title: Serum and urine inhibin A but not free activin A are endocrine biomarkers of severe pre-eclampsia.
abstract: OBJECTIVE
  Elevation of total serum inhibin A and activin A has been interpreted as evidence of placental dysfunction in women who develop pre-eclampsia. We sought to evaluate serum and urine levels of inhibin A and free activin A in normal and hypertensive pregnancies.
  
  
  METHODS
  Inhibin A and free activin A were measured by immunoassay in simultaneously collected serum and urine samples from 75 women: (1) severe pre-eclampsia (n = 30); (2) mild pre-eclampsia (n = 11); (3) chronic hypertension (n = 9); (4) pregnant control women (n = 16); and (5) nonpregnant control women (n = 9). Urine levels were normalized to milligrams urine creatinine, and fractional excretions were calculated.
  
  
  RESULTS
  Serum and urine inhibin A were increased and fractional excretion was decreased in pregnancy. Serum, urine, and fractional excretion of inhibin A were increased in severe pre-eclampsia, compared with other gravidas. The only difference observed in free activin A was a decrease in serum free activin A in chronic hypertension, compared with severe pre-eclampsia and pregnant control women. Urine inhibin A showed the greatest discrimination between severe pre-eclampsia and pregnant control women: a cut-off of 45 pg/mg urine creatinine had 96.8% sensitivity, 87.5% specificity, and 93.6% accuracy. Women with urine inhibin A greater than 90 pg/mg urine creatinine had a 17-fold relative risk (95% confidence interval 9.7-459.5) of a clinically indicated delivery due to pre-eclampsia.
  
  
  CONCLUSIONS
  Serum and urine levels of inhibin A are altered in severe pre-eclampsia. Urine inhibin A may have application in the diagnosis and management of pre-eclampsia. Those with chronic hypertension have lower serum but not urine free activin A levels, compared with severe pre-eclampsia and mild pre-eclampsia.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA. ben.hamar@yale.edu
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Hamar
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
authors.forename: Anna K
authors.initials: AK
authors.lastname: Sfakianaki
authors.forename: Christian M
authors.initials: CM
authors.lastname: Pettker
authors.forename: Lissa K
authors.initials: LK
authors.lastname: Magloire
authors.forename: Edmund F
authors.initials: EF
authors.lastname: Funai
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Copel
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
mesh_terms: D028341:Activins / Q000097:blood* / Q000652:urine*; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000652:urine; D007118:Immunoassay; D007265:Inhibins / Q000097:blood* / Q000652:urine*; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology* / Q000652:urine; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood / Q000652:urine; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C422405:activin A; C094377:inhibin-alpha subunit; D028341:Activins; D007265:Inhibins; D003404:Creatinine