title: The impact of environmental and genetic factors on neonatal late-onset sepsis.
abstract: OBJECTIVE
  To assess the genetic contribution to late-onset sepsis in twins in the newborn intensive care unit.
  
  
  METHODS
  A retrospective cohort analysis of twins born from 1994 to 2009 was performed on data collected from the newborn intensive care units at Yale University and the University of Connecticut. Sepsis concordance rates were compared between monozygotic and dizygotic twins. Mixed-effects logistic regression analysis was performed to determine the impact of selected nongenetic factors on late-onset sepsis. The influence of additive genetic and common and residual environmental effects were analyzed and quantified.
  
  
  RESULTS
  One hundred seventy monozygotic and 665 dizygotic twin pairs were analyzed, and sepsis identified in 8.9%. Mean gestational age and birth weight of the cohort was 31.1 weeks and 1637 grams, respectively. Mixed-effects logistic regression determined birth weight (regression coefficient, -0.001; 95% CI, -0.003 to 0.000; P = .028), respiratory distress syndrome (regression coefficient, 1.769; 95% CI, 0.943 to 2.596; P < .001), and duration of total parenteral nutrition (regression coefficient, 0.041; 95% CI, 0.017 to 0.064; P < .001) as significant nongenetic factors. Further analysis determined 49.0% (P = .002) of the variance in liability to late-onset sepsis was due to genetic factors alone, and 51.0% (P = .001) the result of residual environmental factors.
  
  
  CONCLUSIONS
  Our data support significant genetic susceptibility to late-onset sepsis in the newborn intensive care unit population.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8064, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bizzarro
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Naveed
authors.initials: N
authors.lastname: Hussain
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gruen
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.forename: Heping
authors.initials: H
authors.lastname: Zhang
mesh_terms: D017668:Age of Onset; D001724:Birth Weight; D017848:Blood-Borne Pathogens / Q000302:isolation & purification*; D015331:Cohort Studies; D016001:Confidence Intervals; D003428:Cross Infection / Q000453:epidemiology / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D016015:Logistic Models; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D018805:Sepsis / Q000453:epidemiology / Q000235:genetics*; D015996:Survival Rate; D013997:Time Factors; D014427:Twins; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics