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

• Published in: Nature communications Vol. 12; no. 1; pp. 4408 - 14
• Main Authors: Afshar, Yalda, Dong, Jiantong, Zhao, Pan, Li, Lei, Wang, Shan, Zhang, Ryan Y., Zhang, Ceng, Yin, Ophelia, Han, Christina S., Einerson, Brett D., Gonzalez, Tania L., Zhang, Huirong, Zhou, Anqi, Yang, Zhuo, Chou, Shih-Jie, Sun, Na, Cheng, Ju, Zhu, Henan, Wang, Jing, Zhang, Tiffany X., Lee, Yi-Te, Wang, Jasmine J., Teng, Pai-Chi, Yang, Peng, Qi, Dongping, Zhao, Meiping, Sim, Myung-Shin, Zhe, Ruilian, Goldstein, Jeffrey D., Williams, John, Wang, Xietong, Zhang, Qingying, Platt, Lawrence D., Zou, Chang, Pisarska, Margareta D., Tseng, Hsian-Rong, Zhu, Yazhen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.08.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 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
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-24627-2

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.