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J C Forest

Publications and source records attributed to J C Forest.

At least 19 recordsLinked to original sources

Evaluation of the analytical performance of the Boehringer Mannheim Elecsys 2010 immunoanalyzer.

OBJECTIVES: We evaluated the analytical performance of the Elecsys 2010 immunoanalyzer (Boehringer Mannheim Canada), which is based on a new detection technology, electrochemical luminescence. DESIGN AND METHODS: We used six representative assays from the initial launch menu of the instrument: thyroid stimulating hormone (TSH), free thyroxine (FT4), troponin T, human chorionic gonadotropin (hCG), carcinoembryonic antigen (CEA), and prostate specific antigen (PSA). Within-run and between-day imprecision were evaluated using pools of human specimens at low, mid and high concentrations. Linearity was evaluated by diluting specimens with high analyte concentrations with specimens that had a low level of this analyte. Carry over and hook effect were investigated using specimens with high concentrations of hCG. Functional sensitivity was studied by running low TSH specimens over 21 daily runs, and by comparing the scatterplot of FT4 as a function of TSH. Over 100 specimens distributed across the analytical range were analyzed with two comparison methods: ES 300 (Boehringer Mannheim Canada) and AxSYM (Abbott Laboratories). RESULTS: Within-run and between-day imprecisions were less than 4% and 10%, respectively, for most assays. All assays were linear over the whole analytical range. Carry over was minimal (< 0.0002%). A hook effect was present for hCG levels greater than 560,000 U/L. The functional sensitivity of the TSH assay was lower than 0.02 mlU/L. Correlation coefficients were all > 0.94. Small proportional errors were observed in comparison studies for the CEA and PSA assays. CONCLUSIONS: The Elecsys 2010 system was shown to have an acceptable analytical performance for the rapid analysis of a wide variety of analytes. The hook effect observed with hCG assay would imply that the laboratory informs the clinicians of the possibility of falsely low values in trophoblastic diseases or that all specimens with values greater than 3000 U/L are reassayed after dilution.

Autoanalysis

A prospective longitudinal study of platelet angiotensin II receptors for the prediction of preeclampsia.

OBJECTIVES: We developed a simplified method using a relatively small volume of blood for the determination of platelet angiotensin II receptors by saturation analysis and we evaluated its performance for the prediction of preeclampsia. DESIGN AND METHODS: A platelet suspension with minimal contamination by leukocytes and erythrocytes is obtained by centrifugation and washing. The platelet concentrate is incubated in a multi-well plate with increasing concentration of radiolabelled angiotensin II in the presence or absence of an excess of unlabelled angiotensin II. Bound and free fractions are separated using an oil mixture. Maximum binding is determined by Scatchard plot. This method was compared with a previously reported method. Our method was prospectively evaluated in 801 women attending our institution for routine prenatal care. A specimen was obtained at each trimester of pregnancy whenever possible. Diagnosis of preeclampsia was done postnatally by an experienced obstetrician. RESULTS: The method showed acceptable correlation with a previously published method although a proportional bias of 2.1 was observed between the two methods. No differences in mean maximum binding were observed between normal and affected pregnancies at either trimester. Even when the results were analyzed longitudinally, using the change in maximum binding between two trimesters for each patient, no significant increase could be documented in preeclamptic pregnancies. CONCLUSIONS: Platelet angiotensin II receptor measurement is not a clinically useful marker for the prediction of preeclampsia.

Blood Platelets

Platelet angiotensin II binding sites and early detection of preeclampsia.

OBJECTIVE: To determine if platelet angiotensin II binding density during the second or third trimester of pregnancy can be used as a marker for early detection of women who will develop preeclampsia. METHODS: We collected blood samples from 412 nulliparous pregnant women during their second or third trimesters. They were classified in four groups after delivery: normotensive (n=297), transient hypertensive (n=54), preeclamptic (n=39), and chronic hypertensive (n=22). We also studied 35 nonpregnant women and 122 women in the peripartum period. The binding capacity of platelet angiotensin II receptors was analyzed in each patient. RESULTS: In normotensive pregnancies, there was a significant decrease in mean (+/-standard error of the mean [SEM]) platelet binding in the second trimester (1.6+/-0.2 fmol/10(9) cells) compared with nonpregnant women (3.3+/-0.7 fmol/10[9] cells). No statistical differences were observed in the mean (+/-SEM) number of platelet angiotensin II binding sites between the groups studied in the third trimester (normal: 1.7+/-0.1 fmol/10(9) cells; transient hypertensive: 2.3+/-0.4 fmol/10(9) cells; preeclamptic: 1.6+/-0.4 fmol/10(9) cells, and chronic hypertensive: 1.6+/-0.6 fmol/10(9) cells), nor were any significant differences found in second-trimester values. At cutoff levels providing identical sensitivities, angiotensin II binding showed significantly lower positive predictive values than mean arterial pressure (P < .05). With this study's sample size, we could have demonstrated an improvement in positive predictive values of 20% with a statistical power (1-beta) of 90%. CONCLUSION: The measurement of platelet angiotensin II receptor density cannot be recommended for the early detection of preeclampsia.

Adult

Prediction of pre-eclampsia, low birthweight for gestation and prematurity by uterine artery blood flow velocity waveforms analysis in low risk nulliparous women.

OBJECTIVE: To assess the performance of four previously reported Doppler abnormalities of uterine artery velocity waveforms (presence of a protodiastolic notch, peak systolic over protodiastolic velocities (A:C ratio) > 2.5, peak systolic over end diastolic velocities (A:B ratio) > 90th centile, resistance index (RI) ([A-B]/A) > or = 0.58) in predicting pre-eclampsia, low birthweight and prematurity. DESIGN: Prospective cohort study. SETTING: Tertiary care university hospital in Quebec City. POPULATION: 1311 nulliparous women. METHODS: Evaluation of pulsed Doppler abnormalities of uterine artery velocity waveforms was carried out in 1000 and 1194 of women at 18.3 (SD 0.9) or 26.7 (SD 0.9) weeks of pregnancy. MAIN OUTCOME MEASURES: Pre-eclampsia, birthweight below the 10th centile for gestational age and spontaneous preterm birth (< 37 completed gestation weeks). RESULTS: Pre-eclampsia, low birthweight for gestation and prematurity occurred in 4%, 11% and 7% of the pregnancies, respectively. At 26 weeks all the abnormalities of the studied Doppler indices were significantly associated with pre-eclampsia and low birthweight for gestation as reflected by the 95% confidence intervals of the positive likelihood ratios which did not include the value 1. However, sensitivities (26% to 34%) and positive predictive values (7% to 28%) were low. No Doppler indices performed significantly better than the others. The abnormalities of the Doppler indices were not associated with spontaneous prematurity. The performance of the Doppler measurements performed at 18 weeks was poor. CONCLUSIONS: Uterine artery Doppler velocimetry waveform analysis does not qualify as a reliable screening test for pre-eclampsia or low birthweight for gestation in low risk pregnancies but may be useful in selected high risk populations.

Blood Flow Velocity

Do prostacyclin and thromboxane contribute to the "protective effect" of pregnancies with chronic hypertension? A preliminary prospective longitudinal study.

OBJECTIVE: The aim of this study was to assess prospectively the urinary excretion of renal and systemic metabolites of thromboxane and prostacyclin in normotensive and chronic hypertensive pregnancies. STUDY DESIGN: Pregnant hospital employees were invited to collect 24-hour urine samples weekly from the seventh week until delivery. Concentrations of renal metabolites (thromboxane B2, 6-keto-prostaglandin F1alpha) were measured by radioimmunoassay after extraction. Systemic metabolites (2,3-dinor-thromboxane B2, 2,3-dinor-6-keto-prostaglandin F1alpha) were assessed by enzyme immunoassay after extraction and high-pressure liquid chromatographic separation. RESULTS: Thromboxane B2 excretion was similar in normotensive and hypertensive pregnancies, whereas a twofold increase of 6-keto-prostaglandin F1alpha was observed in hypertensive compared with normotensive pregnancies (7537 +/- 349 vs 3857 +/- 202 pg/mg creatinine, p < 0.001). During pregnancy in both conditions measurements displayed uniform excretion of thromboxane B2 with progressively increased levels of 6-keto-prostaglandin F1alpha in chronic hypertension (R2 = 0.60, p < 0.005). Mean excretion of 2,3-dinor-thromboxane B2 averaged 1208 +/- 65 and 898 +/- 48 pg/mg creatinine in normotensive and hypertensive pregnancies (p < 0.001), mainly due to significant decreased concentrations in hypertension in the first half of pregnancy. Conversely, 2,3-dinor-6-keto-prostaglandin F1alpha levels were 845 +/- 39 and 1226 +/- 67 pg/mg creatinine in normotensive and hypertensive pregnancies (p < 0.001), mostly because of significantly increased production in hypertension from 22 weeks onward. Ratios of both renal and systemic metabolites favored increased prostacyclin production in chronic hypertension. CONCLUSION: In contrast to preeclampsia, uncomplicated mild to moderate chronic hypertensive pregnancies are characterized by an excess production of prostacyclin with unaltered or even lower thromboxane concentrations, which may contribute to the general favorable outcome of this hypertensive condition.

6-Ketoprostaglandin F1 alpha

Screening for Down syndrome during first trimester: a prospective study using free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A.

OBJECTIVES: Early screening for Down syndrome is desirable so that more time is left for intervention in the event of a positive test. In retrospective first trimester studies, maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A have been reported as useful markers. Our objective was to confirm these results in a prospective study carried on an unselected population. DESIGN AND METHODS: In a cohort of pregnant women recruited prospectively between 9 and 13 weeks' gestation, we measured maternal free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A in all affected pregnancies and 500 representative uneffected pregnancies. Serum concentrations were transformed to multiples of the median value in normal pregnancies of the same length of gestation, and rates of detection of various combinations of the markers were estimated by multivariate analysis. RESULTS: Down syndrome was observed in 18 fetuses from the 10, 160 women recruited. Levels of free beta-human chorionic gonadotropin were elevated in affected pregnancies with an overall median value 1.8 times the median of women with normal pregnancies while pregnancy-associated plasma protein A was significantly diminished (0.51 multiples of the median). At a fixed false-positive risk of 10%, 33% (11-55), 50% (27-73), 44% (11-67), and 67% (45-89) of the affected pregnancies would have been detected (95% CI) with maternal age alone or combined with with free beta-human chorionic gonadotropin, pregnancy-associated plasma protein A or both, respectively. CONCLUSIONS: We confirm in a prospective noninterventional study that maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A can be used in the first trimester of pregnancy to screen for Down syndrome with a performance similar to second trimester screening programs.

Adult

Effect of repeated freeze-thaw cycles on maternal serum biological markers for the detection of fetal trisomies.

OBJECTIVES: We studied the stability of maternal blood markers for screening for Down syndrome (alpha-fetoprotein, unconjugated estriol, intact human chorionic gonadotropin (hCG) and free beta-human chorionic gonadotropin) upon repeated freeze-thaw cycles. DESIGN AND METHODS: Forty-three samples collected from second trimester normal pregnancies were submitted to five freeze-thaw cycles. After each cycle, the markers were measured using kits and instruments from Wallac Canada (AutoDelfia). Results were compared by repeated measures analysis of variance and by analysis of linear trend (after mathematical transformation of the results in order to decrease between-sample variation) as a function of the number of freeze-thaw cycles. RESULTS: No significant differences were observed by ANOVA (p > 0.1) for any marker. Intact hCG showed a statistically significant linear downward trend (slope = -0.0063, p = 0.009) while free beta-hCG increased (slope = 0.011, p = 0.004). After five freeze-thaw cycles, a mean decrease of 3.2% is predicted for intact hCG while free beta-hCG would increase by 5.5% on average. CONCLUSION: We conclude that the studied markers do not show clinically significant changes under the evaluated conditions. The observed changes of intact hCG and free beta-hCG would have a limited impact on the screening performance.

Analysis of Variance

Microalbumin as a marker of premature delivery.

OBJECTIVE: To determine if microalbumin excretion can predict the development of premature delivery. METHODS: The possibility of predicting, early in pregnancy, the development of a preterm delivery using urinary albumin was investigated in 1422 nulliparous women recruited prospectively. A first morning urine sample was collected at three occasions during pregnancy (8-14, 15-24, 25-34 weeks' gestation) for the determination of urinary albumin excretion. RESULTS: No significant correlation was found between gestational age and urinary albumin (absolute concentration, albumin-creatinine ratio, or relative clearance of albumin) at either visit (r ranging from -0.043 to 0.036; P > .1). The incidence of preterm birth was similar for the first and fourth quartiles of the urinary albumin-creatine ratio for the second visit (5.8 and 5.7%, respectively). CONCLUSION: Urinary albumin is not a useful marker of preterm birth in a low-risk general population.

Adult

Maternal hematocrit and albumin as predictors of intrauterine growth retardation and preterm delivery.

OBJECTIVE: To determine if maternal hematocrit and serum albumin can predict intrauterine growth retardation and/or preterm delivery. METHODS: Analyses were performed during each trimester of pregnancy to evaluate the predictive value of these two common laboratory parameters as predictors of intrauterine growth retardation and/or prematurity. RESULTS: 1468 women participated in the study. Intrauterine growth retardation occurred in 9.9% and preterm delivery in 6.1%. A significant inverse correlation between hematocrit and albumin and birth weight was found (r = -0.005, p = 0.04, and r = -0.07, p = 0.007, respectively), albumin being a stronger predictor as demonstrated by multiple regression. Low hematocrit at the third visit was associated with a longer pregnancy duration (r = -0.06, p = 0.02). Woman with higher serum albumin levels at the second visit, had a longer pregnancy duration, possibly reflecting a better nutritional status (r = 0.057, p = 0.03). To determine the predictive value of hematocrit and serum albumin, the prevalence of intrauterine growth retardation and premature delivery in the highest quartiles were compared with the lowest, and no significant differences were observed (p > 0.1). CONCLUSION: Maternal hematocrit and serum albumin concentration cannot be used as useful predictors of intrauterine growth retardation or preterm delivery.

Adult

Peak systolic over protodiastolic ratio as an objective substitute for the uterine artery notch.

OBJECTIVE: To measure the inter-rater agreement for the identification of a uterine artery notch, as well as the association between an observed notch and the peak systolic over protodiastolic (A/C) ratio. DESIGN: Cohort study. SETTING: Tertiary care university hospital. POPULATION AND METHODS: Six hundred and sixty-five nulliparous women in whom 1022 examinations of uterine artery velocity waveforms were performed by pulsed Doppler at 18 and at 26 weeks of gestation. Agreement between two independent raters was analysed using Cohen's kappa statistics. A/C ratios of flow velocity waveforms with or without a notch were compared. The agreement between A/C values and the presence of a notch was estimated by measuring the surface under the receiver operating characteristic (ROC) curve. RESULTS: Inter-rater agreement for the identification of a notch was 0.74 (95% CI 0.64-0.83) at 18 weeks and 0.72 (95% CI 0.64-0.80) at 26 weeks. A/C ratios were higher when a notch was present (P < 0.0001). The area under the ROC curve was 0.86 (95% CI 0.81-0.91) for the placental uterine artery and 0.93 (95% CI 0.90-0.96) for the nonplacental artery. An A/C value > or = 2.5 in any uterine artery had a sensitivity of 88% and a specificity of 86% to detect a notch. CONCLUSION: Although there is no definitive definition of the notch, its detection is reproducible within a center. However, published prevalences between centers in unselected populations vary. The measure of the A/C ratio can serve as an objective substitute.

Adult

Development of an enzyme-linked immunosorbent assay for 2,3-dinor-6-keto-prostaglandin F1 alpha in urine using a monoclonal antibody.

OBJECTIVES: To develop and validate an enzyme-linked immunosorbent assay (ELISA) for measurement of urinary 2,3-dinor-6-keto-prostaglandin F1 alpha (2,3D6KPGF1 alpha) using a monoclonal antibody and a horseradish peroxidase-linked antigen. DESIGN AND METHODS: Assay validation included optimization of the standard curve, antibody cross-reactivity, accuracy and imprecision studies together with preliminary measurement of clinical samples. RESULTS: Optimal conditions of the standard curve (0.078-10.0 micrograms/L) used 2 mg/L of antibody and 3 micrograms/L of peroxidase conjugate in each well, at pH 7.2. The coefficient of variation of various concentrations of the standard curve averaged 6.8%. Antibody cross-reactivity was < 0.01% for related prostanoids. Recovery of known amounts (0.1-5.0 micrograms/L) of 2,3D6KPGF1 alpha added to an urinary sample was 101.2 +/- 6.3%. Imprecision studies with non-pregnant (0.24 microgram/L) and pregnant (2.5 micrograms/L) samples displayed an intraassay variability of 8.9 and 9.9%, and an interassay variability of 9.6 and 10.0%, respectively. Urinary measurements in the non-pregnant and pregnant states were similar to those previously reported. An apparent decreased concentration was observed early in pregnancy in future preeclampsia. CONCLUSION: With similar precision and validity, our assay method is time- and cost-saving. Preliminary urinary measurements show that this analyte may be of interest as an early marker for preeclampsia.

6-Ketoprostaglandin F1 alpha

Screening for Down syndrome during the first and second trimesters: impact of risk estimation parameters.

OBJECTIVES: To evaluate impact of risk estimation parameters for screening for Down Syndrome during the first and second trimesters. METHODS: We prospectively examined for their performance in the prenatal prediction of trisomy 21, alphafetoprotein (AFP), unconjugated estriol (uE3), total human chorionic gonadotropin (hCG), and its free subunits (free alpha-hCG, free beta-hCG) at both the first and second trimesters, and the impact of three sets of published risk estimation parameters. A total of 14,612 pregnancies were studied. All Down syndrome specimens (12 and 11 cases for first and second trimesters, respectively) and a sample of the unaffected pregnancies were analyzed. RESULTS: The median multiple of median (MoM) for total hCG was lower in the first trimester (1.83 vs. 2.01 in the second trimester) but no loss in discriminative power was observed if the lower variability of the results in the first trimester is taken into account (interquartile range of 0.251 vs. 0.338). The choice of distribution parameters did not alter significantly the detection rates for the various combinations of markers (p > 0.05). False positive rates were affected significantly however and for the combination AFP-uE3-free beta-hCG they varied from 14.6% to 22.6% (p < 0.001). CONCLUSIONS: Our results suggest that specific distribution parameters would be necessary to account for the lower variability of the markers in the first trimester and the peculiarity of the total hCG assay we used.

Adult

Increased immunohistochemical expression of neutral metalloendopeptidase (enkephalinase; EC 3.4.24.11) in villi of the human placenta with pre-eclampsia.

The purpose of this study was to identify the presence of placental neutral metalloendopeptidase (NEP; enkephalinase; EC 3.4.24.11) in human normotensive and pre-eclamptic pregnancy. The localization of NEP in placentae from normotensive, chronic hypertensive and pre-eclamptic pregnancies was carried out on fresh frozen tissues by using a monoclonal primary antibody developed against human common acute lymphoblastic leukaemia antigen (CD10) together with the avidin-biotin-peroxidase method. In placentae from normotensive, chronic hypertensive and superimposed pre-eclamptic pregnancies, intense staining was found in the extravillous trophoblast, and also in fibroblasts of the chorionic plate and stem villi. Light to moderate staining was noted in the villous-associated trophoblast and in some cells from the villous core. In cases of pre-eclampsia, very intense staining was detected not only on the surface, but also in the cytoplasm of the villous-associated trophoblast. The increased expression of placental NEP in pre-eclampsia suggests that this enzyme may be involved in the regulation of the local concentration of circulating biologically active peptides at the fetomaternal interface, and thus could be implicated in the pathophysiological changes of this syndrome.

Adult

Glucose tolerance test during pregnancy: the significance of one abnormal value.

To determine the perinatal impacts of one abnormal oral glucose tolerance test (GTT) value, we conducted a retrospective study of pregnancy outcome in our population. Pregnant women (4314) were screened for gestational diabetes (GDM) between 24 and 32 weeks with the 50-g glucose challenge test and 183 were directly tested with the 100-g GTT. The subjects who had a serum glucose value equal or greater than 7.8 mmol/L 1 h after a 50-g glucose challenge were scheduled for a 100-g GTT (904). Another 32 subjects, who were not screened, were found to have gestational diabetes identified by repeated fasting and postprandial serum glucose measurements. Retrospectively, the study population was divided in four groups: I, normal (4138); II, GDM (237); III, subjects with one abnormal GTT value treated like GDM (85); IV, subjects with one abnormal GTT value untreated (69). Patient characteristics of groups II, III, and IV were similar. The area under the glycemic curve was similar between groups III and IV and was statistically inferior to that of Group II. GTT periodicity was the greatest in group II. Group II showed a higher rate of delivery before 37 weeks, of chronic and pregnancy induced hypertension, and of cesarian section but groups III and IV were not statistically different from group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Electrophoretic method for separating small peptides in serum without extraction of macromolecules: application to the detection of preeclampsia.

We optimized the electrophoretic separation using sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE) and silver staining to detect small peptides in serum, without extraction of major proteins and applied this method to the search for specific peptides that may be used as early markers of preeclampsia during pregnancy. Appropriate separation of peptides was possible by modifying several parameters: increasing total proportion of monomers (%T) from 3 to 5% in the stacking gel; decreasing total proportion of crosslinker (%C) from 2.7 to 1.5% in the separating gel; selecting alkaline stacking gel buffer (pH 8.8) and alkaline sample buffer (pH 8.0); adding glycerol to both gels; and processing with weak current (15 mA). Silver nitrate staining was improved by using glutaraldehyde as the fixing agent, by reducing cross-linker concentration and by eliminating oxidizing and reducing agents. Sensitivity of the improved silver nitrate staining was 50 ng. We compared the electrophoretic pattern of serum peptides in the range of 2-14 kDa of 20 preeclamptic women with and without proteinuria and of 25 women in their third trimester who later developed preeclampsia to that of 24 normal pregnant women at term. No differences were found in the electrophoretic patterns among the groups and there was no correlation between the intensity of the bands and the severity of preeclampsia. We conclude that there is no characteristic electrophoretic pattern associated with preeclampsia.

Biomarkers

A new rapid immunoinhibition pancreatic amylase assay: diagnostic value for pancreatitis.

A new rapid immunoinhibition pancreatic amylase assay was compared to total amylase and lipase in an unbiased sample of 1005 emergency department patients with suspicion of pancreatitis, of which 55 had a final diagnosis of pancreatitis. Imprecision of the assays for both amylases (less than 2.5%) were better than for lipase (less than 6.1%). Correlation (R2) of pancreatic amylase with total amylase was 0.991 but only 0.789 with lipase. Using Receiver Operator Characteristics analysis, the best diagnostic cutoff point for all three enzymes was near the upper limit of the reference interval. With pancreatic amylase, sensitivity, specificity, and predictive values for positive and negative results are, respectively, 85.5, 92.5, 39.8, and 99.1%; we found similar values for lipase but poorer values (78.2, 92.0, 36.1, and 98.7%) for total amylase. Tests combination did not improve the diagnostic performance significantly. In the diagnosis of pancreatitis, pancreatic amylase (p = 0.037) and lipase (p = 0.049) had better diagnostic performance than total amylase. The correct diagnosis of pancreatitis could be achieved in 47 instead of 43 patients with either pancreatic amylase or lipase as opposed to total amylase among 1005 patients in this study. We conclude that pancreatic amylase and lipase are incrementally better diagnostic tools than total amylase for the diagnosis of pancreatitis.

Acute Disease

A prospective study of several potential biologic markers for early prediction of the development of preeclampsia.

OBJECTIVE: The purpose of this study was to prospectively evaluate the predictive performance of several potential biologic markers of preeclampsia used alone or in combination. STUDY DESIGN: A prospective cohort of 1366 nulliparous women was followed up longitudinally on three occasions during pregnancy. The predictive performance of the tests, used either alone or in combination (stepwise multiple logistic regression), was assessed and compared with that of the mean arterial pressure. RESULTS: Preeclampsia occurred in 109 of the pregnant women. At a specificity of 80% the sensitivity and the positive and negative predictive values for mean arterial pressure (at a threshold of 87 mm Hg) were 46.6%, 23.5%, and 92.0%, respectively, and the corresponding values for a multiple logistic model at 15 to 24 weeks that included some biologic markers, as well as the mean arterial pressure, were 57.1%, 26.9%, and 93.7%, respectively. CONCLUSION: Preeclampsia can be predicted by a combination of simple biologic tests with a performance similar to second-trimester mean arterial pressure. However, this procedure is insufficient in terms of clinical usefulness.

Biomarkers