Dataset Information

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

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.

SUBMITTER: Afshar Y

PROVIDER: S-EPMC8333096 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Afshar Yalda Y Dong Jiantong J Zhao Pan P Li Lei L Wang Shan S Zhang Ryan Y RY Zhang Ceng C Yin Ophelia O Han Christina S CS Einerson Brett D BD Gonzalez Tania L TL Zhang Huirong H Zhou Anqi A Yang Zhuo Z Chou Shih-Jie SJ Sun Na N Cheng Ju J Zhu Henan H Wang Jing J Zhang Tiffany X TX Lee Yi-Te YT Wang Jasmine J JJ Teng Pai-Chi PC Yang Peng P Qi Dongping D Zhao Meiping M Sim Myung-Shin MS Zhe Ruilian R Goldstein Jeffrey D JD Williams John J Wang Xietong X Zhang Qingying Q Platt Lawrence D LD Zou Chang C Pisarska Margareta D MD Tseng Hsian-Rong HR Zhu Yazhen Y

Nature communications 20210803 1

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 th ...[more]

PMID: 34344888

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Project description:BackgroundPlacenta accreta spectrum disorders are a complex range of placental pathologies that are associated with significant maternal morbidity and mortality. A diagnosis of placenta accreta spectrum relies on ultrasonographic findings with modest positive predictive value. Exosomal microRNAs are small RNA molecules that reflect the cellular processes of the origin tissues.ObjectiveWe aimed to explore exosomal microRNA expression to understand placenta accreta spectrum pathology and clinical use for placenta accreta spectrum detection.Study designThis study was a biomarker analysis of prospectively collected samples at 2 academic institutions from 2011 to 2022. Plasma specimens were collected from patients with suspected placenta accreta spectrum, placenta previa, or repeat cesarean deliveries. Exosomes were quantified and characterized by nanoparticle tracking analysis and western blotting. MicroRNA were assessed by polymerase chain reaction array and targeted single quantification. MicroRNA pathway analysis was performed using the Ingenuity Pathway Analyses software. Placental biopsies were taken from all groups and analyzed by polymerase chain reaction and whole cell enzyme-linked immunosorbent assay. Receiver operating characteristic curve univariate analysis was performed for the use of microRNA in the prediction of placenta accreta spectrum. Clinically relevant outcomes were collected from abstracted medical records.ResultsPlasma specimens were analyzed from a total of 120 subjects (60 placenta accreta spectrum, 30 placenta previa, and 30 control). Isolated plasma exosomes had a mean size of 71.5 nm and were 10 times greater in placenta accreta spectrum specimens (20 vs 2 particles/frame). Protein expression of exosomes was positive for intracellular adhesion molecule 1, flotilin, annexin, and CD9. MicroRNA analysis showed increased detection of 3 microRNAs (mir-92, -103, and -192) in patients with placenta accreta spectrum. Pathway interaction assessment revealed differential regulation of p53 signaling in placenta accreta spectrum and of erythroblastic oncogene B2 or human epidermal growth factor 2 in control specimens. These findings were subsequently confirmed in placental protein analysis. Placental microRNA paralleled plasma exosomal microRNA expression. Biomarker assessment of placenta accreta spectrum signature microRNA had an area under the receiver operating characteristic curve of 0.81 (P<.001; 95% confidence interval, 0.73-0.89) with a sensitivity and specificity of 89.2% and 80%, respectively.ConclusionIn this large cohort, plasma exosomal microRNA assessment revealed differentially expressed pathways in placenta accreta spectrum, and these microRNAs are potential biomarkers for the detection of placenta accreta spectrum.

Project description:BackgroundTo identify incidence and underlying risk factors for unsuspected placenta accreta spectrum (PAS) and compare the maternal outcomes between suspected and unsuspected cases in three large academic referral centers.MethodsA retrospective cohort study was conducted in three university-based tertiary referral centers from Jan 1st, 2013, to Dec 31st, 2022. All cases of PAS confirmed by pathology were included in the study. Unsuspected PAS cases were diagnosed at the time of delivery, while suspected cases served as the control group. Potential risk factors were compared between the two groups. Multivariable regression model was also performed to identify risk factors. Maternal outcomes were also evaluated.ResultsA total of 339 pathology-confirmed PAS cases were included in the study out of 415,470 deliveries, of which 35.4% (n = 120) were unsuspected cases. Unsuspected PAS cases were 7.9 times more likely to have a history of intrauterine adhesions (adjusted odds ratio [aOR] 7.93; 95% confidence interval [CI] 2.35-26.81), 7.0 times more likely to have a history of clinically confirmed PAS (aOR, 6.99; 95% CI 2.85-17.18), 6.3 times more likely to have a posterior placenta (aOR, 6.30; 95% CI 3.48-11.40), and 3.4 times more likely to have a history of placenta previa (aOR, 3.41; 95% CI 1.18-9.82). On the other hand, cases with gravidity > 3, placenta previa, and/or a history of previous cesarean delivery were more likely to be diagnosed antenatally (aOR 0.40, 0.19, 0.36; 95% CI 0.22-0.74, 0.09-0.40, 0.19-0.70). Although the suspected PAS group had a higher proportion of invasive cases and abdominal and pelvic organ injuries (74.4% vs. 25.8%, p < 0.001; 6.8% vs. 1.7%, p = 0.037), the maternal outcomes were more favorable in the sPAS group, with a lower median volume of 24-hour blood loss and blood product transfusion (estimated blood loss in 24 h, 1000 [800-2000] vs. 2000 [1400-2400], p < 0.001; RBC unit transfusion, 0 [0-800] vs. 800 [600-1000], p < 0.001; fresh-frozen plasma transfusion, 0 [0-450] vs. 600 [400-800], p < 0.001).ConclusionsOur findings indicate that 35% of patients with PAS were unsuspected prior to delivery. Factors associated with PAS being unsuspected prior to delivery include a history of intrauterine adhesions, a history of clinically confirmed PAS, a posterior placenta, and a history of placenta previa. Additionally, gravidity > 3, a history of previous cesarean delivery, and placenta previa increase the likelihood of antenatal diagnosis.

Project description:BackgroundPlacenta accreta spectrum (PAS) is a rare, life-threatening complication of pregnancy. Predicting PAS severity is critical to individualise care planning for the birth. We aim to explore whether radiomic analysis of T2-weighted magnetic resonance imaging (MRI) can predict severe cases by distinguishing between histopathological subtypes antenatally.MethodsThis was a bi-centre retrospective analysis of a prospective cohort study conducted between 2018 and 2022. Women who underwent MRI during pregnancy and had histological confirmation of PAS were included. Radiomic features were extracted from T2-weighted images. Univariate regression and multivariate analyses were performed to build predictive models to differentiate between non-invasive (International Federation of Gynecology and Obstetrics [FIGO] grade 1 or 2) and invasive (FIGO grade 3) PAS using R software. Prediction performance was assessed based on several metrics including sensitivity, specificity, accuracy and area under the curve (AUC) at receiver operating characteristic analysis.ResultsForty-one women met the inclusion criteria. At univariate analysis, 0.64 sensitivity (95% confidence interval [CI] 0.0-1.00), specificity 0.93 (0.38-1.0), 0.58 accuracy (0.37-0.78) and 0.77 AUC (0.56-.097) was achieved for predicting severe FIGO grade 3 PAS. Using a multivariate approach, a support vector machine model yielded 0.30 sensitivity (95% CI 0.18-1.0]), 0.74 specificity (0.38-1.00), 0.58 accuracy (0.40-0.82), and 0.53 AUC (0.40-0.85).ConclusionOur results demonstrate a predictive potential of this machine learning pipeline for classifying severe PAS cases.Relevance statementThis study demonstrates the potential use of radiomics from MR images to identify severe cases of placenta accreta spectrum antenatally.Key points• Identifying severe cases of placenta accreta spectrum from imaging is challenging. • We present a methodological approach for radiomics-based prediction of placenta accreta. • We report certain radiomic features are able to predict severe PAS subtypes. • Identifying severe PAS subtypes ensures safe and individualised care planning for birth.

Dataset Information

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

Publications

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

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