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Molecular Medicine

, Volume 21, Issue 1, pp 496–504 | Cite as

Postnatal Age Is a Critical Determinant of the Neonatal Host Response to Sepsis

  • James L. Wynn
  • Scott O. Guthrie
  • Hector R. Wong
  • Patrick Lahni
  • Ricardo Ungaro
  • M. Cecilia Lopez
  • Henry V. Baker
  • Lyle L. Moldawer
Research Article

Abstract

Neonates manifest a unique host response to sepsis even among other children. Preterm neonates may experience sepsis soon after birth or during often-protracted birth hospitalizations as they attain physiologic maturity. We examined the transcriptome using genome-wide expression profiling on prospectively collected peripheral blood samples from infants evaluated for sepsis within 24 h after clinical presentation. Simultaneous plasma samples were examined for alterations in inflammatory mediators. Group designation (sepsis or uninfected) was determined retrospectively on the basis of clinical exam and laboratory results over the next 72 h from the time of evaluation. Unsupervised analysis showed the major node of separation between groups was timing of sepsis episode relative to birth (early, <3 d, or late, ≥3 d). Principal component analyses revealed significant differences between patients with early or late sepsis despite the presence of similar key immunologic pathway aberrations in both groups. Unique to neonates, the uninfected state and host response to sepsis is significantly affected by timing relative to birth. Future therapeutic approaches may need to be tailored to the timing of the infectious event based on postnatal age.

Notes

Acknowledgments

Grant support for this work was provided by National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS) (GM106143 to JL Wynn and GM096994 to HR Wong), The Gerber Foundation (to JL Wynn), and Vanderbilt Turner-Hazinski awards (to JL Wynn).

Supplementary material

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Authors and Affiliations

  • James L. Wynn
    • 1
    • 6
  • Scott O. Guthrie
    • 1
    • 2
  • Hector R. Wong
    • 3
  • Patrick Lahni
    • 3
  • Ricardo Ungaro
    • 4
  • M. Cecilia Lopez
    • 5
  • Henry V. Baker
    • 5
  • Lyle L. Moldawer
    • 4
  1. 1.Department of Pediatrics, Division of NeonatologyVanderbilt UniversityNashvilleUSA
  2. 2.Ayers Children’s Medical CenterJackson-Madison County General HospitalJacksonUSA
  3. 3.Cincinnati Children’s Hospital Medical Center and Cincinnati Children’s Research Foundation, Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiUSA
  4. 4.Department of SurgeryUniversity of Florida College of MedicineGainesvilleUSA
  5. 5.Department of Molecular Genetics and MicrobiologyUniversity of Florida College of MedicineGainesvilleUSA
  6. 6.Department of PediatricsUniversity of FloridaGainesvilleUSA

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