The usefulness of CYFRA 21-1 to diagnose and predict preeclampsia: a nested case-control study.
The ability to identify patients at risk for developing preeclampsia is important for preventing morbidity and mortality in both the mother and child. Although CYFRA 21-1 (a fragment of Cytokeratin 19) is considered a promising biomarker for diagnosing preeclampsia, little is known regarding the levels of CYFRA 21-1 during pregnancy. Here, we measured serum CYFRA 21-1 levels in women with an uneventful pregnancy and in women whose pregnancy was complicated by preeclampsia. Furthermore we evaluated whether maternal CYFRA 21-1 levels can be used to predict and/or diagnose preeclampsia.



Longitudinal, sequential blood samples were collected prospectively at seven predetermined visits during pregnancy. Maternal CYFRA 21-1 levels were measured in 50 women with an uneventful pregnancy (control group) and in 10 asymptomatic women whose pregnancy was later complicated by preeclampsia (PE_long group). In addition, CYFRA 21-1 levels were measured from a single sample collected from a separate group of 50 pregnant women with symptomatic preeclampsia (PE_state group).



The CYFRA 21-1 levels were significantly higher in the PE_state group compared to the control group (p < 0.001). In the PE_long group, CYFRA 21-1 levels were lower from gestational week 11 through 17, but were higher than the control group from gestational weeks 18 through 36. Out of the ROC curves that were calculated to investigate the predictive and diagnostic properties of CYFRA 21-1 levels for preeclampsia, the ROC curve for diagnosing preeclampsia in gestational week 28-32 showed the largest AUC of 0.92, at a cut-off point of 3.1 ng/ml, leading to sensitivity of 92 % and specificity of 80 %.



The elevated serum levels of CYFRA 21-1 observed in both groups of women with preeclampsia may reflect endothelial damage and/or dysfunction. Our results suggest that maternal serum CYFRA 21-1 is a promising biomarker for diagnosing preeclampsia. Although its value for predicting the long-term occurrence of subsequent preeclampsia may be limited, our findings indicate a trend towards elevated maternal CYFRA 21-1 levels preceding the short-term occurrence of preeclampsia in asymptomatic women. Additional prospective longitudinal studies are needed in order to determine the value of measuring maternal serum CYFRA 21-1 in predicting preeclampsia.
Department of Gynecology and Obstetrics, Medical University of Vienna, Waehringerguertel 18-20, A-1090, Vienna, Austria.
Lorenz
L
Kuessel
Department of Gynecology and Obstetrics, Medical University of Vienna, Waehringerguertel 18-20, A-1090, Vienna, Austria. harald.zeisler@meduniwien.ac.at.
Harald
H
Zeisler
Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
Robin
R
Ristl
Department of Gynecology and Obstetrics, Medical University of Vienna, Waehringerguertel 18-20, A-1090, Vienna, Austria.|Fetal Medicine Unit, St George's Hospital, Blackshaw Road, London, SW17 0QT, UK.
Julia
J
Binder
Department of Gynecology and Obstetrics, Medical University of Vienna, Waehringerguertel 18-20, A-1090, Vienna, Austria.
Petra
P
Pateisky
Department of Gynecology and Obstetrics, Medical University of Vienna, Waehringerguertel 18-20, A-1090, Vienna, Austria.
Maximilian
M
Schmid
Department of Gynecology and Obstetrics, Medical University of Vienna, Waehringerguertel 18-20, A-1090, Vienna, Austria.
Julian
J
Marschalek
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Thomas
T
Perkmann
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Helmuth
H
Haslacher
Department of Gynecology and Obstetrics, Medical University of Vienna, Waehringerguertel 18-20, A-1090, Vienna, Austria.
Heinrich
H
Husslein
D000328:Adult; D000951:Antigens, Neoplasm / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D053539:Keratin-19 / Q000097:blood*; D008137:Longitudinal Studies; D062145:Maternal Serum Screening Tests / Q000379:methods / Q000706:statistics & numerical data*; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011264:Pregnancy Trimesters / Q000097:blood*; D011446:Prospective Studies; D012680:Sensitivity and Specificity
D000951:Antigens, Neoplasm; D015415:Biomarkers; D053539:Keratin-19; C102012:antigen CYFRA21.1
CYFRA 21–1; Cytokeratin-19; Diagnosis; Endothelial dysfunction; Prediction; Preeclampsia