Protective effect of depot-medroxyprogesterone acetate on surgically treated uterine leiomyomas: a multicentre case-control study

Objective To assess the protective effect of depot-medroxyprogesterone acetate (DMPA) on uterine leiomyomas. DMPA has been widely used in Thailand for many years; uterine leiomyomas is the most common female tumour.
Design A multicentre hospital-based case-control study.
Setting University and regional hospitals.
Patients Cases were all newly diagnosed patients with pathologically proven diagnosis of uterine leiomyomas, who were admitted to eight hospitals in three regions of Thailand from January 1991; to June 1993;. Three controls matched with cases by sex, age within five years and date of admission within three months were recruited.
Main outcome measures Information on socio-demographic factors, personal and family history, current disease, reproductive and contraceptive history was collected from cases and controls by interview.
Results There were 910 cases and 2709; controls. After univariate and unconditional multiple logistic regression analysis, risk factors associated positively with uterine leiomyomas are tubal ligation, family history of uterine leiomyomas, higher education, obesity and abortion. In contrast, DMPA, use of oral contraceptives, higher parity and smoking are associated with a lower relative risk suggesting that they have a protective effect against uterine leiomyomas. This causative relation is further strengthened by the strong duration-response relation between DMPA and uterine leiomyomas. This protection may persist for more than 10 years after the last dose.
Conclusion We have demonstrated a strong, duration dependent protective effect of DMPA against uterine leiomyomas.     

Side effects of oral misoprostol during the first 24 hours after administration in the third stage of labour

Objective To evaluate the side effects of 600 μg misoprostol orally during the first 24 hours after administration in the third stage of labour.
Design Double blind randomised controlled trial.
Setting Tertiary care hospitals in Nigeria and Thailand.
Sample All women participating in the WHO Misoprostol trial in these two hospitals between January 1, 1999 and June 17, 1999.
Methods All women were followed up during the first 24 hours postpartum to evaluate the occurrence of shivering, nausea, vomiting, diarrhoea and other misoprostol-related side effects.
Main outcome measures Rates of shivering, nausea, vomiting, diarrhoea and pyrexia within 1 hour and in the intervals 2–6, 7–12, 13–18 and 19–24 hours after delivery.
Results A total of 1686 women were enrolled. Women who received misoprostol had higher incidence than the oxytocin group of 'any' shivering in the first hour (RR 6.4, 95% CI 3.9 to 10.4) and the period covering 2–6 hours following delivery (RR 4.7, 95% CI 1.9 to 11.2). Pyrexia was also more common in the misoprostol group in both the same time intervals (RR 2.8, 95% CI 1.4 to 5.3 and RR 6.3, 95% CI 3.7 to 10.8, respectively). Diarrhoea was not present in the first hour in either group but appeared in the second time period (2–6 hours) and third time period (7–12 hours) more frequently in the misoprostol group than with oxytocin.
Conclusion The increased incidence of shivering and pyrexia that occurs with postpartum use of misoprostol persists up to 6 hours following delivery. Approximately 5% of women experience diarrhoea that starts after 1 hour and subsides within 12 hours.     

Active management of the third stage of labour without controlled cord traction: a randomized non-inferiority controlled trial

Background

It has been suggested that the study of women who survive life-threatening complications related to pregnancy (maternal near-miss cases) may represent a practical alternative to surveillance of maternal morbidity/mortality since the number of cases is higher and the woman herself is able to provide information on the difficulties she faced and the long-term repercussions of the event. These repercussions, which may include sexual dysfunction, postpartum depression and posttraumatic stress disorder, may persist for prolonged periods of time, affecting women's quality of life and resulting in adverse effects to them and their babies.

Objective

The aims of the present study are to create a nationwide network of scientific cooperation to carry out surveillance and estimate the frequency of maternal near-miss cases, to perform a multicenter investigation into the quality of care for women with severe complications of pregnancy, and to carry out a multidimensional evaluation of these women up to six months.

Methods/Design

This project has two components: a multicenter, cross-sectional study to be implemented in 27 referral obstetric units in different geographical regions of Brazil, and a concurrent cohort study of multidimensional analysis. Over 12 months, investigators will perform prospective surveillance to identify all maternal complications. The population of the cross-sectional component will consist of all women surviving potentially life-threatening conditions (severe maternal complications) or life-threatening conditions (the maternal near miss criteria) and maternal deaths according to the new WHO definition and criteria. Data analysis will be performed in case subgroups according to the moment of occurrence and determining cause. Frequencies of near-miss and other severe maternal morbidity and the association between organ dysfunction and maternal death will be estimated. A proportion of cases identified in the cross-sectional study will comprise the cohort of women for the multidimensional analysis. Various aspects of the lives of women surviving severe maternal complications will be evaluated 3 and 6 months after the event and compared to a group of women who suffered no severe complications in pregnancy. Previously validated questionnaires will be used in the interviews to assess reproductive function, posttraumatic stress, functional capacity, quality of life, sexual function, postpartum depression and infant development.     

A cluster randomized controlled trial to evaluate the effectiveness of the clinically integrated RHL evidence -based medicine course

Objective

to develop and validate a questionnaire on severe maternal morbidity and to evaluate the maternal recall of complications related to pregnancy and childbirth. Design: validity of a questionnaire as diagnostic instrument. Setting: a third level referral maternity in Campinas, Brazil. Population: 386 survivors of severe maternal complications and 123 women that delivered without major complications between 2002 and 2007.

Methods

eligible women were traced and interviewed by telephone on the occurrence of obstetric complications and events related to their treatment. Their answers were compared with their medical records as gold standard. Sensitivity, specificity and likelihood ratios plus their correspondent 95% confidence intervals were used as main estimators of accuracy. Main outcomes: diagnosis of severe maternal morbidity associated with past pregnancies, including hemorrhage, eclampsia, infections, jaundice and related procedures (hysterectomy, admission to ICU, blood transfusion, laparotomy, inter-hospital transfer, mechanical ventilation and post partum stay above seven days).

Results

Women did not recall accurately the occurrence of obstetric complications, especially hemorrhage and infection. The likelihood ratios were < 5 for hemorrhage and infection, while for eclampsia it almost reached 10. The information recalled by women regarding hysterectomy, intensive care unit admission and blood transfusion were found to be highly correlated with finding evidence of the event in the medical records (likelihood ratios ranging from 12.7-240). The higher length of time between delivery and interview was associated with poor recall.

Conclusion

Process indicators are better recalled by women than obstetric complication and should be considered when applying a questionnaire on severe maternal morbidity.     

Perinatal research in developing countries--is it possible?

Maternal mortality remains the health statistic for which there is the greatest disparity between developing and developed countries. The risk of stillbirth or neonatal death is also high in developing countries. The inequality of research funding between rich and poor countries is dramatic, with only 10% of research funding directed towards diseases which contribute 90% of the global burden of disease. The need for high-quality, relevant perinatal research in developing countries is compelling. There are many examples of good perinatal research in developing countries. Nevertheless, significant challenges remain and are being tackled. We need better information about maternal and perinatal health, and about performance of the health services, we need more evaluation of what helps and what harms within the existing health services, and we need improved strategies for implementation of research findings.     

Misoprostol dose-related shivering and pyrexia in the third stage of labour

Objective To select the misoprostol dose to be used in a large multicentre randomised trial comparing misoprostol with oxytocin in the routine management of the third stage of labour.
Design Randomised pilot trial, double-blinded with the use of double placebos.
Setting Two of the nine hospitals that will participate in the main multicentre trial. The hospitals were
Population Women during second stage of labour about to be delivered vaginally.
Methods located in Johannesburg, South Africa and Khon Kaen, Thailand. The trial had three arms: misoprostol 400 μg versus misoprostol 600 μg versus intramuscular oxytocin 10 IU. Each group received an injection and three tablets immediately after the birth of the baby.
Main outcome measures Shivering and pyrexia rates were the main outcome measures. Data on other side effects and characteristics of the third stage of labour were also collected. Side effects were noted as none, mild, moderate or severe.
Results Both shivering and pyrexia (temperature > 38°C) were most common in the 600 μg misoprostol group (28% and 7.5% for shivering and pyrexia, respectively) compared with 400 μg misoprostol (19% and 2%), and the oxytocin group (12.5% and 3%). The increase in shivering in the misoprostol 600 pg group was due primarily to a higher rate of moderate shivering. None of the women had a temperature > 40°C. There were no increases in severe side effects and other adverse events in the misoprostol 600 μg group.
Conclusions When used in the management of the third stage of labour oral misoprostol is associated with an increase in the rate of moderate shivering and pyrexia which seems to be dose-related. Based on the results of this pilot trial, the Steering Committee has decided to use 600 μg misoprostol in the main trial, comparing it with oxytocin, in order to achieve higher effectiveness.     

Factors Associated with Failure to Receive Antenatal Care

A community-based case-control study was conducted to characterize pregnant women who did not receive antenatal care. 1,274 deliveries over a 1-year period were documented by weekly visits to 120 study villages. Eighty five women (6.7%) received no antenatal care. By univariate analysis, factors found to be associated with failure to receive antenatal care included maternal age, paternal age, paternal education, home ownership, availability of toilet, annual income, housing condition, gravidity, parity, history of infant death and birth intervals. After logistic regression analysis, only paternal age, paternal education, parity and lack of toilet in the household were found to be associated with failure to receive antenatal care.     

Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in human sepsis

Pathogenic bacteria use quorum-sensing signal molecules to co-ordinate the expression of virulence genes. Animal-based studies have demonstrated the immunomodulatory effects of quorum-sensing signal molecules. In the present study, we have examined the impact of these molecules on normal human immune function in vitro and compared this with immune changes in patients with sepsis where quorum-sensing signal molecules were detected in the sera of patients. Quorum-sensing signal molecules inhibited normal dendritic cell and T-cell activation and proliferation, and down-regulated the expression of co-stimulatory molecules on dendritic cells; in MLDCRs (mixed lymphocyte dendritic cell reactions), secretion of IL (interleukin)-4 and IL-10 was enhanced, but TNF-alpha (tumour necrosis factor-alpha), IFN-gamma (interferon-gamma) and IL-6 was reduced. Quorum-sensing signal molecules induced apoptosis in dendritic cells and CD4(+) cells, but not CD8(+) cells. Dendritic cells from patients with sepsis were depleted and ex vivo showed defective expression of co-stimulatory molecules and dysfunctional stimulation of allogeneic T-lymphocytes. Enhanced apoptosis of dendritic cells and differential CD4(+) Th1/Th2 (T-helper 1/2) cell apoptotic rate, and modified Th1/Th2 cell cytokine profiles in MLDCRs were also demonstrated in patients with sepsis. The pattern of immunological changes in patients with sepsis mirrors the effects of quorum-sensing signal molecules on responses of immune cells from normal individuals in vitro, suggesting that quorum-sensing signal molecules should be investigated further as a cause of immune dysfunction in sepsis.