Elsevier

The Journal of Pediatrics

Volume 159, Issue 3, September 2011, Pages 392-397
The Journal of Pediatrics

Original Article
Antibiotic Exposure in the Newborn Intensive Care Unit and the Risk of Necrotizing Enterocolitis

https://doi.org/10.1016/j.jpeds.2011.02.035Get rights and content

Objective

To determine whether duration of antibiotic exposure is an independent risk factor for necrotizing enterocolitis (NEC).

Study design

A retrospective, 2:1 control-case analysis was conducted comparing neonates with NEC to those without from 2000 through 2008. Control subjects were matched on gestational age, birth weight, and birth year. In each matched triad, demographic and risk factor data were collected from birth until the diagnosis of NEC in the case subject. Bivariate and multivariate analyses were used to assess associations between risk factors and NEC.

Results

One hundred twenty-four cases of NEC were matched with 248 control subjects. Cases were less likely to have respiratory distress syndrome (P = .018) and more likely to reach full enteral feeding (P = .028) than control subjects. Cases were more likely to have culture-proven sepsis (P < .0001). Given the association between sepsis and antibiotic use, we tested for and found a significant interaction between the two variables (P = .001). When neonates with sepsis were removed from the cohort, the risk of NEC increased significantly with duration of antibiotic exposure. Exposure for >10 days resulted in a nearly threefold increase in the risk of developing NEC.

Conclusions

Duration of antibiotic exposure is associated with an increased risk of NEC among neonates without prior sepsis.

Section snippets

Methods

A retrospective, 2:1 control/case analysis was performed to investigate the association between the duration of antimicrobial therapy and subsequent diagnosis of NEC among neonates born from January 1, 2000 to December 31, 2008, and admitted to the Newborn Special Care Unit (NBSCU) at Yale-New Haven Children’s Hospital. The NBSCU is a 54-bed, level IIIc16 NICU for infants with complex medical and surgical conditions.

Cases included neonates diagnosed with NEC modified Bell’s stage ≥IIA.17 Each

Results

The 124 cases of NEC were matched with 248 control subjects. Neonates with NEC were diagnosed, on average, at day of life 22 ± 15, with 51% receiving only medical treatment and 49% undergoing surgical intervention. Cases and control subjects were well matched with respect to gestational age (28.2 ± 3.4 weeks in cases vs 28.1 ± 3.4 weeks in control subjects; P = .849), birth weight (1162 ± 573 g in cases vs 1169 ± 584 g in control subjects; P = .902), and year of admission to the NBSCU (P =

Discussion

The findings support our hypothesis that increased duration of antibiotic exposure in NICU patients may increase their risk of NEC although, because of the confounding relationship between sepsis and antibiotic use, this was only found in neonates without a prior documented bloodstream infection. Antibiotic use in the neonatal population has been previously described as a potential contributing factor in the development of NEC. Antibiotic administration may result in suppression or eradication

References (30)

  • E.C. Claude et al.

    Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis

    FASEB J

    (2001)
  • A.S. Neish et al.

    Prokaryotic regulation of epithelial responses by inhibition of IkapptaB-alpha

    Science

    (2000)
  • M. Millar et al.

    Probiotics for preterm infants?

    Arch Dis Child Fetal Neonatal Ed

    (2003)
  • H.J. Harmsen et al.

    Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods

    J Pediatr Gastroenterol Nutr

    (2000)
  • A. Schwiertz et al.

    Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants

    Pediatr Res

    (2003)
  • Cited by (301)

    • Special Populations—Surgical Infants

      2023, Clinics in Perinatology
    • Antibiotic therapy and necrotizing enterocolitis

      2023, Seminars in Pediatric Surgery
    • Models of necrotizing enterocolitis

      2023, Seminars in Perinatology
    View all citing articles on Scopus

    Supported by the National Center for Research Resources (NCRR) (CTSA grant UL1 RR024139), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. The authors declare no conflicts of interest.

    View full text