title: Correlation of preterm infant illness severity with placental histology.
abstract: BACKGROUND
  A major goal of neonatal medicine is to identify neonates at highest risk for morbidity and mortality. Previously, we developed PhysiScore (Saria et al., 2010), a novel tool for preterm morbidity risk prediction. We now further define links between overall individual morbidity risk, specific neonatal morbidities, and placental pathologies.
  
  
  METHODS
  102 placentas, including 38 from multiple gestations, were available from the previously defined PhysiScore cohort (gestational age ≤ 34 weeks and birth weight ≤ 2000 g). Placentas were analyzed for gross and histologic variables including maternal malperfusion, amniotic fluid infection sequence, chronic inflammation, and fetal vascular obstruction. Risk as determined by PhysiScore and recorded neonatal morbidities were tested for statistical association with placental findings.
  
  
  RESULTS
  In pair-wise correlations, respiratory distress syndrome, bronchopulmonary dysplasia, acute hemodynamic instability, post-hemorrhagic hydrocephalus, culture-positive sepsis, and necrotizing enterocolitis each significantly correlated with at least one placenta histology variable. Amniotic fluid infection sequence (p = 0.039), specifically the fetal inflammatory response (p = 0.017), correlated with higher PhysiScores (greater morbidity) but was not independent of gestational age and birth weight. In multivariate analyses correlating variables with all nine morbidities, gestational age (p < 0.001), placental size <10th percentile (p = 0.031), full thickness perivillous fibrin deposition (p = 0.001), and amniotic fluid infection sequence (umbilical arteritis, p = 0.031; ≥2 chorionic plate vessels with vasculitis, p = 0.0125), each were significant associations.
  
  
  CONCLUSIONS
  Amniotic fluid infection sequence plays a significant role in neonatal morbidity. Less neonatal morbidity was observed in older and heavier infants and those with small placental size and full thickness perivillous fibrin deposition. The combined assessment of placental gross and histologic findings together with physiologic risk evaluation may allow more precise prediction of neonatal morbidity risk soon after delivery.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: karenmarie.kc@gmail.com.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Chisholm
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Heerema-McKenney
authors.affiliation: Department of Health Research & Policy, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Rajani
authors.affiliation: Department of Computer Science, Stanford University, Stanford, CA, USA.
authors.forename: Suchi
authors.initials: S
authors.lastname: Saria
authors.affiliation: Department of Computer Science, Stanford University, Stanford, CA, USA.
authors.forename: Daphne
authors.initials: D
authors.lastname: Koller
authors.affiliation: Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: apenn@childrensnational.org.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Penn
mesh_terms: D000653:Amniotic Fluid / Q000382:microbiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000453:epidemiology*; D008297:Male; D009017:Morbidity; D007752:Obstetric Labor, Premature / Q000473:pathology*; D010920:Placenta / Q000473:pathology*; D010922:Placenta Diseases / Q000453:epidemiology*; D011247:Pregnancy; D012720:Severity of Illness Index
keywords: Fetal inflammatory response; Histology; Morbidity; Placenta; Preterm infant