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Macrolides for the prevention and treatment of feeding intolerance in preterm low birth weight infants: a systematic review and meta-analysis

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Abstract

The role of macrolides for the prevention and treatment of feeding intolerance (FI) in preterm low birth weight (LBW) infants has not been well established. To assess the efficacy and safety of macrolides to prevent or treat FI in preterm LBW infants. A systematic review and meta-analysis (PROSPERO ID: CRD42020170519) was conducted for English articles published since inception to March 2020, using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. Search terms included preterm low birth weight infants, macrolides, erythromycin, azithromycin, clarithromycin, and feeding intolerance. Randomized controlled trials (RCTs) assessing the effects of macrolide therapy on the time to achieve full enteral feeding (FEF;150 mL/kg/day), duration of parenteral nutrition (PN), hospitalization, and adverse events in preterm LBW infants were included. Independent extraction of data was done by both authors using predefined data-sheet. Very-low to low-quality evidence from 21 RCTs, 19 for erythromycin (prophylaxis-6, rescue-13) and 2 for clarithromycin (prophylaxis-1, rescue-1) demonstrated a significantly beneficial role of erythromycin for an earlier FEF, both as a prophylaxis (SMD-0.53, 95% CI − 0.74,− 0.33; 6 studies, n = 368) as well as rescue (SMD-1.16, 95% CI − 1.88, − 0.44; 11 studies, n = 664). Rescue therapy was also beneficial for a significant reduction in the duration of PN, hospitalization, incidences of sepsis, necrotizing enterocolitis, and cholestasis. No arrhythmia or infantile hypertrophic pyloric stenosis was reported.

Conclusions: Erythromycin therapy, both as prophylaxis and rescue, is beneficial to reduce the time to achieve FEF in preterm LBW infants, at no higher risk of adverse events.

Trial registration: PROSPERO ID: CRD42020170519

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Authors and Affiliations

  1. Department of Neonatology, All India Institute of Medical Sciences, Rishikesh, India

    Sriparna Basu

  2. School of Health Sciences, University of Southampton, Southampton, UK

    Susan Smith

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Sriparna Basu (SB) and Susan Smith (SS) conceptualized and planned this systematic review. SB searched the literature, collected the study details and outcome data using a predetermined form designed for this purpose in consultation with SS. The disagreement was resolved by discussion. The risk of bias for each study was assessed by SB. Both the authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Sriparna Basu.

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Electronic supplementary material

Web Figure 1

Forest plots for the days to achieve full enteral feeding (150 mL/kg/day): A Low-dose erythromycin prophylaxis, B High-dose erythromycin prophylaxis (PNG 54 kb)

High resolution image (TIF 141 kb)

Web Figure 2

Forest plots for the days to achieve full enteral feeding (150 mL/kg/day): A Low-dose erythromycin rescue, B High-dose erythromycin rescue (PNG 378 kb)

High resolution image (TIF 507 kb)

Web Figure 3

Forest plots for the days to achieve full enteral feeding (150 mL/kg/day) after erythromycin rescue therapy: A Infants of gestational age ≥ 32 weeks B Infants of gestational age < 32 weeks (PNG 342 kb)

High resolution image (TIF 483 kb)

Web Figure 4

Forest plots for the duration of hospitalization after erythromycin rescue therapy: A Infants of gestational age ≥ 32 weeks B Infants of gestational age < 32 weeks (PNG 292 kb)

High resolution image (TIF 396 kb)

Web Table 1

Details of database search (DOCX 13 kb)

Web Table 2

Details of excluded articles (DOCX 21 kb)

Web Table 3

Meta-regression of individual outcome on mean gestation for studies using erythromycin as prophylaxis (DOCX 13 kb)

Web Table 4

Meta-regression of individual outcome on mean gestation for studies using erythromycin as treatment (DOCX 14 kb)

Web Table 5

Publication bias for individual outcome (Egger’s regression) for studies using erythromycin as prophylaxis (DOCX 13 kb)

Web Table 6

Publication bias for individual outcome (Egger’s regression) for studies using erythromycin as treatment (DOCX 14 kb)

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Basu, S., Smith, S. Macrolides for the prevention and treatment of feeding intolerance in preterm low birth weight infants: a systematic review and meta-analysis. Eur J Pediatr 180, 353–378 (2021). https://doi.org/10.1007/s00431-020-03814-1

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