Objectives

To identify first trimester circulating microRNAs associated with preeclampsia (PE) and assess their predictive value in two independent cohorts

Methods

Circulating microRNAs were quantified from plasma samples collected at first trimester of pregnancy in women from Gen3G (discovery; N = 385 normotensives/22 PE) and 3D (replication; N = 260 normotensives/24 PE) prospective birth cohorts. MicroRNAs associated with PE in Gen3G were identified using DESeq2 (p-value ≤ 0.05). Replicated microRNAs (selection criteria: p-value ≤ 0.05 in Gen3G, same direction of association, nominal one-side p-value ≤ 0.1 in 3D) were included in a stepwise logistic regression model to assess their predictive values alone and in combination with PE risk factors.

Results

Seventy-three circulating microRNAs were associated with PE (p-value ≤ 0.05) in Gen3G. Five microRNAs were replicated in 3D and included in a stepwise logistic regression model with PE clinical risk factors (maternal age, body mass index and mean arterial pressure (MAP) at first trimester, parity, and smoking status) and gestational age at first visit. The best model included miR-194-5p, miR-1278, maternal age, MAP at first trimester and parity and results in an area under the curve (AUC) of 0.861 [CI 95 %: 0.787–0.935] in Gen3G. Compared to risk factors only, the addition of microRNAs improves the AUC (from 0.826 to 0.861; p = 0.03). In 3D, the best model reached an AUC of 0.842 [CI 95 %: 0.769–0.914].

Conclusions

Circulating miR-194-5p and miR-1278 enhance early detection of women at risk of PE and offer great potential as predictors of PE in combination with classic risk factors.

中文翻译：

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妊娠早期循环 miR-194-5p 和 miR-1278 改善先兆子痫的预测

目标

识别与先兆子痫 (PE) 相关的妊娠早期循环 microRNA，并评估其在两个独立队列中的预测价值

方法

对来自 Gen3G（发现；N = 385 正常血压/22 PE）和 3D（复制；N = 260 正常血压/24 PE）前瞻性出生队列的妇女在妊娠前三个月收集的血浆样本中的循环 microRNA 进行定量。使用 DESeq2 鉴定与 Gen3G 中的 PE 相关的 MicroRNA（p 值 ≤ 0.05）。复制的 microRNA（选择标准：Gen3G 中的 p 值 ≤ 0.05，相关方向相同，3D 中名义单侧 p 值 ≤ 0.1）被纳入逐步逻辑回归模型中，以单独评估其预测值以及与 PE 结合的预测值风险因素。

结果

Gen3G 中，73 个循环 microRNA 与 PE 相关（p 值 ≤ 0.05）。5 个 microRNA 以 3D 形式复制，并包含在逐步逻辑回归模型中，其中包含 PE 临床危险因素（孕妇年龄、体重指数和妊娠早期平均动脉压 (MAP)、产次和吸烟状况）以及首次就诊时的孕龄。最佳模型包括 miR-194-5p、miR-1278、母亲年龄、妊娠早期 MAP 和胎次，Gen3G 的曲线下面积 (AUC) 为 0.861 [CI 95 %: 0.787–0.935]。与仅危险因素相比，添加 microRNA 提高了 AUC（从 0.826 至 0.861；p = 0.03）。在 3D 中，最佳模型的 AUC 为 0.842 [CI 95 %：0.769–0.914]。

结论

循环中的 miR-194-5p 和 miR-1278 增强了对有 PE 风险的女性的早期检测，并与经典危险因素相结合作为 PE 的预测因子具有巨大的潜力。