Published online October 2, 2006
PEDIATRICS Vol. 118 No. 4 October 2006, pp. 1795-1796 (doi:10.1542/peds.2006-1906)

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LETTER TO THE EDITOR

H2-Blocker Therapy and Necrotizing Enterocolitis for Very Low Birth Weight Preterm Infants: In Reply

Ronnie Guillet, MD, PhD
Dale Phelps, MD
Division of Neonatology
Department of Pediatrics
University of Rochester
Rochester, NY 14642

Barbara Stoll, MD
Department of Pediatrics
School of Medicine and Children's Healthcare of Atlanta at Egleston
Emory University
Atlanta, GA 30322-1062

Michael Cotten, MD
Division of Neonatology
Department of Pediatrics
Duke University
Durham, NC 27708

Marie Gantz, PhD
Scott McDonald, PhD
W. Kenneth Poole, PhD
RTI International
Research Triangle Park, NC 27709-2194

We thank Drs Lin, Su, and Chen for their interest in our article¹ on H2-blocker therapy and necrotizing enterocolitis (NEC) in very low birth weight infants. We agree that there is insufficient evidence to suggest that H2 blockers should never be considered for use in this population. It is clear that additional work is needed to identify and then validate the mechanism behind the possible link between H2-blocker exposure and NEC.

We are intrigued with the possible link between H2-blocker use, infection risk, and probiotics' potential use in this population. In a recently published article, Brzozowski et al² tested a rodent model of gastric ulcer and showed that (1) persistent gastric colonization with Candida was enhanced in rats treated with ranitidine, (2) candidiasis alone reduced gastric acid secretion and delayed ulcer healing and healing was further delayed with addition of ranitidine, (1) and probiotic therapy (Lactobacillus) was associated with a more rapid healing of ulcers in Candida-colonized animals.

These findings speak to the potential for ranitidine to increase risk and severity of Candida colonization in the gastrointestinal tract, hint at the possible beneficial role for probiotics, and further support the need to account for H2-blocker use as a possible confounder in studies of safety and efficacy of probiotics in this population.

As is true with most, if not all, retrospective analyses of data, there are inherent limitations to the conclusions that may be drawn. We do not know that H2-blocker therapy increases the incidence of NEC, only that exposure to these drugs seems to have a strong association. Only a randomized, controlled trial could provide direct evidence to that effect. Thus, we feel that we have interpreted the results in context and tried to avoid overinterpretation. A difficulty in an analysis such as ours is the need to avoid creating a bias by defining the exposure by using the outcome. Thus, the suggestion that we might more clearly define the relationship between H2 blockers and NEC by limiting the exposure parameters may not achieve the desired result. Statistical and ascertainment biases are possible factors of importance in current discussions of whether there is a true association between gastric acid suppression and Clostridium difficile disease in adults.^3–6

Additional research is needed to define the potential link between H2 blockers and disease and to assess the safety and efficacy of these medications in the very low birth weight population. Until these data are available, we urge practitioners to use H2 blockers only when there is a clear clinical indication and to avoid their use as routine prophylaxis.

REFERENCES

1. Guillet R, Stoll BJ, Cotton CM, et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2006;117(2) . Available at: www.pediatrics.org/cgi/content/full/117/2/e137
2. Brzozowski T, Zwolinska-Wcislo M, Konturek PC, et al. Influence of gastric colonization with Candida albicans on ulcer healing in rats: effect of ranitidine, aspirin and probiotic therapy. Scand J Gastroenterol. 2005;40 :286 –296[CrossRef][Web of Science][Medline]
3. Dial S, Delaney AC, Barkun AN, Suissa S. Use of gastric acid–suppressive agents and the risk of community-acquired Clostridium difficile–associated disease [letter]. JAMA. 2005;294 :2989 –2995[Abstract/Free Full Text]
4. Dial S, Delaney AC, Barkun AN, Suissa S. Gastric acid–suppressive agents and risk of Clostridium difficile–associated disease [reply letter]. JAMA. 2006;295 :2600 –2601[Free Full Text]
5. Leffler D, Cloud JW, Kelly CP. Gastric acid-suppressive agents and risk of Clostridium difficile-associated disease [letter]. JAMA. 2006;295 :2599 –2600[Free Full Text]
6. van Staa TP, de Vries F, Leufkens HG. Gastric acid-suppressive agents and risk of Clostridium difficile-associated disease [letter]. JAMA. 2006;295 :2599[Free Full Text]

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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Guillet, R. Articles by Poole, W. K. Search for Related Content PubMed Articles by Guillet, R. Articles by Poole, W. K. Related Collections Premature & Newborn Related AAP Red Book topics: Yersinia enterocolitica and... Clostridium difficile Candidiasis (Moniliasis, Thrush) Social Bookmarking                         What's this?