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使用无细胞信号作为生物标志物用于子痫前期的早期及简易预测。

Use of cell-free signals as biomarkers for early and easy prediction of preeclampsia.

作者信息

Gekas Jean, Boomer Theresa Hopkins, Rodrigue Marc-André, Jinnett Kristine N, Bhatt Sucheta

机构信息

Department of Medical Genetics, Quebec University Mother and Child Center, Laval Medical University, Quebec City, QC, Canada.

Illumina, Inc., San Diego, CA, United States.

出版信息

Front Med (Lausanne). 2023 May 24;10:1191163. doi: 10.3389/fmed.2023.1191163. eCollection 2023.

DOI:10.3389/fmed.2023.1191163
PMID:37293304
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10244626/
Abstract

INTRODUCTION

Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity worldwide. However, current methods of screening are complicated and require special skill sets. In this observational study of prospectively collected samples, we wanted to evaluate if cell-free () DNA could be an efficient biomarker for identification of at-risk patients.

METHODS

One hundred patients attending a private prenatal clinic in Canada were enrolled in their first trimester of pregnancy and a blood draw was carried out at 11 + 0 to 14 + 2 weeks' (timepoint A) and 17 + 6 to 25 + 5 weeks of gestation (timepoint B). CfDNA signals, namely concentration, fetal fraction, and fragment size distribution, were correlated with clinical outcomes in the test population to develop the logistic regression model.

RESULTS

Twelve patients developed PE-four early-stage and eight late-stage PE. Significant differences were observed between PE patients and control cases for all three cfDNA signals at timepoint A, while both fetal fraction and concentration were significantly different between PE patients and control cases at timepoint B. Overall, the model had a sensitivity of up to 100% and specificity of up to 87.5% at Timepoint A.

CONCLUSION

This proof-of-principle study showed that use of this logistic regression model could identify patients at risk of preeclampsia in the first trimester of pregnancy.

摘要

引言

子痫前期(PE)是全球孕产妇和围产儿发病的主要原因。然而,目前的筛查方法复杂,需要特殊技能。在这项对前瞻性收集样本的观察性研究中,我们想评估游离()DNA是否可以作为识别高危患者的有效生物标志物。

方法

加拿大一家私立产前诊所的100名患者在妊娠早期入组,在妊娠11 + 0至14 + 2周(时间点A)和17 + 6至25 + 5周(时间点B)进行采血。游离DNA信号,即浓度、胎儿分数和片段大小分布,与测试人群中的临床结局相关,以建立逻辑回归模型。

结果

12名患者发生了子痫前期,其中4例为早期子痫前期,8例为晚期子痫前期。在时间点A,子痫前期患者与对照病例在所有三个游离DNA信号上均观察到显著差异,而在时间点B,子痫前期患者与对照病例之间的胎儿分数和浓度均存在显著差异。总体而言,该模型在时间点A的敏感性高达100%,特异性高达87.5%。

结论

这项原理验证研究表明,使用该逻辑回归模型可以在妊娠早期识别子痫前期高危患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41c3/10244626/8ff5237a0202/fmed-10-1191163-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41c3/10244626/df0628aa3f97/fmed-10-1191163-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41c3/10244626/8ff5237a0202/fmed-10-1191163-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41c3/10244626/df0628aa3f97/fmed-10-1191163-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41c3/10244626/8ff5237a0202/fmed-10-1191163-g002.jpg

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本文引用的文献

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Preeclampsia pathophysiology and adverse outcomes during pregnancy and postpartum.子痫前期的病理生理学以及妊娠和产后的不良结局。
Front Med (Lausanne). 2023 Mar 16;10:1144170. doi: 10.3389/fmed.2023.1144170. eCollection 2023.
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Potential biomarkers for late-onset and term preeclampsia: A scoping review.晚发型和足月子痫前期的潜在生物标志物:一项范围综述。
Front Physiol. 2023 Mar 10;14:1143543. doi: 10.3389/fphys.2023.1143543. eCollection 2023.
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Preeclampsia.子痫前期
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Non-invasive prediction of preeclampsia using the maternal plasma cell-free DNA profile and clinical risk factors.利用母体血浆游离DNA图谱和临床危险因素对先兆子痫进行无创预测。
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Pregnancy Hypertens. 2022 Mar;27:148-169. doi: 10.1016/j.preghy.2021.09.008. Epub 2021 Oct 9.
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Optimal Screening for Preeclampsia in the First Trimester of Pregnancy.妊娠早期子痫前期的最佳筛查
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Low fetal fraction in cell-free DNA testing is associated with adverse pregnancy outcome: Analysis of a subcohort of the TRIDENT-2 study.游离胎儿 DNA 检测中低胎儿分数与不良妊娠结局相关:TRIDENT-2 研究的亚队列分析。
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At Preeclampsia Diagnosis, Total Cell-Free DNA Concentration is Elevated and Correlates With Disease Severity.子痫前期诊断时,总游离 DNA 浓度升高,并与疾病严重程度相关。
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Fetal fraction of cell free DNA in screening for hypertensive disorders at 11-13 weeks.游离胎儿 DNA 细胞分数在 11-13 周筛查高血压疾病中的应用。
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Association between low fetal fraction of cell free DNA at the early second-trimester and adverse pregnancy outcomes.早期妊娠中期游离胎儿 DNA 低胎儿分数与不良妊娠结局的关系。
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