Screening for gestational disorders

Abstract

The invention relates to methods and compositions for identifying subjects having, or predisposed to having, gestational diabetes, preeclampsia, and gestational hypertension. The methods are applicable to urine and/or blood samples and can be conducted prior to the third trimester of pregnancy.

1 . A method of determining whether a pregnant subject has, or is predisposed to having, a gestational disorder selected from the group consisting of preeclampsia or gestational diabetes mellitus, the method comprising:
 a) measuring a level of sex hormone binding globulin (SHBG) in a biological sample comprising serum or urine obtained from a pregnant subject;   b) measuring the level of soluble fins-like tyrosine kinase-1 receptor (sFlt-1) in a biological sample comprising serum obtained from the pregnant subject;   c) comparing the SHBG level obtained from the pregnant subject with an SHBG level obtained from at least one subject having a normal pregnancy;   d) comparing the sFlt-1 level obtained from the pregnant subject with a sFlt-1 level obtained from at least one subject having a normal pregnancy; and   wherein low levels of SHBG and high levels of sFlt-1 present in the sample obtained from the pregnant subject, as compared to the levels present in the at least one subject having a normal pregnancy, indicate that the pregnant subject has, or is predisposed to having, a gestational disorder.   
     
     
         2 . The method of  claim 1 , wherein the gestational disorder is preeclampsia. 
     
     
         3 . The method of  claim 1 , wherein the gestational disorder is gestational diabetes mellitus. 
     
     
         4 . The method of  claim 1 , wherein the samples are obtained from the pregnant subject at about 9 to 13 weeks of gestation. 
     
     
         5 . The method of  claim 1 , wherein the samples obtained from the pregnant subject and the subject having a normal pregnancy are obtained during the same week of pregnancy, plus or minus 2 weeks. 
     
     
         6 . The method of  claim 1 , wherein the samples obtained from the pregnant subject and the subject having a normal pregnancy are each obtained during the same week of pregnancy. 
     
     
         7 . The method of  claim 1 , further comprising correlating the SHBG and sFlt-1 levels derived from the pregnant subject with: 1) the gestational age at the time SHBG and sFlt-1 levels are measured; 2) the pregnant subject's age; 3) the pregnant subject's parity; and 4) the pregnant subject's body mass index. 
     
     
         8 . The method of  claim 1 , further comprising measuring the level of at least one marker selected from the group consisting of interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α), in the subject sample, and comparing the level of the marker obtained from the pregnant subject with a level of the marker obtained from at least one subject having a normal pregnancy, wherein an increased level of IL-6, MCP-1, or TNF-α, or a decreased level of IL-8, indicates that the pregnant subject has, or is predisposed to having, a gestational disorder. 
     
     
         9 . The method of  claim 8 , wherein the levels of SHBG, sFlt-1, and the at least one marker are used to generate a subject profile comprising a plurality of values, each value representing a level of SHBG, sFlt-1, and the at least one marker, and comparing the subject profile with a reference profile, wherein the reference profile comprises a value or plurality of values, each value representing a level of SHBG, sFlt-1, and the at least one marker in a reference sample obtained from a reference subject. 
     
     
         10 . The method of  claim 8 , wherein the level of the at least one marker is measured in a serum sample. 
     
     
         11 . The method of  claim 8 , wherein the level of the at least one marker is measured in a urine sample. 
     
     
         12 . The method of  claim 1 , wherein the level of SHBG and the level of sFlt-1 in the sample obtained from the pregnant subject are measured with two or more different biomolecules, wherein a first biomolecule specifically interacts with SHBG and a second biomolecule specifically interacts with sFlt-1. 
     
     
         13 . The method of  claim 12 , further comprising preparing a subject profile by detecting a modification of the biomolecules, wherein the modification is indicative of a level of SHBG and sFlt-1 in the sample; and comparing the subject profile with a reference profile, wherein the reference profile comprises one or more values, each value representing a level of SHBG and sFlt-1 in a reference sample obtained from one or more reference subjects having a normal pregnancy; wherein lower levels of SHBG and sFlt-1 in the subject profile as compared to the reference profile is indicative of a subject having, or predisposed to having, a gestational disorder. 
     
     
         14 . The method of  claim 12 , wherein the biomolecules are immobilized to form an array. 
     
     
         15 . The method of  claim 14 , wherein the array comprises a first set of a plurality of the first biomolecule and a second set of a plurality of the second biomolecule. 
     
     
         16 . The method of  claim 12 , wherein the biomolecules are antibodies. 
     
     
         17 . The method of  claim 16 , wherein the antibodies are monoclonal antibodies. 
     
     
         18 . The method of  claim 12 , wherein the biomolecules are antigens. 
     
     
         19 . The method of  claim 18 , wherein the antigens are viral antigens. 
     
     
         20 . The method of  claim 12 , wherein the biomolecules are receptors. 
     
     
         21 . The method of  claim 13 , wherein the modification is binding of SHBG or sFlt-1 to a biomolecule.