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Article ; Online: Exclusion criteria for reference studies: Context is key.

Dockree, Samuel / Shine, Brian / James, Tim / Vatish, Manu

2023 Volume 60, Issue 4, Page(s) 290–291

MeSH term(s)	Humans ; Patient Selection
Language	English
Publishing date	2023-03-19
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	390309-6
ISSN	1758-1001 ; 0004-5632
ISSN (online)	1758-1001
ISSN	0004-5632
DOI	10.1177/00045632231159785
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Zs.A 889: Show issues

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Article ; Online: FIGO good practice recommendations for preterm labor and preterm prelabor rupture of membranes: Prep-for-Labor triage to minimize risks and maximize favorable outcomes.

Ubom, Akaninyene Eseme / Vatish, Manu / Barnea, Eytan R

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics

2023 Volume 163 Suppl 2, Page(s) 40–50

Abstract: Preterm labor occurs in around 10% of pregnancies worldwide. Once diagnosed, significant efforts must be made to reduce the likelihood of morbidity and mortality associated with preterm birth. In high-resource settings, access to hospitals with a ... ...

Abstract	Preterm labor occurs in around 10% of pregnancies worldwide. Once diagnosed, significant efforts must be made to reduce the likelihood of morbidity and mortality associated with preterm birth. In high-resource settings, access to hospitals with a neonatal intensive care unit (NICU) is readily available, whereas access to NICU care is limited in low- and middle-income countries (LMICs) and many rural settings. Use of FIGO's Prep-for-Labor triage method rapidly identifies low- and high-risk patients with preterm labor to enable clinicians to decide whether the patient can be managed on site or if transfer to a level II-IV facility is needed. The management steps described in this paper aim to minimize the morbidity and mortality associated with preterm labor and in the setting of preterm labor with preterm premature rupture of membranes (PPROM). The methods for accurate diagnosis of PPROM and chorioamnionitis are described. When the risk of preterm birth is high, antenatal corticosteroids should be administered for lung maturation combined with limited tocolysis for 48 hours to permit the corticosteroid course to be completed. Magnesium sulfate is also administered for fetal neuroprotection. Implementation of FIGO's Prep-for-Labor triage method in an LMIC setting will help improve maternal and neonatal outcomes.
MeSH term(s)	Pregnancy ; Infant, Newborn ; Humans ; Female ; Premature Birth/prevention & control ; Triage ; Obstetric Labor, Premature/diagnosis ; Obstetric Labor, Premature/prevention & control ; Fetal Membranes, Premature Rupture/diagnosis ; Fetal Membranes, Premature Rupture/therapy ; Adrenal Cortex Hormones/therapeutic use
Chemical Substances	Adrenal Cortex Hormones
Language	English
Publishing date	2023-10-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	80149-5
ISSN	1879-3479 ; 0020-7292
ISSN (online)	1879-3479
ISSN	0020-7292
DOI	10.1002/ijgo.15113
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Zs.A 355: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 183: Show issues

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Article ; Online: Novel therapeutic and diagnostic approaches for preeclampsia.

Vatish, Manu / Powys, Veronica R / Cerdeira, Ana Sofia

Current opinion in nephrology and hypertension

2023 Volume 32, Issue 2, Page(s) 124–133

Abstract: Purpose of review: This review will summarize recent findings relating to the diagnostic approach to preeclampsia and current avenues of research aimed at modifying the underlying disease process.: Recent findings: Growing international consensus ... ...

Abstract	Purpose of review: This review will summarize recent findings relating to the diagnostic approach to preeclampsia and current avenues of research aimed at modifying the underlying disease process. Recent findings: Growing international consensus supports a broad preeclampsia definition that incorporates maternal end-organ and uteroplacental dysfunction. Recent evidence demonstrates that this definition better identifies women and babies at risk of adverse outcomes compared to the traditional definition of hypertension and proteinuria. Multiple studies have demonstrated the usefulness and cost-effectiveness of angiogenic biomarkers such as soluble fms-like tyrosine kinase-1 and placental growth factor as a clinical adjunct to diagnose and predict severity of preeclampsia associated outcomes. Current novel therapeutic approaches to preeclampsia target pathogenic pathways (e.g. antiangiogenesis) or downstream effects such as oxidative stress and nitric oxide. Recent findings relating to these promising candidates are discussed. Multicenter clinical trials are needed to evaluate their effectiveness and ability to improve fetal and maternal outcomes. Summary: We provide an updated framework of the current approaches to define and diagnose preeclampsia. Disease modifying therapies (in particular, targeting the angiogenic pathway) are being developed for the first time and promise to revolutionize the way we manage preeclampsia.
MeSH term(s)	Female ; Humans ; Pregnancy ; Biomarkers/metabolism ; Multicenter Studies as Topic ; Placenta Growth Factor ; Pre-Eclampsia/diagnosis ; Pre-Eclampsia/therapy ; Vascular Endothelial Growth Factor Receptor-1/metabolism
Chemical Substances	Biomarkers ; Placenta Growth Factor (144589-93-5) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1)
Language	English
Publishing date	2023-01-09
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	1151092-4
ISSN	1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
ISSN (online)	1473-6543 ; 1535-3842
ISSN	1062-4813 ; 1062-4821
DOI	10.1097/MNH.0000000000000870
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Zs.A 3686: Show issues

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Article ; Online: Clinical utility of sFlt-1 and PlGF in screening, prediction, diagnosis and monitoring of pre-eclampsia and fetal growth restriction.

Stepan, H / Galindo, A / Hund, M / Schlembach, D / Sillman, J / Surbek, D / Vatish, M

Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology

2022 Volume 61, Issue 2, Page(s) 168–180

Abstract: Pre-eclampsia (PE) is characterized by placental and maternal endothelial dysfunction, and associated with fetal growth restriction (FGR), placental abruption, preterm delivery and stillbirth. The angiogenic factors soluble fms-like tyrosine kinase-1 ( ... ...

Abstract	Pre-eclampsia (PE) is characterized by placental and maternal endothelial dysfunction, and associated with fetal growth restriction (FGR), placental abruption, preterm delivery and stillbirth. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are altered in pregnancies complicated by placenta-related disorders. In this Review, we summarize the existing knowledge, examining the performance of maternal PlGF, sFlt-1 and the sFlt-1/PlGF ratio for screening PE, predicting development of PE in the short term, diagnosing PE, monitoring established PE and predicting other placenta-related disorders in singleton pregnancy. We also discuss the performance of PlGF and the sFlt-1/PlGF ratio for predicting PE in twin pregnancy. For first-trimester screening in singleton pregnancy, a more accurate way of identifying high-risk women than current practice is to combine maternal PlGF levels with clinical risk factors and ultrasound markers. Later in pregnancy, the sFlt-1/PlGF ratio has advantages over PlGF because it has a higher pooled sensitivity and specificity for diagnosing and monitoring PE. It has clinical value because it can rule out the development of PE in the 1-4-week period after the test. Once a diagnosis of PE is established, repeat measurement of sFlt-1 and PlGF can help monitor progression of the condition and may inform clinical decision-making regarding the optimal time for delivery. The sFlt-1/PlGF ratio is useful for predicting FGR and preterm delivery, but the association between stillbirth and the angiogenic factors is unclear. The sFlt-1/PlGF ratio can be used to predict PE in twin pregnancy, although different sFlt-1/PlGF ratio cut-offs from those for singleton pregnancy should be applied for optimal performance. In summary, PlGF, sFlt-1 and the sFlt-1/PlGF ratio are useful for screening, diagnosing, predicting and monitoring placenta-related disorders in singleton and twin pregnancy. We propose that tests for these angiogenic factors are integrated more fully into clinical practice.© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
MeSH term(s)	Infant, Newborn ; Pregnancy ; Female ; Humans ; Placenta Growth Factor ; Pre-Eclampsia/diagnosis ; Pre-Eclampsia/metabolism ; Fetal Growth Retardation/diagnosis ; Premature Birth ; Stillbirth ; Predictive Value of Tests ; Biomarkers ; Vascular Endothelial Growth Factor Receptor-1 ; Placenta/metabolism ; Vascular Endothelial Growth Factor A
Chemical Substances	Placenta Growth Factor (144589-93-5) ; Biomarkers ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1) ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2022-12-02
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1073183-0
ISSN	1469-0705 ; 0960-7692
ISSN (online)	1469-0705
ISSN	0960-7692
DOI	10.1002/uog.26032
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Zs.A 3214: Show issues

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Article ; Online: Protein Profiling of Placental Extracellular Vesicles in Gestational Diabetes Mellitus.

Kandzija, Neva / Payne, Sophie / Cooke, William R / Seedat, Faheem / Fischer, Roman / Vatish, Manu

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Throughout pregnancy, some degree of insulin resistance is necessary to divert glucose towards the developing foetus. In gestational diabetes mellitus (GDM), insulin resistance is exacerbated in combination with insulin deficiency, causing new-onset ... ...

Abstract	Throughout pregnancy, some degree of insulin resistance is necessary to divert glucose towards the developing foetus. In gestational diabetes mellitus (GDM), insulin resistance is exacerbated in combination with insulin deficiency, causing new-onset maternal hyperglycaemia. The rapid reversal of insulin resistance following delivery strongly implicates the placenta in GDM pathogenesis. In this case-control study, we investigated the proteomic cargo of human syncytiotrophoblast-derived extracellular vesicles (STBEVs), which facilitate maternal-fetal signalling during pregnancy, in a UK-based cohort comprising patients with a gestational age of 38-40 weeks. Medium/large (m/l) and small (s) STBEVs were isolated from GDM (n = 4) and normal (n = 5) placentae using ex vivo dual-lobe perfusion and subjected to mass spectrometry. Bioinformatics were used to identify differentially carried proteins and mechanistic pathways. In m/lSTBEVs, 56 proteins were differently expressed while in sSTBEVs, no proteins reached statistical difference. Differences were also observed in the proteomic cargo between m/lSTBEVs and sSTBEVs, indicating that the two subtypes of STBEVs may have divergent modes of action and downstream effects. In silico functional enrichment analysis of differentially expressed proteins in m/lSTBEVs from GDM and normal pregnancy found positive regulation of cytoskeleton organisation as the most significantly enriched biological process. This work presents the first comparison of two populations of STBEVs' protein cargos (m/l and sSTBEVs) from GDM and normal pregnancy isolated using placenta perfusion. Further investigation of differentially expressed proteins may contribute to an understanding of GDM pathogenesis and the development of novel diagnostic and therapeutic tools.
MeSH term(s)	Pregnancy ; Humans ; Female ; Infant ; Placenta/metabolism ; Diabetes, Gestational/metabolism ; Insulin Resistance/physiology ; Proteomics/methods ; Case-Control Studies ; Extracellular Vesicles/metabolism
Language	English
Publishing date	2024-02-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25041947
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Article ; Online: A method to isolate syncytiotrophoblast-derived medium-large extracellular vesicle small RNA from maternal plasma.

Cooke, William R / Zhang, Wei / Kandzija, Neva / Jones, Gabriel Davis / Redman, Christopher Wg / Vatish, Manu

Placenta

2024

Abstract: Syncytiotrophoblast-derived extracellular vesicles (STB-EVs) have an important role in placental research: both as mediators of feto-maternal signalling and as liquid biopsies reflecting placental health. Recent evidence highlights the importance of STB- ... ...

Abstract	Syncytiotrophoblast-derived extracellular vesicles (STB-EVs) have an important role in placental research: both as mediators of feto-maternal signalling and as liquid biopsies reflecting placental health. Recent evidence highlights the importance of STB-EV RNA. Isolation of STB-EV RNA from maternal blood is therefore an important challenge. We describe a novel technique where we first separate medium-large particles from plasma using centrifugation then use a highly specific bead-bound antibody to placental alkaline phosphatase to separate STB-EVs from other similar-sized particles. We demonstrate the yield and size profile of small RNA obtained from plasma STB-EVs. We present data confirming isolation of placenta-derived micro RNA from maternal plasma using this method. The technique has been successfully applied to validate novel RNA discoveries from placental perfusion models. We propose it could offer new insights through transcriptomic analyses, providing a syncytiotrophoblast-specific signal from maternal blood.
Language	English
Publishing date	2024-04-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	603951-0
ISSN	1532-3102 ; 0143-4004
ISSN (online)	1532-3102
ISSN	0143-4004
DOI	10.1016/j.placenta.2024.03.010
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Zs.A 1578: Show issues

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Article ; Online: Pregnancy-specific reference intervals: should we exclude women based on body mass index?

Dockree, Samuel / Shine, Brian / James, Tim / Vatish, Manu

Annals of clinical biochemistry

2022 Volume 60, Issue 2, Page(s) 146–147

MeSH term(s)	Pregnancy ; Female ; Humans ; Body Mass Index ; Thyroid Gland ; Thyroid Function Tests ; Reference Values
Language	English
Publishing date	2022-11-03
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	390309-6
ISSN	1758-1001 ; 0004-5632
ISSN (online)	1758-1001
ISSN	0004-5632
DOI	10.1177/00045632221138023
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Article ; Online: The diagnostic value of angiogenic and antiangiogenic factors in differential diagnosis of preeclampsia.

Cerdeira, Ana Sofia / James, Tim / Vatish, Manu

American journal of obstetrics and gynecology

2021 Volume 226, Issue 1, Page(s) 156

MeSH term(s)	Diagnosis, Differential ; Female ; Humans ; Placenta Growth Factor ; Pre-Eclampsia/diagnosis ; Pregnancy ; Vascular Endothelial Growth Factor Receptor-1
Chemical Substances	Placenta Growth Factor (144589-93-5) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1)
Language	English
Publishing date	2021-09-02
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	80016-8
ISSN	1097-6868 ; 0002-9378
ISSN (online)	1097-6868
ISSN	0002-9378
DOI	10.1016/j.ajog.2021.08.048
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Article ; Online: Differential 5'-tRNA Fragment Expression in Circulating Preeclampsia Syncytiotrophoblast Vesicles Drives Macrophage Inflammation.

Cooke, William R / Jiang, Peiyong / Ji, Lu / Bai, Jinyue / Jones, Gabriel Davis / Lo, Y M Dennis / Redman, Christopher / Vatish, Manu

Hypertension (Dallas, Tex. : 1979)

2024 Volume 81, Issue 4, Page(s) 876–886

Abstract: Background: The relationship between placental pathology and the maternal syndrome of preeclampsia is incompletely characterized. Mismatch between placental nutrient supply and fetal demands induces stress in the syncytiotrophoblast, the layer of ... ...

Abstract	Background: The relationship between placental pathology and the maternal syndrome of preeclampsia is incompletely characterized. Mismatch between placental nutrient supply and fetal demands induces stress in the syncytiotrophoblast, the layer of placenta in direct contact with maternal blood. Such stress alters the content and increases the release of syncytiotrophoblast extracellular vesicles (STB-EVs) into the maternal circulation. We have previously shown 5'-tRNA fragments (5'-tRFs) constitute the majority of small RNA in STB-EVs in healthy pregnancy. 5'-tRFs are produced in response to stress. We hypothesized STB-EV 5'-tRF release might change in preeclampsia. Methods: We perfused placentas from 8 women with early-onset preeclampsia and 6 controls, comparing small RNA expression in STB-EVs. We used membrane-affinity columns to isolate maternal plasma vesicles and investigate placental 5'-tRFs in vivo. We quantified 5'-tRFs from circulating STB-EVs using a placental alkaline phosphatase immunoassay. 5'-tRFs and scrambled RNA controls were added to monocyte, macrophage and endothelial cells in culture to investigate transcriptional responses. Results: 5'-tRFs constitute the majority of small RNA in STB-EVs from both preeclampsia and normal pregnancies. More than 900 small RNA fragments are differentially expressed in preeclampsia STB-EVs. Preeclampsia-dysregulated 5'-tRFs are detectable in maternal plasma, where we identified a placentally derived load. 5'-tRF-Glu-CTC, the most abundant preeclampsia-upregulated 5'-tRF in perfusion STB-EVs, is also increased in preeclampsia STB-EVs from maternal plasma. 5'-tRF-Glu-CTC induced inflammation in macrophages but not monocytes. The conditioned media from 5'-tRF-Glu-CTC-activated macrophages reduced eNOS (endothelial NO synthase) expression in endothelial cells. Conclusions: Increased release of syncytiotrophoblast-derived vesicle-bound 5'-tRF-Glu-CTC contributes to preeclampsia pathophysiology.
MeSH term(s)	Pregnancy ; Female ; Humans ; Placenta/metabolism ; Pre-Eclampsia ; Endothelial Cells/metabolism ; Trophoblasts/metabolism ; Extracellular Vesicles/metabolism ; RNA, Transfer/metabolism ; Macrophages/metabolism ; Inflammation/metabolism
Chemical Substances	RNA, Transfer (9014-25-9)
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/HYPERTENSIONAHA.123.22292
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Zs.A 1488: Show issues

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Article: MicroRNA analysis of medium/large placenta extracellular vesicles in normal and preeclampsia pregnancies.

Awoyemi, Toluwalase / Jiang, Shuhan / Rahbar, Maryam / Logentherian, Prasanna / Collett, Gavin / Zhang, Wei / Cribbs, Adam / Cerdeira, Sofia / Vatish, Manu

Frontiers in cardiovascular medicine

2024 Volume 11, Page(s) 1371168

Abstract: Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy, affecting 2%-8% of pregnancies worldwide, and is the leading cause of adverse maternal and fetal outcomes. The disease is characterized by oxidative and cellular stress and ... ...

Abstract	Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy, affecting 2%-8% of pregnancies worldwide, and is the leading cause of adverse maternal and fetal outcomes. The disease is characterized by oxidative and cellular stress and widespread endothelial dysfunction. While the precise mechanisms are not entirely understood, the pathogenesis of PE is closely linked to placental dysfunction and, to some extent, syncytiotrophoblast extracellular vesicle release (STB-EVs). These vesicles can be divided into the less well-studied medium/large EVs (220-1,000 nm) released in response to stress and small EVs (<220 nm) released as a component of intercellular communication. The previously described production of m/lSTB-EVs in response to cellular stress combined with the overwhelming occurrence of cellular and oxidative stress in PE prompted us to evaluate the microRNAome of PE m/lSTB-EVs. We hypothesized that the microRNAome profile of m/lSTB-EVs is different in PE compared to normal pregnancy (NP), which might permit the identification of potential circulating biomarkers not previously described in PE. Methods/study design: We performed small RNA sequencing on medium/large STB-EVs isolated from PE and NP placentae using dual-lobe ex vivo perfusion. The sequencing data was bioinformatically analyzed to identify differentially regulated microRNAs. Identified microRNAs were validated with quantitative PCR analysis. We completed our analysis by performing an in-silico prediction of STB-EV mechanistic pathways. Results: We identified significant differences between PE and NP in the STB-EVs micro ribonucleic acid (microRNA) profiles. We verified the differential expression of Conclusions: We identified a differentially regulated micro-RNA,
Language	English
Publishing date	2024-04-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2024.1371168
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