First trimester inflammatory mediators in women with chronic hypertension

Diane Nzelu, Dan Dumitrascu-Biris, Theodoros Karampitsakos, Kypros K Nicolaides, Nikos A Kametas
Acta Obstetricia et Gynecologica Scandinavica 2020 April 1

INTRODUCTION: Chronic hypertension complicates 1-2% of pregnancies and is one of the most significant risk factors for the development of preeclampsia. Inflammatory mediators, such as interleukin-6 (IL-6), tumor necrosis factor-a (TNF-α), vascular cell adhesion molecule (VCAM) and endothelin have been implicated in the endothelial dysfunction that is pathognomonic of preeclampsia and may serve as useful first trimester biomarkers for the prediction of preeclampsia. The objectives of this study are: first, to investigate differences in serum levels of IL-6, TNF-α, VCAM and endothelin at 11+0 to 13+6 weeks' gestation in women with chronic hypertension who developed superimposed preeclampsia to those who did not and normotensive controls, and second, to evaluate the performance of these biomarkers in the prediction of preeclampsia.

MATERIAL AND METHODS: The study population comprised of 650 women with chronic hypertension, including 202 who developed superimposed preeclampsia and 448 who did not, and 142 normotensive controls matched to the chronic hypertension group for storage time and racial origin. Serum concentrations of IL-6, TNF-α, VCAM and endothelin were measured and the values were converted into multiples of the expected median using multivariate regression analysis in the control group. The multiples of the median values of the biomarkers between the two groups of women with chronic hypertension and the controls were compared and Receiver Operating Characteristic Curve (ROC) were used to assess the performance of these variables for the prediction of preeclampsia.

RESULTS: In women with chronic hypertension, compared to the normotensive controls, there was a significantly higher first trimester median concentration of endothelin but not of VCAM, IL-6 and TNF-α. Within the cohort of women with chronic hypertension those who developed superimposed preeclampsia, compared to those who did not, had higher first trimester serum concentration of VCAM but not of endothelin, IL-6 and TNF-α. However, serum VCAM provided poor prediction of superimposed preeclampsia (area under the ROC curve 0.537, 95% CI 0.487-0.587).

CONCLUSIONS: Women with chronic hypertension have increased serum endothelin in the first trimester of pregnancy and those who develop superimposed preeclampsia have higher levels of VCAM. None of the inflammatory mediators performed well in the first trimester in the prediction of preeclampsia.

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