The Log-Normal zero-inflated cure regression model for labor time in an African obstetric population.

In obstetrics and gynecology, knowledge about how women's features are associated with childbirth is important. This leads to establishing guidelines and can help managers to describe the dynamics of pregnant women's hospital stays. Then, time is a variable of great importance and can be described by survival models. An issue that should be considered in the modeling is the inclusion of women for whom the duration of labor cannot be observed due to fetal death, generating a proportion of times equal to zero. Additionally, another proportion of women's time may be censored due to some intervention. The aim of this paper was to present the Log-Normal zero-inflated cure regression model and to evaluate likelihood-based parameter estimation by a simulation study. In general, the inference procedures showed a better performance for larger samples and low proportions of zero inflation and cure. To exemplify how this model can be an important tool for investigating the course of the childbirth process, we considered the Better Outcomes in Labor Difficulty project dataset and showed that parity and educational level are associated with the main outcomes. We acknowledge the World Health Organization for granting us permission to use the dataset.

Understanding abortion-related complications in health facilities: results from WHO multicountry survey on abortion (MCS-A) across 11 sub-Saharan African countries.

INTRODUCTION: Complications due to unsafe abortions are an important cause of morbidity and mortality in many sub-Saharan African countries. We aimed to characterise abortion-related complication severity, describe their management, and to report women's experience of abortion care in Africa. METHODS: A cross-sectional study was implemented in 210 health facilities across 11 sub-Saharan African countries. Data were collected on women's characteristics, clinical information and women's experience of abortion care (using the audio computer-assisted self-interviewing (ACASI) system). Severity of abortion complications were organised in five hierarchical mutually exclusive categories based on indicators present at assessment. Descriptive bivariate analysis was performed for women's characteristics, management of complications and reported experiences of abortion care by severity. Generalised linear estimation models were used to assess the association between women's characteristics and severity of complications. RESULTS: There were 13 657 women who had an abortion-related complication: 323 (2.4%) women were classified with severe maternal outcomes, 957 (7.0%) had potentially life-threatening complications, 7953 (58.2%) had moderate complications and 4424 (32.4%) women had mild complications. Women who were single, multiparous, presenting ≥13 weeks of gestational age and where expulsion of products of conception occurred prior to arrival to facility were more likely to experience severe complications. For management, the commonly used mechanical methods of uterine evacuation were manual vacuum aspiration (76.9%), followed by dilation and curettage (D&C) (20.1%). Most frequently used uterotonics were oxytocin (50∙9%) and misoprostol (22.7%). Via ACASI, 602 (19.5%) women reported having an induced abortion. Of those, misoprostol was the most commonly reported method (54.3%). CONCLUSION: There is a critical need to increase access to and quality of evidence-based safe abortion, postabortion care and to improve understanding around women's experiences of abortion care.

Early evaluation of the 'STOP SEPSIS!' WHO Global Maternal Sepsis Awareness Campaign implemented for healthcare providers in 46 low, middle and high-income countries.

OBJECTIVE: To evaluate changes in awareness of maternal sepsis among healthcare providers resulting from the WHO Global Maternal Sepsis Study (GLOSS) awareness campaign. DESIGN: Independent sample precampaign/postcampaign through online and paper-based surveys available for over 30 days before campaign roll-out (pre) and after study data collection (post). Descriptive statistics were used for campaign recognition and exposure, and odds ratio (OR) and percentage change were calculated for differences in awareness, adjusting for confounders using multivariate logistic regression. SETTING AND PARTICIPANTS: Healthcare providers from 398 participating facilities in 46 low, middle and high-income countries. INTERVENTION: An awareness campaign to accompany GLOSS launched 3 weeks prior to data collection and lasting the entire study period (28 November 2017 to 15 January 2018) and beyond. MAIN OUTCOME MEASURES: Campaign recognition and exposure, and changes in awareness. RESULTS: A total of 2188 surveys were analysed: 1155 at baseline and 1033 at postcampaign. Most survey respondents found the campaign materials helpful (94%), that they helped increase awareness (90%) and that they helped motivate to act differently (88%). There were significant changes with regard to: not having heard of maternal sepsis (-63.4% change, pre-OR/post-OR 0.35, 95% CI 0.18 to 0.68) and perception of confidence in making the right decisions with regard to maternal sepsis identification and management (7.3% change, pre-OR/post-OR 1.44, 95% CI 1.01 to 2.06). CONCLUSIONS: Awareness raising campaigns can contribute to an increase in having heard of maternal sepsis and an increase in provider perception of confidence in making correct decisions. Offering the information to make accurate and timely decisions while promoting environments that enable self-confidence and support could improve maternal sepsis identification and management.

How women are treated during facility-based childbirth in four countries: a cross-sectional study with labour observations and community-based surveys.

BACKGROUND: Women across the world are mistreated during childbirth. We aimed to develop and implement evidence-informed, validated tools to measure mistreatment during childbirth, and report results from a cross-sectional study in four low-income and middle-income countries. METHODS: We prospectively recruited women aged at least 15 years in twelve health facilities (three per country) in Ghana, Guinea, Myanmar, and Nigeria between Sept 19, 2016, and Jan 18, 2018. Continuous observations of labour and childbirth were done from admission up to 2 h post partum. Surveys were administered by interviewers in the community to women up to 8 weeks post partum. Labour observations were not done in Myanmar. Data were collected on sociodemographics, obstetric history, and experiences of mistreatment. FINDINGS: 2016 labour observations and 2672 surveys were done. 838 (41·6%) of 2016 observed women and 945 (35·4%) of 2672 surveyed women experienced physical or verbal abuse, or stigma or discrimination. Physical and verbal abuse peaked 30 min before birth until 15 min after birth (observation). Many women did not consent for episiotomy (observation: 190 [75·1%] of 253; survey: 295 [56·1%] of 526) or caesarean section (observation: 35 [13·4%] of 261; survey: 52 [10·8%] of 483), despite receiving these procedures. 133 (5·0%) of 2672 women or their babies were detained in the facility because they were unable to pay the bill (survey). Younger age (15-19 years) and lack of education were the primary determinants of mistreatment (survey). For example, younger women with no education (odds ratio [OR] 3·6, 95% CI 1·6-8·0) and younger women with some education (OR 1·6, 1·1-2·3) were more likely to experience verbal abuse, compared with older women (≥30 years), adjusting for marital status and parity. INTERPRETATION: More than a third of women experienced mistreatment and were particularly vulnerable around the time of birth. Women who were younger and less educated were most at risk, suggesting inequalities in how women are treated during childbirth. Understanding drivers and structural dimensions of mistreatment, including gender and social inequalities, is essential to ensure that interventions adequately account for the broader context. FUNDING: United States Agency for International Development and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO.

Use of histograms to assess the efficacy of uterotonic treatment for post-partum haemorrhage: A feasibility study.

Post-partum haemorrhage (PPH) is a major pathological condition leading to mortality of women worldwide. Its initial treatment has largely been focused on uterotonics. This paper examines the use of histograms to assess the efficacy of uterotonic treatment for PPH. Previous examinations of large datasets in which women were treated at 700 ml of measured blood loss according to strict protocols have shown a quantifiable peak in the histogram at 700-800 ml following treatment. It is not clear whether this is commonly seen in other studies. The main aim was therefore to assess whether post-treatment peaks are routinely seen in postpartum blood loss histograms and whether the peaks are seen only in treated women. Four datasets of more than 1000 women with measured blood loss were identified and the original data examined. The secondary peak was not only seen in histograms attributed to treatment, but also many of the histograms where women had not received uterotonic treatment. Many women received treatment despite having blood loss of less than 500 ml, and many women who stopped bleeding with final blood losses of more than 500 ml did not receive any uterotonics. The routine use of histogram analysis to assess the efficiency of uterotonic therapy is not recommended. The paper also provides further insights into clinical practice, with clinicians frequently using uterotonic therapies even when the volume of the blood loss is low. This demonstrates how uterotonic use in practice is often not linked to the standard 500 ml definition of post-partum haemorrhage.

A prospective study of severity of complications associated with use of misoprostol and other abortion methods in South West Nigeria.

OBJECTIVES: To assess the severity of complications following misoprostol used to induce abortion compared with other methods among women admitted for postabortion complications. METHODS: A cross-sectional study of women who presented with complications of induced abortion at nine secondary and tertiary hospitals in South West Nigeria between April 1, 2013 and May 31, 2014. Face-to-face interviews were conducted and information on the current admission was extracted from patient records. Associations between abortion method used and severity of abortion complications were evaluated using χ2 and Fisher exact tests. RESULTS: Of 522 women included in the study, 177 reported an induced abortion: 41 women (23.2%) had used misoprostol at the first attempt to induce abortion, whereas 79 (44.6%) women had undergone surgical abortion. Occurrence of fever (P=0.06), bleeding (P=0.3), and lower abdominal pain (P=0.32) was not significantly different between the misoprostol and surgical abortion/other methods groups. Severe complications were rare with misoprostol, but more common among women in the surgical abortion/other methods group. Maternal mortality occurred only among women in the surgical abortion/other methods group. CONCLUSION: Use of misoprostol for induced abortion was associated with fewer complications and no maternal mortality compared with surgical abortion/other methods.

Secondary analysis of the WOMAN trial to explore the risk of sepsis after invasive treatments for postpartum hemorrhage.

OBJECTIVE: To examine the association between the use of invasive treatments for postpartum hemorrhage and the risk of sepsis and severe sepsis. METHODS: Secondary data analysis of the WOMAN randomized controlled trial, including 20 060 women with postpartum hemorrhage in 21 countries. Logistic regression with random effects was used. RESULTS: The cumulative incidence was 1.8% for sepsis and 0.5% for severe sepsis. All-cause mortality was 40.4% in women with severe sepsis versus 2.2% for women without. After adjusting for bleeding severity and other confounders, intrauterine tamponade, hysterectomy, and laparotomy increased the risk of sepsis (aOR 1.77 [95% CI 1.21-2.59], P=0.004; aOR 1.97 [95% CI 1.49-2.65], P<0.001; and aOR 6.63 [95% CI 4.29-10.24], P<0.001, respectively) and severe sepsis (aOR 2.60 [95% CI 1.47-4.59], P=0.002; aOR 1.97 [95% CI 0.83-2.46], P=0.033; and aOR 5.35 [95% CI 2.61-10.98], P<0.001, respectively). CONCLUSION: In this secondary data analysis, certain invasive treatments for postpartum hemorrhage appear to increase the risk of sepsis. Further research is needed to confirm this finding and investigate the role of prophylactic antibiotics during these procedures. The harms and benefits of such interventions must be carefully weighed, both in treatment guidelines and during individual patient management. TRIAL REGISTRATION: ISRCTN76912190.

Narratives of women presenting with abortion complications in Southwestern Nigeria: A qualitative study.

Unsafe abortion continues to impact negatively on women's health in countries with restrictive abortion laws. It remains one of the leading causes of maternal mortality and morbidity. Paradoxically, modern contraceptive prevalence remains low and the unmet need for contraception continues to mirror unwanted pregnancy rates in many countries within sub-Saharan Africa. This qualitative study assessed women's knowledge; their expectation and experiences of the methods employed for abortion; and their health care-seeking decisions following a complicated abortion. Women who presented with abortion complications were purposively sampled from seven health facilities in south-west Nigeria. In-depth interviews were conducted by social scientists with the aid of a semi-structured interview guide. Coding schemes were developed and content analysis was performed with WEFTQDA software. Thirty-one women were interviewed. Misoprostol was used by 16 women; 15 women used other methods. About one-fifth of respondents were aged ≤ 20 years; almost one-third were students. Common reasons for terminating a pregnancy were: "too young/still in school/training"; "has enough number of children"; "last baby too young" and "still breastfeeding". Women had little knowledge about methods used. Friends, nurses or pharmacists were the commonest sources of information. Awareness about use of misoprostol for abortion among women was high. Women used misoprostol to initiate an abortion and were often disappointed if misoprostol did not complete the abortion process. Given its clandestine manner, women were financially exploited by the abortion providers and only presented to hospitals for post-abortion care as a last resort. Women's narratives of their abortion experience highlight the difficulties and risks women encounter to safeguard and protect their sexual and reproductive health. To reduce unsafe abortion therefore, urgent and synergized efforts are required to promote prompt access to family planning and post-abortion care services.

Tranexamic acid for the prevention of postpartum bleeding in women with anaemia: study protocol for an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Postpartum haemorrhage (PPH) is responsible for about 100,000 maternal deaths every year, most of which occur in low- and middle-income countries. Tranexamic acid (TXA) reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. TXA decreases blood loss in surgery and reduces death due to bleeding after trauma. When given within 3 h of birth, TXA reduces deaths due to bleeding in women with PPH. However, for many women, treatment of PPH is too late to prevent death. Over one third of pregnant women in the world are anaemic and many are severely anaemic. These women have an increased risk of PPH and suffer more severe outcomes if PPH occurs. There is an urgent need to identify a safe and effective way to reduce postpartum bleeding in anaemic women. METHODS/DESIGN: The WOMAN-2 trial is an international, multicentre, randomised, double-blind, placebo-controlled trial to quantify the effects of TXA on postpartum bleeding in women with moderate or severe anaemia. Ten thousand women with moderate or severe anaemia who have given birth vaginally will be randomised to receive 1 g of TXA or matching placebo by intravenous injection immediately (within 15 min) after the umbilical cord is cut or clamped. The primary outcome is the proportion of women with a clinical diagnosis of primary PPH. The cause of PPH will be described. Data on maternal health and wellbeing, maternal blood loss and its consequences, and other health outcomes will be collected as secondary outcomes. The main analyses will be on an 'intention-to-treat' basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses will be based on the severity of anaemia (moderate versus severe) and type of labour (induced or augmented versus spontaneous). A study with 10,000 patients will have over 90% power to detect a 25% relative reduction from 10 to 7.5% in PPH. The trial will be conducted in hospitals in Africa and Asia. DISCUSSION: The WOMAN-2 trial should provide reliable evidence for the effects of TXA for preventing postpartum bleeding in women with anaemia. TRIAL REGISTRATION: ISRCTN, ISRCTN62396133 . Registered on 7 December 2017; ClincalTrials.gov, ID: NCT03475342 . Registered on 23 March 2018.

Methodological development of tools to measure how women are treated during facility-based childbirth in four countries: labor observation and community survey.

BACKGROUND: Efforts to improve maternal health are increasingly focused on improving the quality of care provided to women at health facilities, including the promotion of respectful care and eliminating mistreatment of women during childbirth. A WHO-led multi-country research project aims to develop and validate two tools (labor observation and community survey) to measure how women are treated during facility-based childbirth. This paper describes the development process for these measurement tools, and how they were implemented in a multi-country study (Ghana, Guinea, Myanmar and Nigeria). METHODS: An iterative mixed-methods approach was used to develop two measurement tools. Methodological development was conducted in four steps: (1) initial tool development; (2) validity testing, item adjustment and piloting of paper-based tools; (3) conversion to digital, tablet-based tools; and (4) data collection and analysis. These steps included systematic reviews, primary qualitative research, mapping of existing tools, item consolidation, peer review by key stakeholders and piloting. RESULTS: The development, structure, administration format, and implementation of the labor observation and community survey tools are described. For the labor observations, a total of 2016 women participated: 408 in Nigeria, 682 in Guinea, and 926 in Ghana. For the community survey, a total of 2672 women participated: 561 in Nigeria, 644 in Guinea, 836 in Ghana, and 631 in Myanmar. Of the 2016 women who participated in the labor observations, 1536 women (76.2%) also participated in the community survey and have linked data: 779 in Ghana, 425 in Guinea, and 332 in Nigeria. CONCLUSIONS: An important step to improve the quality of maternity care is to understand the magnitude and burden of mistreatment across contexts. Researchers and healthcare providers in maternal health are encouraged to use and implement these tools, to inform the development of more women-centered, respectful maternity healthcare services. By measuring the prevalence of mistreatment of women during childbirth, we will be able to design and implement programs and policies to transform maternity services.

Tranexamic acid for significant traumatic brain injury (The CRASH-3 trial): Statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial.

Background: Worldwide, traumatic brain injury (TBI) kills or hospitalises over 10 million people each year. Early intracranial bleeding is common after TBI, increasing the risk of death and disability. Tranexamic acid reduces blood loss in surgery and death due to bleeding in trauma patients with extra-cranial injury. Early administration of tranexamic acid in TBI patients might limit intracranial bleeding, reducing death and disability. The CRASH-3 trial aims to provide evidence on the effect of tranexamic acid on death and disability in TBI patients. We will randomly allocate about 13,000 TBI patients (approximately 10,000 within 3 hours of injury) to an intravenous infusion of tranexamic acid or matching placebo in addition to usual care. This paper presents a protocol update (version 2.1) and statistical analysis plan for the CRASH-3 trial. Results: The primary outcome is head injury death in hospital within 28 days of injury for patients treated within 3 hours of injury (deaths in patients treated after 3 hours will also be reported). Because there are reasons to expect that tranexamic acid will be most effective in patients treated immediately after injury and less effective with increasing delay, the effect in patients treated within one hour of injury is of particular interest. Secondary outcomes are all-cause and cause-specific mortality, vascular occlusive events, disability based on the Disability Rating Scale and measures suggested by patient representatives, seizures, neurosurgical intervention, neurosurgical blood loss, days in intensive care and adverse events. Sub-group analyses will examine the effect of tranexamic acid on head injury death stratified by time to treatment, severity of TBI and baseline risk. Conclusion: The CRASH-3 trial will provide reliable evidence of the effectiveness and safety of tranexamic acid in patients with acute TBI. Registration: International Standard Randomised Controlled Trials registry ( ISRCTN15088122) 19/07/2011, and ClinicalTrials.gov ( NCT01402882) 25/07/2011.

Effect of tranexamic acid on coagulation and fibrinolysis in women with postpartum haemorrhage (WOMAN-ETAC): a single-centre, randomised, double-blind, placebo-controlled trial.

Background: Postpartum haemorrhage (PPH) is a leading cause of maternal death. The WOMAN trial showed that tranexamic acid (TXA) reduces death due to bleeding in women with PPH. We evaluated the effect of TXA on fibrinolysis and coagulation in a sample of WOMAN trial participants. Methods: Adult women with a clinical diagnosis of PPH were randomised to receive 1 g TXA or matching placebo in the WOMAN trial. Participants in the WOMAN trial at University College Hospital (Ibadan, Nigeria) also had venous blood taken just before administration of the first dose of trial treatment and again 30 (±15) min after the first dose (the ETAC study).  We aimed to determine the effects of TXA on fibrinolysis (D-dimer and rotational thromboelastometry maximum clot lysis (ML)) and coagulation (international normalized ratio and clot amplitude at 5 min). We compared outcomes in women receiving TXA and placebo using linear regression, adjusting for baseline measurements. Results: Women (n=167) were randomised to receive TXA (n=83) or matching placebo (n=84). Due to missing data, seven women were excluded from analysis. The mean (SD) D-dimer concentration was 7.1 (7.0) mg/l in TXA-treated women and 9.6 (8.6) mg/l in placebo-treated women (p=0.09). After adjusting for baseline, the D-dimer concentration was 2.16 mg/l lower in TXA-treated women (-2.16, 95% CI -4.31 to 0.00, p=0.05). There was no significant difference in ML between TXA- and placebo-treated women (12.3% (18.4) and 10.7% (12.6), respectively; p=0.52) and no significant difference after adjusting for baseline ML (1.02, 95% CI -3.72 to 5.77, p=0.67).  There were no significant effects of TXA on any other parameters. Conclusion: TXA treatment was associated with reduced D-dimer levels but had no apparent effects on thromboelastometry parameters or coagulation tests. Registration: ISRCTN76912190 (initially registered 10/12/2008, WOMAN-ETAC included on 22/03/2012) and NCT00872469 (initially registered 31/03/2009, WOMAN-ETAC included on 22/03/2012).

The impact of early outcome events on the effect of tranexamic acid in post-partum haemorrhage: an exploratory subgroup analysis of the WOMAN trial.

BACKGROUND: In severe post-partum haemorrhage, death can occur within hours of bleeding onset so interventions to control the bleeding must be given immediately. In clinical trials of treatments for life-threatening bleeding, established treatments are given priority and the trial treatment is usually given last. However, enrolling patients in whom severe maternal morbidity or death is imminent or inevitable at the time of randomisation may dilute the effects of a trial treatment. METHODS: We conducted an exploratory analysis of data from the WOMAN trial, an international, randomised placebo-controlled trial of the effects of tranexamic acid on death and surgical intervention in 20,060 women with post-partum haemorrhage. We assessed the impact of early maternal death or hysterectomy due to exsanguination on the effect of tranexamic acid on each of these respective outcomes. We conducted repeated analyses excluding patients with these outcomes at increasing intervals from the time of randomisation. We quantified treatment effects using risk ratios (RR) and 99% confidence intervals (CI) and prepared cumulative failure plots. RESULTS: Among 14,923 women randomised within 3 h of delivery (7518 tranexamic acid and 7405 placebo), there were 216 bleeding deaths (1.5%) and 383 hysterectomies due to bleeding (2.8%). After excluding deaths from exsanguination at increasing time intervals following randomization, there was a significant reduction in the risk of death due to bleeding with tranexamic acid (RR = 0.41; 99% CI 0.19-0.89). However, after excluding hysterectomies at increasing time intervals post-randomization, there was no reduction in the risk of hysterectomy due to bleeding with tranexamic acid (RR = 0.79; 99% CI 0.33-1.86). CONCLUSIONS: Findings from this analysis provide further evidence that tranexamic acid reduces the risk of death from exsanguination in women who experience postpartum haemorrhage. It is uncertain whether tranexamic acid reduces the risk of hysterectomy for bleeding after excluding early hysterectomies. TRIAL REGISTRATION: ISRCTN trial registration number ISRCTN76912190, 8 Dec 2008; ClinicalTrials.gov number NCT00872469, 30 March 2009; PACTR number PACTR201007000192283, 9 Feb 2010; EudraCT number 2008-008441-38, 8 Dec 2010 (retrospectively registered).

Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth.

BACKGROUND: Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in many countries. In a large trial, we compared a novel formulation of heat-stable carbetocin with oxytocin. METHODS: We enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 µg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively. RESULTS: A total of 29,645 women underwent randomization. The frequency of blood loss of at least 500 ml or the use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4% in the oxytocin group (relative risk, 1.01; 95% confidence interval [CI], 0.95 to 1.06), a finding that was consistent with noninferiority. The frequency of blood loss of at least 1000 ml was 1.51% in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence interval crossing the margin of noninferiority. The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between the two groups. CONCLUSIONS: Heat-stable carbetocin was noninferior to oxytocin for the prevention of blood loss of at least 500 ml or the use of additional uterotonic agents. Noninferiority was not shown for the outcome of blood loss of at least 1000 ml; low event rates for this outcome reduced the power of the trial. (Funded by Merck Sharpe & Dohme; CHAMPION Australian New Zealand Clinical Trials Registry number, ACTRN12614000870651 ; EudraCT number, 2014-004445-26 ; and Clinical Trials Registry-India number, CTRI/2016/05/006969 .).

Haematological and fibrinolytic status of Nigerian women with post-partum haemorrhage.

BACKGROUND: Early treatment with tranexamic acid reduces deaths due to bleeding after post-partum haemorrhage. We report the prevalence of haematological, coagulation and fibrinolytic abnormalities in Nigerian women with postpartum haemorrhage. METHODS: We performed a secondary analysis of the WOMAN trial to assess laboratory data and rotational thromboelastometry (ROTEM) parameters in 167 women with postpartum haemorrhage treated at University College Hospital, Ibadan, Nigeria. We defined hyper-fibrinolysis as EXTEM maximum lysis (ML) > 15% on ROTEM. We defined coagulopathy as EXTEM clot amplitude at 5 min (A5) < 40 mm or prothrombin ratio > 1.5. RESULTS: Among the study cohort, 53 (40%) women had severe anaemia (haemoglobin< 70 g/L) and 17 (13%) women had severe thrombocytopenia (platelet count < 50 × 109/L). Thirty-five women (23%) had ROTEM evidence of hyper-fibrinolysis. Based on prothrombin ratio criteria, 16 (12%) had coagulopathy. Based on EXTEM A5 criteria, 49 (34%) had coagulopathy. CONCLUSION: Our findings suggest that, based on a convenience sample of women from a large teaching hospital in Nigeria, hyper-fibrinolysis may commonly occur in postpartum haemorrhage. Further mechanistic studies are needed to examine hyper-fibrinolysis associated with postpartum haemorrhage. Findings from such studies may optimize treatment approaches for postpartum haemorrhage. TRIAL REGISTRATION: The Woman trial was registered: NCT00872469; ISRCTN76912190 (Registration date: 22/03/2012).

Risk factors for peripartum hysterectomy among women with postpartum haemorrhage: analysis of data from the WOMAN trial.

BACKGROUND: Peripartum hysterectomy can cause significant morbidity and mortality. Most studies of peripartum hysterectomy are from high income countries. This cohort study examined risk factors for peripartum hysterectomy using data from Africa, Asia, Europe and the Americas. METHODS: We used data from the World Maternal Antifibrinolytic (WOMAN) trial carried out in 193 hospitals in 21 countries. Peripartum hysterectomy was defined as hysterectomy within 6 weeks of delivery as a complication of postpartum haemorrhage. Univariable and multivariable random effects logistic regression models were used to analyse risk factors. A hierarchical conceptual framework guided our multivariable analysis. RESULTS: Five percent of women had a hysterectomy (1020/20,017). Haemorrhage from placenta praevia/accreta carried a higher risk of hysterectomy (17%) than surgical trauma/tears (5%) and uterine atony (3%). The adjusted odds ratio (AOR) for hysterectomy in women with placenta praevia/accreta was 3.2 (95% CI: 2.7-3.8), compared to uterine atony. The risk of hysterectomy increased with maternal age. Caesarean section was associated with fourfold higher odds of hysterectomy than vaginal delivery (AOR 4.3, 95% CI: 3.6-5.0). Mothers in Asia had a higher hysterectomy incidence (7%) than mothers in Africa (5%) (AOR: 1.2, 95% CI: 0.9-1.7). CONCLUSIONS: Placenta praevia/accreta is associated with a higher risk of peripartum hysterectomy. Other risk factors for hysterectomy are advanced maternal age, caesarean section and giving birth in Asia.

The global maternal sepsis study and awareness campaign (GLOSS): study protocol.

BACKGROUND: Maternal sepsis is the underlying cause of 11% of all maternal deaths and a significant contributor to many deaths attributed to other underlying conditions. The effective prevention, early identification and adequate management of maternal and neonatal infections and sepsis can contribute to reducing the burden of infection as an underlying and contributing cause of morbidity and mortality. The objectives of the Global Maternal Sepsis Study (GLOSS) include: the development and validation of identification criteria for possible severe maternal infection and maternal sepsis; assessment of the frequency of use of a core set of practices recommended for prevention, early identification and management of maternal sepsis; further understanding of mother-to-child transmission of bacterial infection; assessment of the level of awareness about maternal and neonatal sepsis among health care providers; and establishment of a network of health care facilities to implement quality improvement strategies for better identification and management of maternal and early neonatal sepsis. METHODS: This is a facility-based, prospective, one-week inception cohort study. This study will be implemented in health care facilities located in pre-specified geographical areas of participating countries across the WHO regions of Africa, Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific. During a seven-day period, all women admitted to or already hospitalised in participating facilities with suspected or confirmed infection during any stage of pregnancy through the 42nd day after abortion or childbirth will be included in the study. Included women will be followed during their stay in the facilities until hospital discharge, death or transfer to another health facility. The maximum intra-hospital follow-up period will be 42 days. DISCUSSION: GLOSS will provide a set of actionable criteria for identification of women with possible severe maternal infection and maternal sepsis. This study will provide data on the frequency of maternal sepsis and uptake of effective diagnostic and therapeutic interventions in obstetrics in different hospitals and countries. We will also be able to explore links between interventions and maternal and perinatal outcomes and identify priority areas for action.

Progression of the first stage of spontaneous labour: A prospective cohort study in two sub-Saharan African countries.

BACKGROUND: Escalation in the global rates of labour interventions, particularly cesarean section and oxytocin augmentation, has renewed interest in a better understanding of natural labour progression. Methodological advancements in statistical and computational techniques addressing the limitations of pioneer studies have led to novel findings and triggered a re-evaluation of current labour practices. As part of the World Health Organization's Better Outcomes in Labour Difficulty (BOLD) project, which aimed to develop a new labour monitoring-to-action tool, we examined the patterns of labour progression as depicted by cervical dilatation over time in a cohort of women in Nigeria and Uganda who gave birth vaginally following a spontaneous labour onset. METHODS AND FINDINGS: This was a prospective, multicentre, cohort study of 5,606 women with singleton, vertex, term gestation who presented at ≤ 6 cm of cervical dilatation following a spontaneous labour onset that resulted in a vaginal birth with no adverse birth outcomes in 13 hospitals across Nigeria and Uganda. We independently applied survival analysis and multistate Markov models to estimate the duration of labour centimetre by centimetre until 10 cm and the cumulative duration of labour from the cervical dilatation at admission through 10 cm. Multistate Markov and nonlinear mixed models were separately used to construct average labour curves. All analyses were conducted according to three parity groups: parity = 0 (n = 2,166), parity = 1 (n = 1,488), and parity = 2+ (n = 1,952). We performed sensitivity analyses to assess the impact of oxytocin augmentation on labour progression by re-examining the progression patterns after excluding women with augmented labours. Labour was augmented with oxytocin in 40% of nulliparous and 28% of multiparous women. The median time to advance by 1 cm exceeded 1 hour until 5 cm was reached in both nulliparous and multiparous women. Based on a 95th percentile threshold, nulliparous women may take up to 7 hours to progress from 4 to 5 cm and over 3 hours to progress from 5 to 6 cm. Median cumulative duration of labour indicates that nulliparous women admitted at 4 cm, 5 cm, and 6 cm reached 10 cm within an expected time frame if the dilatation rate was ≥ 1 cm/hour, but their corresponding 95th percentiles show that labour could last up to 14, 11, and 9 hours, respectively. Substantial differences exist between actual plots of labour progression of individual women and the 'average labour curves' derived from study population-level data. Exclusion of women with augmented labours from the study population resulted in slightly faster labour progression patterns. CONCLUSIONS: Cervical dilatation during labour in the slowest-yet-normal women can progress more slowly than the widely accepted benchmark of 1 cm/hour, irrespective of parity. Interventions to expedite labour to conform to a cervical dilatation threshold of 1 cm/hour may be inappropriate, especially when applied before 5 cm in nulliparous and multiparous women. Averaged labour curves may not truly reflect the variability associated with labour progression, and their use for decision-making in labour management should be de-emphasized.

Trends in misoprostol use and abortion complications: A cross-sectional study from nine referral hospitals in Nigeria.

OBJECTIVE: The study aimed to assess the use of misoprostol and complications associated with abortions in referral hospitals in Nigeria, a country with restrictive abortion laws. METHODS: A cross-sectional study at nine referral hospitals in South-west Nigeria. Nine years' data were retrieved from medical records, including 699 induced abortions. Independent variable was the method of abortion; dependent variables were complications, need for treatment and mortality. Statistical significance was tested with Chi-square, Fishers' exact and chi-square for trend tests (p<0.05). RESULTS: There were 699 induced abortions amongst 2,463 abortions found in records. Nearly 70% were surgical abortions, but misoprostol use significantly increased over the study period in a linear trend (Χ2 trend: 30.96, P <0.001). Patients who used misoprostol were significantly less likely to have infectious morbidity, genital tract injuries or medical complications. There was no difference in incomplete abortion in the groups. Patients were more likely to have in-patient care with surgical abortions (p<0.001), to need prolonged antibiotic regimens (p = 0.003), need further surgeries or additional specialist care (p = 0.009). CONCLUSION: Misoprostol abortion has significantly increased over time, and was associated with less morbidity and need for further treatment, in this study. It appears to be the safer option.

Defining quality of care during childbirth from the perspectives of Nigerian and Ugandan women: A qualitative study.

OBJECTIVE: To explore what "quality of care" means to childbearing women in Nigeria and Uganda, as a means of ensuring that women's voices and opinions are prioritized when developing interventions to improve quality in maternity care provision. METHODS: Qualitative methods, with a purposive sample of women in Nigeria and Uganda. Participants were asked to define quality of care and to provide examples of when it was and was not provided. Thematic analysis was used to synthesize findings based on an a priori framework (the WHO quality of care framework). RESULTS: 132 in-depth interviews and 21 focus group discussions are included. Participants spontaneously discussed each of the WHO framework domains of quality of care. Data were richest across the domains of effective communication, respect and dignity, emotional support, competent and motivated human resources, and essential physical resources. Women believed that good quality of care ensured optimal psychological and physiological outcomes for the woman and her baby. Positive interpersonal relationships between women and health providers were important. These included supportive care, building rapport, and using positive and clear language. CONCLUSION: To provide good quality of care, maternity services should consider and act on the expectations and experiences of women and their families.