1. Maternal serum glycosylated fibronectin as a short-term predictor of preeclampsia: a prospective cohort study
- Author
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Charles T. Roberts, Soeren Lange, Begoña Martinez de Tejada, I Hoffmann, Evelyn A. Huhn, Michael Gravett, Olav Lapaire, Srinivasa R. Nagalla, and Kylie M. Sage
- Subjects
Glycation End Products, Advanced ,Placental growth factor ,Pregnancy Proteins ,030204 cardiovascular system & hematology ,Cohort Studies ,Vascular Endothelial Growth Factor Receptor-1 / blood ,0302 clinical medicine ,Pre-Eclampsia ,Pregnancy ,Risk Factors ,Prospective Studies ,Prospective cohort study ,Placenta Growth Factor / blood ,reproductive and urinary physiology ,Immunoassay ,ddc:618 ,030219 obstetrics & reproductive medicine ,Obstetrics ,Obstetrics and Gynecology ,Gestational age ,female genital diseases and pregnancy complications ,embryonic structures ,Cohort ,Female ,Fibronectins / blood ,Research Article ,Cohort study ,Adult ,medicine.medical_specialty ,Gestational Age ,lcsh:Gynecology and obstetrics ,Sensitivity and Specificity ,Preeclampsia ,03 medical and health sciences ,medicine ,Biomarkers / blood ,Humans ,lcsh:RG1-991 ,Placenta Growth Factor ,Vascular Endothelial Growth Factor Receptor-1 ,business.industry ,Case-control study ,medicine.disease ,Fibronectins ,ROC Curve ,Case-Control Studies ,business ,Pre-Eclampsia / blood ,Biomarkers ,Pregnancy Proteins / blood - Abstract
Background Preeclampsia is a major pregnancy complication that results in significant maternal and infant mortality, most of which occurs in low and middle-income countries. The accurate and timely diagnosis of preeclampsia is critical in management of affected pregnancies to reduce maternal and fetal/neonatal morbidity and mortality, yet difficulties remain in establishing the rigorous diagnosis of preeclampsia based on clinical parameters alone. Biomarkers that detect biochemical disease have been proposed as complements or alternatives to clinical criteria to improve diagnostic accuracy. This cohort study assessed the performance of several biomarkers, including glycosylated fibronectin (GlyFn), to rule-in or rule-out preeclampsia within 4 weeks in a cohort of women at increased risk for preeclampsia. Methods 151 women with risk factors for or clinical signs and symptoms of preeclampsia were selected from a prospective cohort. Maternal serum samples were collected between 20 and 37 weeks of gestation. Clinical suspicion of preeclampsia was defined as presence of new-onset proteinuria, or clinical symptoms of preeclampsia. Subjects with a clinical diagnosis of preeclampsia at the time of enrollment were excluded. GlyFn, pregnancy-associated plasma protein-A2 (PAPPA2), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured by immunoassay. GlyFn was also determined using a rapid point-of care (POC) test format. Receiver-operating characteristic (ROC) curves derived from logistic regression analysis were used to determine the classification performance for each analyte. Results 32 of 151 (21%) women developed a clinical diagnosis of preeclampsia within 4 weeks. All biomarkers exhibited good classification performance [GlyFn (area under the curve (AUROC) = 0.94, 91% sensitivity, 86% specificity); PAPPA2 AUC = 0.92, 87% sensitivity, 77% specificity; PlGF AUC = 0.90, 81% sensitivity, 83% specificity; sFlt-1 AUC = 0.92, 84% sensitivity, 91% specificity. The GlyFn immunoassay and the rapid POC test showed a correlation of r = 0.966. Conclusions In this prospective cohort, serum biomarkers of biochemical disease were effective in short-term prediction of preeclampsia, and the performance of GlyFn in particular as a POC test may meet the needs of rapid and accurate triage and intervention.
- Published
- 2020
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