Are antibiotics a risk factor for the development of necrotizing enterocolitis—case-control retrospective study
Previous studies have identified numerous risk factors associated with necrotizing enterocolitis (NEC) in very low birth weight (VLBW; birth weight less than 1500 g) infants. One of the potential pathophysiological contributors could be antibiotic therapy. Our aim was to explore the association between antibiotic exposure and NEC in VLBW infants. We designed a retrospective 1:2 case-control cohort study in a level III neonatal intensive care unit. Our study group composed of VLBW infants born between January 2012 and December 2014 with a diagnosis of NEC stage IIA or greater (Bell’s modified criteria). Our intent was to match every case in the study group to two controls. Our primary outcome was an association between antibiotic exposure and NEC. Twenty-two cases of NEC were matched to 32 controls. The infants who developed NEC were exposed to a statistically significantly more frequent number of antibiotic courses and to more days on any antibiotic prior to the development of NEC. There were significant differences between cases and controls with respect to the duration of exposure to gentamicin and meropenem specifically.
What is known:
• Early antibiotic exposure is a risk factor for the development of necrotising enterocolitis (NEC) in very low birth weight infants
• Prolonged initial empirical antibiotic course for ≥ 5 days, despite sterile blood culture, is associated with an increased risk of developing NEC
What is new:
• The cumulative total number of days of antibiotic exposure is associated with an increased risk of developing NEC
• Gentamicin and meropenem, but not other antibiotics, had a significant association with the incidence of NEC in our study
KeywordsNecrotising enterocolitis Antibiotics Very-low-birth-weight infant Case-control study
Early onset sepsis
Intrauterine growth restriction
Late onset sepsis
Neonatal intensive care unit
Patent ductus arteriosus
Spontaneous vaginal delivery
Very low birth weight
Dr. Ali Raba designed the study, contributed substantially to the data collection and analysis and drafted the initial manuscript.
Ms. O’Sullivan contributed substantially to the data collection and analysis and reviewed and revised the manuscript.
Dr. Semberova contributed substantially to the study concept and design and reviewed and revised the manuscript.
Prof Martin contributed substantially to the study concept and design and reviewed and revised the manuscript critically for important intellectual content.
Prof Miletin conceptualised and designed the study, supervised the conduct of the study and coordinated the data analysis. He reviewed and revised the manuscript critically for important intellectual content.
All the authors approved the final manuscript as submitted. They agree to be accountable for all aspects of the work.
Jana Semberova’s work was supported by the HIP Trial funding (the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 260777).
Compliance with ethical statements
Conflict of interest
The authors declare that they have no conflict of interest.
The research ethics committee of the Coombe Women and Infants University Hospital approved the study.
Informed consent was not required because of the retrospective nature of the study.
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