title: Proteomic profiling of the amniotic fluid to detect inflammation, infection, and neonatal sepsis.
abstract: BACKGROUND
  Proteomic analysis of amniotic fluid shows the presence of biomarkers characteristic of intrauterine inflammation. We sought to validate prospectively the clinical utility of one such proteomic profile, the Mass Restricted (MR) score.
  
  
  RESULTS
  We enrolled 169 consecutive women with singleton pregnancies admitted with preterm labor or preterm premature rupture of membranes. All women had a clinically indicated amniocentesis to rule out intra-amniotic infection. A proteomic fingerprint (MR score) was generated from fresh samples of amniotic fluid using surface-enhanced laser desorption ionization (SELDI) mass spectrometry. Presence or absence of the biomarkers of the MR score was interpreted in relationship to the amniocentesis-to-delivery interval, placental inflammation, and early-onset neonatal sepsis for all neonates admitted to the Newborn Special Care Unit (n = 104). Women with "severe" amniotic fluid inflammation (MR score of 3 or 4) had shorter amniocentesis-to-delivery intervals than women with "no" (MR score of 0) inflammation or even "minimal" (MR score of 1 or 2) inflammation (median [range] MR 3-4: 0.4 d [0.0-49.6 d] versus MR 1-2: 3.8 d [0.0-151.2 d] versus MR 0: 17.0 d [0.1-94.3 d], p < 0.001). Nonetheless, a "minimal" degree of inflammation was also associated with preterm birth regardless of membrane status. There was a significant association between the MR score and severity of histological chorioamnionitis (r = 0.599, p < 0.001). Furthermore, neonatal hematological indices and early-onset sepsis significantly correlated with the MR score even after adjusting for gestational age at birth (OR for MR 3-4: 3.3 [95% CI, 1.1 to 9.2], p = 0.03). When compared with other laboratory tests routinely used to diagnose amniotic fluid inflammation and infection, the MR score had the highest accuracy to detect inflammation (white blood cell count > 100 cells/mm3), whereas the combination of Gram stain and MR score was best for rapid prediction of intra-amniotic infection (positive amniotic fluid culture).
  
  
  CONCLUSIONS
  High MR scores are associated with preterm delivery, histological chorioamnionitis, and early-onset neonatal sepsis. In this study, proteomic analysis of amniotic fluid was shown to be the most accurate test for diagnosis of intra-amniotic inflammation, whereas addition of the MR score to the Gram stain provides the best combination of tests to rapidly predict infection.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Science, Yale University School of Medicine, New Haven, Connecticut, United States of America. catalin.buhimschi@yale.edu
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Hamar
authors.forename: Mert-Ozan
authors.initials: MO
authors.lastname: Bahtiyar
authors.forename: Guomao
authors.initials: G
authors.lastname: Zhao
authors.forename: Anna K
authors.initials: AK
authors.lastname: Sfakianaki
authors.forename: Christian M
authors.initials: CM
authors.lastname: Pettker
authors.forename: Lissa
authors.initials: L
authors.lastname: Magloire
authors.forename: Edmund
authors.initials: E
authors.lastname: Funai
authors.forename: Errol R
authors.initials: ER
authors.lastname: Norwitz
authors.forename: Michael
authors.initials: M
authors.lastname: Paidas
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Copel
authors.forename: Carl P
authors.initials: CP
authors.lastname: Weiner
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
mesh_terms: D000293:Adolescent; D000328:Adult; D000649:Amniocentesis / Q000379:methods; D000653:Amniotic Fluid / Q000737:chemistry*; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism*; D008875:Middle Aged; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis / Q000378:metabolism* / Q000382:microbiology; D011256:Pregnancy Outcome; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000175:diagnosis / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D020543:Proteome