The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: An exploratory, randomized placebo controlled study.

BACKGROUND: Epidemiological findings suggest that the link between poverty and pre-eclampsia might be dietary calcium deficiency. Calcium supplementation has been associated with a modest reduction in pre-eclampsia, and also in blood pressure (BP). METHODS: This exploratory sub-study of the WHO Calcium and Pre-eclampsia (CAP) trial aims to determine the effect of 500mg/day elemental calcium on the blood pressure of non-pregnant women with previous pre-eclampsia. Non-pregnant women with at least one subsequent follow-up trial visit at approximately 12 or 24weeks after randomization were included. RESULTS: Of 836 women randomized by 9 September 2014, 1st visit data were available in 367 women of whom 217 had previously had severe pre-eclampsia, 2nd visit data were available in 201 women. There was an overall trend to reduced BP in the calcium supplementation group (1-2.5mmHg) although differences were small and not statistically significant. In the subgroup with previous severe pre-eclampsia, the mean diastolic BP change in the calcium group (-2.6mmHg) was statistically larger than in the placebo group (+0.8mmHg), (mean difference -3.4, 95% CI -0.4 to -6.4; p=0.025). The effect of calcium on diastolic BP at 12weeks was greater than in those with non-severe pre-eclampsia (p=0.020, ANOVA analysis). CONCLUSIONS: There is an overall trend to reduced BP but only statistically significant in the diastolic BP of women with previous severe pre-eclampsia. This is consistent with our hypothesis that this group is more sensitive to calcium supplementation, however results need to be interpreted with caution.

A cluster randomized controlled trial of the non-pneumatic anti-shock garment for obstetric haemorrhage: sub-analysis of the Zimbabwean Arm.

Objectives: To determine whether earlier application of the Non-pneumatic Anti-Shock Garment (NASG) at clinic level compared to the referral hospital level reduces maternal morbidity and mortality and recovery time from shock due to severe Obstetric Haemorrhage (OH) and to determine the safety of the NASG when applied at clinic level. Design: A cluster Randomized Controlled Trial (RCT) Setting: Harare and Parirenyatwa Referral Hospitals (RH) in Harare and the twelve Harare City Council clinics that offer maternity care. Subjects: Women who had suffered severe OH at clinic level and were being transferred to a Referral Hospital (RH). Iterventions: The clinics were randomized into two groups. In the early NASG group eligible women were given the standard management for OH and had the NASG applied at the clinic level before transport to RH. In the control group, eligible women were given the standard management for OH at the clinic level, transferred to the RH, and received the NASG at the RH. All women received equivalent OH/hypovolemic shock management at the RH. Main Outcome Measures: The main outcome measures were maternal mortality and morbidity, blood loss, recovery from shock and the occurrence of side effects whilst in the NASG. Results: There were few maternal deaths and morbidities, and no statistically significant differences between the two groups were noted. Women in the early NASG group spent a statistically significant shorter time in the NASG at referral hospital level (OR 0.64, 95% CI 0.52 - 0.79, p < 0.001) and had a non-significant 40% faster recovery from shock (HR 1.39; 95% CI 0.98-1.97, p=0.07). There were no differences in reported side effects. Conclusion: Earlier NASG application at the clinic level was associated with faster recovery from shock in women who had suffered severe OH and appears safe to use.

Bed rest during pregnancy for preventing miscarriage.

BACKGROUND: Miscarriage is pregnancy loss before 23 weeks of gestational age and it happens in 10% to 15% of pregnancies depending on maternal age and parity. It is associated with chromosomal defects in about a half or two thirds of cases. Many interventions have been used to prevent miscarriage but bed rest is probably the most commonly prescribed especially in cases of threatened miscarriage and history of previous miscarriage. Since the etiology of miscarriage in most of the cases is not related to an excess of activity, it is unlikely that bed rest could be an effective strategy to reduce spontaneous miscarriage. OBJECTIVES: To evaluate the effect of prescription of bed rest during pregnancy to prevent miscarriage in women at high risk of miscarriage. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2004). In addition, we searched The Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, POPLINE, LILACS and EMBASE. SELECTION CRITERIA: We included all published, unpublished and ongoing randomized trials with reported data which compare clinical outcomes in pregnant women who were prescribed bed rest in hospital or at home for preventing miscarriage compared with alternative care or no intervention. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the methodological quality of included trials using the methods described in the Cochrane Reviewers' Handbook. Studies were included irrespective of their methodological quality. MAIN RESULTS: Only two studies including 84 women were identified. There was no statistically significant difference in the risk of miscarriage in the bed rest group versus the no bed rest group (placebo or other treatment) (relative risk (RR) 1.54, 95% confidence interval (CI) 0.92 to 2.58). Neither bed rest in hospital nor bed rest at home showed a significant difference in the prevention of miscarriage. There was a higher risk of miscarriage in those women in the bed rest group than in those in the human chorionic gonadotrophin therapy group with no bed rest (RR 2.50, 95% CI 1.22 to 5.11). It seems that the small number of participants included in these studies is a main factor to make this analysis inconclusive. AUTHORS' CONCLUSIONS: There is insufficient evidence of high quality that supports a policy of bed rest in order to prevent miscarriage in women with confirmed fetal viability and vaginal bleeding in first half of pregnancy.

Bed rest in singleton pregnancies for preventing preterm birth.

BACKGROUND: Bed rest in hospital or at home is widely recommended for the prevention of preterm birth. This advice is based on the observation that hard work and hard physical activity during pregnancy could be associated with preterm birth and with the idea that bed rest could reduce uterine activity. However, bed rest may have some adverse effects on other outcomes. OBJECTIVES: To evaluate the effect of prescription of bed rest in hospital or at home for preventing preterm birth in pregnant women at high risk of preterm birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (July 2003), LILACS (July 2003), EMBASE (July 2003), POPLINE (July 2003) and bibliographies of relevant papers. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials with reported data that assess clinical outcomes in women at high risk of spontaneous preterm birth who were prescribed bed rest in hospital or at home for preventing preterm birth, and their babies. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility, trial quality and extracted data. MAIN RESULTS: One study met the inclusion criteria (1266 women). This trial has uncertain methodological quality due to lack of reporting. Four hundred and thirty-two women were prescribed bed rest at home and a total of 834 women received a placebo (412) or no intervention (422). Preterm birth before 37 weeks was similar in both groups (7.9% in the intervention group versus 8.5% in the control group), and the relative risk was 0.92 with a 95% confidence interval from 0.62 to 1.37. No other results were available. REVIEWER'S CONCLUSIONS: There is no evidence, either supporting or refuting the use of bed rest at home or in hospital, to prevent preterm birth. Although bed rest in hospital or at home is widely used as the first step of treatment, there is no evidence that this practice could be beneficial. Due to the potential adverse effects that bed rest could have on women and their families, and the increased costs for the healthcare system, clinicians should not routinely advise women to rest in bed to prevent preterm birth. Potential benefits and harms should be discussed with women facing an increased risk of preterm birth. Appropriate research is mandatory. Future trials should evaluate both the effectiveness of bed rest, and the effectiveness of the prescription of bed rest, to prevent preterm birth.

Ambulatory versus conventional methods for monitoring blood pressure during pregnancy.

BACKGROUND: Hypertensive disorders are among the most common medical complications of pregnancy and a leading cause of maternal and perinatal morbidity and mortality world-wide. Blood pressure measurement plays a central role in the screening and management of hypertension during pregnancy. In recent years the validity of conventional (clinic) blood pressure measurement has been questioned and efforts have been made to improve the technique with ambulatory automated devices that provide a large number of measurements over a period of time, usually a 24-hour period. OBJECTIVES: To assess whether the use of ambulatory blood pressure monitoring during pregnancy improves subsequent maternal and feto-neonatal outcomes, women-newborn quality of life or use of health service resources, compared with conventional (clinic) blood pressure measurements. These effects will be assessed for the following subgroups: (1) Women at low or average risk of hypertensive disorders of pregnancy (unselected). (2) Women defined as high risk of hypertensive disorders of pregnancy. (3) Women with hypertension without other signs of pre-eclampsia. (4) Women with established pre-eclampsia. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register, MEDLINE, LILACS and EMBASE were searched. Date of last search: July 2001. SELECTION CRITERIA: All randomised trials comparing ambulatory blood pressure monitoring versus conventional (clinic) blood pressure monitoring in pregnancy. Quasi-random designs will be excluded. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated all potentially relevant articles, examined each study for possible inclusion and assessed the methodological quality using the Cochrane guidelines. MAIN RESULTS: No trials included. REVIEWER'S CONCLUSIONS: There is no randomised controlled trial evidence to support the use of ambulatory blood pressure monitoring during pregnancy. Randomized trials with adequate design and sample sizes are needed to evaluate the possible advantages and risks of ambulatory blood pressure monitoring during pregnancy, in particular in hypertensive pregnant women. These trials should evaluate not only clinical outcomes, but also use of health care resources and women's views.

Umbilical vein injection for management of retained placenta.

BACKGROUND: If a retained placenta is left untreated, there is a high risk of maternal death. However, manual removal of the placenta is an invasive procedure with its own serious complications of haemorrhage, infection or genital tract trauma. OBJECTIVES: The objective of this review was to assess the use of umbilical vein injection of saline solution alone or with oxytocin in comparison either with expectant management or with an alternative solution or other uterotonic agent for retained placenta. The main comparisons include the following agents: saline solution alone, saline solution plus oxytocin, saline solution plus prostaglandin and plasma expander. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register (latest search 20 March 2001). SELECTION CRITERIA: Randomised trials comparing umbilical vein injection of saline or other fluids, with or without oxytocics, either with expectant management or with an alternative solution or other uterotonic agent, in the management of retained placenta. DATA COLLECTION AND ANALYSIS: The two reviewers assessed trial quality and extracted data. MAIN RESULTS: Twelve trials were included. The trials were of variable quality. Compared with expectant management, umbilical vein injection of saline solution alone did not show any significant difference in the incidence of manual removal of the placenta (relative risk (RR): 0.97; 95% confidence interval (CI): 0.83 to 1.14). Umbilical vein injection of saline solution plus oxytocin compared with expectant management showed a reduction in manual removal, although this was not statistically significant (RR: 0.86; 95% CI: 0.72 to 1.01). Saline solution with oxytocin compared with saline solution alone showed a significant reduction in manual removal of the placenta (RR: 0.79; 95% CI: 0.69 to 0.91) (number needed to treat: 8; 95% CI: 5 to 20). No discernible difference was detected in length of third stage of labour, blood loss, haemorrhage, haemoglobin, blood transfusion, curettage, infection, hospital stay, fever, abdominal pain and oxytocin augmentation. Umbilical vein injection of saline solution plus oxytocin compared with umbilical vein injection of plasma expander showed higher, but not statistically significant, incidence of manual removal of placenta (RR: 1.34; 95% CI: 0.97 to 1.85) and no difference in blood loss but there is only one small trial contributing to this comparison. Saline solution plus prostaglandin, compared with saline solution alone, was associated with a statistically significant lower incidence in manual removal of placenta (RR: 0.05; 95% CI: 0.00 to 0.73 ) but no difference was observed in blood loss, fever, abdominal pain, and oxytocin augmentation but there is only one small trial contributing to these results. There were no significant differences between saline solution plus prostaglandin and saline solution plus oxytocin (RR: 0.10; 95% CI: 0.01 to 1.59) but again there is only one small trial contributing to this meta-analysis. REVIEWER'S CONCLUSIONS: Umbilical vein injection of saline solution plus oxytocin appears to be effective in the management of retained placenta. Saline solution alone does not appear be more effective than expectant management. Further research into umbilical vein injection of oxytocin, prostaglandins or plasma expander is warranted.

Perinatal factors associated with blood pressure during childhood.

This study aims to determine whether variables reflecting an adverse intrauterine environment are associated with childhood blood pressure. The authors conducted a secondary analysis of data from a prospective cohort of children born to healthy, nulliparous women enrolled in a randomized controlled trial. A total of 518 children were traced in 1995-1996 from 614 eligible children born in a clinic in Rosario, Argentina. The outcome was systolic blood pressure at 5-9 years. Hemoglobin during pregnancy was positively associated with children's pressure. Other maternal characteristics during pregnancy (blood pressure, smoking, weight gain, weight at 20 weeks' gestation, and glycemia) and size at birth (birth weight, ponderal index, head circumference/length ratio, and small for gestational age) were not associated with children's pressure. Among children in the upper quartile of body mass index, there was a weak inverse correlation between birth weight and systolic pressure, and systolic pressure was 14.8 mmHg (95 percent confidence interval: 3.3, 26.4) higher in low birth weight children than in others. The main predictors of childhood pressure were childhood body mass index and maternal pressure outside pregnancy. In this healthy population, the authors found weak support for an association between variables reflecting an adverse fetal environment and childhood blood pressure. Low birth weight was a risk factor for high blood pressure only in overweight children.

Managing data for a randomised controlled clinical trial: experience from the WHO Antenatal Care Trial. WHO Antenatal Care Trial Research Group.

The World Health Organisation, in collaboration with four developing countries, is conducting a randomised controlled clinical trial to evaluate a new programme of antenatal care. In a city or region in Argentina, Cuba, Saudi Arabia and Thailand, 53 clinical units were randomly allocated to provide either the new programme or the programme currently in use. This paper describes the organisation of the data management system used to collect the data. Each woman participating in the trial is uniquely identified, and information such as her name, address and expected delivery date is recorded in the trial 'subject number list'. If the clinic belongs to the intervention group, information about the woman's eligibility is recorded on the classification form. Details of the outcome of the pregnancy are indicated on two additional case report forms: the antenatal hospital admission form and the summary form. When forms are completed by the investigators, they are submitted to the country data coordinating centre (CDCC). The CDCCs are responsible for the processing of the country study forms. This includes verification of the batch of forms, data capture into computer files, data verification, data validation, production of query sheets for data problems, maintenance and updating of study master files. All operations on data such as additions or modifications are performed using transaction processing. At monthly intervals, recruitment reports and transaction files are sent to the trial coordinating centre in Geneva. All transaction files are processed to accumulate data on the trial's consolidated master files. A monthly report including number of women recruited in the trial, adverse events reported by the countries, recruitment charts by clinic and analyses on eligible women in the intervention group is prepared and submitted to the data safety and monitoring committee. A workshop was organised in 1995, before the start of the trial, to introduce the data management system to the four participating countries. Annual site visits were made to each CDCC to monitor progress. Additional visits were made when major or critical problems could not be solved by the CDCC. At the closure of data collection, a visit is made to review and assess all data management procedures including form filling, maintenance of registers, computer files, query sheets, data modifications. In addition, final cleaning of the data is performed, and an analysis file is produced for inclusion in the centralised trial analyses and in the country-specific analyses. Based on the experience gained in this trial, the decentralised data management model can be advocated only if CDCCs that will be involved in the trial are already in place with competent and experienced staff. Uniformity of the data management system and of standard operating procedures across countries is also a crucial issue for the effective management of the data collection phase.

Intra-umbilical vein injection and retained placenta: evidence from a collaborative large randomised controlled trial. Grupo Argentino de Estudio de Placenta Retenida.

OBJECTIVE: To determine whether intra-umbilical vein injection with saline solution, with or without oxytocin, reduces the need for manual removal of placenta compared with expectant management. DESIGN: Multicenter, randomised controlled trial. SETTING: Eleven hospitals in four cities of Argentina: Buenos Aires, Corrientes, Rosario, and Salta. PARTICIPANTS: Two hundred and ninety-one women showing no evidence of placental separation thirty minutes after vaginal delivery. INTERVENTIONS: Three different management strategies: 1. intra-umbilical vein injection of saline solution plus oxytocin; 2. intra-umbilical vein injection of saline solution alone; and 3. expectant management. MAIN OUTCOME MEASURES: Primary: manual removal of the placenta. Secondary: blood loss after trial entry, haemoglobin level at 24 to 48 hours and at 40 to 45 days after delivery, blood transfusion, curettage, infection, and days of hospital stay. RESULTS: Rates of subsequent manual removal were similar: intra-umbilical vein injection of saline solution plus oxytocin (58%; RR 0.92; 95% CI 0.73-1.15), or saline alone (63%; RR 1.00; 95% CI 0.80-1.24), compared with expectant management (63%). There were also no detectable effects of the active managements on any of the secondary measures of outcome. CONCLUSIONS: Based on evidence available from randomised controlled trials, including this trial, it is unlikely that intra-umbilical injection with or without oxytocin, is clinically useful. We recommend that this intervention should not be used in third stage management of labour.

Long-term effect of calcium supplementation during pregnancy on the blood pressure of offspring: follow up of a randomised controlled trial.

OBJECTIVE: To explore the long-term effect of calcium supplementation during pregnancy on the offspring's blood pressure during childhood. DESIGN: Follow up of a population enrolled in a double blind, randomised, placebo controlled trial. SETTING: Perinatal research unit, World Health Organisation's collaborative research centre. SUBJECTS: 591 children at a mean age of 7 years whose mothers were randomly assigned during pregnancy to receive 2 g/day of elemental calcium (n = 298) or placebo (n = 293). MAIN OUTCOME MEASURES: Mean blood pressure and rate of high blood pressure of children. RESULTS: Overall, systolic blood pressure was lower in the calcium group (mean difference -1.4 mm Hg; 95% confidence interval -3.2 to 0.5) than in the placebo group. The effect was found predominantly among children whose body mass index at assessment was above the median for this population (mean difference in systolic blood pressure -5.8 mm Hg (-9.8 mm Hg to -1.7 mm Hg) for children with an index > 17.5 and -3.2 mm Hg (-6.3 mm Hg to -0.1 mm Hg) for those with an index of > 15.7 to 17.5). The risk of high systolic blood pressure was also lower in the calcium group than in the placebo group (relative risk 0.59; 0.39 to 0.90) and particularly among children in the highest fourth of body mass index (0.43; 0.26 to 0.71). CONCLUSION: Calcium supplementation during pregnancy is associated with lower systolic blood pressure in the offspring, particularly among overweight children.

The measurement of diastolic blood pressure during pregnancy: which Korotkoff phase should be used?

OBJECTIVE: The aim of this study was to compare the two Korotkoff phases, to estimate diastolic blood pressure during pregnancy. STUDY DESIGN: A cohort of 1194 nulliparous pregnant women were followed up prospectively from the twentieth week of pregnancy until delivery. Blood pressure measurements were obtained with random-zero sphygmomanometers at 20, 23, 25, 27, 31, and 35 weeks and then weekly until delivery. After 10 minutes of rest five blood pressure measurements were obtained in each position: supine, lateral, and seated. Korotkoff phases IV and V were obtained in each measurement. RESULTS: The frequency of 0 values was always < 0.5% (n = 10,501 in each time and position). Mean differences between both phases throughout pregnancy fluctuates around 6 mm Hg. Minor differences (mean 3.7 mm Hg) without outlier values were observed in women with diastolic hypertension. Phase 5 showed a better association with other outcome variables related to hypertension, such as proteinuria, intrauterine growth retardation, and hyperuricemia. CONCLUSION: Considering that phase 5 is easier to obtain, its use implies very few 0 values, that the difference between the two Korotkoff phases is around 6 mm Hg, and that the association with hypertension-related complications is similar to that of phase 4.

What does an elevated mean arterial pressure in the second half of pregnancy predict--gestational hypertension or preeclampsia?

OBJECTIVE: The purpose of this study was to determine the predictive value of elevated mean arterial pressure in the second half of pregnancy for both preeclampsia and gestational hypertension. STUDY DESIGN: This was a cohort of 588 nulliparous pregnant women studied prospectively from the twentieth week until delivery. Mean arterial pressure was obtained by means of a random-zero sphygmomanometer at 20, 26, and 31 weeks of gestation. The best cutoff point for the determination of predictive values was established by a receiver-operator characteristic curve. RESULTS: Patterns of mean arterial pressure throughout pregnancy were different between preeclamptic and gestational hypertensive women. Receiver-operator characteristic curves for mean arterial pressure showed better predictive capacity for gestational hypertension than for preeclampsia. Sensitivity of mean arterial pressure to predict preeclampsia ranged between 39% and 48%, whereas for prediction of gestational hypertension it varied from 72% to 92%. Specificities for both groups were moderate (60% to 86%). Positive predictive values were low for all groups (5% to 33%). CONCLUSION: Elevated mean arterial pressure in the second half of pregnancy is a good predictor of gestational hypertension but is a poor predictor of preeclampsia.

Calcium supplementation to prevent hypertensive disorders of pregnancy.

BACKGROUND: Calcium supplementation has been reported to reduce blood pressure in pregnant and nonpregnant women. We undertook this prospective study to determine the effect of calcium supplementation on the incidence of hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) and to determine the value of urinary calcium levels as a predictor of the response. METHODS: We studied 1194 nulliparous women who were in the 20th week of gestation at the beginning of the study. The women were randomly assigned to receive 2 g per day of elemental calcium in the form of calcium carbonate (593 women) or placebo (601 women). Urinary excretion of calcium and creatinine was measured before calcium supplementation was begun. The women were followed to the end of their pregnancies, and the incidence of hypertensive disorders of pregnancy was determined. RESULTS: The rates of hypertensive disorders of pregnancy were lower in the calcium group than in the placebo group (9.8 percent vs. 14.8 percent; odds ratio, 0.63; 95 percent confidence interval, 0.44 to 0.90). The risk of these disorders was lower at all times during gestation, particularly after the 28th week of gestation (P = 0.01 by life-table analysis), in the calcium group than in the placebo group, and the risk of both gestational hypertension and preeclampsia was also lower in the calcium group. Among the women who had low ratios of urinary calcium to urinary creatinine (less than or equal to 0.62 mmol per millimole) during the 20th week of gestation, those in the calcium group had a lower risk of hypertensive disorders of pregnancy (odds ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09) and less of an increase in diastolic and systolic blood pressure than the placebo group. The pattern of response was similar among the women who had a high ratio of urinary calcium to urinary creatinine during the 20th week of gestation, but the differences were smaller. CONCLUSIONS: Pregnant women who receive calcium supplementation after the 20th week of pregnancy have a reduced risk of hypertensive disorders of pregnancy.

Possible unconscious significance of the positions of the analysand and analyst in psychoanalysis.

When Freud chose to have his patients lie on a couch and seated himself at their head out of sight, none of these procedures were without precedents in the medical culture of his day. The recumbent position was standard for the examination of the abdomen and for many surgical procedures. Sitting at the patient's head was routine for the anesthetist. Being out of the patient's sight was necessary for the examination of the lungs and spine (not to mention the Roman Catholic confession box). Yet, the combination of these three factors was unique and was quickly recognized as a hallmark of psychoanalysis. It is remarkable that relatively little has been written concerning the symbolic meaning of the positions of the analysand and analyst considering that this is a daily feature of every analyst's work and that lying on the couch has become a vernacular equivalent for the psychoanalytic process itself. This paper is an attempt to examine some unconscious symbolic meanings of these positions, which may have been involved even before Freud's choice made them standard.