Glycosylated Fibronectin as a First-Trimester Biomarker for Prediction of Gestational Diabetes

Rasanen, Juha P. MD, PhD; Snyder, Caryn K. MPH; Rao, Paturi V. MD, PhD; Mihalache, Raluca MPHN; Heinonen, Seppo MD, PhD; Gravett, Michael G. MD; Roberts, Charles T. Jr PhD; Nagalla, Srinivasa R. MD

doi: 10.1097/AOG.0b013e3182a0c88b
Original Research

OBJECTIVE: To evaluate the potential clinical utility of serum biomarkers for first-trimester prediction of gestational diabetes mellitus (GDM).

METHODS: 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.

RESULTS: 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.

CONCLUSION: First-trimester glycosylated fibronectin is a potential pregnancy-specific biomarker for early identification of women at risk for GDM.

LEVEL OF EVIDENCE: II

Elevated levels of glycosylated fibronectin in first-trimester maternal serum are associated with subsequent gestational diabetes as determined by oral glucose tolerance test.

Departments of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon, and the University of Washington, Seattle, Washington; the Department of Obstetrics and Gynecology, Kuopio University Hospital, and the University of Eastern Finland, Kuopio, Finland; Nizam's Institute of Medical Sciences, Hyderabad, India; and DiabetOmics, Beaverton, Oregon.

Corresponding author: Srinivasa R. Nagalla, MD, DiabetOmics, Inc. 20,000 NW Walker Rd. Beaverton, OR 97006; e-mail: nagallas@diabetomics.com.

Financial Disclosure Caryn K. Snyder and Srinivasa R. Nagalla are employees of DiabetOmics. Michael G. Gravett and Charles T. Roberts Jr are consultants for DiabetOmics. Paturi V. Rao, Charles T. Roberts, and Srinivasa R. Nagalla are shareholders in DiabetOmics. The other authors did not report any potential conflicts of interest.

Presented in part at the 72nd Annual American Diabetes Association Scientific Sessions, June 8–12, 2012, Philadelphia, Pennsylvania.

Funded by DiabetOmics, Inc.

The authors thank John A. Michaels for expert technical assistance.

© 2013 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.