Systematic review and meta-analysis of human milk intake and retinopathy of prematurity: a significant update

J Perinatol. 2016 Nov;36(11):913-920. doi: 10.1038/jp.2016.98. Epub 2016 Jul 14.


Objective: Two recent meta-analyses have studied the association of exclusive or mainly human milk intake (HMI) on retinopathy of prematurity (ROP). One of these meta-analysis found a protective effect of only or mainly HMI on Severe ROP but not on any stage ROP. However, both these meta-analyses did not find protection from any stage ROP or Severe ROP with any amount of HMI. The objective of this study was to study the association between any amount of HMI and the development of All ROP and Severe ROP in very-low birth weight infants (VLBWI) and extremely low birth weight infants (ELBWI) by systematic review using PRISMA-P guidelines and meta-analysis.

Study design: Exposure, controls and outcomes studied were any amount of HMI vs no HMI and All ROP/Severe ROP in VLBWI/ELBWI. All ROP was defined as all stages of ROP pooled together, and Severe ROP as ⩾stage 3 ROP and ROP requiring intervention. Results and effect sizes are expressed as odds ratio (OR), relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (95% CI). Data sources used were PubMed, MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, Scopus and CINAHL until 24 April 2015. Extracted data were pooled using a fixed effects model. Heterogeneity was assessed. Sensitivity analysis was performed.

Results: Five hundred nine of 1701 infants who received any amount of HMI developed All ROP vs 310 of 760 infants without HMI developed All ROP with a pooled OR 0.63* (0.51,0.78), RR 0.76* (0.67,0.86) and RD -0.09* (-0.13,-0.05). The NNT with any amount of HMI was 11* (8,20) (*P<0.0001) to prevent one case of All ROP. 204 of 2465 infants who received any amount of HMI developed Severe ROP vs 85 of 764 infants without HMI developed Severe ROP with a pooled OR 0.74* (0.56,0.98), RR 0.77* (0.60,0.98) and RD -0.03* (-0.05,-0.00). The NNT with any amount of HMI was 33* (*P=0.04) to prevent one case of Severe ROP.

Conclusion: Any amount of HMI is strongly associated with the protection from All ROP and Severe ROP.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Breast Feeding / statistics & numerical data*
  • Case-Control Studies
  • Female
  • Humans
  • Infant
  • Infant Nutritional Physiological Phenomena / immunology*
  • Infant, Very Low Birth Weight / immunology
  • Milk, Human / immunology*
  • Observational Studies as Topic
  • Retinopathy of Prematurity / etiology
  • Retinopathy of Prematurity / prevention & control*
  • Risk
  • Severity of Illness Index