Prediction of postpartum hellp syndrome, postpartum eclampsia or postpartum preeclampsia

Abstract

The present invention is directed to a method for predicting the risk of a female subject to develop postpartum HELLP syndrome, postpartum preeclampsia, or postpartum eclampsia. The method is based on the determination of the levels of i) sFlt-1 and PlGF, or ii) Endoglin and PlGF in a first sample obtained from said subject before delivery of baby, and a second sample of from said subject obtained after delivery of baby. Moreover, encompassed by the invention are devices and kits for carrying out the method of the present invention.

1 . A method for predicting the risk of a female subject to develop at least one preeclampsia related adverse outcome after delivery of baby, said method comprising the steps of
 a) measuring in a first sample obtained from a female subject with an uneventful pregnancy before delivery of baby
 i) the level of the biomarker sFlt-1 (soluble fms-like tyrosine kinase-1) or the level of the biomarker Endoglin, and 
 ii) the level of the biomarker PlGF (Placental Growth Factor), 
   b) calculating a first ratio of the levels of the biomarkers as measured in step a),   c) measuring in a second sample obtained from said female subject after delivery of baby the levels of the biomarkers as measured in step a),   d) calculating a second ratio of the levels measured in step c), and   e) comparing the second ratio to the first ratio.   
     
     
         2 . The method of  claim 1 , wherein in steps a) and c) the levels of the biomarkers sFlt-1 and PlGF are measured. 
     
     
         3 . The method of  claim 2 , wherein the at least one preeclampsia related adverse outcome is selected from the group consisting of postpartum preeclampsia, postpartum eclampsia and postpartum HELLP syndrome. 
     
     
         4 . The method of  claim 1 , wherein the female subject with an uneventful pregnancy did not exhibit preeclampsia, severe preeclampsia, eclampsia and/or a HELLP syndrome before delivery of baby. 
     
     
         5 . The method of  claim 1 , wherein the first sample has been obtained within 48 hours before delivery of baby. 
     
     
         6 . The method of  claim 1 , wherein the second sample has been obtained within 24 hours after delivery of baby. 
     
     
         7 . The method of  claim 1 , wherein the first and the second ratio are the ratios of sFlt-1 to PlGF, or of Endoglin to PlGF, and wherein an increase of the second ratio, or an essentially unchanged second ratio as compared to the first ratio is indicative for a subject who is at risk of developing at least one preeclampsia related adverse outcome after delivery of baby, and/or wherein a decrease of the second ratio as compared to the first ratio is indicative for a subject who is not at risk of developing a preeclampsia related adverse outcome after delivery of baby. 
     
     
         8 . The method of  claim 1 , wherein the first and the second ratio are the ratios of PlGF to sFlt-1, or of PlGF to Endoglin, and wherein decrease of the second ratio or an essentially unchanged second ratio as compared to the first ratio is indicative for a subject who is at risk of developing at least one preeclampsia related adverse outcome after delivery of baby, and/or wherein an increase of the second ratio as compared to the first ratio is indicative for a subject who is not at risk of developing a preeclampsia related adverse outcome after delivery of baby. 
     
     
         9 . The method of  claim 1 , wherein the subject is human. 
     
     
         10 . The method of  claim 1 , wherein the sample is a blood, serum or plasma sample, or wherein the sample is a urine sample. 
     
     
         11 . The method of  claim 1 , wherein the risk to develop at least one preeclampsia related adverse outcome within seven days after delivery of baby is predicted. 
     
     
         12 . A device adapted for predicting the risk of a female subject to develop at least one preeclampsia related adverse outcome after delivery of baby, said device comprising:
 a) an analyzer unit comprising an agent which specifically binds to sFlt-1 and/or Endoglin, and an agent which specifically binds to PlGF, said unit being adapted for measuring the level of sFlt-1 and/or Endoglin and the level of PlGF in a first sample of a female subject obtained before delivery of baby and a second sample of said female subject obtained after delivery of baby; and   b) an evaluation unit comprising a data processor having implemented an algorithm for carrying out the following steps of:
 i) calculating a first ratio from said levels of sFlt-1 or Endoglin and PlGF determined in the first sample and a second ratio from said levels of sFlt-1 or Endoglin and PlGF determined in the second sample; and 
 ii) comparing the value of the said first and the said second ratio, and 
 iii) predicting the risk of said subject to develop at least one preeclampsia related adverse outcome after delivery of baby.