Published online October 2, 2006
PEDIATRICS Vol. 118 No. 4 October 2006, pp. 1794-1795 (doi:10.1542/peds.2006-1607)

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LETTER TO THE EDITOR

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

Hung-Chih Lin, MD
Bai-Horng Su, MD, PhD
Ann-Chi Chen, MD
Department of Pediatrics
Children's Hospital
China Medical University
Taichung 404, Taiwan

To the Editor.—

We read with interest the retrospective case-control study by Guillet et al,¹ who found that H2-blocker therapy increases the incidence of necrotizing enterocolitis (NEC) for very low birth weight (VLBW) preterm infants. Although indirectly, Guillet et al proved that bacteria play a critical role in the pathogenesis of NEC, a finding that further supports our previous report that oral probiotics can be used to prevent NEC. Their finding was not unique; linkage between sepsis and NEC in preterm infants has been reported in the literature.²,³ Furthermore, it is well known that antacid therapy results in nosocomial infections in ICUs.⁴,⁵

We would like to comment on a number of methodologic and conceptual issues.

Although stress ulcers with bleeding seldom cause death in NICUs, it does not mean that a stress ulcer with bleeding does not need to be treated. H2-blocker therapy has been shown to effectively inhibit gastric acid production in neonates.⁶,⁷ The effectiveness depended on the dosage and gestational age; the higher the dose, the faster the gastric pH rose. Reports have stated that H2 blockers begin to increase gastric pH very quickly (mean: 0.9 hours) in a dose-dependent manner and that the half-life of H2 blockers is short (2–4 hours). The mean time that gastric pH values stayed >4 in preterm infants after receiving 3 different doses of ranitidine at 0.5, 1.0, and 1.5 mg/kg were 10.17, 12.75, and 20.75 hours, respectively.⁸ In the article, they stated that the median time that infants were taking H2 blockers before NEC developed was 14 days; that is, 50% of the infants were taking H2 blockers within14 days before developing NEC, and nearly 85% of the infants were taking H2 blockers within 34 days before developing NEC. H2 blockers could have been discontinued long before NEC developed and the pH fell below 4. It is difficult to interpret the relationship between H2 blockers and NEC in this way. Although no data show how many doses of H2 blockers are needed to result in proliferation of pathogenic flora in the intestine, we believe the relationship between H2 blockers and NEC could have been clearly defined by analyzing infants who took an H2 blocker at least 10 hours before the onset of NEC and continuously took an H2 blocker until NEC occurred.

It seems that the authors did not have solid confidence in the interpretation of their results. They knew that there were serious limitations in this retrospective study, because there was a lack of very important information such as breast milk or formula feeding, feeding protocol, fluid management, patent ductus arterious, and indomethacin usage.

Although lactic acid probiotics such as bifidobacteria and lactobacilli could survive in gastric acid and break down ingested sugars to form lactic acid, which, in turn, would decrease intraluminal pH,⁹ no data showed whether lactic acid probiotics contributed to gastric pH. It would be very interesting if someone could prove that lactic acid probiotics decrease pH in the stomach; it would further support the rationale of probiotics use for preterm VLBW infants.

Caution should be taken before we decide not to use H2 blockers to treat preterm VLBW infants who are sick with upper gastrointestinal bleeding or gastroesophageal reflux because of an incomplete retrospective study. Before definitive conclusions can be reached, we believe the relationship between H2 blockers and NEC needs to be further analyzed with adequate clinical information.

FOOTNOTES

Statements appearing here are those of the writers and do not represent the offcial position of the American Academy of Pediatrics or its Committees. Comments on any topic, including the contents of PEDIATRICS, are invited from all members of the profession; those accepted for publication will not be subject to major editorial revision but generally must be no more than 400 words in length. The editors reserve the right to publish replies and may solicit responses from authors and others.

Please see www.pediatrics.org for instructions on submitting letters.

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. Krediet TG, van Lelyveld N, Vijlbrief DC, et al. Microbiological factors associated with neonatal necrotizing enterocolitis: protective effect of early antibiotic treatment. Acta Paediatr. 2003;92 :1180 –1182[CrossRef][Web of Science][Medline]
3. Neu J. Neonatal necrotizing enterocolitis: an update. Acta Paediatr Suppl. 2005;94 :100 –105[CrossRef][Medline]
4. Graham PL 3rd, Begg MD, Larson E, Della-Latta P, Allen A, Saiman L. Risk factors for late onset gram-negative sepsis in low birth weight infants hospitalized in the neonatal intensive care unit. Pediatr Infect Dis J. 2006;25 :113 –117[CrossRef][Web of Science][Medline]
5. Singh-Naz N, Sprague BM, Patel KM, Pollack MM. Risk factors for nosocomial infection in critically ill children: a prospective cohort study. Crit Care Med. 1996;24 :875 –878[CrossRef][Web of Science][Medline]
6. Fontana M, Tornaghi R, Petrillo M, Lora E, Porro GB, Principi N. Ranitidine treatment in newborn infants: effects on gastric acidity and serum prolactin levels. J Pediatr Gastroenterol Nutr. 1993;16 :406 –411[Web of Science][Medline]
7. Kuusela AL, Ruuska T, Karikoski R, et al. A randomized, controlled study of prophylactic ranitidine in preventing stress-induced gastric mucosal lesions in neonatal intensive care unit patients. Crit Care Med. 1997;25 :346 –351[CrossRef][Web of Science][Medline]
8. Kuusela AL. Long-term gastric pH monitoring for determining optimal dose of ranitidine for critically ill preterm and term neonates. Arch Dis Child Fetal Neonatal Ed. 1998;78 :F151 –F153[Abstract/Free Full Text]
9. Ogawa K, Ben RA, Pons S, de Paolo MI, Fernandez LB. Volatile fatty acids, lactic acid, and pH in the stools of breast-fed and bottle-fed infants. J Pediatr Gastroenterol Nutr. 1991;15 :248 –252

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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) 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 Similar articles in PubMed 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 Lin, H.-C. Articles by Chen, A.-C. Search for Related Content PubMed PubMed Citation Articles by Lin, H.-C. Articles by Chen, A.-C. Related Collections Premature & Newborn Related AAP Red Book topics: Yersinia enterocolitica and... Social Bookmarking                         What's this?