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Background The CRADLE-3 trial is a stepped-wedge randomised controlled trial aiming to reduce maternal mortality and morbidity by implementing a novel vital sign device (CRADLE Vital Sign Alert) and training package into routine maternity care in 10 low-income sites. The MRC Guidance on complex interventions proposes that interventions and implementation strategies be shaped by early phase piloting and development work. We present the findings of a three-month mixed-methodology feasibility study for this trial, describe how this was informed by the MRC guidance and the study design was refined. Methods The fidelity, dose, feasibility and acceptability of implementation and training materials were assessed in three representative non-trial sites (Zimbabwe, Ethiopia, India) using multiple-choice questionnaires, evaluation of clinical management (action log), healthcare provider (HCP) semi-structured interviews and focus groups 4–10 weeks after implementation. Simultaneously, the 10 sites included in the main trial (eight countries) collected primary outcome data to inform the power calculation and randomisation allocation and assess the feasibility of data collection. Results The package was implemented with high fidelity (85% of HCP trained, n  = 204). The questionnaires indicated a good understanding of device use with 75% of participants scoring > 75% ( n  = 97; 90% of those distributed). Action logs were inconsistently completed but indicated that the majority of HCP responded appropriately to abnormal results. From 18 HCP interviews and two focus groups it was widely reported that the intervention improved capacity to make clinical decisions, escalate care and make appropriate referrals. Nine of the ten main trial sites achieved ethical approval for pilot data collection. Intensive care was an inconsistent marker of morbidity and stroke an infrequent outcome and therefore they were removed from the main trial composite outcome. Tools and methods of data collection were optimized and event rates used to inform randomisation. Conclusions This feasibility study demonstrates that the components of the intervention were acceptable, methods of implementing were successful and the main trial design would be feasible. Qualitative work identified key moderators that informed the main trial process evaluation. Changes to the training package, implementation strategy, study design and processes were identified to refine the implementation in the main trial. Trial registration ISRCTN41244132 ; Registered 24/11/2015.

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).

Background Preterm birth is the leading cause of infant mortality globally, including Brazil. We will evaluate whether oral magnesium citrate reduces the risk of placental dysfunction and its negative consequences for both the fetus and mother, which, in turn, should reduce the need for indicated preterm delivery. Methods/Design We will complete a multicenter, randomized double-blind clinical trial comparing oral magnesium citrate 150 mg twice daily (n = 2000 women) to matched placebo (n = 1000 women), starting at 12 1/7 to 20 6/7  weeks gestation and continued until delivery. We will include women at higher risk for placental dysfunction, based on clinical factors from a prior pregnancy (e.g., prior preterm delivery, stillbirth or preeclampsia) or the current pregnancy (e.g., chronic hypertension, pre-pregnancy diabetes mellitus, maternal age > 35 years or pre-pregnancy maternal body mass index > 30 kg/m 2 ). The primary perinatal outcome is a composite of preterm birth < 37 weeks gestation, stillbirth > 20 weeks gestation, neonatal death < 28 days, or SGA birthweight < 3rd percentile. The primary composite maternal outcome is preeclampsia arising < 37 weeks gestation, severe non-proteinuric hypertension arising < 37 weeks gestation, placental abruption, maternal stroke during pregnancy or ≤ 7 days after delivery, or maternal death during pregnancy or ≤ 7 days after delivery. Discussion The results of this randomized clinical trial may be especially relevant in low and middle income countries that have high rates of prematurity and limited resources for acute newborn and maternal care. Trial registration ClinicalTrials.gov Identifier NCT02032186 , registered December 19, 2013.

Millennium Development Goal 5 calls for a 75% reduction in the maternal mortality ratio (MMR) between 1990 and 2015. We estimated levels and trends in maternal mortality for 183 countries to assess progress made. Based on MMR estimates for 2015, we constructed projections to show the requirements for the Sustainable Development Goal (SDG) of less than 70 maternal deaths per 100 000 livebirths globally by 2030. We updated the UN Maternal Mortality Estimation Inter-Agency Group (MMEIG) database with more than 200 additional records (vital statistics from civil registration systems, surveys, studies, or reports). We generated estimates of maternal mortality and related indicators with 80% uncertainty intervals (UIs) using a Bayesian model. The model combines the rate of change implied by a multilevel regression model with a time-series model to capture data-driven changes in country-specific MMRs, and includes a data model to adjust for systematic and random errors associated with different data sources. We had data for 171 of 183 countries. The global MMR fell from 385 deaths per 100 000 livebirths (80% UI 359–427) in 1990, to 216 (207–249) in 2015, corresponding to a relative decline of 43·9% (34·0–48·7), with 303 000 (291 000–349 000) maternal deaths worldwide in 2015. Regional progress in reducing the MMR since 1990 ranged from an annual rate of reduction of 1·8% (0·0–3·1) in the Caribbean to 5·0% (4·0–6·0) in eastern Asia. Regional MMRs for 2015 ranged from 12 deaths per 100 000 livebirths (11–14) for high-income regions to 546 (511–652) for sub-Saharan Africa. Accelerated progress will be needed to achieve the SDG goal; countries will need to reduce their MMRs at an annual rate of reduction of at least 7·5%. Despite global progress in reducing maternal mortality, immediate action is needed to meet the ambitious SDG 2030 target, and ultimately eliminate preventable maternal mortality. Although the rates of reduction that are needed to achieve country-specific SDG targets are ambitious for most high mortality countries, countries that made a concerted effort to reduce maternal mortality between 2000 and 2010 provide inspiration and guidance on how to accomplish the acceleration necessary to substantially reduce preventable maternal deaths. National University of Singapore, National Institute of Child Health and Human Development, USAID, and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

To improve maternal health requires action to ensure quality maternal health care for all women and girls, and to guarantee access to care for those outside the system. In this paper, we highlight some of the most pressing issues in maternal health and ask: what steps can be taken in the next 5 years to catalyse action toward achieving the Sustainable Development Goal target of less than 70 maternal deaths per 100 000 livebirths by 2030, with no single country exceeding 140? What steps can be taken to ensure that high-quality maternal health care is prioritised for every woman and girl everywhere? We call on all stakeholders to work together in securing a healthy, prosperous future for all women. National and local governments must be supported by development partners, civil society, and the private sector in leading efforts to improve maternal–perinatal health. This effort means dedicating needed policies and resources, and sustaining implementation to address the many factors influencing maternal health-care provision and use. Five priority actions emerge for all partners: prioritise quality maternal health services that respond to the local specificities of need, and meet emerging challenges; promote equity through universal coverage of quality maternal health services, including for the most vulnerable women; increase the resilience and strength of health systems by optimising the health workforce, and improve facility capability; guarantee sustainable finances for maternal–perinatal health; and accelerate progress through evidence, advocacy, and accountability.

Within the past decade, pulmonary arteriovenous malformations (PAVMs) have evolved from rare curiosities to not uncommon clinical states, with the latest estimates suggesting a prevalence of ~1 in 2,600. PAVMs provide anatomic right-to-left shunts, allowing systemic venous blood to bypass gas exchange and pulmonary capillary bed processing. Hypoxemia and enhanced ventilatory demands result, although both are usually asymptomatic. Paradoxical emboli lead to strokes and cerebral abscesses, and these commonly occur in individuals with previously undiagnosed PAVMs. PAVM hemorrhage is rare but is the main cause of maternal death in pregnancy. PAVM occlusion by embolization is the standard of care to reduce these risks. However, recent data demonstrate that currently recommended management protocols can result in levels of radiation exposure that would be classified as harmful. Recent publications also provide a better appreciation of the hematologic and cardiovascular demands required to maintain arterial oxygen content and oxygen consumption in hypoxemic patients, identify patient subgroups at higher risk of complications, and emphasize the proportion of radiologically visible PAVMs too small to treat by embolization. This review, therefore, outlines medical states that exacerbate the consequences of PAVMs. Chief among these is iron deficiency, which is commonly present due to concurrent hereditary hemorrhagic telangiectasia: iron deficiency impairs hypoxemia compensations by restricting erythropoiesis and increases the risk of ischemic strokes. Management of periodontal disease, dental interventions, pulmonary hypertension, and pregnancy also requires specific consideration in the setting of PAVMs. The review concludes by discussing to what extent previously recommended protocols may benefit from modification or revision.

Lucy Chappell and colleagues examine the dramatic reduction in maternal deaths from hypertensive disorders of pregnancy in the UK and discuss how systematic confidential inquiries may have contributed

Maternal and perinatal death surveillance and response (MPDSR) systems aim to understand and address key contributors to maternal and perinatal deaths to prevent future deaths. From 2016-2017, the US Agency for International Development's Maternal and Child Survival Program conducted an assessment of MPDSR implementation in Nigeria, Rwanda, Tanzania, and Zimbabwe. A cross-sectional, mixed-methods research design was used to assess MPDSR implementation. The study included a desk review, policy mapping, semistructured interviews with 41 subnational stakeholders, observations, and interviews with key informants at 55 purposefully selected facilities. Using a standardised tool with progress markers defined for six stages of implementation, each facility was assigned a score from 0-30. Quantitative and qualitative data were analysed from the 47 facilities with a score above 10 ('evidence of MPDSR practice'). The mean calculated MPDSR implementation progress score across 47 facilities was 18.98 out of 30 (range: 11.75-27.38). The team observed variation across the national MPDSR guidelines and tools, and inconsistent implementation of MPDSR at subnational and facility levels. Nearly all facilities had a designated MPDSR coordinator, but varied in their availability and use of standardised forms and the frequency of mortality audit meetings. Few facilities (9%) had mechanisms in place to promote a no-blame environment. Some facilities (44%) could demonstrate evidence that a change occurred due to MPDSR. Factors enabling implementation included clear support from leadership, commitment from staff, and regular occurrence of meetings. Barriers included lack of health worker capacity, limited staff time, and limited staff motivation. This study was the first to apply a standardised scoring methodology to assess subnational- and facility-level MPDSR implementation progress. Structures and processes for implementing MPDSR existed in all four countries. Many implementation gaps were identified that can inform priorities and future research for strengthening MPDSR in low-capacity settings.

Background While there is widespread acknowledgment of the need for improved quality and quantity of information on births and deaths, there has been less movement towards systematically capturing and reviewing the causes and avoidable factors linked to deaths, in order to affect change. This is particularly true for stillbirths and neonatal deaths which can fall between different health care providers and departments. Maternal and perinatal mortality audit applies to two of the five objectives in the Every Newborn Action Plan but data on successful approaches to overcome bottlenecks to scaling up audit are lacking. Methods We reviewed the current evidence for facility-based perinatal mortality audit with a focus on low- and middle-income countries and assessed the status of mortality audit policy and implementation. Based on challenges identified in the literature, key challenges to completing the audit cycle and affecting change were identified across the WHO health system building blocks, along with solutions, in order to inform the process of scaling up this strategy with attention to quality. Results Maternal death surveillance and review is moving rapidly with many countries enacting and implementing policies and with accountability beyond the single facility conducting the audits. While 51 priority countries report having a policy on maternal death notification in 2014, only 17 countries have a policy for reporting and reviewing stillbirths and neonatal deaths. The existing evidence demonstrates the potential for audit to improve birth outcomes, only if the audit cycle is completed. The primary challenges within the health system building blocks are in the area of leadership and health information. Examples of successful implementation exist from high income countries and select low- and middle-income countries provide valuable learning, especially on the need for leadership for effective audit systems and on the development and the use of clear guidelines and protocols in order to ensure that the audit cycle is completed. Conclusions Health workers have the power to change health care routines in daily practice, but this must be accompanied by concrete inputs at every level of the health system. The system requires data systems including consistent cause of death classification and use of best practice guidelines to monitor performance, as well as leaders to champion the process, especially to ensure a no-blame environment, and to access change agents at other levels to address larger, systemic challenges.