ArticleBMJ open2021
Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation.
Article in BMJ open, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Prediction of pregnancy-related hypertensive disorders using metabolomics: a systematic review.BMJ open · 2022Pooled it
- Phospholipid transfer protein: The link between lipid metabolism and inflammation in healthy pregnancy and pregnancy with cardiometabolic complications.Journal of medical biochemistry · 2026Article
- Emerging Role of Leptin in Vascular and Placental Dysfunction in Preeclampsia.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Identification and validation of key biomarkers associated with immune and oxidative stress for preeclampsia by WGCNA and machine learning.Frontiers in genetics · 2025Article
- Multidimensional roles of cfDNA fragmentomics in preeclampsia: from placental hypoxia and TLR9 inflammation to clinical risk stratification.Frontiers in medicine · 2025Review
- Paradoxes: Cholesterol and Hypoxia in Preeclampsia.Biomolecules · 2024Review
- High placental expression of FLT1, LEP, PHYHIP and IL3RA - In persons of African ancestry with severe preeclampsia.Placenta · 2023Article
- Ceramides during Pregnancy and Obstetrical Adverse Outcomes.Metabolites · 2023Review
- Midgestation Leptin Infusion Induces Characteristics of Clinical Preeclampsia in Mice, Which Is Ablated by Endothelial Mineralocorticoid Receptor Deletion.Hypertension (Dallas, Tex. : 1979) · 2022Article
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 MEASURES: Biomarker 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.
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