Purpose

Preeclampsia (PE) is one of the most common and serious complications of pregnancy, and novel methods for the early prediction of PE are needed for clinical application.

Methods

In this study, a circulating cell-free RNA (cfRNA) panel of target genes for PE prediction was designed and validated in a case–control cohort and a nested case–control cohort. The QPCR was applied to quantify the copy number of cfRNA, and the data were normalized as multiples of the median. Ratios of serum placental growth factor (PIGF) and soluble fms-like tyrosine kinase 1 (sFLT-1) were also measured, and transabdominal ultrasonography was conducted for subjects in the prospective cohort. Binary logistic regression models for PE prediction were constructed and tested.

Results

Our results revealed that the women with PE showed significant alterations in serum cfRNA profiles from early pregnancy onward and before the onset of PE symptoms. Compared with PIGF/sFLT-1 measurement and ultrasonographic imaging, cfRNA test can detect PE at a very early stage of pregnancy. The predictive model exhibited the best performance at gestation week 32, with a detection rate of 100%. At 12 weeks of gestation, the model still manifested an area under curve (AUC) of 0.9144, and sensitivity of 1.0000. If combined with clinical parameters and ultrasonographic indicators, the model can achieve the highest AUC for PE prediction at early gestation.

Conclusion

Measurement of cfRNA can be used to effectively predict PE with high performance, providing an additional method for monitoring PE throughout the course of pregnancy.

中文翻译：

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使用妊娠早期母体循环 mRNA 预测先兆子痫

目的

先兆子痫（PE）是最常见、最严重的妊娠并发症之一，临床应用需要新的早期预测PE的方法。

方法

在这项研究中，设计了用于 PE 预测的循环游离 RNA (cfRNA) 靶基因组，并在病例对照队列和嵌套病例对照队列中进行了验证。应用 QPCR 来量化 cfRNA 的拷贝数，并将数据标准化为中位数的倍数。还测量了血清胎盘生长因子 (PIGF) 和可溶性 fms 样酪氨酸激酶 1 (sFLT-1) 的比率，并对前瞻性队列中的受试者进行了经腹部超声检查。构建并测试了 PE 预测的二元逻辑回归模型。

结果

我们的结果显示，患有早泄的女性从妊娠早期开始以及早泄症状出现之前，其血清 cfRNA 谱表现出显着的变化。与PIGF/sFLT-1测量和超声成像相比，cfRNA检测可以在妊娠极早期阶段检测PE。预测模型在妊娠第 32 周表现出最佳性能，检出率为 100%。妊娠 12 周时，模型的曲线下面积 (AUC) 仍为 0.9144，敏感性为 1.0000。如果结合临床参数和超声指标，该模型可以达到妊娠早期PE预测的最高AUC。

结论

cfRNA 的测量可用于高效预测 PE，为整个妊娠过程中监测 PE 提供另一种方法。