Erythromycin for feeding intolerance in preterm infants.
BACKGROUND
Functional immaturity of gastrointestinal motility predisposes preterm infants to feeding intolerance. Motilin, a gastrointestinal peptide, stimulates propagative contractile activity during phase III of the migratory motor complex in the interdigestive state. Erythromycin (EM) is a motilin agonist with prokinetic effect at low doses (1-3mg/kg).


OBJECTIVE
To evaluate the effectiveness of EM in promoting gastrointestinal motility in preterm infants with feeding intolerance and assess clinically significant adverse effects associated with its use.


METHODS
Systematic literature search in accordance with the Cochrane Neonatal Collaborative Review Group search strategy. Randomized and quasi-randomized controlled trials of EM use, at any dose, in preterm infants to promote gastrointestinal motility were identified by searching MEDLINE, EMBASE, CINAHL, the Cochrane Library, reference lists of published studies, personal files, and abstracts published in Pediatric Research.


METHODS
Randomized controlled trials of oral or intravenous EM use at dose range of 3 to 12 mg/kg/day in preterm infants less than or equal to 36 weeks gestational age with feeding tolerance were included in this review.


METHODS
Data regarding the primary clinical outcome of days to achieve full enteral feeding were compared among studies. Data on secondary outcomes including adverse effects associated with the use of EM (diarrhea, nosocomial infections, cardiac arrhythmias, or theophylline toxicity), duration of parenteral nutrition, weight gain, incidence of necrotizing enterocolitis (NEC), hypertrophic pyloric stenosis, and length of hospital stay were assessed.


RESULTS
Two randomized controlled studies of EM use in preterm infants for improving gastrointestinal motility were identified. Since both studies involved preterm infants treated with EM at dose >12mg/kg/day at commencement of feeding, they did not meet inclusion criteria defined a priori for this review. There was no statistically significant difference in the incidence of NEC (RR 0.59, 95%CI 0.11, 3.01; RD -0.021, 95%CI -0.087, 0.045). No statistically significant difference was noted in days to achieve full enteral feeds, length of hospital stay, and adverse events between groups.


CONCLUSIONS
EM at antimicrobial doses may not be effective in preterm infants with feeding intolerance. Further studies are needed to determine whether EM in lower doses is effective as a prokinetic agent in such infants.
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Division of Neonatology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8. eugeneng@canada.com
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D004917:Erythromycin / Q000009:adverse effects / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D005769:Gastrointestinal Motility; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D005765:Gastrointestinal Agents; D004917:Erythromycin