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

  • Conclusions changed
  • Review
  • Intervention

Authors

  • Eugene Ng,

    Corresponding author
    1. Sunnybrook Health Sciences Centre, Department of Newborn and Developmental Paediatrics, Toronto, Ontario, Canada
    • Eugene Ng, Department of Newborn and Developmental Paediatrics, Sunnybrook Health Sciences Centre, C/O Women's College Hospital, 76 Grenville Street, Toronto, Ontario, M5S1B2, Canada. eugene.ng@sunnybrook.ca.

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  • Vibhuti S Shah

    1. Mount Sinai Hospital, Department of Paediatrics, Toronto, Ontario, Canada
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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 methods

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.

摘要

背景

紅黴素預防及治療早產兒餵養不耐受

胃腸運動功能不成熟使早產兒易患上餵養不耐受。紅黴素是一種胃動素(motilin)增效劑,經由刺激消化間期的傳增性收縮活動而促進胃腸動力作用。

目標

評價紅黴素預防及治療早產兒餵食耐受不良的效果。並評估其應用所引起的臨床重要不良反應。

搜尋策略

按照Cochrane新生兒協作評價組的檢索方法進行系統文獻檢索。通過檢索MEDLINE、EMBASE、CINAHL、Cochrane 圖書館、已發表研究的參考文獻目錄、個人檔案和發表在兒科研究上的摘要,查找以任何劑量應用EM促進早產兒胃腸蠕動的隨機和半隨機對照試驗。

選擇標準

本評價納入對患餵養不耐受的36孕週或不足36孕週早產兒,使用劑量範圍3-12毫克/公斤/日的EM進行口服或靜注治療的隨機對照試驗。然而,有不少研究使用較高劑量的紅徾素(> 12 毫克/公斤/天) 或用於有餵食耐受不良高危險的預防性使用. 事後決定將這些研究也納入此次的回顧.

資料收集與分析

研究區分為預防性以及治療性研究,從每個區間得到的資料分別分析.每個區間內根據紅徾素低機量(3到12毫克/公斤/天)或高劑量(>12毫克/公斤/天)再分組分析. 主要結果為達到完全腸內餵養所需時間 次要結果包括EM使用引起的不良副作用,腸外營養的持續時間、體重增加、壞死性小腸結腸炎(NEC)發病率和住院時間數。

主要結論

10個隨機對照研究(3個預防試驗和7個治療試驗)被納入。因為定義餵養不耐受和測量結果,分析和報告差異過大,使得要進行Metaanalysis大部分的結果是不可能的。然而觀察到,使用紅黴素高治療劑量(40至50毫克/公斤/日)或使用於> 32週嬰兒的研究發現對餵養不耐有較正面的結果。高劑量預防研究的Metaanalysis發現對於壞死性腸炎無顯著差異(typical RR 0.59, 95% CI 0.11, 3.01; typical RD −0.021, 95% CI −0.087, 0.045)。 而高劑量治療的Metaanalysis對敗血症也無顯著差異(typical RR 0.83, 95% CI 0.47, 1.45; typical RD −0.04, 95% CI −0.17, 0.08)。

作者結論

現在仍沒有足夠的證據可以建議對餵養不耐受或有此危險性的的早產兒使用低或高劑量的紅徾素。有必要開展進一步研究以決定紅黴素用於>32周懷孕週數早產兒作為促胃腸動力劑時是否有一個更確切的劑量範圍。

翻譯人

本摘要由臺中榮民總醫院薛榮華翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

沒有足夠的證據證明大或小劑量紅黴素用於預防或治療早產兒餵養問題有益處。需要重症照顧的早產兒經常有餵食的問題。通常情況下,一些食物停留在胃而沒有被消化。早點餵養能促進胃腸道正常發展和可避免使用靜脈營養的健康問題。紅黴素是一種抗生素,對胃腸道有一種效果,可能有助於嬰幼兒餵養問題。不過,這次回顧發現,沒有足夠的證據推薦使用小或大劑量紅黴素可以預防或治療早產兒的餵養問題。

Plain language summary

Erythromycin for preventing and treating preterm infants with feeding difficulties

There is not enough evidence to show any benefit from erythromycin used in large or small doses for the prevention or treatment of feeding problems in premature infants. Premature infants who need intensive care often have feeding problems. Frequently, some food stays in the stomach without being digested. Earlier feeding can facilitate normal development of the gastrointestinal tract and can avoid health problems related to feeding by intravenous lines. Erythromycin is an antibiotic that has an effect on the gastrointestinal tract and may help infants with feeding problems. However, this review found that there is not enough evidence to recommend the use of erythromycin in small or large doses to prevent or treat premature infants with feeding problems.