Midregional pro-adrenomedullin plasma concentrations are blunted in severe preeclampsia

Abstract

Levels of the peptide hormone adrenomedullin (AM) are elevated during normal pregnancy, but whether this differs during complications of pregnancy remains unresolved. AM can be quantified by measuring its pre-prohormone byproduct, midregional pro-adrenomedullin (MR-proADM). MR-proADM has shown prognostic value as a biomarker of heart failure, sepsis, and community-acquired pneumonia. Given the relevance of AM to pregnancy, we tested the hypothesis that MR-proADM provides a biomarker for preeclampsia. We find that MR-proADM plasma concentrations are blunted in severe preeclampsia and that MR-proADM is similarly effective as established biomarkers endoglin and placental growth factor at discriminating patients with severe preeclampsia from controls.

Keywords: Adrenomedullin; Midregional pro-adrenomedullin; Preeclampsia; Pregnancy.

Figure 1

(A) Patients excluded from the original 60 patient cohort and (B-D) plasma concentrations of (B) endoglin, (C) placental growth factor (PlGF), and (D) MR-proADM measured by ELISA (A, B) or sandwich immunoassay (C) in controls and women with severe preeclampsia (PE). Boxes extend from the 25^th to the 75^th percentile. Whiskers extend 1.5 times the interquartile range below and above the 25^th and 75^th percentiles, respectively. Horizontal lines dividing the boxes identify the median of each group. Significant outliers, determined by Grubbs' test, are identified by a solid black dot and excluded from the analysis in this figure. Four plasma samples were too concentrated to be detected within the range of the endoglin ELISA standard curve; one of these samples belonged to the control group, while the other three belonged to the PE group. Likewise, four plasma samples were too dilute to be detected within the range of the PlGF ELISA standard curve; all four of these samples belonged to the PE group. These too-concentrated or too-dilute samples were excluded from analysis. Groups were compared by Student's t-test. *p=0.046 (A) and 0.007 (B), and 0.041 (C). PP, postpartum.

Figure 2

ROC curves for five logistic regression models of current severe preeclampsia based on biomarker concentrations. Plus signs separate covariates. Samples that fell above (endoglin, n=4) or below (PlGF, n=5) the ELISA standard curve were equated with the upper and lower bounds, respectively, of the standard curve. ENG, endoglin.