Biomarkers for assessment of preeclampsia

Abstract

Disclosed herein are screening tools for fetal/maternal wellness, such as biomarkers for assessing preeclampsia. More specifically, methods are disclosed for assessing the risk of preeclampsia in a subject, the methods including obtaining a first serum sample from the subject, determining a level of glycosylated fibronectin (GlyFn) in the first serum sample, and comparing the determined level of GlyFn with a control value, wherein an elevation in the determined level of GlyFn in the first serum sample relative to the control value indicates that the subject is at increased risk of preeclampsia. Also disclosed are methods of determining the risk of preeclampsia in a subject during a first, second, or third trimester, methods of assessing severity and progression of preeclampsia and complications of a risk of low birth weight or HELLP syndrome.

1 . A method for assessing the risk of preeclampsia in a subject, comprising:
 obtaining a first biological sample from the subject;   determining a level of glycosylated fibronectin (GlyFn) in the first biological sample; and   comparing the determined level of GlyFn with a control value; wherein an elevation in the determined level of GlyFn in the first biological sample relative to the control value indicates that the subject is at increased risk of preeclampsia.   
     
     
         2 . The method of  claim 1 , wherein the biological sample is a serum sample or a saliva sample. 
     
     
         3 . The method of  claim 2 , wherein obtaining a first serum sample from the subject comprises obtaining a first serum sample from the subject during a first trimester. 
     
     
         4 . The method of  claim 3 , wherein the control value is a reference value representative of a level of GlyFn in a sample from a first trimester subject who will not develop preeclampsia. 
     
     
         5 . The method of  claim 4 , wherein the elevation in the determined level of GlyFn in the first serum sample relative to the control value is at least a 15% elevation. 
     
     
         6 . The method of  claim 4 , wherein the elevation in the determined level of GlyFn in the first serum sample relative to the control value is at least a 50% elevation. 
     
     
         7 . The method of  claim 2 , wherein obtaining a first serum sample from the subject comprises obtaining a first serum sample from the subject during a second trimester. 
     
     
         8 . The method of  claim 7 , wherein the control value is a reference value representative of a level of GlyFn in a sample from a second trimester subject who will not develop preeclampsia. 
     
     
         9 . The method of  claim 8 , wherein the elevation in the determined level of GlyFn in the first serum sample relative to the control value is at least a 15% elevation. 
     
     
         10 . The method of  claim 8 , wherein the elevation in the determined level of GlyFn in the first serum sample relative to the control value is at least a 50% elevation. 
     
     
         11 . The method of  claim 2 , wherein obtaining a first serum sample from the subject comprises obtaining a first serum sample from the subject during a third trimester. 
     
     
         12 . The method of  claim 11 , wherein the control value is a reference value representative of a level of GlyFn in a sample from a third trimester subject who will not develop preeclampsia. 
     
     
         13 . The method of  claim 12 , wherein the elevation in the determined level of GlyFn in the first serum sample relative to the control value is at least a 30% elevation. 
     
     
         14 . The method of  claim 12 , wherein the elevation in the determined level of GlyFn in the first serum sample relative to the control value is at least a 100% elevation. 
     
     
         15 . The method of  claim 2 , wherein the method further comprises determining whether the determined level of GlyFn is equal to or greater than 250 μg/ml, wherein a determined level of GlyFn equal to or greater than 250 μg/ml indicates that the subject is at risk of low birth weight or HELLP syndrome. 
     
     
         16 . The method of  claim 2 , wherein the method further comprises determining whether the determined level of GlyFn is equal to or greater than 500 μg/ml, wherein a determined level of GlyFn equal to or greater than 500 μg/ml indicates that the subject is at high risk of low birth weight or HELLP syndrome. 
     
     
         17 . The method of  claim 2 , wherein obtaining a first serum sample from the subject comprises obtaining a first serum sample from the subject during a first or second trimester, and wherein a determined level of GlyFn equal to or greater than 175 μg/ml indicates that the subject has preeclampsia. 
     
     
         18 . The method of  claim 17 , wherein obtaining a first serum sample from the subject comprises obtaining a first serum sample from the subject during a third trimester, and wherein a determined level of GlyFn in the first serum sample from the subject that is equal to or greater than 200 μg/ml indicates that the subject has preeclampsia. 
     
     
         19 . The method of  claim 17 , wherein obtaining a first serum sample from the subject comprises obtaining a first serum sample from the subject during a third trimester, and wherein a determined level of GlyFn in the first serum sample from the subject that is equal to or greater than 250 μg/ml indicates that the subject has severe preeclampsia. 
     
     
         20 . The method of  claim 2 , wherein obtaining a first serum sample from the subject comprises obtaining a first serum sample from the subject during a third trimester, and wherein the method further comprises comparing the determined level of GlyFn in samples from at least two different time points to distinguish between mild preeclampsia and severe preeclampsia. 
     
     
         21 . The method of  claim 20 , wherein the method further comprises:
 obtaining a second serum sample from the subject at least one week after the first serum sample was obtained;   determining a level of glycosylated fibronectin (GlyFn) in the second serum sample; and   comparing the determined level of GlyFn in the second serum sample with the determined level of GlyFn in the first serum sample;   wherein a weekly increase in the determined level of GlyFn in the second serum sample compared to the determined level of GlyFn in the first serum sample of between 25 μg/ml and 125 μg/ml indicates that the subject has mild preeclampsia; and   wherein a weekly increase in the determined level of GlyFn in the second serum sample compared to the determined level of GlyFn in the first serum sample of greater than 150 μg/ml indicates that the subject has severe preeclampsia.   
     
     
         22 . A method for monitoring preeclampsia in a subject, comprising:
 obtaining a first biological sample from the subject;   determining a level of glycosylated fibronectin (GlyFn) in the first biological sample;   obtaining a second biological sample from the subject at least one week after the first serum sample was obtained;   determining a level of glycosylated fibronectin (GlyFn) in the second serum sample; and   comparing the determined level of GlyFn in the second serum sample with the determined level of GlyFn in the first serum sample;   wherein a weekly increase in the determined level of GlyFn in the second serum sample compared to the determined level of GlyFn in the first serum sample of less than 25 μg/ml indicates that the subject does not have preeclampsia;   wherein a weekly increase in the determined level of GlyFn in the second serum sample compared to the determined level of GlyFn in the first serum sample of between 25 μg/ml and 125 μg/ml indicates that the subject has mild preeclampsia; and   wherein a weekly increase in the determined level of GlyFn in the second serum sample compared to the determined level of GlyFn in the first serum sample of greater than 150 μg/ml indicates that the subject has severe preeclampsia.   
     
     
         23 . A test device for carrying out the method of  claim 1 , the test device comprising:
 a housing   a test strip contained within the housing, the test strip comprising one or more immunoreagents, wherein one of the one or more immunoreagents is an anti-GlyFn antibody;   means for quantifying binding of the anti-GlyFn antibody to GlyFn in the biological sample.