Using proteomic analysis of the human amniotic fluid to identify histologic chorioamnionitis.
OBJECTIVE
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.


CONCLUSIONS
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.


METHODS
II.
Buhimschi
Irina A
IA
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA. irina.buhimschi@yale.edu
Zambrano
Eduardo
E
Pettker
Christian M
CM
Bahtiyar
Mert Ozan
MO
Paidas
Michael
M
Rosenberg
Victor A
VA
Thung
Stephen
S
Salafia
Carolyn M
CM
Buhimschi
Catalin S
CS
D000293:Adolescent; D000328:Adult; D001741:Black or African American; D000649:Amniocentesis / Q000379:methods; D000653:Amniotic Fluid / Q000737:chemistry*; D015415:Biomarkers / Q000032:analysis; D002821:Chorioamnionitis / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis*; D011256:Pregnancy Outcome; D015995:Prevalence; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D044465:White People
D015415:Biomarkers; D020543:Proteome