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Values of Certain Clinical and Biochemical Tests for Prediction of Pre-Eclampsia

1996; King Faisal Specialist Hospital and Research Centre; Volume: 16; Issue: 3 Linguagem: Inglês

10.5144/0256-4947.1996.280

0975-4466

Mohamed H. Soltan, Zeinab A. Ismail, Sayed M. Kafafi, Kamal A. Abdulla, Mohamed B. Sammour,

Bone health and osteoporosis research

Original ArticlesValues of Certain Clinical and Biochemical Tests for Prediction of Pre-Eclampsia Mohamed H. Soltan, PhD, FRCOG Zeinab A. Ismail, MD Sayed M. Kafafi, MD Kamal A. Abdulla, and MD Mohamed B. SammourMD, PhD Mohamed H. Soltan Address reprint requests and correspondence to Dr. Soltan: Consultant and Assistant Professor, Department of Obstetrics and Gynecology, King Khalid University Hospital, P.O. Box 2925, Riyadh 11461, Saudi Arabia. From the Department of Obstetrics and Gynecology, El-Menia and Ain Shams Universities, Egypt Search for more papers by this author , Zeinab A. Ismail From the Department of Clinical Pathology, El-Menia and Ain Shams Universities, Egypt Search for more papers by this author , Sayed M. Kafafi From the Department of Obstetrics and Gynecology, El-Menia and Ain Shams Universities, Egypt Search for more papers by this author , Kamal A. Abdulla From the Department of Obstetrics and Gynecology, El-Menia and Ain Shams Universities, Egypt Search for more papers by this author , and Mohamed B. Sammour From the Department of Obstetrics and Gynecology, El-Menia and Ain Shams Universities, Egypt Search for more papers by this author Published Online::1 May 1996https://doi.org/10.5144/0256-4947.1996.280SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutAbstractTo evaluate different predictive tests for pre-eclampsia, either individually or in combination, we prospectively studied 100 primigravid females. Eighty-eight of the subjects continued the follow-up until delivery and 17 developed pre-eclampsia. Venous blood samples were taken for determination of plasma fibronectin, and urine samples were taken for determination of microalbuminuria and calcium-creatinine ratio. Isometric handgrip exercise tests were also performed. Evaluation of predictive tests, as well as t and chi-squared statistical tests, were used for analysis of data. Pre-eclampsia developed in 19.3% of the patients studied. Pre-eclamptic and normotensive females showed significant differences in calcium-creatinine ratio and plasma fibronectin levels in both (14-24 weeks and 28-32 weeks) gestation periods (P<.0001). Plasma fibronectin had the best sensitivity, positive, and negative values in gestation period 14-24 weeks, whereas isometric handgrip exercise tests had the best specificity. These values improved for all the tests in the 28-32-week gestation period; even so, plasma fibronectin proved best of all. A combination of tests failed to improve the predictive ability of fibronectin alone. We conclude that plasma fibronectin is the best predictive test for pre-eclampsia.IntroductionPrevention of pre-eclampsia requires knowledge of the pathophysiologic mechanism of the disease, availability of methods for early detection, and means of correcting changes. Although the signs and symptoms of preeclampsia become apparent in the third trimester, the underlying causes thought to be responsible for the disease process appear to occur much earlier in pregnancy.The availability of simple predictors for the development of pre-eclampsia might allow prevention, treatment, and further improvement of outcome. It is known, for example, that early recognition and treatment with bed rest, low-dose aspirin and calcium supplementation can favorably influence this outcome.1–9 Dekker and Sibai10 reviewed the various clinical, biophysical and biochemical tests used to predict preeclampsia, and concluded that the ideal test is not yet available.Among the biochemical factors, microalbuminuria cannot be used alone to predict pre-eclampsia,11 whereas the calcium-creatinine ratio has been shown to be superior to microalbuminuria.12 Total plasma fibronectin has been found to be elevated before the onset of pre-eclampsia and has been used to predict its development.6,10,13–15 Simple clinical tests have also been used to predict the disease.15–17 For example, isometric handgrip exercise tests have given about 80% true-positive results when compared with other clinical tests such as rollover and arterial blood pressure tests.18 A combination of more than one test has been suggested, to predict more precisely the subsequent development of pre-eclampsia.12The aim of this study was to compare the predictive value of different tests, used separately or combined, for detecting pre-eclampsia. These tests looked for the presence of microalbuminuria, hypocalciuria, and increased plasma fibronectin in the study population. Positive isometric handgrip exercise tests (IHET) were also performed. The findings of these different tests may allow the choice of an easy and practical screening procedure in pre-eclampsia.MATERIAL AND METHODSIn this study, one hundred healthy primigravid attendants at the Antenatal Care Clinic of El-Menia University Hospital were prospectively recruited into the study between September 1991 through September 1992. Women recruited in the study fulfilled the following criteria: 1) Healthy primigravida, 2) no past history of cardiovascular or renal diseases, 3) gestational age when recruited into the study ranging between 14 and 24 weeks, 4) blood pressure as measured by mercury sphygmomanometer at the beginning of the study was less than 140/90 mmHg, and 5) all the subjects were asked to refrain from taking aspirin, other antiprostaglandins or big doses of calcium.On admission into the study, the following were done for all subjects: 1) a complete medical, obstetric and gynecologic examination; 2) ultrasonographic screening using General Electric RT 3000 ultrasound machine, sector and linear probes for estimation of gestational age, detection of any abnormality such as congenital malformations or low-lying placenta which, if present, excluded the patient from the study, and 3) isometric handgrip exercise test as described by Degani et al.16 performed by the same individual.Pre-eclampsia was diagnosed when the patient's systolic blood pressure (BP) increased by 30 mmHg or more and diastolic BP increased by 15 mmHg or more from earlier values before 21 weeks' gestation, or when the patient had proteinuria of 300 mg or more in 24 hours' collection of urine, or the presence of generalized edema with one or both of the above.Laboratory InvestigationsThe following laboratory investigations were carried out on all subjects on admission to the study between 14-24 weeks and repeated in the early third trimester (28-32 weeks). 1) Urine analysis, using total screen urine strips (Behringwerke AG, Marburg, West Germany) to exclude cases with gross albuminuria. 2) Urine culture (cases giving positive results were excluded from the study) to avoid false-positive test for microalbuminuria. 3) Determination of microalbuminuria in the morning sample of urine, using immunodiffusion technique.19 4) Selectivity index of albuminuria, which is the ratio between IgG clearance and albumin clearance, and comprises in addition to microalbuminuria, measurement of serum albumin, serum IgG and urine IgG, using immunodiffusion technique.19 5) Calcium-creatinine ratio in urine, which comprises the estimation of calcium and creatinine concentrations in urine. 6) Plasma fibronectin estimation using immunodiffusion technique. 5 mL venous blood was withdrawn, plasma separated and stored until analysis. All samples were kept at −70° C until the time of assay.Statistical AnalysisData concerning patient's age, gestational age, weight and height were recorded. Quetelet index, that is, weight (kg)/height (m)2, was calculated to get a more sensitive variable compared to weight alone. Unpaired t-test and chi-squared tests were used for statistical comparison of different variables.RESULTSEighty-eight of the 100 females included at the beginning of the study were successfully followed up until the time of delivery. Pre-eclampsia developed in the third trimester in 17 (19.3%) of those who completed the study (nine with proteinuric and eight with non-proteinuric preeclampsia). Three females developed pre-eclampsia between 28-32 weeks, five between 36-38 weeks and nine at delivery. One of these patients had fulminating preeclampsia and delivered prematurely at 28 weeks' gestation.Statistically significant differences were found between those patients who later developed pre-eclampsia and the ones who remained normotensive with regard to the weight and Quetelet index (P<0.0003 and <0.00004 respectively). However, there was no statistically significant difference between the two groups with regard to age, height, and gestational age (Table 1).Table 1. Clinical parameters of both normotensive and pre-eclamptic groups on admission into the study (between 14-24 weeks).Table 1. Clinical parameters of both normotensive and pre-eclamptic groups on admission into the study (between 14-24 weeks).Table 2 and Figure 1 show that there were statistically significant differences in the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) between those who remained normotensive and those who developed pre-eclampsia (P<0.0001), at 28-32 weeks' gestation and at 36-40 weeks' gestation. The differences between the two groups were also significant at delivery. However, there was no statistically significant difference found in early pregnancy between the two groups.Figure 1. Blood pressure changes in normotensive, preeclamptic groups throughout the study.Download FigureTable 2. Blood pressure changes in the normotensive and pre-eclamptic groups throughout the study.Table 2. Blood pressure changes in the normotensive and pre-eclamptic groups throughout the study.Table 3 compares the predictive values of different tests in the gestational periods of 14-24 and 28-32 weeks. The differences between normotensive and pre-eclamptic groups were statistically significant with respect to calcium-creatinine ratio and plasma fibronectin (P<0:0001) at each gestational period, but not so with microalbuminuria.Table 3. Laboratory predictive tests in normotensive and pre–eclamptic groups in the studied gestation periods, 14-24 weeks and 28-32 weeks.Table 3. Laboratory predictive tests in normotensive and pre–eclamptic groups in the studied gestation periods, 14-24 weeks and 28-32 weeks.The sensitivities for calcium/creatinine ratio, microalbuminuria, plasma fibronectin and positive IHET for the period of 14-24 weeks were 53%, 41%, 65% and 35% respectively and for the period of 28-32 weeks were 70%, 47%, 76%, and 53% respectively. The specificity of the same tests for the gestation period of 14-24 weeks were 94%, 72%, 94% and 96% respectively and for the period 28-32 weeks were 94%, 75%, 96% and 96% respectively. The positive predictive values of these tests at the gestation period of 14-24 weeks were 69%, 26%, 73% and 67% respectively, while the negative predictive values of the same tests at gestation period of 14-24 weeks were 89%, 84%, 92% and 86% respectively and for the period of 28-32 weeks were 93%, 85%, 94% and 89% respectively. Plasma fibronectin had the best sensitivity, positive and negative values (65%, 73% and 92% respectively) in the gestation period of 14-24 weeks, whereas the IHET had the best specificity (96%). These values improved for all tests in the gestation period of 28-32 weeks, even though plasma fibronectin still proved best of all (Table 4, Figures 2 and 3).Figure 2. Predictive value of the different tests on admission (14-24 weeks).Download FigureFigure 3. Predictive value of the different tests between 28-32 weeks.Download FigureTable 4. Predictive values of the different predictive tests in the two gestation periods studied, 14-24 weeks and 28-32 weeks.Table 4. Predictive values of the different predictive tests in the two gestation periods studied, 14-24 weeks and 28-32 weeks.A combination of different predictive tests did not improve the ability of fibronectin alone and a combination of other test results with fibronectin decreased the sensitivity of fibronectin alone in predicting pre-eclampsia.DISCUSSIONOur motivation in undertaking this study was to find the least expensive, easiest and yet most accurate test which can be used either separately or in combination to screen for pre-eclampsia before it appears clinically. The ideal predictive test for pre-eclampsia should be simple, easy to perform early in pregnancy, reproducible and non-invasive, with high sensitivity and high positive predictive value. Such an ideal predictive test does not exist at this moment.Quetelet index (body mass index) was used in the study, as it is a more sensitive parameter than just body weight. However, on admission to this study at 14-24 weeks' gestation, both body weight and Quetelet index were significantly higher in females who developed preeclampsia than the normotensive ones. Similar results were reported by Esknazi et al.,20 who have considered this to be a risk factor for subsequent development of pre-eclampsia.Degani et al.16 and Marya et al.18 showed that the diastolic blood pressure response to IHET might reflect vascular reactivity in pregnant females and may be used to detect vascular hyperactivity that occurs in pre-eclampsia. Similar results were obtained in our study with regards to the specificity, and positive and negative predictive values of IHET. However, the sensitivity of the test was different. This may be because these authors had performed therollover test prior to IHET, without stating the interval between the two tests. In our study, the IHET had the best specificity among the predictive tests in the gestation period of 14-24 weeks.Microalbuminuria was used to predict pre-eclampsia development by Mostafa and Mostafa17 and Rodriguez et al.,12 with a varying degree of sensitivity. The findings in our study showed low predictive values when compared to the other predictive tests used. This may be due to the fact that proteinuric pre-eclampsia is not preceded by a phase of increasing albumin loss, which can be predicted by a more sensitive assay.21 Furthermore, Konstantin-Hansen et al.11 showed that microalbuminuria cannot be used to predict pre-eclampsia among normal pregnant females. The results of our study would tend to support this view, as there were a large number of false-positive tests seen.Pre-eclampsia is associated with hypocalciuria.22 Reduced urinary calcium excretion may be the result of dietary, renal or hormonal factors. Although the amount of calcium was not specifically quantitated in this study, females who developed pre-eclampsia were consuming a normal diet at the time of urine collection. Therefore, dietary deficiency alone could not explain hypocalciuria in these patients. Even then, there was no statistically significant difference between the calcium-creatinine ratio reported in the two gestational periods studied, a result similar to that reported by Rodriguez et al.12 and Sanchez-Ramos et al.23The predictive value of plasma fibronectin was found to be the best when compared with the other pre-eclampsia predictive tests used in this study. This is with regards to the sensitivity, positive and negative values in both gestational periods studied. Knowledge of the predictive value of plasma fibronectin in mid-trimester is scarce. Lockwood and Peters24 and Ballegeer et al.1 concluded from their studies that the increase in plasma fibronectin is the best predictor of proteinuric and non-proteinuric preeclampsia, as its level increases several weeks before hypertension develops. The ideal predictive test should have extremely high positive and negative predictivity. Plasma fibronectin was the nearest to this. However, preeclampsia still tended to escape this screening test as well as the others.Plasma fibronectin is derived primarily from the liver and endothelial cells. The release of fibronectin into the plasma is a marker for vascular disruption. Its levels decrease in cases of liver insufficiency, disseminated intravascular coagulation, respiratory distress syndrome, sepsis and multiple trauma and increase in cases of rheumatoid arthritis. In this study, although thorough investigation of these conditions was not done for the females with elevated fibronectin level, none of these patients had clinical manifestations of the above-mentioned disorders.Rodriguez et al.12 suggested the use of a combination of predictive tests as a better predictor of pre-eclampsia. In our study, the best combination in both gestational periods was plasma fibronectin and calcium-creatinine ratio. However, this failed to improve the predictive ability of plasma fibronectin alone.Further investigations should continue in order to find out a better, more specific and sensitive test of high negative and positive capability, to predict this serious disease with more certainty and minimize its complications.ARTICLE REFERENCES:1. 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