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Ultra-high sensitive C-reactive protein during normal pregnancy and in preeclampsia

a pilot study

Raio, Luigia; Bersinger, Nick A.a; Malek, Antoinea; Schneider, Henninga; Messerli, Franz H.b; Hürter, Hannaa; Rimoldi, Stefano F.b; Baumann, Marc U.a

doi: 10.1097/HJH.0000000000002003

Introduction: Angiogenic and inflammatory factors have been shown to play an important role in the pathogenesis of preeclampsia. However, there is little information on their interaction. The aims of this study were to investigate the longitudinal pattern of inflammatory markers, such as interleukin-6 (IL-6) and C-reactive protein (CRP) using a novel ultra-high sensitive assay method (uhsCRP), and to explore their relationship with angiogenic factors such as placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and vascular endothelial growth factor (VEGF) in normal pregnancies and pregnancies complicated by preeclampsia.

Materials and methods: Serum levels of uhsCRP, IL-6, PLGF, VEGF and s-Flt-1 were longitudinally determined in 16 women with normal, singleton healthy pregnancies at 7–13, 17–22, 27–31 and 37–41 weeks of gestation by ELISA. uhsCRP was measured using a ultra-high sensitivity ELISA test. Serum of women with preeclampsia (n = 15) was available only once, usually in the third trimester of pregnancy. Women with premature rupture of membranes (PROM) or infection such as chorioamnionitis were excluded. Spearman rank correlation, logistic regression, ROC analysis, ANOVA and Mann–Whitney U-test were used for statistical purposes.

Results: In normal pregnancies, serum uhsCRP showed a gestational age-dependent increase (r = 0.40; P < 0.001). In women suffering from preeclampsia, uhsCRP levels were higher than in gestational age-matched controls (18010 ± 4763 versus 3026 ± 587 ng/ml; P < 0.001). Similarly, serum IL-6 levels increased throughout pregnancy and correlated with uhsCRP in normal pregnancies and in preeclampsia (n = 64, r = 0.37; P < 0.01 and n = 15, r = 1.00, P < 0.0001). uhsCRP levels were positively correlated with sFlt-1 levels (n = 64, r = 0.34; P < 0.01).

Conclusion: The increases in uhsCRP (and IL-6) serum levels with advancing gestation indicate a shift towards an inflammatory state during normal pregnancy. The excessive rise in uhsCRP and sFlt-1 in preeclampsia indicate that both may be involved in its pathogenesis. uhsCRP may be useful as an early marker for preeclampsia and studies defining the pattern of its rise throughout pregnancies at risk are urgently needed.

aDepartment of Obstetrics and Gynaecology

bDepartment of Cardiology Inselspital, Berne University Hospital, University of Berne, Berne, Switzerland

Correspondence to Luigi Raio, MD, Department of Obstetrics and Gynaecology, Berne University Hospital, University of Berne, Friedbühlstrasse 19, CH-3010, Berne, Switzerland. Tel: +41 031 632 1010; fax: +41 031 632 1227; e-mail:

Abbreviations: ANOVA, analysis of variance; AUC, area under the curve; CRP, C-reactive protein; CVD, cardiovascular diseases; hsCRP, high-sensitivity CRP; IL-6, interleukin-6; IL-8, interleukin-8; NS, not significant; PLGF, placental growth factor; PROM, premature rupture of membranes; ROC analysis, receiver-operating characteristic curve analysis; SD, standard deviation; sFlt-1, soluble fms-like tyrosine kinase-1; SGA, small for gestational age; TMB, 3,3′,5,5′-Tetramethylbenzidine; TNF-α, tumour necrosis factor-alpha; uhsCRP, ultra-high sensitive C-reactive protein; VEGF, vascular endothelial growth factor

Received 2 January, 2018

Accepted 27 October, 2018

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