Introduction:
Bacterial involvement is believed to play a pivotal role in the development and disease outcome of NEC. However, whether a bloodstream infection (BSI) predisposes to NEC (e.g. by activating the pro-inflammatory response) or result from the loss of gut wall integrity during NEC development is a longstanding question.

Objective:
We hypothesize that the occurrence of a BSI plays a complementary role in the pathogenesis of NEC. The first aim of the study was to correlate the occurrence of a BSI during the early phase of NEC with intestinal fatty acid-binding protein (I-FABP) levels, as a marker for loss of gut wall integrity owing to mucosal damage, and Interleukin (IL)-8 levels, as a biomarker for the pro-inflammatory cascade in NEC. The second aim of the study was to investigate the relation between the occurrence of a BSI and disease outcome.

Material and Methods:
We combined data from prospective trials from two large academic pediatric surgical centers. Thirty-eight neonates with NEC, 5 neonates with bacterial sepsis, and 14 controls were included.

Results:
BSIs occurred in 10/38 (26%) neonates at NEC onset. No association between the occurrence of BSIs and I-FABP levels in plasma (cohort 1: median 11ng/mL (range 0.8-298), cohort 2: median 6.8ng/mL (range 1.3-15)) was found in NEC patients (cohort 1: p=0.41; cohort 2: p=0.90). In addition, the occurrence of BSIs did not correlate with IL-8 (median 1562pg/mL (range 150-7,500); p=0.99). While the occurrence of a BSI was not correlated with Bell’s stage (p=0.85), mortality was higher in patients with a BSI (p=0.005).

Conclusion: 
The low incidence of BSIs and the absent association of both the markers for loss of gut wall integrity and the pro-inflammatory response during the early phase of NEC, support the hypothesis that the presence of a BSI does not precede NEC.

Published in the Journal for Pediatric Surgery

Authors /  *corresponding author
* Heida FH. 1, Hulscher JB. 2, Schurink M. 2, van Vliet MJ. 3, Kooi EM. 4, Kasper DC. 5, Pones M. 6, Bos AF. 4, Benkoe TM. 6.

1 Department of Pediatric Surgery, Beatrix Children’s Hospital, University Medical Center, Groningen, the Netherlands; Department of Medical Microbiology, Beatrix Children’s Hospital, University Medical Center, Groningen, the Netherlands. heida@umcg.nl.
2 Department of Pediatric Surgery, Beatrix Children’s Hospital, University Medical Center, Groningen, the Netherlands.
3 Department of Pediatrics, Beatrix Children’s Hospital, University Medical Center, Groningen, the Netherlands.
4 Department of Neonatology, Beatrix Children’s Hospital, University Medical Center, Groningen, the Netherlands.
5 Department of Analytics, Medical University of Vienna, Austria.
6 Department of Pediatric Surgery, Research Core Unit for Pediatric Biochemistry, Medical University of Vienna, Austria.