Abstract

Objectives Plasma levels of adrenomedullin (AM), an anti-inflammatory, vasodilatory peptide hormone, are physiologically elevated during a healthy pregnancy, but it is uncertain whether these levels are altered during complications of pregnancy like preeclampsia. A byproduct of the preprohormone of AM, midregional pro-adrenomedullin (MR-proADM), is produced in a one-to-one ratio with mature AM and can be measured as a surrogate analyte for AM. Therefore, we tested the hypothesis that MR-proADM can serve as a biomarker for preeclampsia. Methods We selected 30 women with preeclampsia and 30 normotensive controls from a prospective study that collected blood and tissue samples as patients presented to Duke University Hospital for delivery. Exclusion criteria were: mild preeclampsia ( n = 5), postpartum plasma collection ( n = 12), twin pregnancies ( n = 3), and smokers ( n = 7). Endoglin, placental growth factor (PlGF), and MR-proADM concentrations were quantified in plasma using a commercial ELISA kit or immunofluorescent assay. Endoglin, PlGF, and MR-proADM were then analyzed as biomarkers of severe preeclampsia by comparing the areas under the curve (AUC) of receiver operating characteristic (ROC) curves generated by logistic regression models of these analytes. Results MR-proADM concentrations were blunted in plasma from women with severe preeclampsia (Matson et al., 2014). In our dataset, endoglin (AUC = 0.73) and MR-proADM (AUC = 0.69) were similarly effective at classifying women with severe preeclampsia and controls, while PlGF was more informative (AUC = 0.85). Endoglin and MR-proADM together (AUC = 0.80) discriminate patients from controls better than they do individually, as do PlGF and MR-proADM together (AUC = 0.87). Conclusions MR-proADM can classify women with severe preeclampsia and controls and may provide a biomarker for severe preeclampsia. However, analysis of MR-proADM levels at earlier gestational ages is needed to determine whether MR-proADM can predict the development of preeclampsia later in pregnancy. Disclosures B. Matson: Research Support Recipient: Ferring Innovation Fellowship. N. Karpinich: None. A. Murtha: None. W. Valdar: None. C.A. Grotegut: None. K.M. Caron: Research Support Recipient; Commercial Interest: Ferring Pharmaceuticals, Inc.

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