title: Using proteomics in perinatal and neonatal sepsis: hopes and challenges for the future.
abstract: OBJECTIVE
  Particularities of the fetal immune response to infection cause a heightened inflammatory state that acts synergistically with microbial insult to induce damage. Proteomics offers the opportunity for detecting fetuses at risk of sepsis and neurological injury.
  
  
  RESULTS
  Molecular tools (16S-rRNA) demonstrate that the diversity of microbial agents of intra-amniotic infection exceeds what is suspected clinically or is documented by cultures. The resulting inflammatory process has the potential to damage the fetus in utero. Stepwise algorithms (mass restricted score) have been developed to extract proteomic profiles characteristic of amniotic fluid inflammation. The mass restricted score includes four proteomic biomarkers: defensin-2, defensin-1, S100A12, and S100A8 proteins. Other amniotic fluid biomarkers relevant for preterm birth are S100A9 and insulin-like growth factor-binding protein 1. S100A12 - ligand for the receptor of advanced glycation end products - has the strongest association with histological chorioamnionitis and funisitis. Presence of S100A12 and S100A8 in amniotic fluid is predictive of early-onset neonatal sepsis and poor neurodevelopmental outcome.
  
  
  CONCLUSIONS
  Presence of amniotic fluid proteomic biomarkers of inflammation is associated with increased inflammatory status of the fetus at birth. Future challenges are to find biomarkers that provide insight into molecular mechanisms of chronic fetal and neonatal cellular damage and to identify candidates for early neuroprotection strategies.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. catalin.buhimschi@yale.edu
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.forename: Yiping W
authors.initials: YW
authors.lastname: Han
authors.forename: Antonette T
authors.initials: AT
authors.lastname: Dulay
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Baumbusch
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Madri
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
mesh_terms: D000653:Amniotic Fluid / Q000737:chemistry*; D015415:Biomarkers; D023082:Defensins / Q000032:analysis; D005315:Fetal Diseases / Q000175:diagnosis*; D006801:Humans; D007231:Infant, Newborn; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D011296:Prenatal Diagnosis / Q000379:methods*; D020543:Proteome / Q000032:analysis*; D009418:S100 Proteins / Q000032:analysis; D018805:Sepsis / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D023082:Defensins; D039841:Leukocyte L1 Antigen Complex; D020543:Proteome; D009418:S100 Proteins