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Obstetrics & Gynecology 2008;111:403-412
© 2008 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Using Proteomic Analysis of the Human Amniotic Fluid to Identify Histologic Chorioamnionitis

Irina A. Buhimschi, MD1, Eduardo Zambrano, MD2, Christian M. Pettker, MD1, Mert Ozan Bahtiyar, MD1, Michael Paidas, MD1, Victor A. Rosenberg, MD1, Stephen Thung, MD1, Carolyn M. Salafia, MD3 and Catalin S. Buhimschi, MD1

From the Departments of 1Obstetrics, Gynecology and Reproductive Sciences and 2Pathology, Yale University School of Medicine, New Haven, Connecticut; and the 3Department of Epidemiology, Mailman School of Public Health, Columbia University College of Physicians and Surgeons, New York, New York.

OBJECTVE: To estimate the relationship between histologic chorioamnionitis and four amniotic fluid proteomic biomarkers characteristic of inflammation (defensins 2 and 1, calgranulins C and A).

METHODS: One hundred fifty-eight women with singleton pregnancies had a clinically indicated amniocentesis to rule out inflammation and infection in the context of preterm labor or preterm premature rupture of membranes. A proteomic fingerprint (Mass Restricted score) was generated from amniotic fluid using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. The Mass Restricted score ranges from 0 to 4 (none to all four biomarkers present) in direct relationship with severity of intra-amniotic inflammation. Presence or absence of biomarkers was analyzed in relationship to placental pathology. Criteria for severity of histologic chorioamnionitis were 3 stages and 4 grades of inflammation of the amnion, choriodecidua and chorionic plate.

RESULTS: The prevalence of histologic chorioamnionitis was 64% (stage I 12%, stage II 16%, and stage III 37%). The Mass Restricted score significantly correlated with stages of histologic chorioamnionitis (r=0.539, P<.001), grades of choriodeciduitis (r=0.465, P<.001), and amnionitis (r=0.536, P<.001). African-American women were overrepresented in the group with severe inflammation (Mass Restricted score 3–4, P=.022). Of the four biomarkers of the Mass Restricted score, calgranulin C had the strongest relationship with presence of stage III chorioamnionitis, independent of race, amniocentesis-to-delivery interval, and gestational age.

CONCLUSION: Proteomic analysis of amniotic fluid provides an opportunity for early recognition of histologic chorioamnionitis. This methodology may in the future identify candidates for antenatal therapeutic interventions.

LEVEL OF EVIDENCE: II






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