Can the quantity of cell‐free fetal DNA predict preeclampsia: a systematic review

Martin, Angela; Krishna, Iris; Martina, Benedict; Samuel, Amber

doi:10.1002/pd.4416

Cited by 59 publications

(52 citation statements)

References 72 publications

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“…It has been shown that the placenta is the major source of circulating cell-free fetal nucleic acids in maternal plasma (5)(6)(7). Significantly elevated levels of total cell-free DNA and selected placenta-specific RNA transcripts have also been reported in the maternal plasma of women with PE (8)(9)(10)(11), restricted fetal growth (12), and preterm birth (13)(14)(15), supporting a role for cell-free nucleic acids as a noninvasive tool for placental monitoring. Previous studies have attempted to provide a comprehensive assessment of maternal plasma nucleic acids by microarray analysis, massively parallel transcriptomic, or methylomic sequencing (16)(17)(18)(19)(20)(21)(22).…”

mentioning

confidence: 94%

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Tsang

Vong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

256

267

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The human placenta is a dynamic and heterogeneous organ critical in the establishment of the fetomaternal interface and the maintenance of gestational well-being. It is also the major source of cell-free fetal nucleic acids in the maternal circulation. Placental dysfunction contributes to significant complications, such as preeclampsia, a potentially lethal hypertensive disorder during pregnancy. Previous studies have identified significant changes in the expression profiles of preeclamptic placentas using whole-tissue analysis. Moreover, studies have shown increased levels of targeted RNA transcripts, overall and placental contributions in maternal cell-free nucleic acids during pregnancy progression and gestational complications, but it remains infeasible to noninvasively delineate placental cellular dynamics and dysfunction at the cellular level using maternal cell-free nucleic acid analysis. In this study, we addressed this issue by first dissecting the cellular heterogeneity of the human placenta and defined individual cell-type-specific gene signatures by analyzing more than 24,000 nonmarker selected cells from full-term and early preeclamptic placentas using large-scale microfluidic single-cell transcriptomic technology. Our dataset identified diverse cellular subtypes in the human placenta and enabled reconstruction of the trophoblast differentiation trajectory. Through integrative analysis with maternal plasma cell-free RNA, we resolved the longitudinal cellular dynamics of hematopoietic and placental cells in pregnancy progression. Furthermore, we were able to noninvasively uncover the cellular dysfunction of extravillous trophoblasts in early preeclamptic placentas. Our work showed the potential of integrating transcriptomic information derived from single cells into the interpretation of cell-free plasma RNA, enabling the noninvasive elucidation of cellular dynamics in complex pathological conditions. single-cell transcriptomics | cell-free RNA | noninvasive prenatal testing | placenta | preeclampsia

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mentioning

confidence: 94%

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Tsang

Vong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

256

267

View full text Add to dashboard Cite

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“…46 Cell-free fetal DNA cfDNA and cffDNA are also probable combined biomarkers of PE, mainly due to their sensitivity and specificity in biological fluids. 47,48 The identification of the methylated RASSF1A promoter gene, which is elevated in early-PE pregnancies, [49][50][51] offers a promising alternative to the quantification of cffDNA, using Y-chromosome-specific sequences. 52 Notably, high doses of human cffDNA did not induce PE-like symptoms in a murine in vivo model, 53 reinforcing the notion that the increase in RASSF1A methylation is a consequence rather than a cause of PE.…”

mentioning

confidence: 99%

Placenta-derived exosomes: potential biomarkers of preeclampsia

Pillay¹,

Moodley²,

Moodley³

et al. 2017

IJN

107

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Preeclampsia remains a leading cause of maternal and fetal mortality, due to ineffective treatment and diagnostic strategies, compounded by the lack of clarity on the etiology of the disorder. Although several clinical and biological markers of preeclampsia have been evaluated, they have proven to be ineffective in providing a definitive diagnosis during the various stages of the disorder. Exosomes have emerged as ideal biomarkers of pathological states, such as cancer, and have more recently gained interest in pregnancy-related complications, due to their role in cellular communication in normal and complicated pregnancies. This occurs as a result of the specific placenta-derived exosomal molecular cargo, which may be involved in normal pregnancy-associated immunological events, such as the maintenance of maternal–fetal tolerance. This review provides perspectives on placenta-derived exosomes as possible biomarkers for the diagnosis/prognosis of preeclampsia. Using keywords, online databases were searched to identify relevant publications to review the potential use of placenta-derived exosomes as biomarkers of preeclampsia.

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“…[76][77][78] However, conclusions about clinical applicability are limited by the heterogeneity in study design, PE definition, and gestational ages at blood draw and/ or approaches used. For example, inclusion of cases of late-onset PE or preexisting hypertension may increase heterogeneity of etiology.…”

Section: Preeclampsiamentioning

confidence: 98%

Noninvasive nucleic acid–based approaches to monitor placental health and predict pregnancy-related complications

Manokhina

Wilson

Robinson

2015

American Journal of Obstetrics and Gynecology

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During pregnancy, the placenta releases a variety of nucleic acids (including deoxyribonucleic acid, messenger ribonucleic acid, or microribonucleic acids) either as a result of cell turnover or as an active messaging system between the placenta and cells in the maternal body. The profile of released nucleic acids changes with the gestational age and has been associated with maternal and fetal parameters. It also can directly reflect pathological changes in the placenta. Nucleic acids may therefore provide a rich source of novel biomarkers for the prediction of pregnancy complications. However, their utility in the clinical setting depends, first, on overcoming some technical considerations in their quantification, and, second, on developing a better understanding of the factors that influence their function and abundance.

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Can the quantity of cell‐free fetal DNA predict preeclampsia: a systematic review

Cited by 59 publications

References 72 publications

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Placenta-derived exosomes: potential biomarkers of preeclampsia

Noninvasive nucleic acid–based approaches to monitor placental health and predict pregnancy-related complications

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