Noninvasive prenatal testing: Advancing through a virtuous circle of science, technology and clinical applications

Lo, Y.M. Dennis

doi:10.1002/pd.5978

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…Emerging knowledge about plasma cfDNA, cell‐free RNA, epigenetics, tissue‐specific molecular signatures, and ‘fragmentomics’ reveals the complexity of this new biology 108,109 . Prenatal screening has proven to be the ‘poster child’ for clinical translation this field and will likely continue to be at the forefront of new applications 110 . Some of the exciting new directions include analysis of plasma cfRNA to monitor placental function 111,112 and the maternal plasma viral DNA to screen for perinatal infections, such as cytomegalovirus 113,114 …”

Section: Future Of Cell‐free Dna Screeningmentioning

confidence: 99%

Position statement from the International Society for Prenatal Diagnosis on the use of non‐invasive prenatal testing for the detection of fetal chromosomal conditions in singleton pregnancies

Hui

Ellis

Mayen³

et al. 2023

Prenatal Diagnosis

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Key points What is already known about this topic? In 2015, the International Society for Prenatal Diagnosis (ISPD) published its first position statement on the use of non‐invasive prenatal testing (NIPT) to screen for aneuploidy. Widespread uptake across the globe and subsequent published research has shed new light on test performance and implementation issues. What does this study add? This new position statement replaces the 2015 statement with updated information on the current technologies, clinical experience, and implementation practices. As an international organization, ISPD recognizes that there are important population‐specific considerations in the organization of prenatal screening and diagnosis. These opinions are designed to apply to high income settings where prenatal screening for aneuploidy is an established part of antenatal care. This position statement is not a clinical practice guideline but represents the consensus opinion of the current ISPD Board based on the current state of knowledge and clinical practice.

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Section: Future Of Cell‐free Dna Screeningmentioning

confidence: 99%

Position statement from the International Society for Prenatal Diagnosis on the use of non‐invasive prenatal testing for the detection of fetal chromosomal conditions in singleton pregnancies

Hui

Ellis

Mayen³

et al. 2023

Prenatal Diagnosis

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“…In pregnancy, the discovery of circulating fetal genetic material in the maternal plasma has enhanced the non-invasive prenatal diagnosis [ 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 ]. The placenta secretes a large number of EVs into maternal circulation since they are shed from the syncytiotrophoblast into the intervillous space and then flushed via the uterine veins into the maternal circulation [ 127 ].…”

Section: Extracellular Vesicles (Evs) As a Source Of Non-invasive Liq...mentioning

confidence: 99%

Placenta-Derived Extracellular Vesicles in Pregnancy Complications and Prospects on a Liquid Biopsy for Hemoglobin Bart’s Disease

Chaemsaithong

Luewan

Taweevisit

et al. 2023

IJMS

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Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original cells and tissues, including the placenta. Placenta-derived EVs can be detected in maternal circulation at as early as six weeks of gestation, and their release can be triggered by the oxygen level and glucose concentration. Placental-associated complications such as preeclampsia, fetal growth restriction, and gestational diabetes have alterations in placenta-derived EVs in maternal plasma, and this can be used as a liquid biopsy for the diagnosis, prediction, and monitoring of such pregnancy complications. Alpha-thalassemia major (“homozygous alpha-thalassemia-1”) or hemoglobin Bart’s disease is the most severe form of thalassemia disease, and this condition is lethal for the fetus. Women with Bart’s hydrops fetalis demonstrate signs of placental hypoxia and placentomegaly, thereby placenta-derived EVs provide an opportunity for a non-invasive liquid biopsy of this lethal condition. In this article, we introduced clinical features and current diagnostic markers of Bart’s hydrops fetalis, extensively summarize the characteristics and biology of placenta-derived EVs, and discuss the challenges and opportunities of placenta-derived EVs as part of diagnostic tests for placental complications focusing on Bart’s hydrop fetalis.

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“…Therefore, deciphering the protein content of EVs could provide further insight into the pathophysiology of pregnancy related complications [38] . In pregnancy, the discovery of circulating fetal genetic material in the maternal plasma has enhanced the non-invasive prenatal diagnosis [39,40,41,42,43,44,45,46,47] . The placenta secretes a large number of EVs into maternal circulation since they are shed from the syncytiotrophoblast into the intervillous space and then ushed via the uterine veins into the maternal circulation [48] .…”

Section: Introductionmentioning

confidence: 99%

Placenta-derived Extracellular Vesicles in Maternal Plasma of Hb Bart’s Fetuses

Chaemsaithong,

Warintaksa,

Ruangvutilert

et al. 2024

Preprint

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Introduction: Alpha-thalassemia is the most common cause of hydrops fetalis among Southeast Asians (also called “Bart’s hydrops fetalis). This condition is considered a fatal disorder; therefore, prenatal screening and diagnosis are extremely important. Changes in soluble analytes in the maternal circulation, such as hormones and angiogenic factors are not predictive of Hb Bart’s fetalis condition. This condition is associated with placental hypoxia, which may trigger the release of placenta-derived extracellular vesicles (EVs) in maternal circulation. Therefore, the determination of changes in placenta-derived exosome and its protein content could provide additional insight into the disease pathways of this disorder. Objectives: We aim to characterize: 1) maternal plasma levels of placenta-derived EVs; and 2) proteomics profiles of maternal plasma EVs in women with Bart’s fetalis fetuses. Methods: This prospective cohort study included women with the following groups: 1) normal pregnancy or control group: women with couple at risk for Hb Bart’s fetuses but subsequently proven as non-Hb Bart’s group and delivered at term without maternal or neonatal complications (Group 1) (n=7); 2) Hb Bart’s with hydropic features group (Group 2) (n=4); 3) Hb Bart’s without hydropic features group (Group 3) (n=7); 4) a disease control group which consisted of women who subsequently delivered with placental associated conditions (Group 4) (n=4); and 5) women with hydrops fetalis from non-Bart’s causes (n=5) (Group 5). Maternal plasma EVs were isolated by the combination of stepwise centrifugation, ultrafiltration and qEV size exclusion chromatography. The EVs were characterized by the particle size, morphology and protein markers. Isolated EVs and their plasma were measured placental alkaline phosphatase (PLAP) level using ELISA. Mass spectrometry was used to determine EV proteomics profile. A p-value of <0.05 was used to infer significance, unless multiple testing was involved, with the false discovery rate controlled at the 10% level (q<0.1). Results: 1) EV particle size in Bart fetuses with hydropic features was significantly smaller than that in normal pregnancy and disease control groups; 2) Bart fetuses with hydropic features had higher maternal placenta-derived PLAP-contained EVs (PLAP-EVs) than that in normal pregnancy; although, PLAP-EV level was highest in the placental associated complications group; 3) Bart fetuses without hydropic features tended to have higher maternal PLAP-EV level compared to normal pregnancy group; 4) hydropic fetuses due to non-Bart’s causes had similar PLAP level compared to normal pregnancy group; 5) among the 16/106 differentially expressed EV proteins, hnRNPA2B1 protein was the highest in Bart fetuses with hydropic features group compared to placental associated complication or normal pregnancy groups; 6) sixteen differentially expressed EV proteins were involved in fibrinogen complex, fibrin clot formation and integrin signaling pathway. Conclusions: This is the first study of placenta-derived EVs in women with Hb Bart’s fetalis. EV particle size is significantly smaller but maternal PLAP-EV level is significantly higher in women with Hb Bart’s fetalis fetuses compared to normal pregnancy. In addition, several EV proteins were differential expressed in women with Bart’s fetuses and these proteins involve in aberrant immune response, pro-inflammatory cytokine regulation mediated by TLRs-MyD88-IRAK4-MAPK axis and vascular injuries as part of pathophysiology of placental edema and hypoxia in Bart’s hydrops. The result of this study supports future research to determine whether placenta-derived EVs in maternal circulation can be used as a liquid biopsy or non-invasive prenatal test for the early identification of Bart’s fetuses. This will ultimately reduce the rate of unnecessary invasive prenatal diagnosis testing.

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Noninvasive prenatal testing: Advancing through a virtuous circle of science, technology and clinical applications

Cited by 5 publications

References 25 publications

Position statement from the International Society for Prenatal Diagnosis on the use of non‐invasive prenatal testing for the detection of fetal chromosomal conditions in singleton pregnancies

Position statement from the International Society for Prenatal Diagnosis on the use of non‐invasive prenatal testing for the detection of fetal chromosomal conditions in singleton pregnancies

Placenta-Derived Extracellular Vesicles in Pregnancy Complications and Prospects on a Liquid Biopsy for Hemoglobin Bart’s Disease

Placenta-derived Extracellular Vesicles in Maternal Plasma of Hb Bart’s Fetuses

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