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 Effects of exclusive versus non-eclusive breastfeeding on specific infant morbidities in Conakry (Guinea)

Background :This study examines the effect of exclusive versus non-exclusive breastfeeding on specific infant morbidities from birth to nine months; in Conakry (Guinea). Method: A cross-sectional study was conducted on 1;167 mother-infant pairs who visited one of 20 immunization centres in Conakry for vaccination between the 45th and 270th days of the child's life. Two data sources were used: the infant health book and an orally administered questionnaire completed with the mother. Data analyses included univariate cross-tabulations and multivariate logistic regression models to estimate the effect of breastfeeding on infant morbidity. Results : Exclusive breastfeeding decreased with the infant's age. At six months of age; the proportion of infants who were exclusively breastfed was only 15.5. After adjusting for the infant's age; and the interaction between the type of breastfeeding and the infant's age; exclusive breastfeeding significantly protected the infants against many of the studied morbidities (OR: 0.28; CI: 0.15-0.51) and specifically against diarrhoea (OR: 0.38; 95CI: 0.17 - 0.86); respiratory infections (OR: 0.27; 95CI: 0.14 - 0.50); and low growth rate (OR: 0.11; 95CI: 0.02 - 0.46); but not for otitis; urinary infection; or meningitis. This investigation confirmed the protective effects of exclusive breastfeeding on some specific infant's morbidities during the first nine months of life. The results of this study are of great importance for the development of an information program designed to encourage the exclusive breastfeeding among the mothers of Conakry; Guinea

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.

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.

Do maternal cerebral vascular changes assessed by transcranial Doppler antedate pre-eclampsia?

OBJECTIVE: To determine whether maternal transcranial Doppler (TCD) evaluation of the middle cerebral artery identifies changes in the cerebral circulation prior to the development of pre-eclampsia. METHODS: In a nested, case-controlled study developed from a previous prospective cohort study, 20 pre-eclamptic and 40 normotensive pregnancies, matched for maternal age, were assessed with the traditional middle cerebrovascular Doppler parameters (pulsatility index, mean cerebral blood flow velocity), together with non-traditional Doppler parameters including time taken to achieve end systole (EST) and percentage time to achieve end systole (% EST). Assessments done at 20-24 and 28-32 weeks' gestational age were compared using Student's t-tests. Significance was set at the P < 0.05 level. RESULTS: In the second trimester (20-24 weeks) there were no significant differences in any of the Doppler waveform characteristics in either group. In the third trimester (28-32 weeks) there was a significant increase in the % EST in the group who subsequently developed pre-eclampsia (45.2 +/- 4.2 vs. 42.3 +/- 4.1; P < 0.01). CONCLUSIONS: Patients who subsequently develop pre-eclampsia show a significant lengthening in the EST in the third trimester as a late finding, which indicates an increase in the cerebrovascular resistance. Earlier prediction of pre-eclampsia using TCD waveform analysis will require more provocative testing (i.e. hand grip and CO(2) reactivity).

Chemoprevention of breast cancer. A joint guideline from the Canadian Task Force on Preventive Health Care and the Canadian Breast Cancer Initiative's Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer.

OBJECTIVE: To assist women and their physicians in making decisions regarding the prevention of breast cancer with tamoxifen and raloxifene. EVIDENCE: Systematic review of English-language literature published from 1966 to August 2000 retrieved from MEDLINE, HealthSTAR, Current Contents and Cochrane Library. VALUES: The strength of evidence was evaluated using the methods of the Canadian Task Force on Preventive Health Care and the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. RECOMMENDATIONS: Women at low or normal risk of breast cancer (Gail risk assessment index < 1.66% at 5 years): There is fair evidence to recommend against the use of tamoxifen to reduce the risk of breast cancer in women at low or normal risk of the disease (grade D recommendation). Women at higher risk of breast cancer (Gail index > or = 1.66% at 5 years): Evidence supports counselling women at high risk on the potential benefits and harms of breast cancer prevention with tamoxifen (grade B recommendation). The cutoff for defining high risk is arbitrary, but the National Surgical Adjuvant Breast and Bowel Project P-1 Study included women with a 5-year projected risk of at least 1.66% according to the Gail index, and the average risk of patients entered in the trial was 3.2%. Examples of high-risk clinical situations are 2 first-degree relatives with breast cancer, a history of lobular carcinoma in situ or a history of atypical hyperplasia. As the risk of breast cancer increases above 5% and the benefits outweigh the harms, a woman may choose to take tamoxifen. The duration of tamoxifen use in such situations is 5 years based on the results from trials of tamoxifen involving women with early breast cancer. If a woman raises concerns or has already been evaluated and is calculated to be at high risk, then individuals experienced and skilled in counselling may discuss the potential benefits and harms of tamoxifen use. Important additional issues: Prevention of breast cancer with raloxifene: Current evidence does not support recommending chemoprevention of breast cancer with raloxifene outside of a clinical trial setting. Screening using the Gail risk assessment index: This index was the main eligibility criterion for enrolling women in the one study that showed potential benefit from chemoprevention. However, it has not been evaluated for use as a routine screening or case-finding instrument; validation of the index is required. Overall, current evidence does not support a shift to its routine use in physicians' offices for screening or case finding. However, when a woman or her physician is concerned about the woman's increased risk of breast cancer, the index can be a useful tool in deciding whether to pursue an in-depth discussion of the potential benefits and harms of chemoprevention. Hence, the approach to identifying women at higher risk who warrant counselling and shared decision-making will vary across practices. (The risk assessment index is available online at http://bcra.nci.nih.gov/brc/). [A patient version of these guidelines appears in Appendix 2.] VALIDATION: The authors' original text was revised by both the Canadian Task Force on Preventive Health Care and the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. The final document reflects a consensus of these contributors. SPONSOR: Health Canada. COMPLETION DATE: February 2001.

[Maternal genital infections and premature delivery]. / Infection génitale maternelle et accouchement prématuré.

The etiology of preterm birth remains elusive being probably multifactorial. Fifty years ago, genital infection was proposed as an important risk factor. Recent advances in the identification of several pathogens together with the potential rôle of bacterial vaginosis have generated renewed interest. However may studies suffered from methodological flaws and definitive answers are yet to come. In addition, studies looking at genital infections on pathological cervices already effaced or dilated, suggested that infection may play an additive interactive role to preterm birth.

Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: a multicenter effectiveness and safety study.

OBJECTIVE: This study was undertaken to compare the efficacy and safety of intravenous administration of atosiban versus ritodrine for the treatment of preterm labor. STUDY DESIGN: Women with preterm labor and intact membranes diagnosed at 23 to 33 gestational weeks (n = 247) were randomly assigned to treatment arms and received atosiban (6.75 mg intravenous bolus, 300 microg/min for 3 hours, then 100 microg/min intravenously) or ritodrine (0.10-0.35 mg/min intravenously) for as long as 18 hours. Tocolytic effectiveness was assessed in terms of the numbers of women who had not been delivered after 48 hours and after 7 days. Safety was assessed in terms of maternal side effects and neonatal morbidity. Secondary outcomes included mean gestational age at delivery and mean birth weight. An intent-to-treat analysis was performed with the Cochran-Mantel-Haenszel test. RESULTS: The proportion of women who had not been delivered at 48 hours was 84.9% (n = 107) in the atosiban group and 86.8% (n = 105) in the ritodrine group. At 7 days 92 women had still not been delivered in both the atosiban (73.0%) and ritodrine (76.0%) groups. Neither of these differences was statistically significant. The incidence of maternal cardiovascular side effects was substantially lower in the atosiban group (4.0% vs 84.3%, P <.001). In addition, intravenous therapy was terminated more frequently as a result of maternal adverse events in the ritodrine group (29.8%) than in the atosiban group (0.8%). The overall occurrences of fetal adverse events in the two treatment groups were comparable. Neonatal morbidity was similar between the treatment groups after adjustment for unbalanced enrollment of women with multiple pregnancies and for gestational ages within treatment groups. CONCLUSION: Atosiban was comparable in clinical effectiveness to conventional ritodrine therapy but was better tolerated than ritodrine, with no evidence of significant maternal or fetal adverse events. Neonatal morbidity, which was similar between the two treatment arms, was apparently related to the gestational age of the infant rather than to the exposure to either tocolytic agent.

A retrospective assessment of Canadian preterm birth prevention efforts: 1979-1999.

OBJECTIVES: To assess the achievements and effectiveness of efforts to reduce preterm deliveries through the collaborative efforts of funding agencies, scientists, obstetricians, pediatricians, and health care providers in Canada. METHODS: Chronological review of studies carried out in Canada within the past two decades using several methodological approaches, including randomized clinical trials, surveys of women and physicians, and prospective cohort studies. RESULTS: Tertiary prevention by treatment of spontaneous preterm labor with beta-agonists was effective in delaying delivery by 48 hr compared with placebo. Ongoing studies tested the comparative efficacy of oxytocin antagonists to beta-adrenergic agents. Recently, nitric oxide donors have been tested. Secondary prevention using various approaches showed that high-risk factors could not be modified by these interventions. Before applying primary prevention approaches, surveys disclosed the lack of knowledge among both physicians and pregnant women. CONCLUSION: A recent Canadian consensus meeting emphasized the potential for success by using multidiscplinary, community-based health promotion approaches to prevent preterm labor; enhancing basic research in predictive markers such as cervical change, infection/inflammation, and psychosocial stress; and increasing political involvement of health decision makers.

Hypertension in pregnancy: new recommendations for management.

Hypertension in pregnancy is a frequent complication that has substantial adverse perinatal outcomes. Hypertension may be preexisting (chronic) essential or secondary hypertension; a second entity is pregnancy induced (gestational hypertension, preeclampsia). Recent advances have identified newer markers for pregnancy hypertension: several potential candidate genes may explain the apparent family inheritance of preeclampsia, and some thrombophilic markers have been associated with the condition. Management options for mild to moderate hypertension include a short hospital stay to exclude ongoing severe hypertension and to ascertain fetal well-being. Outpatient care with appropriate maternal and fetal surveillance, including umbilical artery doppler velocimetry, is recommended for better perinatal outcomes. Acute care for severe hypertension includes the use of magnesium sulfate to prevent eclampsia and antihypertensive medication. Expeditious delivery is recommended when the maternal or fetal states cannot be stabilized. Follow-up after delivery allows the uncovering of any other coexisting hypertensive or cardiovascular disorder.

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.

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.

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.