Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Development of measures for assessing mistreatment of women during facility-based childbirth based on labour observations

Mistreatment of women during childbirth is increasingly recognised as a significant issue globally. Research and programmatic efforts targeting this phenomenon have been limited by a lack of validated measurement tools. This study aimed to develop a set of concise, valid and reliable multidimensional measures for mistreatment using labour observations applicable across multiple settings. Data from continuous labour observations of 1974 women in Nigeria (n=407), Ghana (n=912) and Guinea (n=655) were used from the cross-sectional WHO's multicountry study 'How women are treated during facility-based childbirth' (2016-2018). Exploratory factor analysis was conducted to develop a scale measuring interpersonal abuse. Two indexes were developed through a modified Organisation for Economic Co-operation and Development approach for generating composite indexes. Measures were evaluated for performance, validity and internal reliability. Three mistreatment measures were developed: a 7-item Interpersonal Abuse Scale, a 3-item Exams & Procedures Index and a 12-item Unsupportive Birth Environment Index. Factor analysis results showed a consistent unidimensional factor structure for the Interpersonal Abuse Scale in all three countries based on factor loadings and interitem correlations, indicating good structural construct validity. The scale had a reliability coefficient of 0.71 in Nigeria and approached 0.60 in Ghana and Guinea. Low correlations (Spearman correlation range: -0.06-0.19; p≥0.05) between mistreatment measures supported our decision to develop three separate measures. Predictive criterion validation yielded mixed results across countries. Both items within measures and measure scores were internally consistent across countries; each item co-occurred with other items in a measure, and scores consistently distinguished between 'high' and 'low' mistreatment levels. The set of concise, comprehensive multidimensional measures of mistreatment can be used in future research and quality improvement initiatives targeting mistreatment to quantify burden, identify risk factors and determine its impact on health and well-being outcomes. Further validation and reliability testing of the measures in other contexts is needed

Mistreatment of women during childbirth and postpartum depression: secondary analysis of WHO community survey across four countries

Background Postpartum depression (PPD) is a leading cause of disability globally with estimated prevalence of approximately 20% in low-income and middle-income countries. This study aims to determine the prevalence and factors associated with PPD following mistreatment during facility-based childbirth.Method This secondary analysis used data from the community survey of postpartum women in Ghana, Guinea, Myanmar and Nigeria for the WHO study, ‘How women are treated during facility-based childbirth’. PPD was defined using the Patient Health Questionnaire (PHQ-9) tool. Inferential analyses were done using the generalised ordered partial proportional odds model.Results Of the 2672 women, 39.0% (n=1041) developed PPD. 42.2% and 5.2% of mistreated women developed minimal/mild PPD and moderate/severe PPD, respectively. 43.0% and 50.6% of women who experienced verbal abuse and stigma/discrimination, respectively developed minimal/mild PPD. 46.3% of women who experienced physical abuse developed minimal/mild PPD while 7.6% of women who experienced stigma/discrimination developed moderate/severe PPD. In the adjusted model, women who were physically abused, verbally abused and stigma/discrimination compared with those who were not were more likely to experience any form of PPD ((OR: 1.57 (95% CI 1.19 to 2.06)), (OR: 1.42 (95% CI 1.18 to 1.69)) and (OR: 1.69 (95% CI 1.03 to 2.78))), respectively. Being single and having higher education were associated with reduced odds of experiencing PPD.Conclusion PPD was significantly prevalent among women who experienced mistreatment during childbirth. Women who were single, and had higher education had lower odds of PPD. Countries should implement women-centred policies and programmes to reduce mistreatment of women and improve women’s postnatal experiences

Comparing observed occurrence of mistreatment during childbirth with women's self-report: a validation study in Ghana, Guinea and Nigeria.

BackgroundThere has been substantial progress in developing approaches to measure mistreatment of women during childbirth. However, less is known about the differences in measurement approaches. In this study, we compare measures of mistreatment obtained from the same women using labour observations and community-based surveys in Ghana, Guinea and Nigeria.MethodsExperiences of mistreatment during childbirth are person-centred quality measures. As such, we assessed individual-level and population-level accuracy of labour observation relative to women's self-report for different types of mistreatment. We calculated sensitivity, specificity, percent agreement and population-level inflation factor (IF), assessing prevalence of mistreatment in labour observation divided by 'true' prevalence in women's self-report. We report the IF degree of bias as: low (0.75Results1536 women across Ghana (n=779), Guinea (n=425) and Nigeria (n=332) were included. Most mistreatment items demonstrated better specificity than sensitivity: observation of any physical abuse (44% sensitive, 89% specific), any verbal abuse (61% sensitive, 73% specific) and presence of a labour companion (19% sensitive, 93% specific). Items for stigma (IF 0.16), pain relief requested (IF 0.38), companion present (IF 0.32) and lack of easy access to fluids (IF 0.46) showed high risk of bias, meaning labour observations would substantially underestimate true prevalence. Other items showed low or moderate bias.ConclusionUsing self-report as the reference standard, labour observations demonstrated moderate-to-high specificity (accurately identifying lack of mistreatment) but low-to-moderate sensitivity (accurately identifying presence of mistreatment) among women. For overall prevalence, either women's self-report or observations can be used with low-moderate bias for most mistreatment items. However, given the dynamicity, complexity, and limitations in 'objectivity', some experiences of mistreatment (stigma, pain relief, labour companionship, easy access to fluids) require measurement via women's self-report. More work is needed to understand how subjectivity influences how well a measure represents individual's experiences

Women’s report of mistreatment during facility-based childbirth: validity and reliability of community survey measures

Accountability for mistreatment during facility-based childbirth requires valid tools to measure and compare birth experiences. We analyse the WHO 'How women are treated during facility-based childbirth' community survey to test whether items mapping the typology of mistreatment function as scales and to create brief item sets to capture mistreatment by domain. The cross-sectional community survey was conducted at up to 8 weeks post partum among women giving birth at hospitals in Ghana, Guinea, Myanmar and Nigeria. The survey contained items assessing physical abuse, verbal abuse, stigma, failure to meet professional standards, poor rapport with healthcare workers, and health system conditions and constraints. For all domains except stigma, we applied item-response theory to assess item fit and correlation within domain. We tested shortened sets of survey items for sensitivity in detecting mistreatment by domain. Where items show concordance and scale reliability ≥0.60, we assessed convergent validity with dissatisfaction with care and agreement of scale scores between brief and full versions. 2672 women answered over 70 items on mistreatment during childbirth. Reliability exceeded 0.60 in all countries for items on poor rapport with healthcare workers and in three countries for items on failure to meet professional standards; brief scales generally showed high agreement with longer versions and correlation with dissatisfaction. Brief item sets were ≥85% sensitive in detecting mistreatment in each country, over 90% for domains of physical abuse and health system conditions and constraints. Brief scales to measure two domains of mistreatment are largely comparable with longer versions and can be informative for these four distinct settings. Brief item sets efficiently captured prevalence of mistreatment in the five domains analysed; stigma items can be used and adapted in full. Item sets are suitable for confirmation by context and implementation to increase accountability and inform efforts to eliminate mistreatment during childbirth