Blood biomarkers to predict the onset of pre-eclampsia: A systematic review and meta-analysis

Danielli, Marianna; Thomas, Roisin; Gillies, Clare; Hu, Jiamiao; Khunti, Kamlesh; Tan, Bee K.

doi:10.1016/j.heliyon.2022.e11226

Cited by 9 publications

(6 citation statements)

References 117 publications

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“…Here, we find that in PE, they augment the maternal blood levels of PP13. This may be linked to the cytokine storm or to the changes in the levels of TNF-alpha in PE [34][35][36], which are linked to the loss of immune tolerance in PE.…”

Section: Discussionmentioning

confidence: 99%

Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids

Kazatsker

Sharabi-Nov

Meiri³

et al. 2023

IJMS

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Placental protein 13 (PP13) is a regulatory protein involved in remodeling the vascular system of the pregnancy and extending the immune tolerance of the mother to the growing fetus. PP13 is localized on the surface of the syncytiotrophoblast. An ex vivo placental model shows that the PP13 is released via placental-associated extracellular vesicles (PEVs) to the maternal uterine vein. This exploratory study aimed to determine PEV-associated PP13 in the maternal circulation as compared to the known soluble fraction since each has a specific communication pathway. Patients admitted to Bnai Zion Medical Center for delivery were recruited, and included 19 preeclampsia (PE) patients (7 preterm PE gestational age < 37 weeks’ gestation), 16 preterm delivery (PTD, delivery at GA < 37 weeks’ gestation), and 15 matched term delivery controls. Treatment by corticosteroids (Celestone), which is often given to patients with suspected preterm PE and PTD, was recorded. The PEV proteome was purified from the patients’ plasma by size exclusion chromatography (SEC) to separate the soluble and PEV-associated PP13. The total level of PP13 (soluble and PEV-associated) was determined using mild detergent that depleted the PEV proteome. PP13 fractions were determined by ELISA with PP13 specific antibodies. ELISA with alkaline phosphatase (PLAP)- and cluster differentiation 63 (CD63)-specific antibodies served to verify the placental origin of the PEVs. SPSS was used for statistical analysis. The patients’ medical, pregnancy, and delivery records in all groups were similar except, as expected, that a larger number of PE and PTD patients had smaller babies who were delivered earlier, and the PE patients had hypertension and proteinuria. The SEC analysis detected the presence of PP13 in the cargo of the PEVs and on their surface, in addition to the known soluble fraction. The median soluble PP13 was not significantly different across the PE, PTD, and term delivery control groups. However, after depleting the PEV of their proteome, the total PP13 (soluble and PEV-associated) was augmented in the cases of preterm PE, reaching 2153 pg/mL [IQR 1866–2838] but not in cases of PTD reaching 1576 pg/mL [1011–2014] or term delivery groups reaching 964 pg/mL [875–1636]), p < 0.01. On the surface of the circulating PEV from PTD patients, there was a decrease in PP13. Corticosteroid treatment was accompanied by a massive depletion of PP13 from the PEV, especially in preterm PE patients. This exploratory study is, thus, the first to determine PEV-associated PP13 in maternal circulation, providing a quantitative determination of the soluble and the PEV-associated fractions, and it shows that the latter is the larger. We found an increase in the amount of PP13 carried via the PEV-associated pathway in PE and PTD patients compared to term delivery cases, which was further augmented when the patients were treated with corticosteroids, especially in preterm PE. The signal conveyed by this novel communication pathway warrants further research to investigate these two differential pathways for the liberation of PP13.

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Section: Discussionmentioning

confidence: 99%

Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids

Kazatsker

Sharabi-Nov

Meiri³

et al. 2023

IJMS

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“…The serum and urinary test results during pregnancy are critical for assessing maternal and fetal health status and predicting adverse postnatal outcomes [16][17][18] . For example, the high maternal glucose level is an indication of the risk of developing gestational diabetes 19 , and abnormal maternal hemoglobin levels may be a warning of preterm birth 20,21 .…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of 104 pregnancy phenotypes in 39,194 Chinese women

Xiao,

Li,

Yang

et al. 2023

Preprint

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Maternity is a special period in a woman’s life that involves substantial physiological, psychological, and hormonal changes. These changes may cause alterations in many clinical measurements during pregnancy, which can be used to monitor and diagnose maternal disorders and adverse postnatal outcomes. Exploring the genetic background of these phenotypes is key to elucidating the pathogenesis of pregnancy disorders. In this study, we conducted a large-scale molecular biology analysis of 104 pregnancy phenotypes based on genotype data from 39,194 Chinses women. Genome- wide association analysis identified a total of 407 trait-locus associations, of which 75.18% were previously reported. Among the 101 novel associations for 37 phenotypes, some were potentially pregnancy-specific and worth further experimental investigation. For example,ESR1with fasting glucose, hemoglobin, hematocrit, and several leukocytoses;ZSCAN31with blood urea nitrogen. We further performed pathway- based analysis and uncovered at least one significant pathway for 24 traits, in addition to previously known functional pathways, novel findings included birthweight with “Reactome signaling by NODAL”, twin pregnancy with “Reactome mitotic G1-G1/S phases”. The partitioning heritability analysis recapitulated known trait-relevant tissue/cell types, and also discovered interesting results including twin pregnancy with “embryoid bodies” cell-type enrichment, the delivery type cesarean section with “fallopian tube”, and birth weight with “ovary and embryonic stem cells”. In terms of both sample size and the variety of phenotypes, our work is one of the largest genetic studies of pregnancy phenotypes across all populations. We believe that this study will provide a valuable resource for exploring the genetic background of pregnancy phenotypes and also for further research on pregnancy-related diseases and adverse neonatal outcomes.

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“…Currently, screening to predict pre-eclampsia is limited to obtaining an appropriate medical history, and no biomarker has proven to be effective in the first trimester of pregnancy (when intervention is most likely to be effective) [ 4 ]. As shown in our recent systematic review with meta-analysis focused on all blood biomarkers used to detect PE, even if Placental Growth Factor (PlGF) and soluble Flt-1 (sFlt-1) are the most widely used biomarkers in clinical practice, their use is limited to later stages of pregnancy [ 5 ]. Thus, a robust diagnosis of PE remains a challenge for current clinical practice, and its identification in the first trimester an ambitious goal [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Soluble Vascular Adhesion Protein 1 (sVAP-1) as a biomarker for pregnancy complications: A pilot study

et al. 2023

Self Cite

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Background Vascular adhesion protein 1 (VAP-1) has been implicated in a wide range of clinical conditions. Moreover, serum levels are associated with disease prediction and progression in several clinical studies. There is a paucity of data on VAP-1 and pregnancy. Given the emerging role of VAP-1 in pregnancy, the aim of this study was to examine sVAP-1 as an early biomarker of pregnancy complications, especially hypertension during pregnancy. The objectives of the study are to associate sVAP-1 levels with other pregnancy complications, patient demographics and blood tests performed throughout pregnancy. Methods We conducted a pilot study in a cohort of pregnant women (gestational week lower than 20 at the time of recruitment) attending their first antenatal ultrasound scan at the Leicester Royal Infirmary (LRI, UK). Data were both prospectively generated (from blood sample analysis) and retrospectively collected (from hospital records). Results From July and October 2021, a total of 91 participants were enrolled. Using ELISA (enzyme-linked immunosorbent assay), we found reduced serum levels of sVAP-1 in pregnant women with either pregnancy induced hypertension (PIH) (310 ng/mL) or GDM (366.73 ng/mL) as compared to controls (427.44 ng/mL and 428.34 ng/mL, respectively). No significant difference was found between women with FGR compared to controls (424.32 ng/mL vs 424.52 ng/mL), and patients with any pregnancy complications compared to healthy pregnancies (421.28 ng/mL vs 428.34 ng/mL). Conclusion Further studies are needed to establish whether or not sVAP-1 might be considered as an early, non-invasive, and affordable biomarker to screen women who will develop PIH or GDM. Our data will aid sample size calculations for such larger studies.

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Blood biomarkers to predict the onset of pre-eclampsia: A systematic review and meta-analysis

Cited by 9 publications

References 117 publications

Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids

Augmented Placental Protein 13 in Placental-Associated Extracellular Vesicles in Term and Preterm Preeclampsia Is Further Elevated by Corticosteroids

Genetic analysis of 104 pregnancy phenotypes in 39,194 Chinese women

Soluble Vascular Adhesion Protein 1 (sVAP-1) as a biomarker for pregnancy complications: A pilot study

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