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Is preeclampsia all in the head? First‐trimester prediction of preeclampsia via maternal plasma levels of the vasopressin pro‐segment copeptin (860.20)
Author(s) -
Santillan Mark,
Santillan Donna,
Scroggins Sabrina,
Min James,
Leslie Kimberly,
Hunter Stephen,
Zamba Gideon,
GibsonCorley Katherine,
Grobe Justin
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.860.20
Subject(s) - copeptin , preeclampsia , medicine , pregnancy , vasopressin , endocrinology , gestation , obstetrics , biology , genetics
Background: Preeclampsia, a devastating gestational hypertensive disorder, is characterized by low circulating renin relative to normal pregnancies. Vasopressin plays an important role in selected low‐renin hypertensive states. Therefore, we hypothesized a role for vasopressin in preeclampsia. Methods: Copeptin, a biologically inert, 4 kDa pro‐segment of vasopressin with a stable and slow plasma elimination rate, is secreted in a 1:1 molar ratio with vasopressin. In this case‐control study, copeptin was measured in banked maternal plasma throughout pregnancy from women who did or did not develop preeclampsia. Results: Maternal plasma copeptin was significantly elevated in all trimesters in pregnancies that did (n=51) or did not (n=30) develop preeclampsia (first trimester: 903 vs. 2045 pg/mL, p=0.008; second trimester: 706 vs. 1806, p=0.02; third trimester: 822 vs. 1890, p=0.0006). While controlling for covariates such as age, BMI, chronic hypertension, twin gestation, diabetes, and history of preeclampsia, the association of elevated copeptin and the development of preeclampsia remained significant. ROC analyses reveal that copeptin is significantly predictive of the development of preeclampsia in all trimesters. Further, vasopressin infusion was sufficient to generate preeclampsia phenotypes in pregnant C57Bl/6J mice. Conclusions: These data establish copeptin as a potent predictor of preeclampsia throughout pregnancy, as early as the first trimester (AUC=0.80, p=0.005, at a cutoff of 1018 pg/mL). The temporal order of changes in copeptin (in early first‐trimester) versus other known mechanisms of preeclampsia (mid‐ or late‐pregnancy) supports our working hypothesis that vasopressin secretion may precipitate or induce other known humoral, vascular, immune, and morphological mechanisms of preeclampsia. Grant Funding Source : HD000849, RR024980, HL098276, HL084207