Diagnostic method for determining the susceptibility to delivery and reagent kit for use therefor

Abstract

The invention relates to a diagnostic method for detecting susceptibility to delivery, and to a test kit for this purpose. A low, but higher than baseline level concentration of Insulin-like Growth Factor Binding Protein 1 (IGFBP-1), which is due to leakage from decidual cells, is detected by an immunological assay in a vaginal secretion sample.

1 . A method for determining the susceptibility to delivery which comprises:
 a) detecting that the foetal membranes of said patient are intact;   b) detecting a level of insulin-like growth factor binding protein 1 (IGFBP-1) in a vaginal or cervical secretion sample from said patient with an antibody that recognizes IGFBP-1; and   c) providing medical advice designed to prevent preterm delivery to said patient where said sample, despite intact foetal membranes, has an IGFBP-1 level that is equal to or greater than a normal baseline level of pregnancy,   wherein said level of IGFBP-1 being equal to or greater than said normal baseline level of pregnancy indicates that said patient possesses risk factors indicative of preterm delivery.   
   
   
       2 . The method according to  claim 1 , wherein point b) is performed before point a). 
   
   
       3 . The method according to  claim 1 , wherein said antibody is a monoclonal antibody. 
   
   
       4 . The method according to  claim 1 , wherein said secretion sample is obtained from the cervix. 
   
   
       5 . The method according to  claim 1 , wherein said level of IGFBP-1 is determined by a quantitative, semiquantitative or qualitative immunological assay. 
   
   
       6 . The method according to  claim 1 , wherein said determined level of IGFBP-1 is above about 1 μg/l. 
   
   
       7 . The method according to  claim 1 , wherein detecting that the foetal membranes are intact is made by examination. 
   
   
       8 . The method according to  claim 1 , wherein detecting that the foetal membranes are intact is made by a diagnostic method detecting a level of IGFBP-1 in a vaginal or cervical secretion sample from a patient with an antibody that recognizes IGFBP-1 and wherein said sample has an IGFBP-1 level that is above a high IGFBP-1 level caused by the presence of amniotic fluid resulting from rupture of a fetal membrane. 
   
   
       9 . The method according to  claim 8 , wherein said high IGFBP-1 level is above about 100 μg/l. 
   
   
       10 . A method for identifying a patient possessing risk factors indicative of preterm delivery comprising:
 a) detecting that the foetal membranes of said patient are intact;   b) detecting a level of IGFBP-1 in an essentially blood-free vaginal or cervical secretion sample from said patient with an antibody that recognizes IGFBP-1; and   c) providing medical advice designed to prevent preterm delivery to said patient where said sample, despite intact foetal membranes, has an IGFBP-1 level that is equal to or greater than a normal baseline level of pregnancy,   wherein said level of IGFBP-1 being equal to or greater than said normal baseline level of pregnancy indicates that said patient possesses risk factors indicative of preterm delivery, said risk factors of said patient being increased as compared to patients with an IGFBP-1 level below said normal baseline level of pregnancy.   
   
   
       11 . The method according to  claim 10 , wherein point b) is performed before point a). 
   
   
       12 . The method according to  claim 10 , wherein said antibody is a monoclonal antibody. 
   
   
       13 . The method according to  claim 10 , wherein said secretion sample is obtained from the cervix. 
   
   
       14 . The method according to  claim 10 , wherein said level of IGFBP-1 is determined by a quantitative, semiquantitative or qualitative immunological assay. 
   
   
       15 . The method according to  claim 10 , wherein said determined level of IGFBP-1 is above about 1 μg/l. 
   
   
       16 . The method according to  claim 10 , wherein detecting that the foetal membranes are intact is made by examination. 
   
   
       17 . The method according to  claim 10 , wherein detecting that the foetal membranes are intact is made by a diagnostic method detecting a level of IGFBP-1 in a vaginal or cervical secretion sample from a patient with an antibody that recognizes IGFBP-1 and wherein said sample has an IGFBP-1 level that is above a high IGFBP-1 level caused by the presence of amniotic fluid resulting from rupture of a fetal membrane. 
   
   
       18 . The method according to  claim 17 , wherein said high IGFBP-1 level is above about 100 μg/l. 
   
   
       19 . A method for assessing the maturity of a cervix and predicting a time of delivery comprising:
 a) detecting that the foetal membranes of said patient are intact;   b) detecting a level of IGFBP-1 in an essentially blood-free vaginal or cervical secretion sample from said patient with an antibody that recognizes IGFBP-1; and   c) providing medical advice designed to promote a safe delivery to said patient where said sample, despite intact foetal membranes, has an IGFBP-1 level that is equal to or greater than a normal baseline level of pregnancy,   wherein said level of IGFBP-1 being equal to or greater than said normal baseline level of pregnancy indicates maturation of the cervix of said patient and impending delivery.   
   
   
       20 . The method according to  claim 19 , wherein point b) is performed before point a). 
   
   
       21 . The method according to  claim 19 , wherein said time of delivery is assessed in patients with a post-term pregnancy. 
   
   
       22 . The method according to  claim 19 , wherein said time of delivery is assessed in patients with a risk of pre-term delivery. 
   
   
       23 . The method according to  claim 19 , wherein said antibody is a monoclonal antibody. 
   
   
       24 . The method according to  claim 19 , wherein said secretion sample is obtained from the cervix. 
   
   
       25 . The method according to  claim 19 , wherein said level of IGFBP-1 is determined by a quantitative, semiquantitative or qualitative immunological assay. 
   
   
       26 . The method according to  claim 19 , wherein said determined level of IGFBP-1 is above about 1 μg/l. 
   
   
       27 . The method according to  claim 19 , wherein detecting that the foetal membranes are intact is made by examination. 
   
   
       28 . The method according to  claim 19 , wherein detecting that the foetal membranes are intact is made by a diagnostic method detecting a level of IGFBP-1 in a vaginal or cervical secretion sample from a patient with an antibody that recognizes IGFBP-1 and wherein said sample has an IGFBP-1 level that is above a high IGFBP-1 level caused by the presence of amniotic fluid resulting from rupture of a fetal membrane. 
   
   
       29 . The method according to  claim 28 , wherein said high IGFBP-1 level is above about 100 μg/l. 
   
   
       30 . A method for assessing a time for induction of labor comprising:
 a) detecting that the foetal membranes of said patient are intact;   b) detecting a level of IGFBP-1 in an essentially blood-free vaginal or cervical secretion sample from said patient with an antibody that recognizes IGFBP-1; and   c) initiating induction of labor for said patient where said sample, despite intact foetal membranes, has an IGFBP-1 level that is equal to or greater than a normal baseline level of pregnancy,   wherein said level of IGFBP-1 being equal to or greater than said normal baseline level of pregnancy indicates maturation of the cervix of said patient and impending delivery.   
   
   
       31 . The method according to  claim 30 , wherein point b) is performed before point a). 
   
   
       32 . The method according to  claim 30 , wherein said time of induction is assessed in patients with a post-term pregnancy. 
   
   
       33 . The method according to  claim 30 , wherein said time of induction is assessed in patients with a risk of pre-term delivery.