Meta-Analysis

. 2020 Nov 2;18(1):302.

doi: 10.1186/s12916-020-01766-9.

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

Kym I E Snell¹, John Allotey^{2

3}, Melanie Smuk³, Richard Hooper³, Claire Chan³, Asif Ahmed⁴, Lucy C Chappell⁵, Peter Von Dadelszen⁵, Marcus Green⁶, Louise Kenny⁷, Asma Khalil⁸, Khalid S Khan^{2

3}, Ben W Mol⁹, Jenny Myers¹⁰, Lucilla Poston⁵, Basky Thilaganathan⁸, Anne C Staff¹¹, Gordon C S Smith¹², Wessel Ganzevoort¹³, Hannele Laivuori^{14

15

16}, Anthony O Odibo¹⁷, Javier Arenas Ramírez¹⁸, John Kingdom¹⁹, George Daskalakis²⁰, Diane Farrar²¹, Ahmet A Baschat²², Paul T Seed⁵, Federico Prefumo²³, Fabricio da Silva Costa²⁴, Henk Groen²⁵, Francois Audibert²⁶, Jacques Masse²⁷, Ragnhild B Skråstad^{28

29}, Kjell Å Salvesen^{30

31}, Camilla Haavaldsen³², Chie Nagata³³, Alice R Rumbold³⁴, Seppo Heinonen³⁵, Lisa M Askie³⁶, Luc J M Smits³⁷, Christina A Vinter³⁸, Per Magnus³⁹, Kajantie Eero^{40

41}, Pia M Villa³⁵, Anne K Jenum⁴², Louise B Andersen^{43

44}, Jane E Norman⁴⁵, Akihide Ohkuchi⁴⁶, Anne Eskild^{32

47}, Sohinee Bhattacharya⁴⁸, Fionnuala M McAuliffe⁴⁹, Alberto Galindo⁵⁰, Ignacio Herraiz⁵⁰, Lionel Carbillon⁵¹, Kerstin Klipstein-Grobusch⁵², Seon Ae Yeo⁵³, Joyce L Browne⁵², Karel G M Moons^{52

54}, Richard D Riley⁵⁵, Shakila Thangaratinam⁵⁶; IPPIC Collaborative Network

Collaborators, Affiliations

Collaborators

IPPIC Collaborative Network:
Alex Kwong, Ary I Savitri, Kjell Å Salvesen, Sohinee Bhattacharya, Cuno S P M Uiterwaal, Annetine C Staff, Louise B Andersen, Elisa L Olive, Christopher Redman, George Daskalakis, Maureen Macleod, Baskaran Thilaganathan, Javier Arenas Ramírez, Jacques Massé, Asma Khalil, Francois Audibert, Per M Magnus, Anne K Jenum, Ahmet Baschat, Akihide Ohkuchi, Fionnuala M McAuliffe, Jane West, Lisa M Askie, Fionnuala Mone, Diane Farrar, Peter A Zimmerman, Luc J M Smits, Catherine Riddell, John C Kingdom, Joris van de Post, Sebastián E Illanes, Claudia Holzman, Sander M J van Kuijk, Lionel Carbillon, Pia M Villa, Anne Eskild, Lucy Chappell, Federico Prefumo, Luxmi Velauthar, Paul Seed, Miriam van Oostwaard, Stefan Verlohren, Lucilla Poston, Enrico Ferrazzi, Christina A Vinter, Chie Nagata, Mark Brown, Karlijn C Vollebregt, Satoru Takeda, Josje Langenveld, Mariana Widmer, Shigeru Saito, Camilla Haavaldsen, Guillermo Carroli, Jørn Olsen, Hans Wolf, Nelly Zavaleta, Inge Eisensee, Patrizia Vergani, Pisake Lumbiganon, Maria Makrides, Fabio Facchinetti, Evan Sequeira, Robert Gibson, Sergio Ferrazzani, Tiziana Frusca, Jane E Norman, Ernesto A Figueiró-Filho, Olav Lapaire, Hannele Laivuori, Jacob A Lykke, Agustin Conde-Agudelo, Alberto Galindo, Alfred Mbah, Ana P Betran, Ignacio Herraiz, Lill Trogstad, Gordon G S Smith, Eric A P Steegers, Read Salim, Tianhua Huang, Annemarijne Adank, Jun Zhang, Wendy S Meschino, Joyce L Browne, Rebecca E Allen, Fabricio da Silva Costa, Kerstin Klipstein-Grobusch, Caroline A Crowther, Jan S Jørgensen, Jean-Claude Forest, Alice R Rumbold, Ben W Mol, Yves Giguère, Louise C Kenny, Wessel Ganzevoort, Anthony O Odibo, Jenny Myers, SeonAe Yeo, Francois Goffinet, Lesley McCowan, Eva Pajkrt, Bassam G Haddad, Gustaaf Dekker, Emily C Kleinrouweler, Édouard LeCarpentier, Claire T Roberts, Henk Groen, Ragnhild B Skråstad, Seppo Heinonen, Kajantie Eero

Affiliations

¹ Centre for Prognosis Research, School of Primary, Community and Social Care, Keele University, Keele, UK. k.snell@keele.ac.uk.
² Barts Research Centre for Women's Health (BARC), Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
³ Pragmatic Clinical Trials Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁴ MirZyme Therapeutics, Innovation Birmingham Campus, Birmingham, UK.
⁵ Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.
⁶ Action on Pre-eclampsia (APEC) Charity, Worcestershire, UK.
⁷ Faculty Health & Life Sciences, University of Liverpool, Liverpool, UK.
⁸ Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust and Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
⁹ Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
¹⁰ Maternal and Fetal Health Research Centre, Manchester Academic Health Science Centre, University of Manchester, Central Manchester NHS Trust, Manchester, UK.
¹¹ Division of Obstetrics and Gynaecology, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Oslo, Norway.
¹² Department of Obstetrics and Gynaecology, NIHR Biomedical Research Centre, Cambridge University, Cambridge, UK.
¹³ Department of Obstetrics, Amsterdam UMC University of Amsterdam, Amsterdam, The Netherlands.
¹⁴ Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
¹⁵ Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
¹⁶ Department of Obstetrics and Gynecology, Faculty of Medicine and Health Technology, Tampere University Hospital and Tampere University, Tampere, Finland.
¹⁷ University of South Florida, Tampa, FL, USA.
¹⁸ Department of Obstetrics and Gynaecology, University Hospital de Cabueñes, Gijón, Spain.
¹⁹ Maternal-Fetal Medicine Division, Department OBGYN, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
²⁰ Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Alexandra Hospital, Athens, Greece.
²¹ Bradford Institute for Health Research, Bradford Teaching Hospitals, Bradford, UK.
²² Johns Hopkins Center for Fetal Therapy, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²³ Department of Obstetrics and Gynaecology, University of Brescia, Brescia, Italy.
²⁴ Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
²⁵ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
²⁶ Department of Obstetrics and Gynecology, CHU Ste Justine, Université de Montréal, Montreal, Canada.
²⁷ Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec City, Canada.
²⁸ Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology - NTNU, Trondheim, Norway.
²⁹ Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
³⁰ Department of Obstetrics and Gynecology, Trondheim University Hospital, Trondheim, Norway.
³¹ Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
³² Department of Obstetrics and Gynaecology, Akershus University Hospital, Lørenskog, Norway.
³³ Department of Education for Clinical Research, National Center for Child Health and Development, Tokyo, Japan.
³⁴ South Australian Health and Medical Research Institute and Robinson Research Institute, The University of Adelaide, Adelaide, Australia.
³⁵ Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³⁶ NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
³⁷ Care and Public Health Research Institute, Maastricht University Medical Centre, Maastricht, The Netherlands.
³⁸ Department of Gynecology and Obstetrics, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
³⁹ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
⁴⁰ National Institute for Health and Welfare, Helsinki, Finland.
⁴¹ Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁴² General Practice Research Unit (AFE), Department of General Practice, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁴³ Institute for Clinical Research, University of Southern Denmark, Odense, Denmark.
⁴⁴ Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark.
⁴⁵ MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
⁴⁶ Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Tochigi, Japan.
⁴⁷ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁴⁸ Obstetrics & Gynaecology, Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
⁴⁹ UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland.
⁵⁰ Fetal Medicine Unit, Maternal and Child Health and Development Network (SAMID), Department of Obstetrics and Gynaecology, Hospital Universitario, Instituto de Investigación Hospital, Universidad Complutense de Madrid, Madrid, Spain.
⁵¹ Department of Obstetrics and Gynecology, Assistance Publique-Hôpitaux de Paris Université Paris, Paris, France.
⁵² Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
⁵³ University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵⁴ Cochrane Netherlands, Utrecht, The Netherlands.
⁵⁵ Centre for Prognosis Research, School of Primary, Community and Social Care, Keele University, Keele, UK.
⁵⁶ Institute of Metabolism and Systems Research, WHO Collaborating Centre for Women's Health, University of Birmingham, Birmingham, UK.

PMID: 33131506
PMCID: PMC7604970
DOI: 10.1186/s12916-020-01766-9

Meta-Analysis

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

Kym I E Snell et al. BMC Med. 2020.

. 2020 Nov 2;18(1):302.

doi: 10.1186/s12916-020-01766-9.

Authors

Collaborators

IPPIC Collaborative Network:
Alex Kwong, Ary I Savitri, Kjell Å Salvesen, Sohinee Bhattacharya, Cuno S P M Uiterwaal, Annetine C Staff, Louise B Andersen, Elisa L Olive, Christopher Redman, George Daskalakis, Maureen Macleod, Baskaran Thilaganathan, Javier Arenas Ramírez, Jacques Massé, Asma Khalil, Francois Audibert, Per M Magnus, Anne K Jenum, Ahmet Baschat, Akihide Ohkuchi, Fionnuala M McAuliffe, Jane West, Lisa M Askie, Fionnuala Mone, Diane Farrar, Peter A Zimmerman, Luc J M Smits, Catherine Riddell, John C Kingdom, Joris van de Post, Sebastián E Illanes, Claudia Holzman, Sander M J van Kuijk, Lionel Carbillon, Pia M Villa, Anne Eskild, Lucy Chappell, Federico Prefumo, Luxmi Velauthar, Paul Seed, Miriam van Oostwaard, Stefan Verlohren, Lucilla Poston, Enrico Ferrazzi, Christina A Vinter, Chie Nagata, Mark Brown, Karlijn C Vollebregt, Satoru Takeda, Josje Langenveld, Mariana Widmer, Shigeru Saito, Camilla Haavaldsen, Guillermo Carroli, Jørn Olsen, Hans Wolf, Nelly Zavaleta, Inge Eisensee, Patrizia Vergani, Pisake Lumbiganon, Maria Makrides, Fabio Facchinetti, Evan Sequeira, Robert Gibson, Sergio Ferrazzani, Tiziana Frusca, Jane E Norman, Ernesto A Figueiró-Filho, Olav Lapaire, Hannele Laivuori, Jacob A Lykke, Agustin Conde-Agudelo, Alberto Galindo, Alfred Mbah, Ana P Betran, Ignacio Herraiz, Lill Trogstad, Gordon G S Smith, Eric A P Steegers, Read Salim, Tianhua Huang, Annemarijne Adank, Jun Zhang, Wendy S Meschino, Joyce L Browne, Rebecca E Allen, Fabricio da Silva Costa, Kerstin Klipstein-Grobusch, Caroline A Crowther, Jan S Jørgensen, Jean-Claude Forest, Alice R Rumbold, Ben W Mol, Yves Giguère, Louise C Kenny, Wessel Ganzevoort, Anthony O Odibo, Jenny Myers, SeonAe Yeo, Francois Goffinet, Lesley McCowan, Eva Pajkrt, Bassam G Haddad, Gustaaf Dekker, Emily C Kleinrouweler, Édouard LeCarpentier, Claire T Roberts, Henk Groen, Ragnhild B Skråstad, Seppo Heinonen, Kajantie Eero

Affiliations

¹ Centre for Prognosis Research, School of Primary, Community and Social Care, Keele University, Keele, UK. k.snell@keele.ac.uk.
² Barts Research Centre for Women's Health (BARC), Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
³ Pragmatic Clinical Trials Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁴ MirZyme Therapeutics, Innovation Birmingham Campus, Birmingham, UK.
⁵ Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.
⁶ Action on Pre-eclampsia (APEC) Charity, Worcestershire, UK.
⁷ Faculty Health & Life Sciences, University of Liverpool, Liverpool, UK.
⁸ Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust and Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
⁹ Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
¹⁰ Maternal and Fetal Health Research Centre, Manchester Academic Health Science Centre, University of Manchester, Central Manchester NHS Trust, Manchester, UK.
¹¹ Division of Obstetrics and Gynaecology, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Oslo, Norway.
¹² Department of Obstetrics and Gynaecology, NIHR Biomedical Research Centre, Cambridge University, Cambridge, UK.
¹³ Department of Obstetrics, Amsterdam UMC University of Amsterdam, Amsterdam, The Netherlands.
¹⁴ Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
¹⁵ Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
¹⁶ Department of Obstetrics and Gynecology, Faculty of Medicine and Health Technology, Tampere University Hospital and Tampere University, Tampere, Finland.
¹⁷ University of South Florida, Tampa, FL, USA.
¹⁸ Department of Obstetrics and Gynaecology, University Hospital de Cabueñes, Gijón, Spain.
¹⁹ Maternal-Fetal Medicine Division, Department OBGYN, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
²⁰ Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Alexandra Hospital, Athens, Greece.
²¹ Bradford Institute for Health Research, Bradford Teaching Hospitals, Bradford, UK.
²² Johns Hopkins Center for Fetal Therapy, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²³ Department of Obstetrics and Gynaecology, University of Brescia, Brescia, Italy.
²⁴ Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
²⁵ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
²⁶ Department of Obstetrics and Gynecology, CHU Ste Justine, Université de Montréal, Montreal, Canada.
²⁷ Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec City, Canada.
²⁸ Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology - NTNU, Trondheim, Norway.
²⁹ Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
³⁰ Department of Obstetrics and Gynecology, Trondheim University Hospital, Trondheim, Norway.
³¹ Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
³² Department of Obstetrics and Gynaecology, Akershus University Hospital, Lørenskog, Norway.
³³ Department of Education for Clinical Research, National Center for Child Health and Development, Tokyo, Japan.
³⁴ South Australian Health and Medical Research Institute and Robinson Research Institute, The University of Adelaide, Adelaide, Australia.
³⁵ Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³⁶ NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
³⁷ Care and Public Health Research Institute, Maastricht University Medical Centre, Maastricht, The Netherlands.
³⁸ Department of Gynecology and Obstetrics, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
³⁹ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
⁴⁰ National Institute for Health and Welfare, Helsinki, Finland.
⁴¹ Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁴² General Practice Research Unit (AFE), Department of General Practice, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁴³ Institute for Clinical Research, University of Southern Denmark, Odense, Denmark.
⁴⁴ Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark.
⁴⁵ MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
⁴⁶ Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Tochigi, Japan.
⁴⁷ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁴⁸ Obstetrics & Gynaecology, Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
⁴⁹ UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland.
⁵⁰ Fetal Medicine Unit, Maternal and Child Health and Development Network (SAMID), Department of Obstetrics and Gynaecology, Hospital Universitario, Instituto de Investigación Hospital, Universidad Complutense de Madrid, Madrid, Spain.
⁵¹ Department of Obstetrics and Gynecology, Assistance Publique-Hôpitaux de Paris Université Paris, Paris, France.
⁵² Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
⁵³ University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵⁴ Cochrane Netherlands, Utrecht, The Netherlands.
⁵⁵ Centre for Prognosis Research, School of Primary, Community and Social Care, Keele University, Keele, UK.
⁵⁶ Institute of Metabolism and Systems Research, WHO Collaborating Centre for Women's Health, University of Birmingham, Birmingham, UK.

PMID: 33131506
PMCID: PMC7604970
DOI: 10.1186/s12916-020-01766-9

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 .

Keywords: External validation; Individual participant data; Pre-eclampsia; Prediction model.

PubMed Disclaimer

Conflict of interest statement

The authors disclose support from NIHR HTA for the submitted work. LCC reports being Chair of the HTA CET Committee from January 2019. AK reports being a member of the NIHR HTA board. BWM reports grants from Merck; personal fees from OvsEva, Merck, and Guerbet; and other from NHMRC, Guerbet, and Merch, outside the submitted work. GS reports grants and personal fees from GlaxoSmithKline Research and Development Limited, grants from Sera Prognostics Inc., non-financial support from Illumina Inc., and personal fees and non-financial support from Roche Diagnostics Ltd., outside the submitted work. JK reports personal fees from Roche Canada, outside the submitted work. JM reports grants from National Health Research and Development Program, Health and Welfare Canada, during the conduct of the study. JEN reports grants from Chief Scientist Office Scotland, other from GlaxoSmithKline and Dilafor, outside the submitted work. AG reports personal fees from Roche Diagnostics, outside the submitted work. IH reports personal fees from Roche Diagnostics and Thermo Fisher, outside the submitted work. RR reports personal fees from the BMJ, Roche, and Universities of Leeds, Edinburgh, and Exeter, outside the submitted work.

Figures

**Fig. 1**
Identification of prediction models for validation in IPPIC-UK cohorts

**Fig. 2**
Calibration plots for clinical characteristic and biomarker models predicting any-onset pre-eclampsia (cohorts with ≥ 100 events)

**Fig. 3**
Decision curves for models of any-onset pre-eclampsia

See this image and copyright information in PMC

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

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

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