scholarly journals Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e050963
Author(s):  
Qianyang Huang ◽  
Shiying Hao ◽  
Jin You ◽  
Xiaoming Yao ◽  
Zhen Li ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Maternal Blood ◽  
Maternal Serum ◽  
Ratio Test ◽  
Uncomplicated Pregnancy ◽  
Longitudinal Measurement ◽  
Longitudinal Measurements ◽  
Longitudinal Observation ◽  
Tandem Mass Spectrometric ◽  
Plgf Ratio

ObjectiveThis study aimed to develop a blood test for the prediction of pre-eclampsia (PE) early in gestation. We hypothesised that the longitudinal measurements of circulating adipokines and sphingolipids in maternal serum over the course of pregnancy could identify novel prognostic biomarkers that are predictive of impending event of PE early in gestation.Study designRetrospective discovery and longitudinal confirmation.SettingMaternity units from two US hospitals.ParticipantsSix previously published studies of placental tissue (78 PE and 95 non-PE) were compiled for genomic discovery, maternal sera from 15 women (7 non-PE and 8 PE) enrolled at ProMedDx were used for sphingolipidomic discovery, and maternal sera from 40 women (20 non-PE and 20 PE) enrolled at Stanford University were used for longitudinal observation.Outcome measuresBiomarker candidates from discovery were longitudinally confirmed and compared in parallel to the ratio of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) using the same cohort. The datasets were generated by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays.ResultsOur discovery integrating genomic and sphingolipidomic analysis identified leptin (Lep) and ceramide (Cer) (d18:1/25:0) as novel biomarkers for early gestational assessment of PE. Our longitudinal observation revealed a marked elevation of Lep/Cer (d18:1/25:0) ratio in maternal serum at a median of 23 weeks’ gestation among women with impending PE as compared with women with uncomplicated pregnancy. The Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting impending event of PE with superior sensitivity (85% vs 20%) and area under curve (0.92 vs 0.52) from 5 to 25 weeks of gestation.ConclusionsOur study demonstrated the longitudinal measurement of maternal Lep/Cer (d18:1/25:0) ratio allows the non-invasive assessment of PE to identify pregnancy at high risk in early gestation, outperforming the established sFlt-1/PlGF ratio test.

scholarly journals Case finding of early pregnancies at risk of preeclampsia using maternal blood leptin/ceramide ratio: multi-omics discovery and validation from a longitudinal study

2020 ◽  
Author(s):  
Qianyang Huang ◽  
Shiying Hao ◽  
Jin You ◽  
Xiaoming Yao ◽  
Zhen Li ◽  
...  
Keyword(s):  
At Risk ◽  
Meta Analysis ◽  
Maternal Blood ◽  
Maternal Serum ◽  
Ratio Test ◽  
Longitudinal Assessment ◽  
Longitudinal Measurements ◽  
Tandem Mass Spectrometric ◽  
Plgf Ratio ◽  
Risk Of Preeclampsia

Objective To evaluate whether longitudinal measurements of serological adipokines and sphingolipids can predict preeclampsia early in gestation. Design Retrospective multi-omics discovery and longitudinal validation. Setting Maternity units in two US hospitals. Methods A multi-omics approach integrating genomic and lipidomic discoveries was employed to identify leptin (Lep) and ceramide (Cer) as novel PE early gestational biomarkers. The levels of placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt-1), Lep, and Cer in maternal sera were then determined by enzyme-linked immunosorbent (ELISA) and liquid chromatography-tandem mass spectrometric (LC/MS/MS) assays. Main outcome measures Interval from positive prediction to confirmative diagnosis. Results Genomic meta-analysis compiled six PE placental cohorts with 78 PE and 95 non-PE control placentas. The Testing Cohort included sera from 7 non-PE and 8 PE women collected at confirmatory diagnosis. The Validation Cohort included sera from 20 non-PE and 20 PE women collected longitudinally through gestation. Our findings revealed a marked elevation of maternal serum Leptin/Ceramide (d18:1/25:0) ratio from early gestation (a median of 23 weeks) when comparing later PE-complicated with uncomplicated pregnancies. The maternal Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting PE for sensitivity (85% vs. 40%), positive predictive value (89% vs. 42%), and AUC (0.92 vs. 0.52) from 5 to 25 weeks of gestation. Conclusions Non-invasive longitudinal assessment by serological evaluation of Lep/Cer (d18:1/25:0) ratio can case find early pregnancies at risk of preeclampsia, outperforming sFlt-1/PlGF ratio test.

scholarly journals Case finding of early pregnancies at risk of preeclampsia using maternal blood leptin/ceramide ratio: multi-omics discovery and validation from a longitudinal study

2021 ◽  
Author(s):  
Qianyang Huang ◽  
Shiying Hao ◽  
Jin You ◽  
Xiaoming Yao ◽  
Zhen Li ◽  
...  
Keyword(s):  
At Risk ◽  
Meta Analysis ◽  
Maternal Blood ◽  
Maternal Serum ◽  
Ratio Test ◽  
Longitudinal Assessment ◽  
Non Invasive ◽  
Tandem Mass Spectrometric ◽  
Plgf Ratio ◽  
Risk Of Preeclampsia

Objective To evaluate whether longitudinal measurements of serological adipokines and sphingolipids can predict preeclampsia early in gestation. Design Retrospective multi-omics discovery and longitudinal validation. Setting Maternity units in two US hospitals. Methods A multi-omics approach integrating genomic and lipidomic discoveries was employed to identify leptin (Lep) and ceramide (Cer) as novel PE early gestational biomarkers. The levels of placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt-1), Lep, and Cer in maternal sera were then determined by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays. Main outcome measures Interval from positive prediction to confirmative diagnosis. Results Genomic meta-analysis compiled six PE placental cohorts with 78 PE and 95 non-PE control placentas. The Testing Cohort included sera from 7 non-PE and 8 PE women collected at confirmatory diagnosis. The Validation Cohort included sera from 20 non-PE and 20 PE women collected longitudinally through gestation. Our findings revealed a marked elevation of maternal serum Leptin/Ceramide (d18:1/25:0) ratio from early gestation (a median of 23 weeks) when comparing later PE-complicated with uncomplicated pregnancies. The maternal Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting PE for sensitivity (85% vs. 40%), positive predictive value (89% vs. 42%), and AUC (0.92 vs. 0.52) from 5 to 25 weeks of gestation. Conclusions Non-invasive longitudinal assessment by serological evaluation of Lep/Cer (d18:1/25:0) ratio can case find early pregnancies at risk of preeclampsia, outperforming sFlt-1/PlGF ratio test. Tweetable abstract Non-invasive longitudinal assessment by serological evaluation of Lep and Cer ratio can predict preeclampsia early in gestation.

scholarly journals Localization of a molecule immunochemically similar to eosinophil major basic protein in human placenta.

1984 ◽  
Vol 160 (1) ◽  
pp. 29-41 ◽  
Author(s):  
D E Maddox ◽  
G M Kephart ◽  
C B Coulam ◽  
J H Butterfield ◽  
K Benirschke ◽  
...  
Keyword(s):  
Basic Protein ◽  
Hypereosinophilic Syndrome ◽  
Placental Tissue ◽  
Giant Cells ◽  
Maternal Blood ◽  
Maternal Serum ◽  
Chromatographic Behavior ◽  
Major Basic Protein ◽  
Eosinophil Major Basic Protein ◽  
X Cells

We have recently reported that human pregnancy is characterized by a 10- to 20-fold elevation of eosinophil major basic protein (MBP) immunoreactivity in maternal blood. Here we show, by immunofluorescence, that placental tissue specifically binds antibody to MBP in and around the placental X cells and placental-site giant cells and, using thin plastic sections, that placenta has no infiltrating eosinophils. The X cells line the inner aspects of placental septal cysts, and the cyst fluid, obtained by aspiration, contains immunoreactive MBP at concentrations of 100 micrograms/ml, a sixfold greater concentration than the highest levels measured in maternal blood. The soluble MBP immunoreactivities in placental homogenates and in maternal serum chromatograph identically on Sephadex G-50, and both these gestational MBP molecules migrate as though substantially larger than the MBP found in serum from patients with hypereosinophilic syndrome or purified from the eosinophil granule. Our inability to demonstrate eosinophils in maternal blood or placental tissue, coupled with the large quantities of immunoreactive MBP highly localized in placental cysts and the chromatographic behavior of this molecule, suggest that the MBP detected in human gestation is produced by placenta.

Florid Bacillus cereus Infection of the Placenta Associated With Intrauterine Fetal Demise

2021 ◽  
pp. 109352662199902
Author(s):  
Stephanie Shea ◽  
Alberto Paniz-Mondolfi ◽  
Emilia Sordillo ◽  
Michael Nowak ◽  
Fumiko Dekio
Keyword(s):  
Bacillus Cereus ◽  
Placental Tissue ◽  
Maternal Blood ◽  
Gastrointestinal Infections ◽  
Gram Positive ◽  
Fetal Demise ◽  
Placental Infection ◽  
Intrauterine Fetal Demise ◽  
Acute Necrotizing ◽  
Poor Outcomes

Bacillus cereus is a gram-positive, rod-shaped bacterium that is commonly implicated in foodborne illness but has also become increasingly recognized as a source of serious non-gastrointestinal infections, including sepsis, meningitis, and pneumonia. Non-gastrointestinal B. cereus infections have been identified in children, especially in neonates; however, there are no previously described cases of fetal demise associated with B. cereus placental infection. We present a case of acute chorioamnionitis-related intrauterine fetal demise of twin A at 17 weeks gestation, noted two days after selective termination of twin B. Histological examination revealed numerous gram-positive bacilli in placental tissue, as well as fetal vasculature, in the setting of severe acute necrotizing chorioamnionitis and subchorionitis, intervillous abscesses, acute villitis, and peripheral acute funisitis. Cultures of maternal blood and placental tissue both yielded growth of B. cereus. This case underscores the importance of B. cereus as a human pathogen, and specifically demonstrates its potential as an agent of severe intraamniotic and placental infection with poor outcomes for the fetus.

Quantitative measurement of anti-aquaporin-4 antibodies by enzyme-linked immunosorbent assay using purified recombinant human aquaporin-4

2011 ◽  
Vol 18 (5) ◽  
pp. 578-586 ◽  
Author(s):  
Woojun Kim ◽  
Ji-Eun Lee ◽  
Xue Feng Li ◽  
Su-Hyun Kim ◽  
Byeong-Gu Han ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Activity ◽  
Immunosorbent Assay ◽  
Neurological Diseases ◽  
Aquaporin 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Marker ◽  
Longitudinal Measurement ◽  
Longitudinal Measurements ◽  
Baculovirus System

Background: Antibodies to aquaporin-4 (AQP4-Ab), known as NMO-IgG, are a sensitive and specific marker for neuromyelitis optica (NMO). Methods: To develop an enzyme-linked immunosorbent assay (ELISA) for AQP4-Ab, we expressed M23 isoform of human AQP4 in a baculovirus system, and used it as an antigen. We measured AQP4-Ab in the sera of 300 individuals: 64 with definite NMO, 31 with high-risk NMO, 105 with multiple sclerosis (MS), 57 with other neurological diseases (ONDs), and 43 healthy controls. We also performed longitudinal measurements of AQP4–Ab in 787 samples collected from 51 patients with definite or high-risk NMO. Results: AQP4-Abs were positive in 72% with definite NMO, 55% with high-risk NMO, and 4% with MS, but none of the OND patients and the healthy individuals. The longitudinal measurement showed AQP4-Ab levels correlating with disease activity. Out of 38 initially seropositive patients, 21 became seronegative under effective immunosuppressive therapy. During most relapses, the serum AQP4-Ab levels were either high or rising compared with the previous value, although rising AQP4-Ab levels did not always lead to acute exacerbation. Two of the 13 initially seronegative patients converted to seropositive following acute exacerbations. Conclusions: We established an AQP4-Ab ELISA, which could be a potential monitoring tool of disease activity.

scholarly journals Maternal blood and amnionic oxytocin receptor gene expression and serum oxytocin levels in preterm birth: a case control study

2020 ◽  
Author(s):  
KUMARI ANUKRITI ◽  
KIRAN GULERIA ◽  
VIPIN TYAGI ◽  
AMITA SUNEJA ◽  
BASU DEV BANERJEE
Keyword(s):  
Gene Expression ◽  
Preterm Birth ◽  
Quantitative Polymerase Chain Reaction ◽  
Receptor Gene ◽  
Active Phase ◽  
Maternal Blood ◽  
Oxytocin Receptor ◽  
Maternal Serum ◽  
Oxytocin Receptor Gene ◽  
Gene Expression Studies

BACKGROUND: The oxytocin (OXT)-oxytocin receptor (OXTR) system provides promising candidate gene for studies of genetic contributions to prematurity. OBJECTIVE: Quantification and comparison of oxytocin receptor (OXTR) gene expression and serum OXT levels in the blood and amnion of women delivering preterm and evaluation of the correlation between OXTR gene expression in blood and amnion with serum OXT levels in them. METHODS: 70 pregnant women in spontaneous labor delivering vaginally preterm i.e < 37 weeks and equal number of matched controls delivering spontaneously at term (37-42 weeks) were recruited. Maternal serum OXT levels taken in active stage of labor (i.e 4 cm cervical dilatation) were quantified by ELISA. Gene expression studies in the maternal blood and amnion were done by using real time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The mean serum OXT level in PTL was 48.56 +- 6.97 pg/ml; significantly higher than in controls (43.00 +- 3.96 pg/ml), p<0.001. OXTR gene expression both in maternal blood (2.5 times) and amnion (3.5 times) were significantly higher in PTL. A significant positive correlation was observed between serum OXT levels and OXTR gene expression in amnion (r = -0.190, p = 0.025). CONCLUSIONS: The serum OXT levels and OXTR gene expression in amnion surge significantly in active phase of PTL. Thus, amnion probably links OXT-PTGs autocrine paracrine circuit to facilitate PTL. Future studies are needed to devise better OXTR receptor antagonists preferably acting on amnionic OXTRs to prevent PTL. KEYWORDS: Preterm birth, Preterm labor, Oxytocin, Oxytocin receptor, Placenta, Amnion

First-Trimester Contingent Screening for Trisomy 21 by Fetal Nuchal Translucency and Maternal Serum Biomarkers and Maternal Blood Cell-Free DNA Testing

2018 ◽  
Vol 5 (3) ◽  
pp. 139-143
Author(s):  
Sarang Younesi ◽  
Shahram Savad ◽  
Soudeh Ghafouri-Fard ◽  
Mohammad Mahdi Taheri-Amin ◽  
Pourandokht Saadati ◽  
...  
Keyword(s):  
Blood Cell ◽  
Trisomy 21 ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Maternal Blood ◽  
Maternal Serum ◽  
Serum Biomarkers ◽  
Dna Testing ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Vitamin A intake of Brazilian mothers and retinol concentrations in maternal blood, human milk, and the umbilical cord

2018 ◽  
Vol 46 (4) ◽  
pp. 1555-1569 ◽  
Author(s):  
Thalia Manfrin Martins Deminice ◽  
Ivan Savioli Ferraz ◽  
Jacqueline Pontes Monteiro ◽  
Alceu Afonso Jordão ◽  
Lívia Maria Cordeiro Simões Ambrósio ◽  
...  
Keyword(s):  
Breast Milk ◽  
Vitamin A ◽  
Human Milk ◽  
Pregnant Women ◽  
Umbilical Cord ◽  
Maternal Blood ◽  
Maternal Serum ◽  
Serum Retinol ◽  
Cross Sectional ◽  
Blood Samples

Objectives To analyse intake of vitamin A (VA) and retinol concentrations in maternal blood, breast milk (BM), and the umbilical cord (UC) of newborns, and to determine the associations among these variables. Methods We performed a cross-sectional, epidemiological study of 180 mother–newborn dyads. Maternal and UC blood samples and BM were collected. VA intake by the mother over 30 days was assessed using a questionnaire. Results Mean retinol concentrations in maternal serum, the UC, and BM were 0.65 ± 0.27, 0.36 ± 0.18, and 2.95 ± 2.70 µmol/L, respectively. Retinol concentrations <0.70 µmol/L were found in 57.2% of maternal blood samples and in 94.9% of UC samples. A total of 27.9% of BM samples showed retinol concentrations <1.05 µmol/L. Mean VA intake by the mothers was 1041.33 ± 1187.86 µg retinol activity equivalents/day and was inadequate (<550 µg retinol activity equivalents/day) in 44.7%. Conclusions High proportions of insufficient retinol concentrations were observed in the UC, maternal blood, and BM. A high percentage of pregnant women had inadequate VA intake. Mothers with insufficient serum retinol concentrations had newborns with lower retinol concentrations in the UC. Higher retinol concentrations were observed in maternal blood and the UC with a higher VA intake.

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