Glycosylated Fibronectin as a First-Trimester Biomarker for Prediction of Gestational Diabetes
ABSTRACT To evaluate the potential clinical utility of serum biomarkers for first-trimester prediction of gestational diabetes mellitus (GDM).
Maternal serum concentrations of glycosylated (Sambucus nigra lectin-reactive) fibronectin, adiponectin, sex hormone-binding globulin, placental lactogen, and high-sensitivity C-reactive protein (CRP) were measured at 5-13 weeks of gestation in a case-control study of 90 pregnant women with subsequent development of GDM and in 92 control group participants. Ability to detect GDM was assessed using logistic regression modeling and receiver operating characteristic (ROC) curves. Classification performance and positive and negative predictive values were reported at specific thresholds. Glycosylated fibronectin variation across trimesters was evaluated using a serial-measures analysis of 35 nondiabetic control group participants.
First-trimester serum concentrations of glycosylated fibronectin, adiponectin, high-sensitivity CRP, and placental lactogen were significantly associated (P<.001) with GDM. After adjustment for maternal factors and other biomarkers, glycosylated fibronectin demonstrated an independent association with GDM (P<.001). Adiponectin, high-sensitivity CRP, and placental lactogen demonstrated modest classification performance compared with glycosylated fibronectin (respectively: area under the curve [AUC] 0.63; 95% confidence interval [CI] 0.53-0.71; AUC 0.68; 95% CI 0.60-0.76; and AUC 0.67, 95% CI 0.59-0.75; compared with AUC 0.91; 95% CI 0.87-0.96). Glycosylated fibronectin levels above a threshold of 120 mg/L correctly identified 57 GDM case group participants with a positive predictive value of 63% (95% CI 53-72%) and a negative predictive value of 95% (95% CI 94-95%) at a population prevalence of 12%. There was no association between sex hormone-binding globulin and GDM.
First-trimester glycosylated fibronectin is a potential pregnancy-specific biomarker for early identification of women at risk for GDM. LEVEL OF EVIDENCE:: II.
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ABSTRACT: There has been an increasing drive over the last 2 decades to push the detection of women at risk of adverse pregnancy outcomes into the first trimester. This has led to a plethora of techniques, risk assessments and biomarkers, both fascinating and bewildering in its breadth. Despite the vast amount of knowledge available it is often difficult to determine what is practicable and valuable for clinical practice. This is especially true as earlier diagnosis does not necessarily equate to improved outcomes for mother and child. We suggest that, at least for preeclampsia, fetal growth restriction, spontaneous preterm birth and gestational diabetes, there are effective first trimester tests available to identify the women at risk of subsequently developing complications. Unfortunately, there are not currently reliable first trimester tests available for identifying women at risk of stillbirth. It is likely that this field will continue to develop over time and we hope that new and better strategies will continue to emerge to target these clinically important pathologies. This article is protected by copyright. All rights reserved.Prenatal Diagnosis 05/2014; DOI:10.1002/pd.4406 · 2.68 Impact Factor
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ABSTRACT: OBJECTIVE: We assessed the association of glycosylated fibronectin (GlyFn) with preeclampsia and its performance in a point-of-care (POC) test. STUDY DESIGN: GlyFn, placental growth factor (PlGF), and soluble vascular endothelial growth factor receptor 1 (sFlt1) levels were determined in serum samples from 107 pregnant women. In all, 45 were normotensive and 62 were diagnosed with preeclampsia. The ability of GlyFn to assess preeclampsia status and relationships between GlyFn and maternal characteristics and pregnancy outcomes were analyzed. RESULTS: GlyFn serum levels in the first trimester were significantly higher in women with preeclampsia (P < .01) and remained higher throughout pregnancy (P <. 01). GlyFn, sFlt1, PlGF, and the sFlt1/PlGF ratio were significantly associated (P < .01) with preeclampsia status, and the classification performance of these analytes represented by area under the receiver operating characteristic curve was 0.99, 0.96, 0.94, and 0.98, respectively, with 95% confidence intervals of 0.98-1.00, 0.89-1.00, 0.86-1.00, and 0.94-1.00, respectively. Increased GlyFn levels were significantly associated with gestational age at delivery (P < .01), blood pressure (P = .04), and small-for-gestational-age neonates. Repeated-measures analysis of the difference in weekly GlyFn change in the third trimester demonstrated that mild preeclampsia was associated with a weekly change of 81.7 mu g/mL (SE 94.1) vs 195.2 mu g/mL (SE 88.2) for severe preeclampsia. The GlyFn POC demonstrated similar performance to a plate assay with an area under the receiver operating characteristic curve of 0.93 and 95% confidence interval of 0.85-1.00. CONCLUSION: GlyFn is a robust biomarker for monitoring of preeclampsia in both a standard and POC format, which supports its utility in diverse settings.American Journal of Obstetrics and Gynecology 07/2014; 212(1). DOI:10.1016/j.ajog.2014.07.052 · 3.97 Impact Factor
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ABSTRACT: Great obstetrical syndromes is a collective name for several complications of pregnancy that affect >15% of pregnancies. They may confer adverse pregnancy outcomes and maternal and fetal morbidity, and require close medical monitoring and treatment. The etiology, pathogenesis, and outcome of these syndromes are obscure in the majority of cases. All appear during mid-to-late pregnancy with no reliable biomarkers for early detection and possibly prevention at present. This article focuses on the quest for early reliable markers for preeclampsia and gestational diabetes mellitus (GDM) development, mainly on the involvement of microRNA in the pathogenesis and its possible role as an early biomarker for disease development.Bailliè re s Best Practice and Research in Clinical Obstetrics and Gynaecology 08/2014; 29(2). DOI:10.1016/j.bpobgyn.2014.04.021 · 3.00 Impact Factor