External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis

Abstract Background Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. Methods IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. Results Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model’s calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. Conclusions The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. Trial registration PROSPERO ID: CRD42015029349 .

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PID https://www.doi.org/10.6084/m9.figshare.c.5193872.v1
PID https://www.doi.org/10.6084/m9.figshare.c.5193872
URL http://dx.doi.org/10.6084/m9.figshare.c.5193872.v1
URL http://hdl.handle.net/10138/321182
URL http://dx.doi.org/10.6084/m9.figshare.c.5193872
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Author Snell, Kym I E
Author Allotey, John
Author Smuk, Melanie
Author Hooper, Richard
Author Chan, Claire
Author Ahmed, Asif
Author Chappell, Lucy C
Author Von Dadelszen, Peter
Author Green, Marcus
Author Kenny, Louise
Author Khalil, Asma
Author Khan, Khalid S
Author Mol, Ben W
Author Myers, Jenny
Author Poston, Lucilla
Author Thilaganathan, Basky
Author Staff, Anne C
Author Smith, Gordon C S
Author Ganzevoort, Wessel
Author Laivuori, Hannele
Author Odibo, Anthony O
Author Arenas Ramírez, Javier
Author Kingdom, John
Author Daskalakis, George
Author Farrar, Diane
Author Baschat, Ahmet A
Author Seed, Paul T
Author Prefumo, Federico
Author da Silva Costa, Fabricio
Author Groen, Henk
Author Audibert, Francois
Author Masse, Jacques
Author Skråstad, Ragnhild B
Author Salvesen, Kjell Å
Author Haavaldsen, Camilla
Author Nagata, Chie
Author Rumbold, Alice R
Author Heinonen, Seppo
Author Askie, Lisa M
Author Smits, Luc J M
Author Vinter, Christina A
Author Magnus, Per
Author Eero, Kajantie
Author Villa, Pia M
Author Jenum, Anne K
Author Andersen, Louise B
Author Norman, Jane E
Author Ohkuchi, Akihide
Author Eskild, Anne
Author Bhattacharya, Sohinee
Author McAuliffe, Fionnuala M
Author Galindo, Alberto
Author Herraiz, Ignacio
Author Carbillon, Lionel
Author Klipstein-Grobusch, Kerstin
Author Yeo, Seon A
Author Browne, Joyce L
Author Moons, Karel G M
Author Riley, Richard D
Author Thangaratinam, Shakila
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Collected From HELDA - Digital Repository of the University of Helsinki; Datacite
Hosted By HELDA - Digital Repository of the University of Helsinki; figshare
Publication Date 2020-11-02
Publisher figshare
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Country Finland
Language UNKNOWN
Resource Type Collection; UNKNOWN
keyword FOS: Biological sciences
keyword FOS: Computer and information sciences
keyword FOS: Mathematics
system:type other
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Source https://science-innovation-policy.openaire.eu/search/other?orpId=dedup_wf_001::202acc7ab897488ab39fc1029952c48a
Author jsonws_user
Last Updated 19 December 2020, 13:32 (CET)
Created 19 December 2020, 13:32 (CET)