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Evaluation of 7 Serum Biomarkers and Uterine Artery Doppler Ultrasound for First-Trimester Prediction of Preeclampsia: A Systematic Review

Kuc, Sylwia MD, MSc*; Wortelboer, Esther J. MD, PhD*; van Rijn, Bas B. MD, PhD*†; Franx, Arie MD, PhD; Visser, Gerard H. A. MD, PhD; Schielen, Peter C. J. I. PhD§

Obstetrical & Gynecological Survey: April 2011 - Volume 66 - Issue 4 - p 225-239
doi: 10.1097/OGX.0b013e3182227027

Preeclampsia (PE) affects 1% to 2% of pregnant women and is a leading cause of maternal and perinatal morbidity and mortality worldwide. The clinical syndrome of PE arises in the second half of pregnancy. However, many underlying factors including defective placentation may already be apparent in the first and early second trimester in many patients. In clinical practice, there is currently no reliable screening method in the first trimester of pregnancy with sufficient accuracy to identify women at high risk to develop PE. Early identification of high-risk pregnancy may facilitate the development of new strategies for antenatal surveillance or prevention and thus improve maternal and perinatal outcome. The aim of this systematic review was to study the literature on the predictive potential of first-trimester serum markers and of uterine artery Doppler velocity waveform assessment (Ut-A Doppler). Literature on the 7 most studied serum markers (ADAM12, fβ-hCG, Inhibin A, Activin A, PP13, PlGF, and PAPP-A) and Ut-A Doppler was primarily selected. In the selected literature, a combination of these markers was analyzed, and where relevant, the value of maternal characteristics was added. Measurements of serum markers and Ut-A Doppler were performed between week 8 + 0 and 14 + 0 GA. Low levels of PP13, PlGF, and PAPP-A and elevated level of Inhibin A have been found to be significantly associated with the development of PE later in pregnancy. The detection rates of single markers, fixed at 10% false-positive rate, in the prediction of early-onset PE were relatively low, and ranged from 22% to 83%. Detection rates for combinations of multiple markers varied between 38% and 100%. Therefore, a combination of multiple markers yields high detection rates and is promising to identify patients at high risk of developing PE. However, large scale prospective studies are required to evaluate the power of this integrated approach in clinical practice.

Target Audience: Obstetricians and Gynecologists, Family physicians

Learning Objectives: After completion of this article, the reader should be better able to appraise the recent literature on the development of preeclampsia in the first-trimester, evaluate the predictive value of first-trimester markers and use first-trimester markers, either individually or in combination, to assess the risk of preeclampsia.

*Clinical Researcher, Department of Obstetrics, University Medical Center, Utrecht, The Netherlands; †Clinical Researcher, ‡Professor, Department of Obstetrics and Gynecology, St Antonius Hospital, Nieuwegein, The Netherlands, and §Project Leader, Laboratory for Infectious Diseases and Screening, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands

Chief Editor's Note: This article is part of a series of continuing education activities in this Journal through which a total of 36 AMA/PRA Category 1 Credits™ can be earned in 2009. Instructions for how CME credits can be earned appear on the last page of the Table of Contents.

All authors and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations pertaining to this educational activity.

S.K. and E.J.W. contributed equally.

Correspondence requests to: Sylwia Kuc, MD, MSc, Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, KE.04.123.1, PO Box 85090, 3508 AB Utrecht, The Netherlands. E-mail:

© 2011 by Lippincott Williams & Wilkins.