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Abstract
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.
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1 University of California, Los Angeles, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
2 University of California, Los Angeles, California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); Peking University, Beijing National Laboratory for Molecular Sciences, MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319)
3 The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Clinical Medical Research Center, Shenzhen, China (GRID:grid.440218.b) (ISNI:0000 0004 1759 7210)
4 University of California, Los Angeles, California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); Shandong Provincial Hospital Affiliated to Shandong University, Department of Obstetrics and Gynecology, Jinan, China (GRID:grid.460018.b) (ISNI:0000 0004 1769 9639)
5 University of California, Los Angeles, California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
6 University of California, Los Angeles, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); Center for Fetal Medicine and Women’s Ultrasound, Los Angeles, USA (GRID:grid.19006.3e)
7 University of Utah Health, Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, Salt Lake City, USA (GRID:grid.223827.e) (ISNI:0000 0001 2193 0096)
8 Cedars-Sinai Medical Center, Department of Obstetrics and Gynecology, Los Angeles, USA (GRID:grid.50956.3f) (ISNI:0000 0001 2152 9905)
9 Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, USA (GRID:grid.50956.3f) (ISNI:0000 0001 2152 9905)
10 Peking University, Beijing National Laboratory for Molecular Sciences, MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319)
11 University of California, Los Angeles, Departments of Computational Medicine & Medicine, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
12 University of California, Los Angeles, Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
13 Shandong Provincial Hospital Affiliated to Shandong University, Department of Obstetrics and Gynecology, Jinan, China (GRID:grid.460018.b) (ISNI:0000 0004 1769 9639)
14 University of California, Los Angeles, California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); Fudan University, Department of Obstetrics, Obstetrics and Gynecology Hospital, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443)