Cytokine levels in the preterm infant with neonatal intestinal injury and relationship with outcome Público

Abstract

Background: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation
(SIP) are common newborn surgical diseases primarily affecting preterm infants. Increased
levels of proinflammatory mediators may play a role in short and long-term outcomes in the
preterm infant. Purpose: To characterize the cytokine response in preterm newborns with
surgical NEC or SIP before and after surgical treatment as compared to non-septic, preterm
surgical newborns and to relate this to intestinal disease (NEC vs. SIP) and short-term outcome.
Methods: The study was a 14-month prospective, cohort study of neonates undergoing surgery or
drainage for NEC or SIP or surgical ligation of patent ductus arteriosus (PDA, the non-septic
control group). Bioplex xMAP technology was used to analyse 6 inflammatory markers (IL-2,
IL-6, IL-8, IL-1β, IFN-Ɣ, and TNF-α). Prospectively collected clinical data included:
preoperative risk factors, indications for surgery or drainage, extent of intestinal disease, and
early postoperative morbidity and mortality. Results: NEC had much higher median
preoperative levels than SIP and PDA subjects of the cytokines IL-6 (NEC: 8381 pg/ml; SIP: 36
pg/ml; PDA: 25 pg/ml), IL-8 (NEC: 18438 pg/ml; SIP: 2473 pg/ml; PDA: 1110 pg/ml), and TNF-
α (NEC: 161 pg/ml; SIP: 77 pg/ml; PDA: 61 pg/ml), and IL-1β (NEC: 85 pg/ml; SIP: 35 pg/ml;
PDA: 24 pg/ml). NEC-totalis had the highest levels of IL-6, IL-8, and IL-1β, but only IL-8 was
significantly different from limited NEC (28141 pg/ml vs. 11429 pg/ml). Salvage laparotomy
(reoperation) after primary peritoneal drainage was associated with lower early postoperative IL-
6 and IL-1β (postoperative days 1 and 2) as well as TNF-α levels (postoperative days 2 and 5).
Early mortality (<30 days) was associated with elevated preoperative IL-6, IL-8, and TNF-α, but
5 of 7 deaths were in subjects with NEC-totalis. Conclusions: Surgical NEC is a profoundly
more proinflammatory disease than SIP, which is closer to a non-septic neonate. A strong
proinflammatory response is associated with early postoperative death, likely due to its
association with NEC-totalis.

Table of Contents

Introduction... pp. 1-4
Background... pp. 5-8
Methods... pp. 9-14
Results... pp. 15-16
Discussion... pp. 17-20
References... pp. 21-24
Figure 1a-c... p. 25
Figure 2... p. 26
Table 1... p. 27
Table 2... p. 28
Table 3... p. 29
Table 4... p. 30
Table 5... p. 31
Figure 3... p. 32-33
Table 6... p. 34
Table 7... p. 35

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research Curriculum Program
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, General
Palabra Clave	necrotizing enterocolitis cytokines
Committee Chair / Thesis Advisor	Hamrick, Shannon, Emory University Stoll, Barbara J, Emory University
Committee Members	Kempton, Christine, Emory University Klein, Mitchel, Emory University

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