Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial.

OBJECTIVE: To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of 'less tight' versus 'tight' control of pregnancy hypertension. DESIGN: Secondary analysis of CHIPS Trial cohort. SETTING: International randomised controlled trial (94 sites, 15 countries). POPULATION OR SAMPLE: Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation. METHODS: Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors. MAIN OUTCOME MEASURES: CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight <10th centile, severe maternal hypertension, pre-eclampsia and delivery at <34 or <37 weeks. RESULTS: Methyldopa and labetalol were used commonly at randomisation (243/987, 24.6% and 238/987, 24.6%, respectively) and post-randomisation (224/981, 22.8% and 433/981, 44.1%, respectively). Following adjusted analyses, methyldopa (versus labetalol) at randomisation was associated with fewer babies with birthweight <10th centile [adjusted odds ratio (aOR) 0.48; 95% CI 0.20-0.87]. Methyldopa (versus labetalol) postrandomisation was associated with fewer CHIPS primary outcomes (aOR 0.64; 95% CI 0.40-1.00), birthweight <10th centile (aOR 0.54; 95% CI 0.32-0.92), severe hypertension (aOR 0.51; 95% CI 0.31-0.83), pre-eclampsia (aOR 0.55; 95% CI 0.36-0.85), and delivery at <34 weeks (aOR 0.53; 95% CI 0.29-0.96) or <37 weeks (aOR 0.55; 95% CI 0.35-0.85). CONCLUSION: These nonrandomised comparisons are subject to residual confounding, but women treated with methyldopa (versus labetalol), particularly those with pre-existing hypertension, may have had better outcomes. TWEETABLE ABSTRACT: There was no evidence that women treated with methyldopa versus labetalol had worse outcomes.

Control of Hypertension In Pregnancy Study randomised controlled trial-are the results dependent on the choice of labetalol or methyldopa?

OBJECTIVE: To determine whether the difference in outcomes between 'less tight' (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) in the CHIPS Trial (ISRCTN 71416914, http://pre-empt.cfri.ca/;CHIPS) depended on the choice of labetalol or methyldopa, the two most commonly used antihypertensive agents in CHIPS. DESIGN: Secondary analysis of CHIPS Trial data. SETTING: International multicentre randomised controlled trial (94 sites, 15 countries). POPULATION OR SAMPLE: A total of 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: Logistic regression was used for comparisons of 'less tight' versus 'tight' control among women treated with labetalol (but not methydopa) versus methyldopa (but not labetalol). Analyses were adjusted for the influence of baseline factors, including use of any antihypertensive therapy at randomisation. MAIN OUTCOME MEASURES: Main CHIPS Trial outcomes: primary (perinatal loss or high-level neonatal care for > 48 hours), secondary (serious maternal complications), birthweight < 10th centile, severe maternal hypertension, pre-eclampsia, and delivery at < 34 or < 37 weeks. RESULTS: Of 987 women in CHIPS, antihypertensive therapy was taken by 566 women at randomisation (labetalol 111 ['less tight'] versus 127 ['tight'] or methyldopa 126 ['less tight'] versus 117 ['tight']) and 815 women after randomisation (labetalol 186 ['less tight'] versus 247 ['tight'] and methyldopa by 98 ['less tight'] versus 126 ['tight']). Following adjustment, odds ratios for outcomes in 'less tight' versus 'tight' control were similar between antihypertensive groups according to 'at randomisation' and 'after randomisation' therapy. CONCLUSION: Outcomes for 'less tight' versus 'tight' control were not dependent on use of methyldopa or labetalol. TWEETABLE ABSTRACT: In the CHIPS Trial, maternal and infant outcomes were not dependent on use of labetalol or methyldopa.

Cross-border reprogenetic services.

The purpose of this review is to synthesize the current knowledge on the international movement of patients and biopsied embryo cells for pre-implantation genetic diagnosis and its different applications. Thus far, few attempts have been made to identify the specific nature of this phenomenon called 'cross-border reprogenetic services'. There is scattered evidence, both empirical and speculative, suggesting that these services raise major issues in terms of service provision, risks for patients and the children-to-come, the legal liabilities of physicians, as well as social justice. To compile this evidence, this review uses the narrative overview protocol combined with thematic analysis. Five major themes have emerged from the literature at the conjunction of cross-border treatments and reprogenetics: 'scope', 'scale', 'motivations', 'concerns', and 'governance'. Similar themes have already been observed in the case of other medical tourism activities, but this review highlights their singularity with reprogenetic services. It emphasizes the diagnostic and autologous feature of reprogenetics, the constant risk of misdiagnosis, the restriction on certain tests for medically controversial conditions, and the uncertain accessibility of genetic counseling in cross-border settings.

PIERS proteinuria: relationship with adverse maternal and perinatal outcome.

OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.

Potential biomarkers of preeclampsia: inverse correlation between hydrogen peroxide and nitric oxide early in maternal circulation and at term in placenta of women with preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disease that has been associated with future cardiovascular disease for the mother and her child. The etiology of PE is unclear but oxidative stress seems to play a major role in endothelial dysfunction and permanent systemic vasoconstriction shown in PE. Hydrogen peroxide (H(2)O(2)), a terminal metabolite of the cellular oxidative stress cascade, is also revealed as a component of oxidative ischemia/reperfusion stress in placenta. We were the first to show an increase in the levels of H(2)O(2) in the serum of preeclamptic women at term. H(2)O(2) is already known to reduce the production of NO by increasing the metabolism of arginases. The objective of this study was to investigate a possible correlation between nitric oxide (NO), a potent vasodilator, and H(2)O(2) throughout pregnancy. Thus, we simultaneously assessed the levels of NO and H(2)O(2) in the serum of normal and preeclamptic women at 10-15 and 37-40 weeks of pregnancy, and in placentas at delivery. Our findings showed an inverse correlation between increased levels of H(2)O(2) and decreased levels of NO early in maternal circulation and at term in placenta. This relationship is confirmed by our in vitro experiments which demonstrate that H(2)O(2) inhibits NO synthesis of cytotrophoblasts. In conclusion, our findings highlight an inverse correlation between H(2)O(2) and NO early in maternal circulation and in placenta of women with preeclampsia, paving the way for further studies examining the potential use of NO and H(2)O(2) as biomarkers in the prediction of preeclampsia.

The Control of Hypertension In Pregnancy Study pilot trial.

OBJECTIVE: To determine whether 'less tight' (versus 'tight') control of nonsevere hypertension results in a difference in diastolic blood pressure (dBP) between groups. DESIGN: Randomised controlled trial (ISRCTN#57277508). SETTING: Seventeen obstetric centres in Canada, Australia, New Zealand, and UK. POPULATION: Inclusion: pregnant women, dBP 90-109 mmHg, pre-existing/gestational hypertension; live fetus(es); and 20-33(+6) weeks. Exclusion: systolic blood pressure > or = 170 mmHg and proteinuria, contraindication, or major fetal anomaly. METHODS: Randomisation to less tight (target dBP, 100 mmHg) or tight (target dBP, 85 mmHg) blood pressure control. MAIN OUTCOME MEASURES: Primary: mean dBP at 28, 32 and 36 weeks. Secondary: clinician compliance and women's satisfaction. Other: serious perinatal and maternal complications. RESULTS: A total of 132 women were randomised to less tight (n = 66; seven had no study visit) or tight control (n= 66; one was lost to follow up; seven had no study visit). Mean dBP was significantly lower with tight control: -3.5 mmHg, 95% credible interval (-6.4, -0.6). Clinician compliance was 79% in both groups. Women were satisfied with their care. With less tight (versus tight) control, the rates of other treatments and outcomes were the following: post-randomisation antenatal antihypertensive medication use: 46 (69.7%) versus 58 (89.2%), severe hypertension: 38 (57.6%) versus 26 (40.0%), proteinuria: 16 (24.2%) versus 20 (30.8%), serious maternal complications: 3 (4.6%) versus 2 (3.1%), preterm birth: 24 (36.4%) versus 26 (40.0%), birthweight: 2675 +/- 858 versus 2501 +/- 855 g, neonatal intensive care unit (NICU) admission: 15 (22.7%) versus 22 (34.4%), and serious perinatal complications: 9 (13.6%) versus 14 (21.5%). CONCLUSION: The CHIPS pilot trial confirms the feasibility and importance of a large definitive trial to determine the effects of less tight control on serious perinatal and maternal complications.

Women's views of their experiences in the CHIPS (Control of Hypertension in Pregnancy Study) Pilot Trial.

BACKGROUND: Satisfaction with maternity care is strongly related to the patient-caregiver relationship and involvement in the decision-making process. We sought to compare women's views about their care in a randomized trial of 'less tight' vs. 'tight' control of non-proteinuric pre-existing or gestational hypertension in pregnancy. METHODS: In the CHIPS Pilot Trial, women completed a postpartum questionnaire to assess their likes and dislikes about their blood pressure (BP) management and trial participation. Comparisons were descriptive. RESULTS: Baseline information was similar for the 'less tight' and 'tight' control groups. Of 132 women, 126 (95.5%) from 17 centers completed a postpartum questionnaire, usually within days of delivery. At least 90% of women in both groups were satisfied with their care, and would be willing to participate again or recommend participation to a friend. Women in both the 'less tight' and 'tight' groups were satisfied with BP management (98.4% vs. 95.1%), and the frequency of tests of maternal and fetal well being. Half of women in both groups perceived that their BP was too high and that caregivers thought that their BP was too high. More women in the 'less tight' (vs. the 'tight') control group took less medication than expected (71.7% vs. 38.2%). More women in the 'tight' (vs. the 'less tight') group took more medication than they expected (60.0% vs. 22.2%). At least 60% of all women used home BP monitoring. CONCLUSION: In the CHIPS Pilot Trial, while women stated that they were satisfied with their BP management and care, a surprising 50% in both groups thought that their BP was too high. The majority of women used home BP monitoring, the role of which must be further defined in hypertensive pregnancies.

Current CHS and NHBPEP criteria for severe preeclampsia do not uniformly predict adverse maternal or perinatal outcomes.

OBJECTIVE: To determine the association between adverse maternal/perinatal outcomes and Canadian and U.S. preeclampsia severity criteria. METHODS: Using PIERS data (Preeclampsia Integrated Estimate of RiSk), an international continuous quality improvement project for women hospitalized with preeclampsia, we examined the association between preeclampsia severity criteria and adverse maternal and perinatal outcomes (univariable analysis, Fisher's exact test). Not evaluated were variables performed in <80% of pregnancies (e.g., 24-hour proteinuria). RESULTS: Few of the evaluated variables were associated with adverse maternal (chest pain/dyspnea, thrombocytopenia, 'elevated liver enzymes', HELLP syndrome, and creatinine >110 microM) or perinatal outcomes (dBP >110 mm Hg and suspected abruption) (at p < 0.01). CONCLUSIONS: In the PIERS cohort, most factors used in the Canadian or American classifications of severe preeclampsia do not predict adverse maternal and/or perinatal outcomes. Future classification systems should take this into account.

Twin pregnancy: the impact of the Higgins Nutrition Intervention Program on maternal and neonatal outcomes.

Perinatal outcomes were compared between 354 twins treated with the Higgins Nutrition Intervention Program and 686 untreated twins. After differing distributions of key confounding variables were adjusted for, the twins in the intervention group weighed an average of 80 g more (P less than 0.06) than the nonintervention twins; their low-birth-weight rate was 25% lower (P less than 0.05) and their very-low-birth-weight rate was almost 50% lower (P less than 0.05). Although the rate of preterm delivery was 30% lower in the intervention group (P less than 0.05), the rates of intrauterine growth retardation were similar in the two groups. Fetal mortality was slightly higher (14 vs 12 per 1000, NS), but early neonatal mortality was fivefold lower (3 vs 19 per 1000, P less than 0.06) in the intervention group. Maternal morbidity was significantly lower (P less than 0.05) in the intervention group. There was a trend towards lower infant morbidity in the intervention group. These results suggest that nutritional intervention can significantly improve twin-pregnancy outcome.

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.

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.

Effects of maternal oral salbutamol therapy on neonatal endocrine status at birth.

Cord blood concentrations of insulin, growth hormone (GH), triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) from 20 patients treated with oral salbutamol were compared with those of 18 matched patients who had not received any betamimetic agents. No significant difference was found in circulating insulin, T3, T4, and TSH between both groups. However, GH levels were significantly higher in the treated group (36.5 +/- 17.4 ng/mL) than in the control group (17.4 +/- 6.6 ng/mL; P less than .001). The unexpected increase in GH levels in the treated group could reflect either fluctuating fetal blood glucose in response to episodic betamimetic administration or direct fetal pituitary production through adrenergic stimulation.

Strategy for screening pregnant women for chlamydial infection in a low-prevalence area.

OBJECTIVE: To assess the prevalence and risk factors for chlamydial infection in pregnant women in the Quebec City area and to propose strategies for a screening program. METHODS: From January 1990 to July 1991, pregnant women from six centers were cultured for Chlamydia trachomatis. One hundred thirty-six with positive results and 536 with negative results were included in a case-control study on risk factors for this infection. RESULTS: The prevalence of C trachomatis was 1.9% (136 of 7305). In a logistic regression analysis, young age (P < .0001, test for trend), nulliparity (odds ratio [OR] 3.3; P < .00001), and a new sexual partner in the last year (OR 3.3; P = .0012) were independently associated with infection. With screening restricted to pregnant women under age 25 or those with at least one risk factor, 81.7% of women positive for C trachomatis would have been detected, whereas only 40.6% of all women would have been cultured. CONCLUSION: In a low-prevalence area for chlamydial infection in pregnant women, pre-screening criteria could optimize the use of specific diagnostic tests.

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.

Effects of smoking cessation on maternal airway function and birth weight.

OBJECTIVE: To evaluate the effects of smoking cessation before or early in pregnancy on maternal airway function and birth weight. METHODS: Measurements of forced expiratory spirometry including forced vital capacity, forced expiratory volume in 1 second, forced expiratory flow rates between 0.2 and 1.2 L, 25% and 75%, and 75% and 85%, and instantaneous flows at lung volumes of 25%, 50%, and 75% were carried out by a wedge bellow spirometer in 40 pregnant exsmokers and were compared with those of 175 nonsmoking and 97 currently smoking pregnant women. Spirometric testing was conducted at a mean (+/- SD) gestational age of 21.5 +/- 7.0 weeks. In exsmokers, the average lifetime cigarette consumption was 17.1 +/- 8.1/day for a mean duration of 9.7 +/- 3.9 years, similar to that observed in current smokers. The median duration of smoking abstinence was 20 weeks before study spirometry. RESULTS: All spirometric measurements in exsmokers were similar to those of nonsmokers and were significantly higher than those of current smokers. Spirometric measurements for nonsmokers, current smokers, and exsmokers were respectively: forced expiratory volume in 1 second (3.36 +/- 0.39, 3.09 +/- 0.45, and 3.35 +/- 0.32 L); forced expiratory flow rate between 25% and 75% (ie, mid-expiratory phase) (3.85 +/- 0.69, 3.21 +/- 0.76, and 3.86 +/- 0.66 L/sec); forced expiratory flow rate between 75% and 85% (ie end-expiratory phase) (1.39 +/- 0.35, 1.03 +/- 0.35, and 1.41 +/- 0.39 L/sec); instantaneous flow at lung volume of 50% (4.35 +/- 0.82, 3.76 +/- 0.89 and 4.36 +/- 0.68 L/sec); and instantaneous flow at lung volume of 25% (1.91 +/- 0.47, 1.47 +/- 0.49, and 1.92 +/- 0.46 L/sec). Mean gestational age at delivery was similar among the three groups (277 +/- 11,274 +/- 12, and 274 +/- 11 days for nonsmokers, current smokers, and exsmokers, respectively). The mean birth weight of babies born to exsmokers (3408 +/- 511 g) was similar to that of babies born to nonsmokers (3469 +/- 461 g), but was significantly greater than that of babies born to smoking pregnant women (3189 +/- 485 g; P < .001). CONCLUSION: Smoking cessation either before or at an early stage of pregnancy is associated with early, reversible increments of maternal airway function and mean birth weights that are higher than among women who continue smoking.

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.

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.