Screening for pre-eclampsia early in pregnancy: performance of a multivariable model combining clinical characteristics and biochemical markers.

OBJECTIVE: To investigate the performance of a multivariable model combining a priori clinical characteristics and biomarkers to detect, early in pregnancy, women at higher risk of developing pre-eclampsia (PE). DESIGN: Nested case-control study. SETTING: University medical centre, Quebec, Canada (CHU de Québec). POPULATION: A total of 7929 pregnant women recruited between 10 and 18 weeks of gestation. In all, 350 developed hypertensive disorders of pregnancy (HDP)-of which 139 had PE, comprising 68 with severe PE and 47 with preterm PE-and were matched with two women with a normal pregnancy. METHODS: We selected a priori clinical characteristics and promising markers to create multivariable logistic regression models: body mass index (BMI), mean arterial pressure (MAP), placental growth factor, soluble Fms-like tyrosine kinase-1, pregnancy-associated plasma protein A and inhibin A. MAIN OUTCOME MEASURES: PE, severe PE, preterm PE, HDP. RESULTS: At false-positive rates of 5 and 10%, the estimated detection rates were between 15% (5-29%) and 32% (25-39%), and between 39% (19-59%) and 50% (34-66%), respectively. Considering the low prevalence of PE in this population, the positive predictive values were 7% (5-9%) to 10% (7-13%) for PE and 2% (1-4%) to 4% (3-6%) in the preterm and severe PE subgroups. The multivariable model yielded areas under the receiver operating characteristics curves (AUC) between 0.72 (0.61-0.81) and 0.78 (0.68-0.88). When only BMI and MAP were included in the model, the AUC were similar to those of the a priori model. CONCLUSIONS: In a population with a low prevalence of preterm PE, a multivariable risk algorithm using an a priori combination of clinical characteristics and biochemical markers did not reach a performance justifying clinical implementation as screening test early in pregnancy.

Alteration of calcium homeostasis in primary preeclamptic syncytiotrophoblasts: effect on calcium exchange in placenta.

Preeclampsia (PE) is characterized by maternal hypertension, proteinuria, oedema and, in 30% of cases, by intrauterine growth retardation. Causes are still unknown; however, epidemiological and clinical studies have suggested alterations in maternal calcium metabolism. We suggested that in PE, calcium transport by the syncytiotrophoblast (ST) is disturbed. From total placental tissues, we studied the expression of: calcium channels (TRPV5, TRPV6 [transient receptor potential vanilloid]), calcium binding proteins (CaBP-9K, CaBP-28K), plasma membrane calcium ATPase (PMCA)1,2,3,4 pumps, ATP synthase, genes implicated in Ca(2+) release [inositol-1,4,5-triphosphate receptor (IP3R)1,2,3; Ryanodine receptor (RyR)1,2,3] and replenishment (SERCA1,2,3 [sarcoendoplasmic reticulum Ca(2+) ATPases]) from endoplasmic reticulum, channels implicated in mitochondrial Ca(2+) accumulation (VDAC1,2,3 [voltage-dependent anion channels]) and a marker of oxidative stress (hOGG1 [Human 8-oxoguanine-DNA glycosylase 1]), as well as the influence of these variations on calcium transport in primary ST cultures. The mRNA and protein levels were thereby examined by real-time PCR and Western blot analysis, respectively, in two different groups of pregnant women with similar gestational age: a normal group (n= 16) and a PE group (n= 8), diagnosed by a clinician. Our study showed a significant decrease in calcium transport by the ST cultured from preeclamptic placentas. We found a significant (P < 0.05) decrease in mRNA levels of TRPV5, TRPV6, CaBP-9K, CaBP-28K, PMCA1, PMCA4, ATP synthase, IP3R1, IP3R2, RyR1, RyR2 and RyR3 in PE group compared to normal one. We also noted a significant decrease in protein levels of TRPV5, TRPV6, CaBP-9K, CaBP-28K and PMCA1/4 in PE group. In contrast, SERCA1, SERCA2, SERCA3, VDAC3 and hOGG1 mRNA expressions were significantly increased in PE placentas. Calcium homeostasis and transport through placenta is compromised in preeclamptic pregnancies and it appears to be affected by a lack of ATP and an excess of oxidative stress.

Modulation of placental protein expression of OLR1: implication in pregnancy-related disorders or pathologies.

The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR1) is a newly described receptor for oxidatively modified LDL. The human pregnancy is associated with hyperlipidemia and oxidative stress. It has been reported that modification in maternal lipid profile can induce disturbance during pregnancy. In this study, we have evaluated the expression protein level of OLR1 in human term placenta of women having plasma cholesterol level lower to 7 mM or higher to 8 mM and women of gestational diabetes mellitus (GDM) by western blot analysis. The present study demonstrates that the maternal lipid profile is associated with placental protein expression of OLR1. A significant increase in the protein expression of OLR1 was observed in placenta of women with elevated plasmatic total cholesterol level (>8 mM). In addition, the placental protein expression of OLR1 is increased in mothers having the highest pre-pregnancy body mass index (BMI) and low (<7 mM) plasmatic total cholesterol level at term. Interestingly, the placental protein expression of OLR1 is increased in the presence of GDM pregnancies compared with normal lipids level pregnancies, without the modification of mRNA expression. In conclusion, placental OLR1 protein expression is associated with maternal lipid profile, pre-pregnancy BMI, and pathology of GDM.

The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial.

Phytoestrogens are increasingly incorporated into the diet of menopausal women. However, there are limited data on the efficacy of flaxseed on the consequences of estrogen deficiency in menopausal women. The purpose of the study was to assess the effects of flaxseed incorporation into the diet of healthy menopausal women. One hundred and ninety-nine menopausal women were randomly assigned to consume 40 g flaxseed/d (n = 101) or wheat germ placebo (n = 98) for 12 months. At baseline and at month 12, serum levels of lipids, bone mineral density (BMD), and menopausal symptoms were evaluated. Statistical analysis was performed under the intention to treat principle. Flaxseed reduced serum total (-0.20 +/- 0.51 mmol/liter; P = 0.012) and high-density lipoprotein (-0.08 +/- 0.24 mmol/liter; P = 0.031) cholesterol concentrations compared with wheat germ placebo. BMD did not differ significantly between the two arms. Both flaxseed and wheat germ reduced (P < 0.0001) the severity scores of menopausal symptoms, but no statistical difference was found between the two arms. Our findings suggest that 1-yr incorporation of flaxseed into the diet produced a favorable, but not clinically significant, effect on blood cholesterol and caused no significant change in BMD or symptoms in healthy menopausal women.

Standardization in laboratory medicine: new challenges.

The primary goal of Laboratory Medicine is to provide information that is useful to assist medical decision-making and permits optimal health care. This type of information should be independently obtained of the measurement test kits and instruments, and also of the laboratory where the procedure is carried out. It is therefore important to achieve a level of comparability of laboratory results among the many measurement procedures available so that results are harmonized and interchangeable over space and time. The standardization of measurements is therefore of high priority. In recent years, numerous efforts have been made at the international level under the auspices of the IFCC and other organizations to standardize measurement results for many important analytes, e.g. enzymes, cardiac proteins, etc. The aim of this review is to discuss some concepts related to the achievement of standardization by the implementation of a metrologically correct measurement system, providing some examples on how these concepts can be applied in Laboratory Medicine.

Multicenter evaluation of the Glucometer Elite XL meter, an instrument specifically designed for use with neonates.

OBJECTIVE: To evaluate the clinical performance of the Glucometer Elite XL Diabetes Care System in neonatal settings using a multicenter study RESEARCH DESIGN AND METHODS: A total of 388 blood specimens from 333 neonates were included in the study. A capillary or arterial sample was analyzed for determination of glucose with the Glucometer Elite XL system by an attending trained nurse. Through the same sampling site, a specimen was collected and sent to the laboratory for measurement of plasma glucose, bilirubin, and hematocrit. RESULTS: The regression analysis between the results of the Glucometer Elite XL system and comparative methods resulted in the following: Glucometer Elite XL meter = 1.01 x laboratory method + 0.02 mmol/l (n = 388). For the 1.1-4.0 mmol/l plasma glucose range, the regression was Glucometer Elite XL meter = 1.07 x laboratory method + 0.12 mmol/l (n = 150). A difference plot indicated a mean bias of 0.04 mmol/l (95% CI -0.01 to 0.10). No relationship was found between meter glucose biases and hematocrit levels (r = 0.10, P = 0.14). Although a statistically significant correlation existed between bilirubin levels and the glucose meter biases (r = 0.14, P = 0.005), the predicted mean biases were of little clinical significance. CONCLUSIONS: The Glucometer Elite XL system showed a good performance when used in neonatal settings.

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.

Microporous hydrophilic polyurethane vascular grafts as substitutes in the abdominal aorta of dogs.

Polyurethanes are emerging as promising biomaterials. A microporous vascular graft fabricated from Mitrathane, a new polyetherurethane urea, appeared to be particularly interesting according to in vitro evaluation and was tested in vivo as an infrarenal aortic substitute (i.d. 5 mm) in 24 dogs. After implantation for scheduled periods ranging from 4 h to 6 mnth, morphology evaluation and healing analysis of the grafts were performed. At harvesting, 18 grafts were patent and 6 were thrombosed. The thrombosed grafts had been implanted for 4 h (1 graft), 1 mnth (2 grafts) and 6 mnth (3 grafts). No macroscopic deposits other than red mural thrombi were observed. At 1 mnth complete external encapsulation was observed in 2 grafts. The capsule then contracted and became thinner; over the long term it shrank, became translucent and incomplete at 6 mnth. Yellow and brown stains appeared on many of the grafts. Characterization of the brown stains showed them to be iron (Fe3+) and the yellow stains were associated with the deposition of a bile pigment (bilirubin).

Reference values for the oral glucose tolerance test at each trimester of pregnancy.

A 100-gram oral glucose tolerance test (OGTT) was performed on a selected group of normal women at each trimester of pregnancy to establish reference values for hyperglycemia and hypoglycemia. Ninety three OGTT were performed in the first trimester, 121 in the second trimester, and 98 in the last trimester. The fasting serum glucose did not differ significantly between the trimesters. The values at 60 and 120 minutes were significantly different for the fifth, fiftieth, and ninety-fifth percentiles between each trimester of pregnancy. For the 180-minute readings, the fifth and fiftieth percentiles were not significantly different between the first and second trimester of pregnancy, but the results of the third trimester were significantly higher than those of the other trimesters. The mean fasting insulinemia remained relatively constant during pregnancy. Insulin response to OGTT increased during the progression of the pregnancy. The interpretation of the glucose tolerance tests during pregnancy, either to detect gestational diabetes or hypoglycemia, should take these physiologic changes into account.

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.

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.

Biological markers in major psychosis and alcoholism: phenotypic and genotypic markers.

Some basic concepts and trends which appear to be essential in the search for biological markers in mental disorders are discussed. Comments related to major psychosis and alcoholism are presented under three headings: (i) heterogeneity of disorders (ii) multifactoriality of disorders and (iii) mental disorders as genetically influenced disorders. Tentative classification and terminology of biological markers are given. Various types of phenotypic markers are discussed and alcoholism is taken as a model for a more detailed discussion of available putative phenotypic markers and of research strategies to be used, namely the pharmacological challenge in high risk subjects (e.g. ethanol and TRH challenge). Some highlights from the field of DNA markers are described, mainly the basic procedures which may be used to investigate genetic aspects of mental disorders by recombinant DNA technology.

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.

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.

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)

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.

The Laboratory Information System (LIS): I-Application to the clinical chemistry laboratory.

The Laboratory Information System (LIS) was designed as a "turn-key" system. The main functions are operated interactively on a mini-computer which gives the laboratory complete control over daily processing. Collection of results from automated analyzers is accomplished via a micro-computer/micro-processor network. Links are provided with a central main frame computer for immediate patient identification and historical data processing. LIS is designed to manage all the operations involved in laboratory activities. The system has 14 major functions: registration of test requests, production of specimen collection sheets and identification labels, confirmation of specimen collection, production of aliquot labels, workload inquiry, production of worksheets, manual entry of test results, automated entry of test results, results inquiry, preliminary report, final report, daily activities reports, statistical reports, billing. System security is provided along three directions: data entry validation, system access control, and memory protection. The main advantages of LIS are: reduced clerical work, better evaluation of workload, faster communication, improvement of information given to the clinician: adapted reference values, interpretation, comments, improved retrieval operations, faster billing.

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.

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.

[Preeclampsia: physiopathology and prospects for early detection]. / La prééclampsie: physiopathologie et perspectives de dépistage précoce.

Preeclampsia is a complication of pregnancy characterized by hypertension, edema and proteinuria, beginning after 20 weeks of gestation. Six percent of the pregnant women in North America develop this disease, which is associated with increased morbidity and mortality for the mother and her baby. The physiopathology remains uncertain despite many research efforts. Actual hypotheses seek to explain the vasospasm that characterizes the disease. Among the many factors influencing vascular reactivity and possibly implicated are: the renin-angiotensin system, prostaglandins, progesterone and its metabolites, calcium, magnesium, digoxin-like immunoreactive substance(s), auricular natriuretic factor, substances secreted by platelets and leukotrienes. Prevention of the disease is limited by the absence of a biological or clinical marker with good sensitivity and appropriate specificity. Many biochemical or hematological parameters have been reported: uric acid, calcium, magnesium, proteinuria, blood iron, hematocrit, platelet count, antithrombin III, estrogen and progesterone. The combination of several tests could be superior to the use of each test individually, providing a better sensitivity and improving the positive predictive value. With early detection, new therapies for the prevention of the disease could be experimented on the higher risk women before the apparition of clinical symptoms or signs. Furthermore, those tests could be used in the study of the pathophysiology and in the choice of the best therapy.