Beth Payne

Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model

BACKGROUND Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. METHODS We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. FINDINGS 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84-0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. INTERPRETATION The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. FUNDING Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.

Abnormal Liver Function Tests as Predictors of Adverse Maternal Outcomes in Women With Preeclampsia

OBJECTIVES To evaluate whether (1) the absolute magnitude of liver function test values, (2) the percentage change in liver function test values over time, or (3) the rate of change in liver function test values over time predicts adverse maternal outcomes in women with preeclampsia. METHODS We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a prospective multicentre cohort study assessing predictors of adverse maternal outcomes in women with preeclampsia. Women with at least one liver function test performed at the time of hospital admission were included. Liver functions were tested by serum concentrations of aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), albumin, total bilirubin, and the international normalized prothrombin time ratio. Parameters investigated were absolute levels, change within 48 hours of hospital admission, change from admission to delivery or outcome, and rate of change from admission to delivery or outcome of each liver function test. The ability of these parameters to predict adverse outcomes was assessed using logistic regression analyses and by calculating the receiver operating characteristic (ROC) area under the curve (AUC). RESULTS Of the 2008 women, 1056 (53%) had at least one abnormal liver function test result. The odds of having an adverse maternal outcome were higher in women with any abnormal liver function test than in women with normal results. When test results were stratified into quartiles, women with results in the highest quartile (lowest quartile for albumin) were at higher risk of adverse outcomes than women in the lowest quartile for all parameters (highest for albumin). The absolute magnitude of AST, ALT, and LDH predicted adverse maternal outcomes (AST: ROC AUC 0.73 [95% CI 0.67 to 0.97]; ALT: ROC AUC 0.73 [95% CI 0.67 to 0.79]; LDH: ROC AUC 0.74 [95% CI 0.68 to 0.81]). Neither change of liver function test results, within 48 hours of admission or from admission to delivery or outcome, nor rate of change were predictive. CONCLUSION We found abnormal liver function test results to be associated with an increased risk for adverse maternal outcomes. Levels of AST, ALT, and LDH were found to be modestly predictive of these outcomes.

Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review

Pregnant and postpartum women with severe hypertension are at increased risk of stroke and require blood pressure (BP) reduction. Parenteral antihypertensives have been most commonly studied, but oral agents would be ideal for use in busy and resource‐constrained settings.

Development of mHealth applications for pre-eclampsia triage.

The development of mobile applications for the diagnosis and management of pregnant women with pre-eclampsia is described. These applications are designed for use by community-based health care providers (c-HCPs) in health facilities and during home visits to collect symptoms and perform clinical measurements (including pulse oximeter readings). The clinical data collected in women with pre-eclampsia are used as the inputs to a predictive model providing a risk score for the development of adverse outcomes. Based on this risk, the applications provide recommendations on treatment, referral, and reassessment. c-HCPs can access patient records across multiple visits, using multiple devices that are synchronized using a secure Research Electronic Data Capture server. A unique feature of these applications is the ability to measure oxygen saturation with a pulse oximeter connected to a smartphone (Phone Oximeter). The mobile health application development process, including challenges encountered and solutions are described.

Assessment, surveillance and prognosis in pre-eclampsia

The hypertensive disorders of pregnancy (HDP) remain one of the major causes of maternal mortality and morbidity worldwide. Many international guidelines exist for the classification and assessment of women with hypertension in pregnancy, but definitions and recommendations within these documents are variable. Many recommended investigations do not actually correlate with increased risk of adverse outcomes, making it difficult to determine true prognosis. Although standardised assessment and surveillance has been shown to improve outcomes, the application of these monitoring strategies in many areas of the world is not possible owing to the cost associated with them. Not all of the tests recommended for surveillance of women with pre-eclampsia are independently predictive of adverse outcomes, and many unnecessary tests could be avoided if those tests that are most informative where identified. The Pre-eclampsia Integrated Estimate of RiSk study has identified a group of tests that can be used to predict risk of outcomes accurately up to 7 days after admission to a tertiary hospital with pre-eclampsia. This model needs to be validated in new populations and in different clinical settings before it can be implemented into clinical practice. Until this happens, clinicians should consider the whole clinical picture when assessing women with pre-eclampsia and making decisions around expectant management compared with stabilisation and delivery. Future research in the area of prognosis should focus on women with variable definitions of pre-eclampsia and the other HDP. All studies reviewed were limited to cases of severe pre-eclampsia, and results may not be generalisable across the spectrum of the disorder.

Preeclampsia in Low and Middle Income Countries—Health Services Lessons Learned From the PRE-EMPT (PRE-Eclampsia–Eclampsia Monitoring, Prevention & Treatment) Project

The hypertensive disorders of pregnancy, in particular preeclampsia, matter because adverse events occur in women with preeclampsia and, to a lesser extent, in women with the other hypertensive disorders. These adverse events are maternal, perinatal, and neonatal and can alter the life trajectory of each individual, should that life not be ended by complications. In this review we discuss a number of priorities and dilemmas that we perceive to be facing health services in low and middle income countries as they try to prioritize interventions to reduce the health burden related to preeclampsia. These priorities and dilemmas relate to calcium for preeclampsia prevention, risk stratification, antihypertensive and magnesium sulphate therapy, and mobile health. Significant progress has been and is being made to reduce the impact of preeclampsia in low and middle income countries, but it remains a priority focus as we attempt to achieve Millennium Development Goal 5.

Using Clinical Symptoms to Predict Adverse Maternal and Perinatal Outcomes in Women With Preeclampsia: Data From the PIERS (Pre-eclampsia Integrated Estimate of RiSk) Study

OBJECTIVES Preeclampsia is a leading cause of maternal morbidity. The clinical challenge lies in predicting which women with preeclampsia will suffer adverse outcomes and would benefit from treatment, while minimizing potentially harmful interventions. Our aim was to determine the ability of maternal symptoms (i.e., severe nausea or vomiting, headache, visual disturbance, right upper quadrant pain or epigastric pain, abdominal pain or vaginal bleeding, and chest pain or dyspnea) to predict adverse maternal or perinatal outcomes. METHODS We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a multicentre, prospective cohort study designed to investigate the maternal risks associated with preeclampsia. Relative risks and receiver operating characteristic (ROC) curves were assessed for each preeclampsia symptom and outcome pair. RESULTS Of 2023 women who underwent assessment, 52% experienced at least one preeclampsia symptom, with 5.2% and 5.3% respectively experiencing an adverse maternal or perinatal outcome. No symptom and outcome pair, in either of the maternal or perinatal groups, achieved an area under the ROC curve value > 0.7, which would be necessary to demonstrate a discriminatory predictive value. CONCLUSION Maternal symptoms of preeclampsia are not independently valid predictors of maternal adverse outcome. Caution should be used when making clinical decisions on the basis of symptoms alone in the preeclamptic patient.

Oxygen saturation as a predictor of adverse maternal outcomes in women with preeclampsia.

OBJECTIVE We sought to determine the role of respiratory assessment by cardiorespiratory symptoms and/or oxygen saturation by pulse oximetry (SpO2) in predicting adverse maternal outcomes in women admitted to hospital with preeclampsia. METHODS These data derive from an international, prospective multicentre cohort study, PIERS (Pre-eclampsia Integrated Estimate of RiSk), which assesses predictors of adverse outcomes in women admitted to tertiary perinatal units with preeclampsia. Univariate and multivariate analyses of cardiorespiratory symptoms and pulse oximetry were performed to assess their ability to predict a combined adverse maternal outcome developed through international Delphi consensus. RESULTS SpO2 successfully predicted adverse maternal outcomes; the area under the receiver-operator characteristic curve (AUC ROC) was 0.71 (95% CI 0.65 to 0.77). Combining the symptoms of chest pain and/or dyspnea with pulse oximetry improved this predictive ability (AUC ROC 0.73; 95% CI 0.67 to 0.78). When SpO2 was stratified into risk groups using inflection points on the ROC curve, the highest risk group (SpO2 90% to 93%) had an odds ratio of 18.1 (95% CI 8.2 to 40.2) for all outcomes within 48 hours when compared with the baseline group (SpO2 98% to 100%). CONCLUSION Assessing SpO2 aids in the assessment of maternal risk in women admitted to hospital with preeclampsia. An SpO2 value of ≤ 93% confers particular risk. The symptom complex of chest pain and/or dyspnea adds to the association.

Performance of the fullPIERS model in predicting adverse maternal outcomes in pre‐eclampsia using patient data from the PIERS (Pre‐eclampsia Integrated Estimate of RiSk) cohort, collected on admission

The fullPIERS (Pre‐eclampsia Integrated Estimate of RiSk) model is a promising tool for the prediction of adverse outcomes in pre‐eclampsia, developed using the worst values for predictor variables measured within 48 hours of admission. We reassessed the performance of fullPIERS using predictor variables obtained within 6 and 24 hours of admission, and found that the stratification capacity, calibration ability, and classification accuracy of the model remained high. The fullPIERS model is accurate as a rule‐in test for adverse maternal outcome, with a likelihood ratio of 14.8 (95% CI 9.1–24.1) or 17.5 (95% CI 11.7–26.3) based on 6‐ and 24‐hour data, respectively, for the women identified to be at highest risk (predicted probability ≥30%).

Usability and Feasibility of PIERS on the Move: An mHealth App for Pre-Eclampsia Triage

Background Pre-eclampsia is one of the leading causes of maternal death and morbidity in low-resource countries due to delays in case identification and a shortage of health workers trained to manage the disorder. Pre-eclampsia Integrated Estimate of RiSk (PIERS) on the Move (PotM) is a low cost, easy-to-use, mobile health (mHealth) platform that has been created to aid health workers in making decisions around the management of hypertensive pregnant women. PotM combines two previously successful innovations into a mHealth app: the miniPIERS risk assessment model and the Phone Oximeter. Objective The aim of this study was to assess the usability of PotM (with mid-level health workers) for iteratively refining the system. Methods Development of the PotM user interface involved usability testing with target end-users in South Africa. Users were asked to complete clinical scenario tasks, speaking aloud to give feedback on the interface and then complete a questionnaire. The tool was then evaluated in a pilot clinical evaluation in Tygerberg Hospital, Cape Town. Results After ethical approval and informed consent, 37 nurses and midwives evaluated the tool. During Study 1, major issues in the functionality of the touch-screen keyboard and date scroll wheels were identified (total errors n=212); during Study 2 major improvements in navigation of the app were suggested (total errors n=144). Overall, users felt the app was usable using the Computer Systems Usability Questionnaire; median (range) values for Study 1 = 2 (1-6) and Study 2 = 1 (1-7). To demonstrate feasibility, PotM was used by one research nurse for the pilot clinical study. In total, more than 500 evaluations were performed on more than 200 patients. The median (interquartile range) time to complete an evaluation was 4 min 55 sec (3 min 25 sec to 6 min 56 sec). Conclusions By including target end-users in the design and evaluation of PotM, we have developed an app that can be easily integrated into health care settings in low- and middle-income countries. Usability problems were often related to mobile phone features (eg, scroll wheels, touch screen use). Larger scale evaluation of the clinical impact of this tool is underway.