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Meta-Analysis
. 2008 Jul 16;2008(3):CD001815.
doi: 10.1002/14651858.CD001815.pub2.

Erythromycin for the prevention and treatment of feeding intolerance in preterm infants

Affiliations
Meta-Analysis

Erythromycin for the prevention and treatment of feeding intolerance in preterm infants

Eugene Ng et al. Cochrane Database Syst Rev. .

Abstract

Background: Functional immaturity of gastrointestinal motility predisposes preterm infants to feeding intolerance. Erythromycin is a motilin agonist that exerts its prokinetic effect by stimulating propagative contractile activity in the interdigestive phase.

Objectives: To evaluate the efficacy of erythromycin in the prevention and treatment of feeding intolerance in preterm infants.

Search strategy: Systematic literature search was performed according to the Cochrane Neonatal Collaborative Review Group search strategy. Randomized controlled trials of erythromycin in preterm infants to promote gastrointestinal motility were identified from the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2007), MEDLINE (1966 - December 2007), EMBASE (1980 - December 2007), CINAHL (1982 - December 2007), cross-references, abstracts, and journal hand searching.

Selection criteria: The initial selection criteria limited the review to studies using erythromycin at 3 - 12 mg/kg/day in preterm infants less than 36 weeks gestational age with feeding tolerance. However, a significant number of studies using erythromycin at a higher dose (> 12 mg/kg/day) or as prophylaxis for those at risk of feeding intolerance were identified. A post hoc decision was made to include these studies in the review.

Data collection and analysis: Studies were categorized into prevention and treatment studies, and data from each category were analyzed separately. Within each category, subgroup analyses were performed based on low (3 to 12mg/kg/day) and high doses (> 12mg/kg/day) of erythromycin. Primary outcome was days to full enteral feeding. Secondary outcomes included adverse effects associated with erythromycin, duration of total parenteral nutrition (TPN), weight gain, necrotizing enterocolitis (NEC), and length of hospital stay.

Main results: Ten randomized controlled studies (three prevention and seven treatment studies) were included. Studies varied greatly in the definition of feeding intolerance and how outcomes were measured, analyzed and reported, so meta-analysis of most outcomes was impossible. It was observed, however, that the studies using erythromycin at higher treatment doses (40 to 50 mg/kg/day) or in infants > 32 weeks' GA reported more positive effects in improving feeding intolerance.Meta-analysis of high dose prevention studies showed no significant difference in NEC (typical RR 0.59, 95% CI 0.11, 3.01; typical RD -0.021, 95% CI -0.087, 0.045). Meta-analysis of high dose treatment studies showed no significant difference in septicemia (typical RR 0.83, 95% CI 0.47, 1.45; typical RD -0.04, 95% CI -0.17, 0.08).

Authors' conclusions: There is insufficient evidence to recommend the use of erythromycin in low or high doses for preterm infants with or at risk of feeding intolerance. Future research is needed to determine if there is a more precise dose range where erythromycin might be effective as a prokinetic agent in preterm infants > 32 weeks' GA.

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Conflict of interest statement

None

Figures

1.1
1.1. Analysis
Comparison 1 Prevention Studies of Erythromycin versus Placebo (High dose), Outcome 1 Incidence of NEC.
2.1
2.1. Analysis
Comparison 2 Treatment Studies of Erythromycin versus Placebo (High dose), Outcome 1 Incidence of Septicemia.

Update of

References

References to studies included in this review

Aly 2007 {published data only}
    1. Aly H, Abdel‐Hady H, Khashaba M, El‐Badry N. Erythromycin and feeding intolerance in premature infants: a randomized trial. Journal of Perinatology 2007;27:39‐43. - PubMed
Cairns 2002 {published data only}
    1. Cairns PA, Craig S, Tubman R, Roberts RS, Wilson J, Schmidt B. Randomised controlled trial of low‐dose erythromycin in preterm infants with feed intolerance. Pediatric Research 2002;51:379A.
ElHennawy 2003 {published data only}
    1. ElHennawy AA, Sparks JW, Armentrout D, Huseby V, Berseth CL. Erythromycin fails to improve feeding outcome in feeding‐intolerant preterm infants. JPGN 2003;37:281‐6. - PubMed
Madani 2004 {published data only}
    1. Madani A, Pishva N, Pourarian Sh, Zarkesh M. The efficacy of oral erythromycin in enhancement of milk tolerance in premature infants: A randomized controlled trial. Iranian Journal of Medical Sciences 2004;29:1‐4.
Ng PC 2001 {published data only}
    1. Ng PC, So KW, Fung KSC, Lee CH, Fok TF, Wong E, et al. Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2001;84:F177‐82. - PMC - PubMed
Ng SC 2003 {published data only}
    1. Ng SC, Gomez JM, Rajadurai VS, Saw S, Quak S. Establishing enteral feeding in preterm infants with feeing intolerance; A randomized controlled study of low‐dose erythromycin. JPGN 2003;37:554‐8. - PubMed
Nuntnarumit 2006 {published data only}
    1. Nuntnarumit P, Kiatchoosakun P, Tantiprapa W, Boonkasidecha S. Efficacy of oral erythromycin for treatment of feeding intolerance in preterm infants. Journal of Pediatrics 2006;148:600‐5. - PubMed
Oei 2001 {published data only}
    1. Oei J, Lui K. A placebo‐controlled trial of low‐dose erythromycin to promote feed tolerance in preterm infants. Acta Paediatrica 2001;90:904‐8. - PubMed
Patole 2000 {published and unpublished data}
    1. Almonte R, Patole SK, Kadalraja R, Muller R, Whitehall JS. Erythromycin for feed intolerance in preterm neonate: a randomised, controlled trial. Pediatric Research 1999;45:276A.
    1. Patole SK, Almonte R, Kadalraja R, Tuladhar R, Muller R, Whitehall JS. Can prophylactic oral erythromycin reduce time to full enteral feeds in preterm neonates?. International Journal of Clinical Practice 2000;54:504‐8. - PubMed
Stenson 1998 {published data only}
    1. Stenson BJ, Middlemist L, Lyon AJ. Influence of erythromycin on establishment of feeding in preterm infants: observations from a randomised controlled trial. Archives of Disease in Childhood 1998;79:F212‐4. - PMC - PubMed

References to studies excluded from this review

Costalos 2001 {published data only}
    1. Costalos C, Gavrili V, Skouteri V, Gounaris A. The effect of low‐dose erythromycin on whole gastrointestinal transit time of preterm infants. Early Human Development 2001;65:91‐6. - PubMed
Costalos 2002 {published data only}
    1. Costalos C, Gounaris A, Varhalama E, Kokori F, Alexiou N, Kolovou E. Erythromycin as a prokinetic agent in preterm infants. JPGN 2002;34:23‐5. - PubMed
Curry 2004 {published data only}
    1. Curry JI, Lander AD, Stringer MD. A multicenter, randomized, double‐blind, placebo‐controlled trial of the prokinetic agent erythromycin in the postoperative recovery of infants with gastroschisis. Journal of Pediatric Surgery 2004;39:565‐9. - PubMed
Jadcherla 2002 {published data only}
    1. Jadcherla SR, Berseth CL. Effect of erythromycin on gastroduodenal contractile activity in developing neonates. JPGN 2002;34:16‐22. - PubMed
Nogami 2001 {published data only}
    1. Nogami K, Nishikubo T, Minowa H, Uchida Y, Kamitsuji H, Takahashi Y. Intravenous low‐dose erythromycin administration for infants with feeding intolerance. Pediatrics International 2001;43:605‐10. - PubMed

Additional references

al Tawil 1996
    1. al Tawil Y, Berseth CL. Gestational and postnatal maturation of duodenal motor responses to intragastric feeding. Journal of Pediatrics 1996;129:374‐81. - PubMed
Annese 1992
    1. Annese V, Janssens J, Vantrappen G, Tack J, Peeters TL, Willemse P, Cutsem E. Erythromycin accelerates gastric emptying by inducing antral contractions and improved gastroduodenal coordination. Gastroenterology 1992;102:823‐8. - PubMed
Aynsley‐Green 1983
    1. Aynsley‐Green A. Hormones and postnatal adaptation to enteral nutrition. Journal of Pediatric Gastroenterology and Nutrition 1983;2:418‐27. - PubMed
Berseth 1989
    1. Berseth CL. Gestational evolution of small intestine motility in preterm and term infants. Journal of Pediatrics 1989;115:646‐51. - PubMed
Berseth 1990
    1. Berseth CL. Neonatal small intestinal motility: motor responses to feeding in term and preterm infants. Journal of Pediatrics 1990;117:777‐82. - PubMed
Coulie 1998
    1. Coulie B, Tack J, Peeters T, Janssens J. Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans. Gut 1998;43:395‐400. - PMC - PubMed
Di Lorenzo 1990
    1. Lorenzo C, Lachman R, Hyman PE. Intravenous erythromycin for postpyloric intubation. Journal of Pediatric Gastroenterology and Nutrition 1990;11:45‐7. - PubMed
Dworkin 1976
    1. Dworkin LD, Levine GM, Farber NJ, Spector MH. Small intestinal mass of the rat is partially determined by indirect effects of intraluminal nutrition. Gastroenterology 1976;71:626‐30. - PubMed
George 1968
    1. George, JD. New clinical method for measuring the rate of gastric emptying: the double sampling test meal. Gut 1968;9:237‐42. - PMC - PubMed
Honein 1999
    1. Honein MA, Paulozzi LJ, Himelright M, et al. Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromycin: a case review and cohort study. Lancet 1999;354:2101‐5. - PubMed
Itoh 1984a
    1. Itoh Z, Nakaya M, Suzuki T, Arai H, Wakabayashi K. Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog. American Journal of Physiology 1984;247:G688‐94. - PubMed
Itoh 1984b
    1. Itoh Z, Suzuki T, Nakaya M, Inoue M, Mitsuhashi S. Gastrointestinal motor‐stimulating activity of macrolide antibiotics and analysis of their side effects on the canine gut. Antimicrobial Agents and Chemotherapy 1984;26:863‐9. - PMC - PubMed
Johnson 1976
    1. Johnson LR. The trophic action of gastrointestinal hormones. Gastroenterology 1976;70:278‐88. - PubMed
Kubota 1994
    1. Kubota M, Nakamura T, Motokura T, Mori S, Nishida A. Erythromycin improves gastrointestinal motility in extremely low birthweight infants. Acta Paediatrica Japonica 1994;36:198‐201. - PubMed
Lewin 1996
    1. Lewin MB, Bryant RM, Fenrich AL, Grifka RG. Cisapride‐induced prolonged QT interval. Journal of Pediatrics 1996;128:279‐81. - PubMed
Lyon 1998
    1. Lyon AJ, McColm J, Middlemist L, Fergusson S, McIntosh N, Ross PW. Randomised trial of erythromycin on the development of chronic lung disease in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 1998;78:F10‐4. - PMC - PubMed
Miller 1990
    1. Miller SM, O'DorisioTM, Thomas FB, Mekhjian HS. Erythromycin exerts a prokinetic effect in patients with chronic idiopathic intestinal pseudo‐obstruction. Gastroenterology 1990;98:A375.
Ng 1997
    1. Ng PC, Fok TF, Lee CH, Wong W, Cheung KL. Erythromycin treatment for gastrointestinal dysmotility in preterm infants. Journal of Paediatrics and Child Health 1997;33:148‐50. - PubMed
Otterson 1990
    1. Otterson MF, Sarna SK. Gastrointestinal motor effects of erythromycin. American Journal of Physiology 1990;259:G355‐63. - PubMed
Peeters 1989
    1. Peeters T, Matthijs G, Depoortere I, et al. Erythromycin is a motilin receptor agonist. American Journal of Physiology 1989;257:G470‐4. - PubMed
Sarna 1991
    1. Sarna SK, Soergel KH, Koch TR, et al. Gastrointestinal motor effects of erythromycin in humans. Gastroenterology 1991;101:1488‐96. - PubMed
Simkiss 1994
    1. Simkiss DE, Adams IP, Myrdal U, Booth IW. Erythromycin in neonatal postoperative intestinal dysmotility. Archives of Disease in Childhood 1994;71:128‐9. - PMC - PubMed
Su 1998
    1. Su BH, Lin HC, Peng CT, Tsai CH. Effect of erythromycin on feeding intolerance in very low birth weight infants: a preliminary observation. Acta Paed Sin 1998;39:324‐6. - PubMed
Tack 1992
    1. Tack J, Janssens J, Vantrappen G, Peeters T, Annese V, Depoortere I, Muls E, Bouillon R. Effect of erythromycin on gastric motility in controls and in diabetic gastroparesis. Gastroenterology 1992;103:72‐9. - PubMed
Tomomasa 1985
    1. Tomomasa T, Itoh Z, Koizumi T, Kuroume T. Nonmigrating rhythmic activity in the stomach and duodenum of neonates. Biology of the Neonate 1985;48:1‐9. - PubMed
Zara 1985
    1. Zara GP, Thompson HH, Pilot MA, Ritchie HD. Effects of erythromycin on gastrointestinal tract motility. Journal of Antimicrobial Chemotherapy 1985;16 (Suppl A):175‐9. - PubMed

References to other published versions of this review

Ng 2000
    1. Ng E, Shah V. Erythromycin for feeding intolerance in preterm infants. Cochrane Database of Systematic Reviews 2000, Issue 2. [DOI: 10.1002/14651858.CD001815] - DOI - PubMed

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