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Clinical Chemistry 56: 361-375, 2010. First published December 31, 2009; 10.1373/clinchem.2009.134080
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(Clinical Chemistry. 2010;56:361-375.)
© 2010 American Association for Clinical Chemistry, Inc.

Reviews

Combining Biochemical and Ultrasonographic Markers in Predicting Preeclampsia: A Systematic Review

Yves Giguère1,2, Marc Charland1, Emmanuel Bujold1,3, Nathalie Bernard1, Sonya Grenier1, François Rousseau1,2, Julie Lafond5, France Légaré1,4 and Jean-Claude Forest1,2,a

1 CHUQ Research Center/Hôpital Saint-François d’Assise, Québec City, Québec, Canada; 2 Department of Medical Biology, 3 Department of Obstetrics and Gynecology, and 4 Department of Family Medicine, Faculty of Medicine, Université Laval, Québec City, Québec, Canada; 5 Department of Biological Sciences, BioMed Research Center, UQAM, Montréal, Québec, Canada.

aAddress correspondence to this author at: CHUQ Research Center/Hôpital Saint-François d’Assise, 10, rue de l’Espinay, Québec City, Québec, Canada, G1L 3L5. Fax 418-525-4481; e-mail jean-claude.forest{at}bcx.ulaval.ca.

Background: Early identification of pregnant women at risk for preeclampsia is a priority to implement preventive measures. Some biochemical and ultrasonographic parameters have shown promising predictive performance, but so far there is no clinically validated screening procedure.

Content: Using a series of keywords, we reviewed electronic databases (Medline, Embase, all records to May 2009) reporting the performance of biological and ultrasonographic markers to predict preeclampsia, both single markers and combinations of markers. We analyzed the data according to gestational age and risk levels of the studied populations. We evaluated the methodological quality of included publications using QUADAS (quality assessment of diagnostic accuracy studies). We identified 37 relevant studies that assessed 71 different combinations of biochemical and ultrasonographic markers. Most studies were performed during the second trimester on small-scale high-risk populations with few cases of preeclampsia. Combinations of markers generally led to an increase in sensitivity and/or specificity compared with single markers. In low-risk populations, combinations including placental protein 13 (PP13), pregnancy-associated plasma protein A (PAPP-A), a disintegrin and metalloprotease-12 (ADAM12), activin A, or inhibin A measured in first or early second trimester and uterine artery Doppler in second trimester appear promising (sensitivity 60%–80%, specificity >80%). In high-risk populations, the combination of PP13 and pulsatility index in first trimester showed 90% sensitivity and 90% specificity in a single study limited to severe preeclampsia.

Summary: Combinations of biochemical and ultrasonographic markers improved the performance of early prediction of preeclampsia. From a perspective of integrative medicine, large population-based studies evaluating algorithms combining multiple markers are needed, if screening approaches are to be eventually implemented.