Tang Lee

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.

Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial

To compare pregnancy outcomes, accounting for allocated group, between methyldopa‐treated and labetalol‐treated women in the CHIPS Trial (ISRCTN 71416914) of ‘less tight’ versus ‘tight’ control of pregnancy hypertension.

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%).

The role of platelet counts in the assessment of inpatient women with preeclampsia.

OBJECTIVE Platelet count has been proposed as a screening test for generalized coagulopathy in women with preeclampsia. We performed this study to determine the relationship between platelet counts and the risk of abnormal coagulation and adverse maternal outcomes in women with preeclampsia. METHODS We used data from women in the PIERS (Pre-eclampsia Integrated Estimate of RiSk) database. Abnormal coagulation was defined as either an international normalized ratio result greater than and/or a serum fibrinogen level less than the BC Womens Hospital laboratorys pregnancy-specific normal range. The relationship between platelet counts and adverse maternal outcomes was explored using a logistic regression analysis. The sensitivity, specificity, positive predictive value, and negative predictive value of platelet counts in identifying abnormal coagulation or adverse maternal outcomes were calculated. RESULTS Abnormal coagulation occurred in 105 of 1405 eligible women (7.5%). The odds of having abnormal coagulation were increased for women with platelet counts < 50 × 10(9)/L (OR 7.78; 95% CI 3.36 to 18.03) and between 50 and 99 × 10(9)/L (OR 2.69; 95% CI 1.44 to 5.01) compared with women who had platelet counts above 150 × 10(9)/L. Platelet counts < 100 × 10(9)/L were associated with significantly increased odds of adverse maternal outcomes, most specifically blood transfusion. A platelet count of < 100 × 10(9)/L had good specificity in identifying abnormal coagulation and adverse maternal outcomes (92% [95% CI 91% to 94%] and 92% [95% CI 91% to 94%], respectively), but poor sensitivity (22% [95% CI 15% to 31%] and 16% [95% CI 11% to 23%], respectively). CONCLUSION A platelet count < 100 × 10(9)/L is associated with an increased risk of abnormal coagulation and maternal adverse outcomes in women with preeclampsia. However, the platelet count should not be used in isolation to guide care because of its poor sensitivity. Whether or not a platelet count is normal should not be used to determine whether further coagulation tests are needed.

Prediction of adverse maternal outcomes from pre-eclampsia and other hypertensive disorders of pregnancy: A systematic review

BACKGROUND The hypertensive disorders of pregnancy are a leading cause of maternal and perinatal mortality and morbidity. The ability to predict these complications using simple tests could aid in management and improve outcomes. We aimed to systematically review studies that reported on potential predictors of adverse maternal outcomes among women with a hypertensive disorder of pregnancy. METHODS We searched MEDLINE, Embase and CINAHL (inception - December 2016) for studies of predictors of severe maternal complications among women with a hypertensive disorder of pregnancy. Studies were selected in a two-stage process by two independent reviewers, excluding those reporting only on adverse fetal outcomes. We extracted data on study and test(s) characteristics and outcomes. Accuracy of prediction was assessed using sensitivity, specificity, likelihood ratios and area under the receiver operating curve (AUROC). Strong evidence of prediction was taken to be a positive likelihood ratio >10 or a negative likelihood ratio <0.1, and for multivariable models, an AUROC ≥0.70. Bivariate random effects models were used to summarise performance when possible. RESULTS Of 32 studies included, 28 presented only model development and four examined external validation. Tests included symptoms and signs, laboratory tests and biomarkers. No single test was a strong independent predictor of outcome. The most promising prediction was with multivariable models, especially when oxygen saturation, or chest pain/dyspnea were included. CONCLUSION Future studies should investigate combinations of tests in multivariable models (rather than single predictors) to improve identification of women at high risk of adverse outcomes in the setting of the hypertensive disorders of pregnancy.

Maternal and Newborn Health in Karnataka State, India: The Community Level Interventions for Pre-Eclampsia (CLIP) Trial's Baseline Study Results.

Existing vital health statistics registries in India have been unable to provide reliable estimates of maternal and newborn mortality and morbidity, and region-specific health estimates are essential to the planning and monitoring of health interventions. This study was designed to assess baseline rates as the precursor to a community-based cluster randomized control trial (cRCT)–Community Level Interventions for Pre-eclampsia (CLIP) Trial (NCT01911494; CTRI/2014/01/004352). The objective was to describe baseline demographics and health outcomes prior to initiation of the CLIP trial and to improve knowledge of population-level health, in particular of maternal and neonatal outcomes related to hypertensive disorders of pregnancy, in northern districts the state of Karnataka, India. The prospective population-based survey was conducted in eight clusters in Belgaum and Bagalkot districts in Karnataka State from 2013–2014. Data collection was undertaken by adapting the Maternal and Newborn Health registry platform, developed by the Global Network for Women’s and Child Health Studies. Descriptive statistics were completed using SAS and R. During the period of 2013–2014, prospective data was collected on 5,469 pregnant women with an average age of 23.2 (+/-3.3) years. Delivery outcomes were collected from 5,448 completed pregnancies. A majority of the women reported institutional deliveries (96.0%), largely attended by skilled birth attendants. The maternal mortality ratio of 103 (per 100,000 livebirths) was observed during this study, neonatal mortality ratio was 25 per 1,000 livebirths, and perinatal mortality ratio was 50 per 1,000 livebirths. Despite a high number of institutional deliveries, rates of stillbirth were 2.86%. Early enrollment and close follow-up and monitoring procedures established by the Maternal and Newborn Health registry allowed for negligible lost to follow-up. This population-level study provides regional rates of maternal and newborn health in Belgaum and Bagalkot in Karnataka over 2013–14. The mortality ratios and morbidity information can be used in planning interventions and monitoring indicators of effectiveness to inform policy and practice. Comprehensive regional epidemiologic data, such as that provided here, is essential to gauge improvements and challenges in maternal health, as well as track disparities found in rural areas.

External Validation of the fullPIERS Model for Predicting Adverse Maternal Outcomes in Pregnancy Hypertension in Low- and Middle-Income CountriesNovelty and Significance

The hypertensive disorders of pregnancy are leading causes of maternal mortality and morbidity, especially in low- and middle-income countries. Early identification of women with preeclampsia and other hypertensive disorders of pregnancy at high risk of complications will aid in reducing this health burden. The fullPIERS model (Preeclampsia Integrated Estimate of Risk) was developed for predicting adverse maternal outcomes from preeclampsia using data from tertiary centers in high-income countries and uses maternal demographics, signs, symptoms, and laboratory tests as predictors. We aimed to assess the validity of the fullPIERS model in women with the hypertensive disorders of pregnancy in low-resourced hospital settings. Using miniPIERS data collected on women admitted with hypertensive disorders of pregnancy between July 2008 and March 2012 in 7 hospitals in 5 low- and middle-income countries, the predicted probability of developing an adverse maternal outcome was calculated for each woman using the fullPIERS equation. Missing predictor values were imputed using multivariate imputation by chained equations. The performance of the model was evaluated for discrimination, calibration, and stratification capacity. Among 757 women with complete predictor data (complete-case analyses), the fullPIERS model had a good area under the receiver-operating characteristic curve of 0.77 (95% confidence interval, 0.72–0.82) with poor calibration (P<0·001 for the Hosmer–Lemeshow goodness-of-fit test). Performance as a rule-in tool was moderate (likelihood ratio: 5.9; 95% confidence interval, 4.23–8.35) for women with ≥30% predicted probability of an adverse outcome. The fullPIERS model may be used in low-resourced setting hospitals to identify women with hypertensive disorders of pregnancy at high risk of adverse maternal outcomes in need of immediate interventions.

Temporal and External Validation of the fullPIERS Model for the Prediction of Adverse Maternal Outcomes in Women with Pre-eclampsia

The fullPIERS model is a risk prediction model developed to predict adverse maternal outcomes within 48 h for women admitted with pre-eclampsia. External validation of the model is required before implementation for clinical use. We assessed the temporal and external validity of the fullPIERS model in high income settings using five cohorts collected between 2003 and 2016, from tertiary hospitals in Canada, the United States of America, Finland and the United Kingdom. The cohorts were grouped into three datasets for assessing the primary external, and temporal validity, and broader transportability of the model. The predicted risks of developing an adverse maternal outcome were calculated using the model equation and model performance was evaluated based on discrimination, calibration, and stratification. Our study included a total of 2429 women, with an adverse maternal outcome rate of 6.7%, 6.6%, and 7.0% in the primary external, temporal, and combined (broader) validation cohorts, respectively. The model had good discrimination in all datasets: 0.81 (95%CI 0.75-0.86), 0.82 (95%CI 0.76-0.87), and 0.75 (95%CI 0.71-0.80) for the primary external, temporal, and broader validation datasets, respectively. Calibration was best for the temporal cohort but poor in the broader validation dataset. The likelihood ratios estimated to rule in adverse maternal outcomes were high at a cut-off of ≥30% in all datasets. The fullPIERS model is temporally and externally valid and will be useful in the management of women with pre-eclampsia in high income settings although model recalibration is required to improve performance, specifically in the broader healthcare settings.