Evaluation of a novel device for the management of high blood pressure and shock in pregnancy in low-resource settings: study protocol for a stepped-wedge cluster-randomised controlled trial (CRADLE-3 trial).

BackgroundObstetric haemorrhage, sepsis and pregnancy hypertension account for more than 50% of maternal deaths worldwide. Early detection and effective management of these conditions relies on vital signs. The Microlife® CRADLE Vital Sign Alert (VSA) is an easy-to-use, accurate device that measures blood pressure and pulse. It incorporates a traffic-light early warning system that alerts all levels of healthcare provider to the need for escalation of care in women with obstetric haemorrhage, sepsis or pregnancy hypertension, thereby aiding early recognition of haemodynamic instability and preventing maternal mortality and morbidity. The aim of the trial was to determine whether implementation of the CRADLE intervention (the Microlife® CRADLE VSA device and CRADLE training package) into routine maternity care in place of existing equipment will reduce a composite outcome of maternal mortality and morbidity in low- and middle-income country populations.MethodsThe CRADLE-3 trial was a stepped-wedge cluster-randomised controlled trial of the CRADLE intervention compared to routine maternity care. Each cluster crossed from routine maternity care to the intervention at 2-monthly intervals over the course of 20 months (April 2016 to November 2017). All women identified as pregnant or within 6 weeks postpartum, presenting for maternity care in cluster catchment areas were eligible to participate. Primary outcome data (composite of maternal death, eclampsia and emergency hysterectomy per 10,000 deliveries) were collected at 10 clusters (Gokak, Belgaum, India; Harare, Zimbabwe; Ndola, Zambia; Lusaka, Zambia; Free Town, Sierra Leone; Mbale, Uganda; Kampala, Uganda; Cap Haitien, Haiti; South West, Malawi; Addis Ababa, Ethiopia). This trial was informed by the Medical Research Council guidance for complex interventions. A process evaluation was undertaken to evaluate implementation in each site and a cost-effectiveness evaluation will be undertaken.DiscussionAll aspects of this protocol have been evaluated in a feasibility study, with subsequent optimisation of the intervention. This trial will demonstrate the potential impact of the CRADLE intervention on reducing maternal mortality and morbidity in low-resource settings. It is anticipated that the relatively low cost of the intervention and ease of integration into existing health systems will be of significant interest to local, national and international health policy-makers.Trial registrationISCRTN41244132. Registered on 2 February 2016. Prospective protocol modifications have been recorded and were communicated to the Ethics Committees and Trials Committees. The adapted Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Checklist and the SPIRIT Checklist are attached as Additional file 1

Exploring the effect of implementation and context on a stepped-wedge randomised controlled trial of a vital sign triage device in routine maternity care in low-resource settings

© 2019 The Author(s). Background: Interventions aimed at reducing maternal mortality are increasingly complex. Understanding how complex interventions are delivered, to whom, and how they work is key in ensuring their rapid scale-up. We delivered a vital signs triage intervention into routine maternity care in eight low- and middle-income countries with the aim of reducing a composite outcome of morbidity and mortality. This was a pragmatic, hybrid effectiveness-implementation stepped-wedge randomised controlled trial. In this study, we present the results of the mixed-methods process evaluation. The aim was to describe implementation and local context and integrate results to determine whether differences in the effect of the intervention across sites could be explained. Methods: The duration and content of implementation, uptake of the intervention and its impact on clinical management were recorded. These were integrated with interviews (n = 36) and focus groups (n = 19) at 3 months and 6-9 months after implementation. In order to determine the effect of implementation on effectiveness, measures were ranked and averaged across implementation domains to create a composite implementation strength score and then correlated with the primary outcome. Results: Overall, 61.1% (n = 2747) of health care providers were trained in the intervention (range 16.5% to 89.2%) over a mean of 10.8 days. Uptake and acceptability of the intervention was good. All clusters demonstrated improved availability of vital signs equipment. There was an increase in the proportion of women having their blood pressure measured in pregnancy following the intervention (79.2% vs. 97.6%; OR 1.30 (1.29-1.31)) and no significant change in referral rates (3.7% vs. 4.4% OR 0.89; (0.39-2.05)). Availability of resources and acceptable, effective referral systems influenced health care provider interaction with the intervention. There was no correlation between process measures within or between domains, or between the composite score and the primary outcome. Conclusions: This process evaluation has successfully described the quantity and quality of implementation. Variation in implementation and context did not explain differences in the effectiveness of the intervention on maternal mortality and morbidity. We suggest future trials should prioritise in-depth evaluation of local context and clinical pathways. Trial registration: Trial registration: ISRCTN41244132. Registered on 2 Feb 2016

Incidence of eclampsia and related complications across 10 low- and middle-resource geographical regions:Secondary analysis of a cluster randomised controlled trial

<div><p>Background</p><p>In 2015, approximately 42,000 women died as a result of hypertensive disorders of pregnancy worldwide; over 99% of these deaths occurred in low- and middle-income countries. The aim of this paper is to describe the incidence and characteristics of eclampsia and related complications from hypertensive disorders of pregnancy across 10 low- and middle-income geographical regions in 8 countries, in relation to magnesium sulfate availability.</p><p>Methods and findings</p><p>This is a secondary analysis of a stepped-wedge cluster randomised controlled trial undertaken in sub-Saharan Africa, India, and Haiti. This trial implemented a novel vital sign device and training package in routine maternity care with the aim of reducing a composite outcome of maternal mortality and morbidity. Institutional-level consent was obtained, and all women presenting for maternity care were eligible for inclusion. Data on eclampsia, stroke, admission to intensive care with a hypertensive disorder of pregnancy, and maternal death from a hypertensive disorder of pregnancy were prospectively collected from routine data sources and active case finding, together with data on perinatal outcomes in women with these outcomes. In 536,233 deliveries between 1 April 2016 and 30 November 2017, there were 2,692 women with eclampsia (0.5%). In total 6.9% (<i>n =</i> 186; 3.47/10,000 deliveries) of women with eclampsia died, and a further 51 died from other complications of hypertensive disorders of pregnancy (0.95/10,000). After planned adjustments, the implementation of the CRADLE intervention was not associated with any significant change in the rates of eclampsia, stroke, or maternal death or intensive care admission with a hypertensive disorder of pregnancy. Nearly 1 in 5 (17.9%) women with eclampsia, stroke, or a hypertensive disorder of pregnancy causing intensive care admission or maternal death experienced a stillbirth or neonatal death. A third of eclampsia cases (33.2%; <i>n =</i> 894) occurred in women under 20 years of age, 60.0% in women aged 20–34 years (<i>n =</i> 1,616), and 6.8% (<i>n =</i> 182) in women aged 35 years or over. Rates of eclampsia varied approximately 7-fold between sites (range 19.6/10,000 in Zambia Centre 1 to 142.0/10,000 in Sierra Leone). Over half (55.1%) of first eclamptic fits occurred in a health-care facility, with the remainder in the community. Place of first fit varied substantially between sites (from 5.9% in the central referral facility in Sierra Leone to 85% in Uganda Centre 2). On average, magnesium sulfate was available in 74.7% of facilities (range 25% in Haiti to 100% in Sierra Leone and Zimbabwe). There was no detectable association between magnesium sulfate availability and the rate of eclampsia across sites (<i>p =</i> 0.12). This analysis may have been influenced by the selection of predominantly urban and peri-urban settings, and by collection of only monthly data on availability of magnesium sulfate, and is limited by the lack of demographic data in the population of women delivering in the trial areas.</p><p>Conclusions</p><p>The large variation in eclampsia and maternal and neonatal fatality from hypertensive disorders of pregnancy between countries emphasises that inequality and inequity persist in healthcare for women with hypertensive disorders of pregnancy. Alongside the growing interest in improving community detection and health education for these disorders, efforts to improve quality of care within healthcare facilities are key. Strategies to prevent eclampsia should be informed by local data.</p><p>Trial registration</p><p>ISRCTN: <a href="http://www.isrctn.com/ISRCTN41244132" target="_blank">41244132</a>.</p></div

Effect of a novel vital sign device on maternal mortality and morbidity in low-resource settings: a pragmatic, stepped-wedge, cluster-randomised controlled trial.

BackgroundIn 2015, an estimated 303 000 women died in pregnancy and childbirth. Obstetric haemorrhage, sepsis, and hypertensive disorders of pregnancy account for more than 50% of maternal deaths worldwide. There are effective treatments for these pregnancy complications, but they require early detection by measurement of vital signs and timely administration to save lives. The primary aim of this trial was to determine whether implementation of the CRADLE Vital Sign Alert and an education package into community and facility maternity care in low-resource settings could reduce a composite of all-cause maternal mortality or major morbidity (eclampsia and hysterectomy).MethodsWe did a pragmatic, stepped-wedge, cluster-randomised controlled trial in ten clusters across Africa, India, and Haiti, introducing the device into routine maternity care. Each cluster contained at least one secondary or tertiary hospital and their main referral facilities. Clusters crossed over from existing routine care to the CRADLE intervention in one of nine steps at 2-monthly intervals, with CRADLE devices replacing existing equipment at the randomly allocated timepoint. A computer-generated randomly allocated sequence determined the order in which the clusters received the intervention. Because of the nature of the intervention, this trial was not masked. Data were gathered monthly, with 20 time periods of 1 month. The primary composite outcome was at least one of eclampsia, emergency hysterectomy, and maternal death. This study is registered with the ISRCTN registry, number ISRCTN41244132.FindingsBetween April 1, 2016, and Nov 30, 2017, among 536 223 deliveries, the primary outcome occurred in 4067 women, with 998 maternal deaths, 2692 eclampsia cases, and 681 hysterectomies. There was an 8% decrease in the primary outcome from 79·4 per 10 000 deliveries pre-intervention to 72·8 per 10 000 deliveries post-intervention (odds ratio [OR] 0·92, 95% CI 0·86-0·97; p=0·0056). After planned adjustments for variation in event rates between and within clusters over time, the unexpected degree of variability meant we were unable to judge the benefit or harms of the intervention (OR 1·22, 95% CI 0·73-2·06; p=0·45).InterpretationThere was an absolute 8% reduction in primary outcome during the trial, with no change in resources or staffing, but this reduction could not be directly attributed to the intervention due to variability. We encountered unanticipated methodological challenges with this trial design, which can provide valuable learning for future research and inform the trial design of future international stepped-wedge trials.FundingNewton Fund Global Research Programme: UK Medical Research Council; Department of Biotechnology, Ministry of Science & Technology, Government of India; and UK Department of International Development

Shock index thresholds to predict adverse outcomes in maternal hemorrhage and sepsis:A prospective cohort study

CITATION: Nathan, Hannah L., et al. 2019. Shock index thresholds to predict adverse outcomes in maternal hemorrhage and sepsis : a prospective cohort study. Acta Obstetricia et Gynecologica Scandinavica, 98(9):1178-1186, doi:10.1111/aogs.13626.The original publication is available at https://obgyn.onlinelibrary.wiley.comIntroduction: Shock index (SI) is a predictor of hemodynamic compromise in obstetric patients. The SI threshold for action is not well understood. We aimed to evaluate SI thresholds as predictors of outcomes in obstetric patients. Material and methods: We undertook a prospective cohort study at three South African hospitals of women with postpartum hemorrhage (n = 283) or maternal sepsis (n = 126). The “first” and “worst” SI following diagnosis were recorded. SI was compared with conventional vital signs as predictors of outcomes. The performance of SI <.9, SI .9‐1.69 and SI ≥1.7 to predict outcomes (maternal death; Critical Care Unit admission; major procedure; hysterectomy) and hemorrhage‐specific outcomes (lowest hemoglobin <70 g/l; blood transfusion ≥4 IU) were evaluated. Results: “First” SI was one of two best performing vital signs for every outcome in postpartum hemorrhage and sepsis. In hemorrhage, risk of all outcomes increased with increasing “first” SI; for blood transfusion ≥4 IU odds ratio was 4.24 (95% confidence interval 1.25‐14.36) for SI ≥1.7 vs SI .9‐1.69. In sepsis, risk of all outcomes increased with increasing “worst” SI. Sensitivity, specificity, positive and negative predictive values of “first” SI <.9 vs SI ≥.9 for maternal death were 100.0%, 55.2%, 4.6% and 100.0%, respectively, in hemorrhage and 80.0%, 50.4%, 12.3% and 96.7%, respectively, in sepsis. Conclusions: The shock index was a consistent predictor of outcomes compared with conventional vital signs in postpartum hemorrhage and sepsis. SI <.9 performed well as a rule‐out test and SI .9‐1.69 and SI ≥1.7 indicated increased risk of all outcomes in both cohorts. These thresholds may alert to the need for urgent intervention and prevent maternal deaths.https://obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.13626Publisher's versio

Maternal and perinatal adverse outcomes in women with pre-eclampsia cared for at facility-level in South Africa:a prospective cohort study

CITATION: Nathan, H. L., et al. 2018. Maternal and perinatal adverse outcomes in women with pre-eclampsia cared for at facility-level in South Africa : a prospective cohort study. Journal of Global Health, 8(2):020401, doi:10.7189/jogh.08.020401.The original publication is available at http://jogh.orgBackground: Hypertensive disorders of pregnancy contribute to 14% of all maternal deaths, the majority of which occur in low- and middle-income countries. The aim of the study was to describe the maternal and perinatal clinical outcomes of women with pre-eclampsia living in middle- and low-income countries. Methods The study was a prospective observational study of women with pre-eclampsia (n = 1547, 42 twin pregnancies) at three South African tertiary facilities. Using stepwise logistic regression model area under the receiver operating characteristic curve (AUROC) values, the association between maternal baseline and admission characteristics and risk of adverse outcomes was evaluated. Main outcome measures were eclampsia, kidney injury and perinatal death. Results In 1547 women with pre-eclampsia, 16 (1%) died, 147 (9.5%) had eclampsia, four (0.3%) had a stroke and 272 (17.6%) had kidney injury. Of the 1589 births, there were 332 (21.0%) perinatal deaths; of these, 281 (84.5%) were stillbirths. Of 1308 live births, 913 (70.0%) delivered <37 completed weeks and 544 (41.7%) delivered <34 weeks’ gestation. Young maternal age (AUROC = 0.76, 95% confidence interval (CI) = 0.71- 0.80) and low Body Mass Index BMI (AUROC 0.65, 95% CI = 0.59-0.69) were significant predictors of eclampsia. Highest systolic blood pressure had the strongest association with kidney injury, (AUROC = 0.64, 95% CI = 0.60-0.68). Early gestation at admission was most strongly associated with perinatal death (AUROC = 0.81, 95% CI = 0.77-0.84). Conclusions The incidence of pre-eclampsia complications, perinatal death and preterm delivery in women referred to tertiary care in South Africa was much higher than reported in other low- and middle-income studies and despite access to tertiary care interventions. Teenage mothers and those with low BMI were at highest risk of eclampsia. This information could be used to inform guidelines, the research agenda and policy.http://www.jogh.org/issue201802.htmPublisher's versio

Additional file 1: of Evaluation of a novel vital sign device to reduce maternal mortality and morbidity in low-resource settings: a mixed method feasibility study for the CRADLE-3 trial

Main Trial Cluster Facilities. Table listing the Primary Investigator and all facilities involved in the main trial in each cluster. (DOCX 21 kb

Exploring the effect of implementation and context on a stepped-wedge randomised controlled trial of a vital sign triage device in routine maternity care in low-resource settings

Abstract Background Interventions aimed at reducing maternal mortality are increasingly complex. Understanding how complex interventions are delivered, to whom, and how they work is key in ensuring their rapid scale-up. We delivered a vital signs triage intervention into routine maternity care in eight low- and middle-income countries with the aim of reducing a composite outcome of morbidity and mortality. This was a pragmatic, hybrid effectiveness-implementation stepped-wedge randomised controlled trial. In this study, we present the results of the mixed-methods process evaluation. The aim was to describe implementation and local context and integrate results to determine whether differences in the effect of the intervention across sites could be explained. Methods The duration and content of implementation, uptake of the intervention and its impact on clinical management were recorded. These were integrated with interviews (n = 36) and focus groups (n = 19) at 3 months and 6–9 months after implementation. In order to determine the effect of implementation on effectiveness, measures were ranked and averaged across implementation domains to create a composite implementation strength score and then correlated with the primary outcome. Results Overall, 61.1% (n = 2747) of health care providers were trained in the intervention (range 16.5% to 89.2%) over a mean of 10.8 days. Uptake and acceptability of the intervention was good. All clusters demonstrated improved availability of vital signs equipment. There was an increase in the proportion of women having their blood pressure measured in pregnancy following the intervention (79.2% vs. 97.6%; OR 1.30 (1.29–1.31)) and no significant change in referral rates (3.7% vs. 4.4% OR 0.89; (0.39–2.05)). Availability of resources and acceptable, effective referral systems influenced health care provider interaction with the intervention. There was no correlation between process measures within or between domains, or between the composite score and the primary outcome. Conclusions This process evaluation has successfully described the quantity and quality of implementation. Variation in implementation and context did not explain differences in the effectiveness of the intervention on maternal mortality and morbidity. We suggest future trials should prioritise in-depth evaluation of local context and clinical pathways. Trial registration Trial registration: ISRCTN41244132. Registered on 2 Feb 201