Risk of uterine rupture in Australian women attempting vaginal birth after one prior caesarean section: a retrospective population-based cohort study.

OBJECTIVE: Higher risks of uterine rupture have been reported among women attempting vaginal birth after caesarean (VBAC) particularly following induction with prostaglandins, compared with women who do not labour. This study aimed to estimate these risks as well as that associated with oxytocin use. DESIGN: Population-based retrospective cohort study involving all women who had their first births by caesarean. In their second birth, risks of uterine rupture among women without labour and women who had labour augmented or induced were compared with women who gave birth after spontaneous labour. SETTING: Four Australian states in 1998-2000. POPULATION: Women on pregnancy outcome databases with a second birth after a prior caesarean for their first birth. METHODS: From 29, 008 women identified from the databases, those with uterine rupture were identified and validated using hospital case records. MAIN OUTCOME MEASURE: Uterine rupture. RESULTS: The risk of complete uterine rupture among women without labour was 0.01%. The risk in spontaneous labour without augmentation was 0.15%, considerably higher when there was augmentation with oxytocin (1.91%). The risk with induction of labour was 0.54% for oxytocin alone, 0.68% for prostaglandin alone, 0.63% without either and 0.88% when they were combined. Compared with spontaneous labour, risks were increased three- to five-fold for any induction, six-fold for prostaglandin combined with oxytocin and 14-fold for augmentation with oxytocin. CONCLUSIONS: Careful consideration should be given to the use of oxytocin for augmentation of labour or induction by any method for women with a previous caesarean in view of increased risks of uterine rupture.

WITHDRAWN: Antiplatelet agents for preventing and treating pre-eclampsia.

BACKGROUND: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a platelet-derived vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, and low dose aspirin in particular, might prevent or delay the development of pre-eclampsia. OBJECTIVES: To assess the effectiveness and safety of antiplatelet agents when given to women at risk of developing pre-eclampsia, and to those with established pre-eclampsia. SEARCH STRATEGY: This review drew on the search strategy developed for the Pregnancy and Childbirth Group as a whole. The Cochrane Controlled Trials Register was also searched, The Cochrane Library 1999 Issue 1, Embase was searched from 1994-1999 and hand searches were performed of the congress proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. SELECTION CRITERIA: All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent during pregnancy. Quasi random study designs were excluded. Participants were pregnant women considered to be at risk of developing pre-eclampsia, and those with pre-eclampsia before delivery. Women treated postpartum were excluded. Interventions were any comparisons of an antiplatelet agent (such as low dose aspirin or dipyridamole) with either placebo or no antiplatelet agent. DATA COLLECTION AND ANALYSIS: Assessment of trials for inclusion in the review and extraction of data was performed independently and unblinded by two reviewers. Data were entered into the Review Manager software and double checked. MAIN RESULTS: Forty two trials involving over 32,000 women were included in this review, with 30,563 women in the prevention trials. There is a 15% reduction in the risk of pre-eclampsia associated with the use of antiplatelet agents [32 trials with 29,331 women; relative risk (RR) 0.85, 95% confidence interval (0.78, 0.92); Number needed to treat (NNT) 89, (59, 167)]. This reduction is regardless of risk status at trial entry or whether a placebo was used, and irrespective of the dose of aspirin or gestation at randomisation.Twenty three trials (28,268 women) reported preterm delivery. There is a small (8%) reduction in the risk of delivery before 37 completed weeks [RR 0.92, (0.88, 0.97); NNT 72 (44, 200)]. Baby deaths were reported in 30 trials (30,093 women). Overall there is a 14% reduction in baby deaths in the antiplatelet group [RR 0.86, (0.75, 0.98); NNT 250 (125, >10000)]. Small for gestational age babies were reported in 25 trials (20,349 women), with no overall difference between the groups, RR 0.92, (0.84, 1.01). There were no significant differences between treatment and control groups in any other measures of outcome. Five trials compared antiplatelet agents with placebo or no antiplatelet agent for the treatment of pre-eclampsia. There are insufficient data for any firm conclusions about the possible effects of these agents when used for treatment of pre-eclampsia. AUTHORS' CONCLUSIONS: Antiplatelet agents, in this review largely low dose aspirin, have small-moderate benefits when used for prevention of pre-eclampsia. Further information is required to assess which women are most likely to benefit, when treatment should be started, and at what dose.

Antiplatelet agents for preventing pre-eclampsia and its complications.

BACKGROUND: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia. OBJECTIVES: To assess the effectiveness and safety of antiplatelet agents for women at risk of developing pre-eclampsia. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 1), EMBASE (1994 to November 2005) and handsearched congress proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. SELECTION CRITERIA: All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included. Quasi-random studies were excluded. Participants were pregnant women at risk of developing pre-eclampsia. Interventions were any comparisons of an antiplatelet agent (such as low-dose aspirin or dipyridamole) with either placebo or no antiplatelet. DATA COLLECTION AND ANALYSIS: Two authors assessed trials for inclusion and extracted data independently. MAIN RESULTS: Fifty-nine trials (37,560 women) are included. There is a 17% reduction in the risk of pre-eclampsia associated with the use of antiplatelet agents ((46 trials, 32,891 women, relative risk (RR) 0.83, 95% confidence interval (CI) 0.77 to 0.89), number needed to treat (NNT) 72 (52, 119)). Although there is no statistical difference in RR based on maternal risk, there is a significant increase in the absolute risk reduction of pre-eclampsia for high risk (risk difference (RD) -5.2% (-7.5, -2.9), NNT 19 (13, 34)) compared with moderate risk women (RD -0.84 (-1.37, -0.3), NNT 119 (73, 333)). Antiplatelets were associated with an 8% reduction in the relative risk of preterm birth (29 trials, 31,151 women, RR 0.92, 95% CI 0.88 to 0.97); NNT 72 (52, 119)), a 14% reduction in fetal or neonatal deaths (40 trials, 33,098 women, RR 0.86, 95% CI 0.76 to 0.98); NNT 243 (131, 1,666) and a 10% reduction in small-for-gestational age babies (36 trials, 23,638 women, RR 0.90, 95% CI0.83 to 0.98). There were no statistically significant differences between treatment and control groups for any other outcomes. AUTHORS' CONCLUSIONS: Antiplatelet agents, largely low-dose aspirin, have moderate benefits when used for prevention of pre-eclampsia and its consequences. Further information is required to assess which women are most likely to benefit, when treatment is best started, and at what dose.

Percutaneous transluminal aortic valvuloplasty: acute outcome and follow-up of 125 patients.

Percutaneous transluminal aortic valvuloplasty was performed on 125 patients (59 men [47%], mean age 76 +/- 13 years) between July 1986 and May 1988, with presenting symptoms of severe congestive heart failure in 88 (70%), moribund state in 15 (12%) and syncope in 17 (14%). Surgical valve replacement was considered unsuitable in 79% of cases. A multiple balloon technique was utilized in 119 patients (95%). Valvuloplasty produced significant changes in peak pressure gradient (87 +/- 38 to 32 +/- 17 mm Hg), mean pressure gradient (70 +/- 26 to 30 +/- 13 mm Hg) and valve area (0.6 +/- 0.2 to 1.0 +/- 0.3 cm2). Complications included: in-hospital mortality in 10% (6 of 13 deaths in moribund patients), neurologic deficit in 3% and myocardial infarction in 2%. Arterial repair was required at 12 (4%) of 325 entry sites. Multivariate analysis identified severe congestive heart failure, preprocedure left ventricular ejection fraction and cardiac output as the only independent variables significantly affecting mortality. The cumulative probability of survival at 12 months was 62 +/- 6% and, excluding non-cardiac deaths, was 77 +/- 5%. At a mean of 12 +/- 4 months' follow-up, 55 of 72 patients were symptomatically improved; 10 patients with symptom recurrence underwent repeat valvuloplasty and 5 had valve replacement. Cardiac catheterization was repeated in 12 symptomatically improved patients, 9 of whom had valve restenosis. These data indicate that aortic valvuloplasty should be considered a palliative therapy for elderly patients with symptomatic calcific aortic stenosis who are poor surgical candidates.

Demographic and phenotypic features of 70 families segregating Barrett's oesophagus and oesophageal adenocarcinoma.

BACKGROUND: Based on reported familial patterns, inheritance of a predisposition of developing Barrett's oesesophagus (BO) and oesophageal adenocarcinoma (OAC) likely follows an autosomal dominant model of most inherited cancer syndromes. oesophagus (BO) and oesophageal adenocarcinoma (OAC) likely follows an autosomal dominant model of most inherited cancer syndromes. AIMS: We analysed the phenotypic features of 70 familial BO/OAC families accrued for the purpose of initiating a linkage study to search for genes that contribute to susceptibility for BO/OAC. METHODS: Families with young or familial BO/OAC were recruited from participating institutions and self-referral from advertisement. RESULTS: A total of 70 families (173 affected and 784 unaffected individuals) were recruited into this study. Mean ages of diagnosis of BO and OAC among males were 50.6 and 57.4 years, respectively; among females, 52.1 and 63.5 years, respectively. The standardised incidence ratio (SIR) of cancers other than OAC or oesophagogastric junctional adenocarcinoma (OGJAC), among probands was 0.71. Seventy one percent of the pedigrees have "typical" structures with less than three affected individuals. Power calculations under realistic model assumptions suggest that if genetic heterogeneity is absent or limited, then DNA collection from members of these pedigrees could enable the identification of a novel candidate susceptibility gene for BO/OAC in a genome scan. CONCLUSIONS: This is the largest series of families with BO/OAC yet reported, features of which are consistent with inherited germline predisposition. Further, the SIR of cancers other than OAC/OGJAC was 0.71 among 70 probands, indicating these individuals were not more likely to develop non-OAC cancers.

Risk factors and the anatomic distribution of coronary artery disease.

Differences in the importance of risk factors according to the anatomic location of coronary artery disease (CAD) were assessed in 4722 men and 1069 women who underwent arteriography. Examined characteristics included total and high-density lipoprotein (HDL)-cholesterol, triglycerides, obesity, smoking, alcohol consumption, diabetes, and hypertension. Of these risk factors, the ratio of total to HDL-cholesterol showed the highest correlation with the overall severity of CAD (r = 0.24, men; r = 0.38, women); in contrast, its relation to left main (LM) disease was much lower (r = 0.10, men; r = 0.08 women) than were correlations with stenotic disease in the left anterior descending, circumflex, and right coronary arteries. Other risk factors also showed weaker associations with LM disease than with stenoses in other vessels, and none was related to increased LM disease after controlling for disease in other vessels. For example, as compared with men who had no significant CAD, those with 1-, 2-, and 3-vessel disease had mean increases in total cholesterol of 12, 18, and 19 mg/dl, respectively. In contrast, after adjusting for disease in other vessels, LM disease (present in 293 men) was associated with only a 4 mg/dl increase in mean cholesterol levels (P = 0.20). These results indicate that the relation of risk factors to CAD differs according to the location of the stenotic disease, and that LM disease is poorly predicted by the standard risk factors.

Reappearance of anterior QRS forces after coronary bypass surgery. An electrovectorcardiographic study.

This report describes the reappearance of anterior QRS electrical forces in six patients after direct coronary arterial bypass surgery. Each patient had severe coronary artery disease including a segmental stenosis of the left anterior descending artery. Revascularization was performed by direct anastomosis of the left mammary artery to the left anterior descending coronary artery and saphenous vein bypass of other stenotic coronary arteries. Preoperative electrocardiograms and vectorcardiograms showed patterns of anterior wall myocardial infarction with absent or diminutive anterior QRS forces. In each case, postoperative studies demonstrated the regeneration of anterior QRS forces within 10 days of operation. Although these patients represent a small percent of those with a preoperative pattern of infarction who undergo coronary revascularization, the findings demonstrate that electrically silent areas of myocardium may be altered and are not always synonymous with myocardial cell death. Chronic myocardial ischemia may in certain instances produce electrocardiographic and vectorcardiographic patterns of myocardial infarction that may be reversible upon reestablishment of perfusion to ischemic areas.

The sources, fate, and toxicity of chemical warfare agent degradation products.

We include in this review an assessment of the formation, environmental fate, and mammalian and ecotoxicity of CW agent degradation products relevant to environmental and occupational health. These parent CW agents include several vesicants: sulfur mustards [undistilled sulfur mustard (H), sulfur mustard (HD), and an HD/agent T mixture (HT)]; nitrogen mustards [ethylbis(2-chloroethyl)amine (HN1), methylbis(2-chloroethyl)amine (HN2), tris(2-chloroethyl)amine (HN3)], and Lewisite; four nerve agents (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), tabun (GA), sarin (GB), and soman (GD)); and the blood agent cyanogen chloride. The degradation processes considered here include hydrolysis, microbial degradation, oxidation, and photolysis. We also briefly address decontamination but not combustion processes. Because CW agents are generally not considered very persistent, certain degradation products of significant persistence, even those that are not particularly toxic, may indicate previous CW agent presence or that degradation has occurred. Of those products for which there are data on both environmental fate and toxicity, only a few are both environmentally persistent and highly toxic. Major degradation products estimated to be of significant persistence (weeks to years) include thiodiglycol for HD; Lewisite oxide for Lewisite; and ethyl methyl phosphonic acid, methyl phosphonic acid, and possibly S-(2-diisopropylaminoethyl) methylphosphonothioic acid (EA 2192) for VX. Methyl phosphonic acid is also the ultimate hydrolysis product of both GB and GD. The GB product, isopropyl methylphosphonic acid, and a closely related contaminant of GB, diisopropyl methylphosphonate, are also persistent. Of all of these compounds, only Lewisite oxide and EA 2192 possess high mammalian toxicity. Unlike other CW agents, sulfur mustard agents (e.g., HD) are somewhat persistent; therefore, sites or conditions involving potential HD contamination should include an evaluation of both the agent and thiodiglycol.

Nonsurgical removal of foreign body from right heart. A new percutaneous approach.

A new method is described for the nonsurgical removal of foreign bodies from the right heart. By means of the percutaneous Seldinger Technique, endoscopic forceps were passed throught the internal jugular vein to remove a fragment of polyvinyl catheter from the right atrium of a patient who had had heart surgery. The procedure is atraumatic and can be performed on patients who are critically ill and those who recently have had surgery.

The "bad" left ventricle. Results of coronary surgery and effect on late survival.

Between 1968 and 1971, 252 patients with severe ventricular malfunction underwent revascularization surgery. By means of single-plane ventriculography, the ventricle was divided into six segments, three anteriorly and three inferiorly, and ejection fractions were calculated. Patients were classified into four groups according to these observations. Results were assessed in regard to relief of angina, graft patency status, surgical mortality rate, and survival as determined by actuarial life-table analysis. These results were then compared to over-all medical and surgical experience contained in the Milwaukee Cardiovascular Data Registry as well as to other reported series of medical treatment for similar degrees of coronary artery disease and impairment of left ventricular function. Comparison between the surgical and medical series suggests improved survival and improved quality of life in the surgically treated patients. Thus many patients with severe ventricular malfunction, especially if associated with angina, can be reasonably considered candidates for surgery.

Risk factors among patients undergoing repeat aorta-coronary bypass procedures.

It is estimated that as many as 7% of patients who have an aorta-coronary bypass operation will require a second bypass procedure within 10 to 12 years. Using information from the Milwaukee Cardiovascular Data Registry, we matched 166 men who underwent two coronary bypass operations at least 6 months apart, between 1968 and 1981, with 428 patients who had a single procedure. Patients were matched according to date of operation and left ventricular wall motility function for analysis of risk factors for repeat operation. Elevated triglyceride levels were found to be the strongest risk factors associated with reoperation. In addition, both younger age and less complete revascularization during the first operation were significant predictive factors of repeat operation. The results suggest that efforts to reduce plasma triglyceride levels and ensure adequate revascularization may significantly reduce the need for repeat coronary bypass.

Biologic variation of common hematologic laboratory quantities in the elderly.

Analytic, within-subject, and between-subject biologic variations were estimated for leukocytes, erythrocytes, hemoglobin, hematocrit, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin content (MCHC), platelets, and a three-component differential count (lymphocytes, monocytes, and granulocytes in terms of both concentration and percentage of leukocytes) in cohorts of 12 male and 12 female healthy elderly subjects. The assays were performed with an Ortho ELT-800 automated analyzer. The estimates of within-subject biologic variation were similar to published data on young subjects, indicating that this aspect of homeostasis is not compromised in the elderly. The data were used to derive objective analytic goals; goals were surpassed except for assays of erythrocytes, hematocrit, and the derived MCV, MCH, and MCHC. The changes required for serial results to be significantly different were determined and found to be generally valid because most quantities have no heterogeneity of within-subject variation. All quantities had significant individuality; in consequence, conventional population-based reference values are of limited utility, and screening using reference limits will not detect latent or early disease in many subjects.

High density lipoprotein cholesterol and coronary artery occlusion.

The relationship between the levels of high density lipoprotein cholesterol (HDLC) and the extent of coronary artery occlusion (ascertained by arteriography) was studied in four hundred male patients. The group with HDLC levels over 50 mg/dl showed a significantly lower coronary artery occlusion score and lower plasma triglyceride levels than the patients with HDLC levels less than 35 mg/dl. The former group also imbibed more alcohol and had less smoking experience.

A randomized trial of electronic fetal monitoring in preterm labor.

Intrapartum electronic fetal heart rate (FHR) monitoring and fetal blood gas sampling were compared with periodic auscultation of FHR in a multicentered randomized trial of preterm singleton pregnancies with fetal weights of 700-1750 g. Two hundred forty-six pregnancies were studied (electronic FHR monitoring N = 122, auscultation N = 124). Perinatal or infant death was associated with 14% of pregnancies with electronic FHR monitoring and 15% with auscultation. No significant differences were noted in the prevalence of low five-minute Apgar scores, intrapartum acidosis, intracranial hemorrhage, or frequency of cesarean section (P greater than .10). Compared with electronic FHR monitoring, intrapartum auscultation as done in this study is unlikely to be associated with detectable differences in perinatal outcomes within the high-risk setting of preterm labor.

Restenosis after angioplasty: mechanisms and clinical experience.

The conundrum of restenosis remains the most significant challenge in revascularization techniques. This article reviews the current understanding of restenosis based upon laboratory investigations, clinical experience, and the efficacy of mechanical and pharmacologic interventions that have been attempted to prevent and/or reduce its occurrence. However, terminology really comes into play because restenosis is really the mechanism by which the body heals and is not a rapid deposition of atherosclerotic plaque.

Maternal hypertension and neurodevelopmental outcome in very preterm infants.

AIM: To determine the outcome of preterm infants born to mothers with hypertension during pregnancy, and preterm controls. METHODS: 107 infants of 24-32 weeks gestation, born to hypertensive mothers, and 107 controls matched for gestational age, sex, and multiple pregnancy, born to normotensive mothers, were prospectively enrolled over 2 years. Information on maternal complications and medication was obtained and neonatal mortality and morbidities recorded. Survivors were followed up to at least 2 years, corrected for prematurity. RESULTS: One third of the hypertensive mothers were treated with antihypertensive drugs, while 18% received convulsion prophylaxis with phenytoin. Magnesium sulphate was not prescribed. Both groups had a mean gestational age of 29.9 weeks, with the study infants having a significantly lower birthweight than the controls. Four study and three control infants died in the neonatal period. Cerebral palsy was not diagnosed in any infant of a hypertensive mother compared with five of the controls. The mean general quotient for the two groups was very similar and no difference in the incidence of minor neuromotor developmental problems was shown. CONCLUSIONS: Maternal hypertension seems to protect against cerebral palsy in preterm infants without increasing the risk of cognitive impairment. This was independent of the use of maternally administered magnesium sulphate.

Antiplatelet agents for preventing and treating pre-eclampsia.

BACKGROUND: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a platelet-derived vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, and low dose aspirin in particular, might prevent or delay the development of pre-eclampsia. OBJECTIVES: To assess the effectiveness and safety of antiplatelet agents when given to women at risk of developing pre-eclampsia, and to those with established pre-eclampsia. SEARCH STRATEGY: This review drew on the search strategy developed for the Pregnancy and Childbirth Group as a whole. The Cochrane Controlled Trials Register was also searched, The Cochrane Library 1999 Issue 1, Embase was searched from 1994-1999 and hand searches were performed of the congress proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. SELECTION CRITERIA: All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent during pregnancy. Quasi random study designs were excluded. Participants were pregnant women considered to be at risk of developing pre-eclampsia, and those with pre-eclampsia before delivery. Women treated postpartum were excluded. Interventions were any comparisons of an antiplatelet agent (such as low dose aspirin or dipyridamole) with either placebo or no antiplatelet agent. DATA COLLECTION AND ANALYSIS: Assessment of trials for inclusion in the review and extraction of data was performed independently and unblinded by two reviewers. Data were entered into the Review Manager software and double checked. MAIN RESULTS: Forty two trials involving over 32,000 women were included in this review, with 30,563 women in the prevention trials. There is a 15% reduction in the risk of pre-eclampsia associated with the use of antiplatelet agents [32 trials with 29,331 women; relative risk (RR) 0.85, 95% confidence interval (0.78, 0.92); Number needed to treat (NNT) 89, (59, 167)]. This reduction is regardless of risk status at trial entry or whether a placebo was used, and irrespective of the dose of asprin or gestation at randomisation. Twenty three trials (28,268 women) reported preterm delivery. There is a small (8%) reduction in the risk of delivery before 37 completed weeks [RR 0.92, (0.88, 0.97); NNT 72 (44, 200)]. Baby deaths were reported in 30 trials (30,093 women). Overall there is a 14% reduction in baby deaths in the antiplatelet group [RR 0.86, (0. 75, 0.98); NNT 250 (125, >10000)]. Small for gestational age babies were reported in 25 trials (20,349 women), with no overall difference between the groups, RR 0.92, (0.84, 1.01). There were no significant differences between treatment and control groups in any other measures of outcome. Five trials compared antiplatelet agents with placebo or no antiplatelet agent for the treatment of pre-eclampsia. There are insufficient data for any firm conclusions about the possible effects of these agents when used for treatment of pre-eclampsia. REVIEWER'S CONCLUSIONS: Antiplatelet agents, in this review largely low dose aspirin, have small-moderate benefits when used for prevention of pre-eclampsia. Further information is required to assess which women are most likely to benefit, when treatment should be started, and at what dose.

Antiplatelet agents for preventing pre-eclampsia and its complications.

BACKGROUND: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a platelet-derived vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay the development of pre-eclampsia. OBJECTIVES: To assess the effectiveness and safety of antiplatelet agents when given to women at risk of developing pre-eclampsia. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), EMBASE (1994 to 2003) and we handsearched the congress proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. SELECTION CRITERIA: All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent during pregnancy. Quasi-random study designs were excluded. Participants were pregnant women considered to be at risk of developing pre-eclampsia. Interventions were any comparisons of an antiplatelet agent (such as low-dose aspirin or dipyridamole) with either placebo or no antiplatelet agent. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trials for inclusion in the review and extracted data. We entered data into the Review Manager software and double checked. MAIN RESULTS: Fifty-one trials involving 36,500 women are included in this review. There is a 19% reduction in the risk of pre-eclampsia associated with the use of antiplatelet agents ((43 trials, 33,439 women; relative risk (RR) 0.81, 95% confidence interval (CI) 0.75 to 0.88); number needed to treat (NNT) 69 (51, 109)).Twenty-eight trials (31,845 women) reported preterm birth. There is a small (7%) reduction in the risk of delivery before 37 completed weeks ((RR 0.93, 95% CI 0.89 to 0.98); NNT 83 (50, 238)). Fetal or neonatal deaths were reported in 38 trials (34,010 women). Overall there is a 16% reduction in baby deaths in the antiplatelet group (RR 0.84, 95% CI 0.74 to 0.96); NNT 227 (128, 909)). Small-for-gestational age babies were reported in 32 trials (24,310 women), with an 8% reduction in risk (RR 0.92, 95% CI 0.85 to 1.00). There were no significant differences between treatment and control groups in any other measures of outcome. REVIEWER'S CONCLUSIONS: Antiplatelet agents, in this review largely low-dose aspirin, have small-moderate benefits when used for prevention of pre-eclampsia. Further information is required to assess which women are most likely to benefit, when treatment is best started, and at what dose.

Calcium channel blockers for inhibiting preterm labour.

BACKGROUND: Preterm birth is a major contributor to perinatal mortality and morbidity and affects approximately six to seven per cent of births in developed countries. Tocolytics are drugs used to suppress uterine contractions. The most widely tested tocolytics are betamimetics. Although they have been shown to delay delivery, betamimetics have not been shown to improve perinatal outcome, and they have a high frequency of unpleasant and even fatal maternal side effects. There is growing interest in calcium channel blockers as a potentially effective and well tolerated form of tocolysis. OBJECTIVES: To assess the effects on maternal, fetal and neonatal outcomes of calcium channel blockers, administered as a tocolytic agent, to women in preterm labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's specialised register of controlled trials (June 2002), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2002), MEDLINE (1965 to June 2002), EMBASE (1988 to June 2002), and Current Contents (1997 to June 2002). We also contacted recognised experts and cross referenced relevant material. SELECTION CRITERIA: All published and unpublished randomised trials in which calcium channel blockers were used for tocolysis for women in labour between 20 and 36 weeks' gestation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by three authors. Additional information was sought to enable assessment of methodology and conduct of intention-to-treat analyses. Meta-analysis was conducted assessing the effects of calcium channel blockers compared with any other tocolytic agent. Results are presented using relative risk for categorical data and weighted mean difference for continuous data. MAIN RESULTS: Twelve randomised controlled trials involving 1029 women were included. When compared with any other tocolytic agent (mainly betamimetics), calcium channel blockers reduced the number of women giving birth within seven days of receiving treatment (relative risk (RR) 0.76; 95% confidence interval (CI) 0.60 to 0.97) and prior to 34 weeks' gestation (RR 0.83; 95% CI 0.69 to 0.99). Calcium channel blockers also reduced the requirement for women to have treatment ceased for adverse drug reaction (RR 0.14; 95% CI 0.05 to 0.36), the frequency of neonatal respiratory distress syndrome (RR 0.63; 95% CI 0.46 to 0.88), necrotising enterocolitis (RR 0.21; 95% CI 0.05 to 0.96), intraventricular haemorrhage (RR 0.59 95% CI 0.36 to 0.98) and neonatal jaundice (RR 0.73; 95% CI 0.57 to 0.93). REVIEWER'S CONCLUSIONS: When tocolysis is indicated for women in preterm labour, calcium channel blockers are preferable to other tocolytic agents compared, mainly betamimetics. Further research should address the effects of different dosage regimens and formulations of calcium channel blockers on maternal and neonatal outcomes.

Calcium channel blockers for inhibiting preterm labour.

BACKGROUND: Preterm birth is a major contributor to perinatal mortality and morbidity and affects approximately six to seven per cent of births in developed countries. Tocolytics are drugs used to suppress uterine contractions. The most widely tested tocolytics are betamimetics. Although they have been shown to delay delivery, betamimetics have not been shown to improve perinatal outcome, and they have a high frequency of unpleasant and even fatal maternal side effects. There is growing interest in calcium channel blockers as a potentially effective and well tolerated form of tocolysis. OBJECTIVES: To assess the effects on maternal, fetal and neonatal outcomes of calcium channel blockers, administered as a tocolytic agent, to women in preterm labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's specialised register of controlled trials, the Cochrane Controlled Trials Register (February 2002), MEDLINE, EMBASE, and Current Contents. We also contacted recognised experts and cross referenced relevant material. SELECTION CRITERIA: All published and unpublished randomised trials in which calcium channel blockers were used for tocolysis for women in labour between 20 and 36 weeks gestation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by three authors. Additional information was sought to enable assessment of methodology and conduct of intention-to-treat analyses. Meta-analysis was conducted assessing the effects of calcium channel blockers compared with any other tocolytic agent. Results are presented using relative risk for categorical data and weighted mean difference for continuous data. MAIN RESULTS: Eleven randomised controlled trials involving 870 women were included. When compared with any other tocolytic agent (mainly betamimetics), calcium channel blockers reduced the number of women giving birth within 48 hours (relative risk (RR) 0.73; 95% confidence interval (CI) 0.54, 0.98) and within seven days (RR 0.76; 95% CI 0.59, 0.99). Calcium channel blockers also reduced the requirement for women to have treatment ceased for adverse drug reaction (RR 0.15; 95% CI 0.06, 0.43), the frequency of neonatal respiratory distress syndrome (RR 0.64; 95% CI 0.45, 0.91) and neonatal jaundice (RR 0.73; 95% CI 0.57, 0.93). REVIEWER'S CONCLUSIONS: When tocolysis is indicated for women in preterm labour, calcium channel blockers are preferable to betamimetic agents. Further research should address the effects of different dosage regimens and formulations of nifedipine on maternal and neonatal outcomes.