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Abstract
Pre-eclampsia is a potentially serious condition that still accounts for significant morbidity and mortality for the mother and the neonate, complicating 5-7% of all pregnancies and exposing them to a 3- to 25-fold increased risk of severe obstetric complications. Despite recent efforts to identify the possible cause of pre-eclampsia, it is still considered a disease of theories. Although, the pathogenesis is not fully understood, it is now widely accepted that vascular endothelial dysfunction is the most astonishing and the principal event in the pathophysiology of the disease.
Researchers investigated the fact that ischemic placenta secretes soluble substances in the maternal circulation. Among these is soluble endoglin (sEng), a shed part of endoglin receptor. Soluble endoglin is a potent anti-angiogenic molecule that acts by antagonizing the effects of TGF-β1 in vasculature via capturing and diverting them away from endoglin receptor. Deprived from the angiogenic and NO-dependant vasodilator TGFβ1 molecules, the blood vessels are subjected to intense vasospasm and death of the lining endothelial cells with resultant leakage of proteins in tissues and urine.
In this regard, this study aimed to evaluate the clinical utility of soluble endoglin in diagnosis of pre-eclampsia and assessment of severity of the disease. This work was conducted on 40 pre-eclamptic patients; 20 patients developed pre-eclampsia before 32 weeks of gestation (early-onset pre-eclampsia), 20 patients developed pre-eclampsia at or after 32 weeks of gestation (late-onset pre-eclampsia). In addition to 30 healthy pregnant control subjects classified as early-pregnancy control subjects (15 healthy pregnant females whose gestational age <32 weeks) and late-pregnancy control subjects (15 healthy pregnant females whose gestational age ≥ 32 weeks). Patients were reclassified according to the severity of pre-eclampsia into 28 patients with mild degree of pre-eclampsia and 12 patients with severe degree of pre-eclampsia.
All the studied individuals were subjected to full history taking and complete clinical examination. Blood samples were collected for determination of ALT, CBC and serum soluble endoglin, while 24 hours urine samples were collected for determination of total urinary proteins. Assay of sEng was carried out using an enzyme linked immunosorbent assay technique.
Serum sEng was significantly higher in late-pregnancy control group compared to the early-pregnancy controls (z=4.3, p<0.001). Serum sEng showed a highly significant increase in early-onset pre-eclamptic females compared to their corresponding early-pregnancy controls (z=4.3, p<0.001). However, sEng was insignificantly higher in late-onset pre-eclamptic females compared to their corresponding late-pregnancy controls (z=0.9, p>0.05).
As regards the relation of sEng to the severity of pre-eclampsia, our results revealed a highly significant elevation of sEng in both mild and severe pre-eclamptic women in relation to the control subjects. In addition, serum sEng was significantly higher in severe pre-eclamptic women compared to mild ones. Moreover, significant positive correlation was also found between sEng and both DBP and total urinary protein, which are among the indices of severity of pre-eclampsia.
The ROC curve analysis was applied to assess the diagnostic utility of sEng in early pre-eclamptic patients versus the early pregnancy controls to assess its utility as early indicator of pre-eclampsia. It revealed that the best cutoff level was 9 ng/mL. This had a diagnostic sensitivity of 100%, specificity 100%, efficiency 100%, with a positive predictive value of 100%, and a negative predictive value of 100%. The best diagnostic cutoff level for sEng in late-onset pre-eclampsia was 10ng/mL. This had a diagnostic sensitivity of 70%, specificity 87%, efficiency 77%, positive predictive value 88%, and negative predictive value 68%
In addition, ROC curve analysis of sEng revealed that the best cutoff level for discriminating severe pre-eclamptic patients from mild ones was 13 ng/mL. This had a diagnostic sensitivity of 100%, specificity 90%, efficiency 95%, with a positive predictive value of 91 %, and a negative predictive value of 100%.
In conclusion, the results of this study support the role of sEng in the pathogenesis of pre-eclampsia. SEng may be considered as a useful complementary marker for diagnosis of pre-eclampsia more so in early-onset pre-eclampsia. Furthermore, its level can discriminate mild from severe forms of the disease.