title: Proteomic biomarkers of intra-amniotic inflammation: relationship with funisitis and early-onset sepsis in the premature neonate.
abstract: Our goal was to determine the relationship between 4 amniotic fluid (AF) proteomic biomarkers (human neutrophil defensins 2 and 1, calgranulins C and A) characteristic of intra-amniotic inflammation, and funisitis and early-onset sepsis in premature neonates. The mass restricted (MR) score was generated from AF obtained from women in preterm labor (n = 123). The MR score ranged from 0-4 (none to all biomarkers present). Funisitis was graded histologically and interpreted in relation to the MR scores. Neonates (n = 97) were evaluated for early-onset sepsis. There was significant correlation between the severity of AF inflammation and the presence (53/123) and grades of funisitis (p < 0.001). Funisitis occurred independently of the amniocentesis-to-delivery interval or status of the membranes and was best predicted by an MR score 3-4 and an earlier gestational age (GA) at delivery. Neonates born to women with an MR score 3-4 had an increased incidence of suspected/confirmed sepsis, even after adjusting for GA at birth. Calgranulin C had the highest association with clinically significant funisitis, while calgranulin A had the strongest association with early-onset sepsis. To conclude, AF proteomic analysis shows that women with MR scores 3-4 are more likely to have histologic funisitis, and deliver neonates with early-onset sepsis.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Perinatal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
authors.forename: Sonya
authors.initials: S
authors.lastname: Abdel-Razeq
authors.forename: Victor A
authors.initials: VA
authors.lastname: Rosenberg
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Thung
authors.forename: Guomao
authors.initials: G
authors.lastname: Zhao
authors.forename: Erica
authors.initials: E
authors.lastname: Wang
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D040501:Calgranulin A / Q000378:metabolism; D002821:Chorioamnionitis / Q000378:metabolism* / Q000473:pathology; D023082:Defensins / Q000378:metabolism; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D011247:Pregnancy; D011446:Prospective Studies; D040901:Proteomics; D009418:S100 Proteins / Q000378:metabolism; D000067616:S100A12 Protein; D018805:Sepsis / Q000150:complications / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D040501:Calgranulin A; D023082:Defensins; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human