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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: An individual participant data meta-analysis
Health Technology Assessment, Volume 24, No. 72, Year 2020
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Description
Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. Objectives: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. Design: This was an individual participant data meta-analysis of cohort studies. Setting: Source data from secondary and tertiary care. Predictors: We identified predictors from systematic reviews, and prioritised for importance in an international survey. Primary outcomes: Early-onset (delivery at < 34 weeks’ gestation), late-onset (delivery at ≥ 34 weeks’ gestation) and any-onset pre-eclampsia. Analysis: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration.We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C-statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I2 and 2. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals. Results: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C-statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia. Limitations: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data. Conclusion: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. © 2020, NIHR Journals Library. All rights reserved.
Authors & Co-Authors
Allotey, John
United Kingdom, London
Queen Mary University of London
Snell, Kym I.E.
United Kingdom, Keele
Keele University
Smuk, Melanie
United Kingdom, London
Queen Mary University of London
Hooper, Richard L.
United Kingdom, London
Queen Mary University of London
Chan, Claire Louise
United Kingdom, London
Queen Mary University of London
Ahmed, Asif S.
United Kingdom, Birmingham
Aston University
Chappell, Lucy C.
United Kingdom, London
King's College London
von Dadelszen, Peter
United Kingdom, London
King's College London
Dodds, Julie P.
United Kingdom, London
Queen Mary University of London
Green, Marcus E.
United Kingdom, Evesham
Action on Pre-eclampsia
Kenny, Louise C.
United Kingdom, Liverpool
University of Liverpool
Khalil, Asma A.
United Kingdom, London
St George’s, University of London
Khan, Khalid S.
United Kingdom, London
Queen Mary University of London
Mol, Ben Willem
Australia, Clayton
Monash Medical Centre
Myers, Jenny E.
United Kingdom, Manchester
Health Innovation Manchester
Poston, Lucilla
United Kingdom, London
King's College London
Thilaganathan, Basky
United Kingdom, London
St George’s, University of London
Staff, Anne Cathrine
Norway, Oslo
Oslo Universitetssykehus
Norway, Oslo
Universitetet I Oslo
Smith, Gordon C.S.
United Kingdom, Cambridge
University of Cambridge
Ganzevoort, Wessel J.
Netherlands, Amsterdam
Universiteit Van Amsterdam
Laivuori, Hannele M.
Finland, Helsinki
Helsinki University Hospital
Finland, Helsinki
Helsingin Yliopisto
Finland, Tampere
University Hospital of Tampere
Finland, Tampere
Tampere University
Kingdom, John C.P.
Canada, Toronto
Mount Sinai Hospital of University of Toronto
Baschat, Ahmet Alexander
United States, Baltimore
Johns Hopkins University
Seed, Paul T.
United Kingdom, London
King's College London
Prefumo, Federico
Italy, Brescia
Università Degli Studi Di Brescia
Da Silva Costa, Fabricio
Brazil, Sao Paulo
Universidade de São Paulo
Groen, Henk A.
Netherlands, Groningen
Rijksuniversiteit Groningen
Audibert, François
Canada, Montreal
University of Montreal
Salvesen, Kjell Åsmund Blix
Norway, Trondheim
Norges Teknisk-naturvitenskapelige Universitet
Norway, Trondheim
Universitetssykehuset I Trondheim
Haavaldsen, Camilla
Norway, Lorenskog
Akershus University Hospital
Nagata, Chie
Japan, Tokyo
National Center for Child Health and Development
Askie, Lisa Maree
Australia, Sydney
The University of Sydney
Smits, Luc J.M.
Netherlands, Maastricht
Universiteit Maastricht
Vinter, Christina Anne
Denmark, Odense
Syddansk Universitet
Magnus, Per Minor
Norway, Oslo
Folkehelseinstituttet
Villa, Pia M.
Finland, Helsinki
Helsinki University Hospital
Norman, J. E.
United Kingdom, Edinburgh
Mrc Centre for Reproductive Health
Ohkuchi, Akihide
Japan, Kawachi District
Jichi Medical University
Bhattacharya, Sohinee
United Kingdom, Aberdeen
University of Aberdeen
McAuliffe, Fionnuala M.
Ireland, Dublin
University College Dublin
Carbillon, Lionel
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Klipstein-Grobusch, Kerstin
Netherlands, Utrecht
Universiteit Utrecht
Yeo, Seonae
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Teede, Helena J.
Australia, Clayton
Monash Health
Browne, Joyce Linda
Netherlands, Utrecht
Universiteit Utrecht
Moons, Karel G.M.
Netherlands, Utrecht
Universiteit Utrecht
Riley, Richard David
United Kingdom, Keele
Keele University
Thangaratinam, Shakila
United Kingdom, London
Queen Mary University of London
Statistics
Citations: 16
Authors: 48
Affiliations: 49
Identifiers
Doi:
10.3310/HTA24720
ISSN:
13665278
Research Areas
Genetics And Genomics
Maternal And Child Health
Noncommunicable Diseases
Sexual And Reproductive Health
Study Design
Cross Sectional Study
Cohort Study
Study Approach
Quantitative
Systematic review
Participants Gender
Female