Journal Article

Circulating trophoblast cell clusters for early detection of placenta accreta spectrum disorders

Gonzalez, Tania L., Chou, Shih-Jie, Lee, Yi-Te, Zhao, Meiping, Yin, Ophelia, Teng, Pai-Chi, Zhang, Qingying, Wang, Xietong, Dong, Jiantong, Sun, Na, Einerson, Brett D., Tseng, Hsian-Rong, Yang, Zhuo, Han, Christina S., Zhao, Pan, Qi, Dongping, Wang, Jing, Williams, John, Zhang, Huirong, Afshar, Yalda, Goldstein, Jeffrey D., Platt, Lawrence D., Yang, Peng, Zou, Chang, Cheng, Ju, Zhang, Tiffany X., Wang, Jasmine J., Zhu, Yazhen, Zhu, Henan, Pisarska, Margareta D., Zhe, Ruilian, Zhou, Anqi, Li, Lei, Zhang, Ceng, Zhang, Ryan Y., Sim, Myung-Shin, Wang, Shan

2021

Overview

Placenta accreta spectrum (PAS) is a high-risk obstetrical condition associated with significant morbidity and mortality. Current clinical screening modalities for PAS are not always conclusive. Here, we report a nanostructure-embedded microchip that efficiently enriches both single and clustered circulating trophoblasts (cTBs) from maternal blood for detecting PAS. We discover a uniquely high prevalence of cTB-clusters in PAS and subsequently optimize the device to preserve the intactness of these clusters. Our feasibility study on the enumeration of cTBs and cTB-clusters from 168 pregnant women demonstrates excellent diagnostic performance for distinguishing PAS from non-PAS. A logistic regression model is constructed using a training cohort and then cross-validated and tested using an independent cohort. The combined cTB assay achieves an Area Under ROC Curve of 0.942 (throughout gestation) and 0.924 (early gestation) for distinguishing PAS from non-PAS. Our assay holds the potential to improve current diagnostic modalities for the early detection of PAS. Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/62 / 14 / 14/1 / 14/28 / 14/63 / 38/39 / 38/88 / 38/90 / 631/1647/277 / 631/61/350/2093 / 692/53/2421 / 692/699/2732 / Achievement tests / Adult / Biomarkers - blood / Blood circulation / Cell Aggregation / Clusters / Cohort Studies / Diagnosis, Differential / Diagnostic systems / Enumeration / Feasibility studies / Female / Gestation / Humanities and Social Sciences / Humans / Lab-On-A-Chip Devices / Maternal Serum Screening Tests - instrumentation / Maternal Serum Screening Tests - methods / Middle Aged / Morbidity / Mortality / multidisciplinary / Nanostructures / Placenta / Placenta Accreta - blood / Placenta Accreta - diagnosis / Placenta Previa - blood / Placenta Previa - diagnosis / Pregnancy / Regression models / Reproducibility of Results / ROC Curve / Science / Science (multidisciplinary) / Trophoblasts / Trophoblasts - pathology