于妊娠风险分层的临床实践。