CRADLE (Community blood pressure monitoring in Rural Africa and Asia: Detection of underLying pre-Eclampsia)
Accurate and regular BP monitoring is a cost-effective screening tool for the early identification and management of pre-eclampsia in pregnancy. In low- and middle- income countries (LMICs), pre-eclampsia is frequently under-detected not only because attendance for antenatal care is often low, but also, due to inadequate training in how to take accurate BP measurements, and insufficient, poorly functioning equipment. Firstly, training in the use of a cheap yet technically challenging method, the traditional sphygmomanometer is often lacking amongst health care workers staffing antenatal clinics.
Secondly, there is concern over the robustness and safety of these traditional devices (those containing mercury), while the next generation aneroid instruments are frequently inaccurate through calibration drift and ideally require six-monthly re-calibration to maintain accuracy.
Thirdly, the use of ‘manual’ BP devices such as these which require manual inflation, ausculatory skills and the observer recording the BP from a calibrated scale is associated with user-bias resulting in inaccurate measurement. This has been attributed to terminal digit preference, wrong Korrotkoff sound interpretation, threshold avoidance, and incorrect deflation speeds. Third generation BP devices which automatically inflate the cuff and provide a digital reading, whilst circumventing some of these issues, are also unsuited for use in LMICs as they depend on an expensive power supply to drive the automatic pump, or source of batteries and have poor resistance to shock and fluctuations in temperature; most are inaccurate and worryingly underestimate the BP in hypertensive pregnancy. In addition, for all devices, staff may not always be trained in the interpretation of the BP readings, especially in those settings where it is seldom taken due to lack of equipment.
Accurate BP measurement is not only vital for detecting and monitoring pre-eclampsia and other hypertensive disorders of pregnancy, but also other life threatening maternal conditions such as PPH (as well as intrapartum and antepartum haemorrhage) and sepsis. PPH, sepsis and pre-eclampsia are the leading direct causes of maternal death and morbidity in LMICs. Visual estimation of blood loss at PPH is often unreliable, as is the relationship of blood loss to maternal symptoms. Hypovolaemic shock may be complicated by anaemia, resulting in a greater degree of compromise related to blood loss. Furthermore some blood loss may be concelaedconcealed (e.g.,g abruption).
Given that post partum haemorrhage (PPH) can lead to death kill within two hours, early recognition is essential. A community diagnosis of severe hypotension particularly associated with tachycardia (threshold values to be determined) rather than waiting until the woman is symptomatic or until the blood loss reaches a defined level, would quickly alert the community health care provider (cHCP) to severe maternal illness, and potentially prompt community-based initiation of treatment of the patient (e.g., intravenous (i.v.IV) fluids and antibiotics) and/or emergency transfer for definitive care.
The primary objective of the CRADLE project is to develop an accurate and tested low-cost solution to improve antenatal detection of pre-eclampsia, and hypotension associated with PPH and sepsis, by adapting existing tools for BP measurement for use by frontline health care providers working at a community level and in first-level clinics, who are best placed to both access pregnant women and initiate life-saving interventions. Equipping frontline health workers with novel technology such as this, as well as provision of basic training in its use, enhances their capabilities and performance. Once widely implemented in LMICs, the availability of BP measurements will facilitate referrals of high-risk women to secondary level centres and thereby has potential to improve pregnancy outcome for both the mother and infant.
Our research group had previously developed a BP device (Microlife 3AS1-2) specifically for use in LMICs. It can be manufactured at low cost (<$20/piece) and the manual pump cuff inflation (rather than battery operated) means that battery supply (2 AA alkaline batteries) is only used to power the liquid crystal display showing the BP reading, allowing it to generate 1000-1500 readings on one battery set, with a lifetime use of >20,000 cycles. We clinically validated this device for use in pregnancy (hypertension) in a low resource setting, and piloted its clinical use in a feasibility study in sub-Saharan Africa for detection of pre-eclampsia (Tanzania, Zambia and Zimbabwe). In the pre- and post-intervention study we demonstrated that the BP device was accurate, easy to use and acceptable to health workers in rural antenatal care clinics. The introduction of the device into peripheral clinics increased referrals from the community to hospital facility for suspected pre-eclampsia.
On the basis of this work, the Kings CRADLE group were successful in obtaining generous further funding from the Bill & Melinda Gates Grand Challenges Explorations ($1 Million). The second phase of the project has a number of elements:
- To further technologically adapt the BP device to enhance its suitability for low and middle income country environment and accuracy in hypotension measurement in a simulated environment. By the end of year 4, the team hope to have further refined the device to include sealed long-life batteries, mobile phone style charging system, traffic light style warning system to alert the user re hyper or hypotension.
- Development of an appropriate ‘traffic light warning system’ to identify women at the highest risk of poor clinical outcome by analysing pulse and BP measurements after post partum haemorrhage by retrospective analysis of two large pre-existing datasets (UK, Zambia, Nigeria, Egypt). This work will be done in collaboration with Professor Suellen Miller and her team at UCSF.
- Prospective clinical evaluation of the use of the device in assessment of life threatening maternal conditions associated with hypotension e.g. haemorrhage and sepsis (South Africa and India) in high-risk institutional setting. In collaboration with Annemarie de Greef, South Africa.
- Field evaluation of the device in a community setting, in assessment of hypertensive disorders of pregnancy, and process evaluation of the acceptability, useability and feasibility of the device for use by cHCPs in the CLIP study (India, Pakistan, Mozambique and Nigeria).
We anticipate that the use of a novel, low-cost, accurate, easy to use BP monitor device by cHCPs will be feasible and acceptable, promoting earlier identification and entry into care for women with life-threatening maternal conditions.
With data collection now complete in South Africa, we are busy data cleaning in preparation for our quantitative and qualitative data analyses. Both phases of our qualitative evaluation within the CLIP Trials are now complete and data analysis are ongoing, and due to be complete in January 2017. Quantitative data collection is ongoing as per the CLIP timelines. For CRADLE 3, every two-months a site is randomly receiving the CRADLE package. The CRADLE 3 Trial will run for twenty-one months, with each of the ten sites receiving the intervention, and with data collection ending in November 2017.
Munguambe K, Sevene E, Akeju D, Adetoro OO, Charanthimath U, Bellad MB, De Greeff A, Anthony J, Hall DR. The CRADLE vital signs alert: qualitative evaluation of a novel device designed for use in pregnancy by healthcare workers in low-resource settings. Reproductive health. 2018 Jan;15:5.
Nathan HL, Cottam K, Hezelgrave NL, Seed PT, Briley A, Bewley S, Chappell LC, Shennan AH. Determination of normal ranges of shock index and other haemodynamic variables in the immediate postpartum period: a cohort study. PloS One. 2016 Dec 20;11(12):e0168535.
Nathan HL, Vousden N, Lawley E, Shennan AH. The CRADLE Vital Signs Alert, a simple device for sustainable impact on maternal mortality: from concept to implementation. RCOG International News. 2016; P16–17.
El Ayadi AM, Nathan HL, Seed PT, Butrick EA, Hezelgrave NL, Shennan AH, Miller S. Vital Sign Prediction of Adverse Maternal Outcomes in Women with Hypovolemic Shock: The Role of Shock Index. PloS One. 2016 Feb 22;11(2).
Nathan HL, de Greeff A, Hezelgrave NL, Chappell LC, Shennan AH. Accuracy validation of the Microlife 3AS1-2 blood pressure device in a pregnant population with low blood pressure. Blood Pressure Monitoring. 2015 Oct 1;20(5):299–302.
Nathan HL, El Ayadi A, Hezelgrave NL, Seed P, Butrick E, Miller S, Briley A, Bewley S, Shennan AH. Shock index: an effective predictor of outcome in postpartum haemorrhage?. BJOG. 2015 Jan 1;122(2):268–75.
Nathan H.L., de Greeff A., Hezelgrave N.L., Chappell L.C., Shennan A.H. An accurate semiautomated oscillometric blood pressure device for use in pregnancy (including pre-eclampsia) in a low-income and middle-income country population: the Microlife 3AS1–2. Blood Pressure Monitoring. 2015; 20(1): 52–5.
de Greeff A, Nathan H, Stafford N, Liu B, Shennan AH. Development of an accurate oscillometric blood pressure device for low resource settings. Blood Pressure Monitoring. 2008 Dec 1;13(6):342–8