Research Article: Proteomic Profiling of the Amniotic Fluid to Detect Inflammation, Infection, and Neonatal Sepsis

Date Published: January 16, 2007

Publisher: Public Library of Science

Author(s): Catalin S Buhimschi, Vineet Bhandari, Benjamin D Hamar, Mert-Ozan Bahtiyar, Guomao Zhao, Anna K Sfakianaki, Christian M Pettker, Lissa Magloire, Edmund Funai, Errol R Norwitz, Michael Paidas, Joshua A Copel, Carl P Weiner, Charles J Lockwood, Irina A Buhimschi, Nicholas M Fisk

Abstract: BackgroundProteomic 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.Methods and FindingsWe 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).ConclusionsHigh 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.

Partial Text: Preterm delivery remains a major public health problem with lasting family and societal repercussions [1]. Prevention strategies have failed, and the prevalence of preterm birth in the United States rose to an unprecedented 12.3% in 2003 [2]. Preterm birth accounts for almost 70% of neonatal deaths and up to 75% of neonatal morbidity [1]. The consequences for the neonate can prove devastating when intra-amniotic infection is superimposed upon prematurity [1].

The results of this study indicate that proteomic profiling of the amniotic fluid is an accurate method for diagnosis of clinically relevant intra-amniotic inflammation. High MR scores are associated with preterm delivery, histological chorioamnionitis, and early-onset neonatal sepsis. Our research was motivated by the fact that validity from chance and bias may cause erroneous results and inflate expectations in observational proteomic research. To address such potential bias and to make the scientific community aware of the potential of new technology, it was critical that we design, conduct, and provide interpretation of our proteomic profiling in a totally unrelated population compared to the original study and in fresh samples of AF [14].



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