Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis

Pre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in...

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Main Authors: Pensée Wu, Caroline van den Berg, Zarko Alfirevic, Shaughn O’Brien, Maria Röthlisberger, Philip Newton Baker, Louise C. Kenny, Karolina Kublickiene, Johannes J. Duvekot
Format: Article
Language:English
Published: MDPI AG 2015-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:http://www.mdpi.com/1422-0067/16/9/23035
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author Pensée Wu
Caroline van den Berg
Zarko Alfirevic
Shaughn O’Brien
Maria Röthlisberger
Philip Newton Baker
Louise C. Kenny
Karolina Kublickiene
Johannes J. Duvekot
author_facet Pensée Wu
Caroline van den Berg
Zarko Alfirevic
Shaughn O’Brien
Maria Röthlisberger
Philip Newton Baker
Louise C. Kenny
Karolina Kublickiene
Johannes J. Duvekot
author_sort Pensée Wu
collection DOAJ
description Pre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12), inhibin-A, pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and placental protein 13 (PP-13). The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39–0.41) at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.786 (SE 0.02). When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03). In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s) can be identified in order to improve the management of women destined to develop PE.
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spelling doaj.art-1ac467a258f643f2a98d73694c6251b52022-12-22T03:00:54ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-09-01169230352305610.3390/ijms160923035ijms160923035Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-AnalysisPensée Wu0Caroline van den Berg1Zarko Alfirevic2Shaughn O’Brien3Maria Röthlisberger4Philip Newton Baker5Louise C. Kenny6Karolina Kublickiene7Johannes J. Duvekot8Institute for Science and Technology in Medicine-Keele University, Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, UKDepartment of Obstetrics and Gynecology, Subdivision of Obstetrics and Prenatal Medicine, Erasmus MC-University Medical Centre, PO Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Women’s and Children’s Health, The University of Liverpool, Liverpool L8 7SS, UKInstitute for Science and Technology in Medicine-Keele University, Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, UKDepartment of Obstetrics and Gynecology, University Hospital of Cologne, 50931 Cologne, GermanyCollege of Medicine, Biological Sciences and Psychology, University of Leicester, PO Box 138, Leicester LE1 9HN, UKDepartment of Obstetrics and Gynaecology, Cork University Maternity Hospital (5th Floor), Cork University Hospital, Wilton, Cork T12 YE02, IrelandKarolinska Institutet, Centre for Gender Medicine, Institutions of Medicine and Clinical Science, Intervention and Technology, Department Ob/Gyn, Karolinska University Hospital, 14186 Stockholm, SwedenAcademic Unit of Obstetrics and Gynaecology, Royal Stoke University Hospital, Maternity Centre, Newcastle Road, Hartshill, Stoke-on-Trent ST4 6QG, UKPre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12), inhibin-A, pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and placental protein 13 (PP-13). The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39–0.41) at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.786 (SE 0.02). When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03). In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s) can be identified in order to improve the management of women destined to develop PE.http://www.mdpi.com/1422-0067/16/9/23035pre-eclampsiaearly pregnancy biomarkersmeta-analysis
spellingShingle Pensée Wu
Caroline van den Berg
Zarko Alfirevic
Shaughn O’Brien
Maria Röthlisberger
Philip Newton Baker
Louise C. Kenny
Karolina Kublickiene
Johannes J. Duvekot
Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis
International Journal of Molecular Sciences
pre-eclampsia
early pregnancy biomarkers
meta-analysis
title Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis
title_full Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis
title_fullStr Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis
title_full_unstemmed Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis
title_short Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis
title_sort early pregnancy biomarkers in pre eclampsia a systematic review and meta analysis
topic pre-eclampsia
early pregnancy biomarkers
meta-analysis
url http://www.mdpi.com/1422-0067/16/9/23035
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