Pre-eclampsia Integrated Estimate Of RiSk Research Articles

Economic and cost-effectiveness analysis of the Community-Level Interventions for Pre-eclampsia (CLIP) trials in India, Pakistan and Mozambique

BackgroundThe Community-Level Interventions for Pre-eclampsia (CLIP) trials (NCT01911494) in India, Pakistan and Mozambique (February 2014–2017) involved community engagement and task sharing with community health workers for triage and initial treatment...

Management of Preeclampsia in Low- and Middle-Income Countries: Lessons to Date, and Questions Arising, from the PRE-EMPT and Related Initiatives

Abstract Preeclampsia remains associated with an increased risk of maternal and perinatal morbidity and mortality, and the burden of that excess risk is largely borne by pregnant women and their families in low- and middle-income countries (LMICs). Therefore, the Bill & Melinda Gates Foundation funded the PREeclampsia – Eclampsia Monitoring, Prevention, and Treatment (PRE-EMPT) initiative to accelerate progress. From PRE-EMPT, and related activity, have come a number of impactful findings. First, there is increasing global support for broadening the definition of preeclampsia to include women with hypertension and either significant proteinuria or evidence of target organ damage or fetoplacental compromise (including evidence angiogenic imbalance). Second, using blood pressure (BP) data from the Community-Level Interventions for Preeclampsia trials in India, Mozambique, and Pakistan, acquired on validated-for-pregnancy, semi-automated, low-cost BP devices, there are now population-level, rather than facility-based, estimates for the burden of pregnancy hypertension (sub-categorized into preeclampsia (4%–6%), gestational hypertension (7%–12%), and chronic hypertension (0.3%–0.6%)). Third, there is an identified need to understand biological pathways that underlie the causation of preeclampsia in LMICs. Fourth, the Community-Level Interventions for Preeclampsia trials have shown that providing at least eight antenatal contacts, in this case using digital health-supported community health workers, cost-effectively reduces the burden of maternal (by 60%), fetal (60%), and neonatal (40%) mortality. Fifth, what is the utility and cost-effectiveness of routine proteinuria screening of normotensive pregnant women? Sixth, clinical risk factor-based prediction of preeclampsia remains most relevant for most women in LMICs; calcium replacement (≥1 g/day) and low-dose aspirin (100–175 mg/day) are the most useful directly preventative interventions. However, achieving sustainable development goals (SDGs) not directly related to health are more likely to reduce the global burden of preeclampsia and its consequences. Seventh, should a woman develop preeclampsia, personalized maternal time-of-disease risk estimates are available through the PIERS (Preeclampsia Integrated Estimate of RiSk) models, either with (fullPIERS) or without (miniPIERS) access to laboratory testing. Assessment of perinatal risks in LMICs is largely driven by gestational age; however, evidence of significant angiogenic imbalance may identify risk of intrauterine fetal death. Eighth, Control of Hypertension in Pregnancy Study trial data show that women with non-severe pregnancy hypertension (systolic BP 140–159 mmHg or diastolic BP (dBP) 90–109 mmHg) should receive an antihypertensive medication for a target dBP of 85 mmHg. Ninth, for women with severe pregnancy hypertension (systolic BP ≥160 mmHg or dBP ≥110 mmHg), oral antihypertensive management with either nifedipine, labetalol, or, less so, methyldopa will lower BP into the non-severe hypertension range. Tenth, magnesium sulfate remains the sole agent of choice for preventing and treating eclamptic seizures. Eleventh, corticosteroids should be administered to women at risk of delivery <35+0 weeks’ gestation. Twelfth, although delivery of the placenta initiates resolution of the maternal syndrome of preeclampsia, decisions to initiate delivery should be guided by gestational age and maternal and fetal status. Many women will experience significant postpartum deterioration; delivery should not be equated with “cure”. Thirteenth, whether the development of preeclampsia identifies women at increased risk for early-onset cardiovascular disease in LMICs must be determined.

Prediction models in obstetrics: understanding the treatment paradox and potential solutions to the threat it poses.

Prediction models in obstetrics: understanding the treatment paradox and potential solutions to the threat it poses.

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

BackgroundPre-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.ObjectiveThe aim of this study was to assess the usability of PotM (with mid-level health workers) for iteratively refining the system.MethodsDevelopment 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.ResultsAfter 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).ConclusionsBy 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.

Pre-eclampsia: an update.

Pre-eclampsia remains the second leading direct cause of maternal death, >99 % of which occurs in less developed countries. Over 90 percent of the observed reduction in pre-eclampsia-related maternal deaths in the UK (1952-2008) occurred with antenatal surveillance and timed delivery. In this review, we discuss the pathogenesis, diagnostic criteria, disease prediction models, prevention and management of pre-eclampsia. The Pre-eclampsia Integrated Estimate of RiSk (PIERS) models and markers of angiogenic imbalance identify women at incremental risk for severe pre-eclampsia complications. For women at high risk of developing pre-eclampsia, low doses of aspirin (especially if started <17 weeks) and calcium are evidence-based preventative strategies; heparin is less so. Severe hypertension must be treated and the Control of Hypertension In Pregnancy (CHIPS) Trial (reporting: 2014) will guide non-severe hypertension management. Magnesium sulfate prevents and treats eclampsia; there is insufficient evidence to support alternative regimens. Pre-eclampsia predicts later cardiovascular disease; however, at this time we do not know what to do about it.

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%).

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

ObjectivesTo 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. MethodsWe 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). ResultsOf 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. ConclusionWe 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.

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

ObjectivesPreeclampsia 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. MethodsWe 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. ResultsOf 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. ConclusionMaternal 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

ObjectiveWe 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. MethodsThese 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. ResultsSpO2 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%). ConclusionAssessing 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.

PIERS Proteinuria: Relationship With Adverse Maternal and Perinatal Outcome

ObjectiveTo examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. MethodsWe performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women (“ALL measures”) who had all three proteinuria assessments. ResultsMore women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. ConclusionThe measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.