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 ϭ 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 ϭ 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 Ͻ 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. the rate of preterm birth (PTB) has actually increased over the past 20 y (1). More than 500,000 preterm infants were born in the United States in 2004 (1). Interventions to prevent PTB and its consequences for the fetus should predominantly be targeted at the prevention, early recognition and treatment of several risk factors including intra-amniotic inflammation/ infection (2).Robust scientific evidence has confirmed that when intraamniotic inflammation secondary to, or independent of infection is superimposed upon prematurity, the consequences for the neonate can prove devastating (3,4). This association can be explained by an inflammatory cytokine cascade that seems to be, at least partially, of fetal origin (5,6). Indeed, fetal umbilical vein inflammatory cytokine levels, but not maternal serum values, correlate with the presence and severity of the placental histologic inflammation and umbilical cord vasculitis (7).Funisitis is characterized by perivascular infiltrates of inflammatory cells and is considered one of the strongest hallmarks of microbial invasion of the amniotic cavity and fetal inflammatory syndrome (8,9). While there is some debate with regard to the origin of the amniotic fluid (AF) neutrophilic response to infection (10), there is consensus that the fetal inflammatory neutrophilic response originates initially from the umbilical vein and later from the arteries leading to umbilical cord vasculitis and funisitis (11). Funisitis is a well-recognized risk factor for early-onset sepsis in the premature neonate (12,13).We have previously shown that proteomic mapping of the AF reveals a profile, designated as the Mass Restricted (MR) score, that is highly cha...

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