Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • State of the Art
  • Published:

State-of-the-Art

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

Journal of Perinatology volume 36, pages 913–920 (2016)Cite this article

Subjects

Abstract

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.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

References

  1. Gainsford W . Changing fashions in infant care. J Pediatr 1964; 64: 913–922.

    Article  Google Scholar 

  2. Kao JS, Dawson JD, Murray JC, Dagle JM, Berends SK, Gillen SB et al. Possible roles of bilirubin and breast milk in protection against retinopathy of prematurity. Acta Paediatr 2011; 100 (3): 347–351.

    Article  Google Scholar 

  3. Connor WE, Neuringer M, Reisbick S . Essential fatty acids: the importance of n-3 fatty acids in the retina and brain. Nutr Rev 1992; 50 (4 (Pt 2): 21–29.

    CAS  PubMed  Google Scholar 

  4. Hallman M, Bry K, Hoppu K, Lappi M, Pohjavuori M . Inositol supplementation in premature infants with respiratory distress syndrome. N Engl J Med 1992; 326 (19): 1233–1239.

    Article  CAS  Google Scholar 

  5. Hylander MA, Strobino DM, Pezzullo JC, Dhanireddy R . Association of human milk feedings with a reduction in retinopathy of prematurity among very low birthweight infants. J Perinatol 2001; 21 (6): 356–362.

    Article  CAS  Google Scholar 

  6. Patel AL, Johnson TJ, Engstrom JL, Fogg LF, Jegier BJ, Bigger HR et al. Impact of early human milk on sepsis and health care costs in very low birth weight. J Perinatol 2013; 33 (7): 514–519.

    Article  CAS  Google Scholar 

  7. Johnson L, Quinn G, Abbasi S, Otis C, Goldstein D, Sacks L et al. Effect of sustained pharmacologic vitamin E levels on incidence and severity of retinopathy of prematurity: a controlled clinical trial. J Pediatr 1989; 114: 827–838.

    Article  CAS  Google Scholar 

  8. Manzoni P, Stolfi I, Pedicino R, Vagnarelli F, Mosca F, Pugni L et al. Human milk feeding prevents retinopathy of prematurity (ROP) in preterm VLBW neonates. Early Hum Dev 2013; 89 (suppl 1): S64–S68.

    Article  Google Scholar 

  9. Porcelli PJ, Weaver RG . The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants. Early Hum Dev 2010; 86 (6): 391–396.

    Article  Google Scholar 

  10. Okamoto T, Shirai M, Kokubo M, Takahashi S, Kajino M, Takase M et al. Human milk reduces the risk of retinal detachment in extremely low-birthweight infants. Pediatr Int 2007; 49 (6): 894–897.

    Article  Google Scholar 

  11. Furman L, Taylor G, Minich N, Hack M . The effect of maternal milk on neonatal morbidity of very low-birth-weight infants. Arch Pediatr Adolesc Med 2003; 157 (1): 66–71.

    Article  Google Scholar 

  12. Heller CD, O'Shea M, Yao Q, Langer J, Ehrenkranz RA, Phelps DL et al. Human milk intake and retinopathy of prematurity in extremely low birth weight infants. Pediatrics 2007; 120 (1): 1–9.

    Article  Google Scholar 

  13. Merewood A, Philipp BL, Chawla N, Cimo S . The baby-friendly hospital initiative increases breastfeeding rates in a US neonatal intensive care unit. J Hum Lact 2003; 19 (2): 166–171.

    Article  Google Scholar 

  14. Powers NG, Bloom B, Peabody J, Clark R . Site of care influences breastmilk feedings at NICU discharge. J Perinatol 2003; 23 (1): 10–13.

    Article  Google Scholar 

  15. Joint Commission Online, 2015. Performance measurement: changes to breast milk feeding performance measures PC-05a and PC-05.(cited 25 December 2015). Available at http://www.jointcommission.org/assets/1/23/jconline_May_6_2015.pdf (accessed 25 December 2015).

  16. Nutrition, physical activity and obesity: data, trends and maps. 2012 (cited 25 December 2015). Available at https://nccd.cdc.gov/NPAO_DTM/IndicatorSummary.aspx?category=8&indicator=49 (accessed 25 December 2015).

  17. Zhou J, Shukla VV, John D, Chen C . Human milk feeding as a protective factor for retinopathy of prematurity: a meta-analysis. Pediatrics 2015; 136 (6): e1576–e1586.

    Article  Google Scholar 

  18. Fang JL, Sorita A, Carey WA, Colby CE, Murad HM, Alahdab F . Interventions to prevent retinopathy of prematurity: a meta-analysis. Pediatrics 2016; 137 (4): e20153387.

    Article  Google Scholar 

  19. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283 (15): 2008–2012.

    Article  CAS  Google Scholar 

  20. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015; 349: g7647.

    Article  Google Scholar 

  21. Higgins JP, Thompson SG, Deeks JJ, Altman DG . Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557–560.

    Article  Google Scholar 

  22. Maayan-Metzger A, Avivi S, Schushan-Eisen I, Kuint J . Human milk versus formula feeding among preterm infants: short-term outcomes. Am J Perinatol 2012; 29 (2): 121–126.

    Article  Google Scholar 

  23. Spiegler J, Michael P, Gebauer C, Bendiks M, Herting E, Göpel W . Does breastmilk influence the development of bronchopulmonary dysplasia. J Pediatr 2016; 169: 76–80.

    Article  Google Scholar 

  24. Mansson J, Fellman V, Stjernqvist K . EXPRESS Study Group (authors). Extremely preterm birth affects boys more and socio-economic and neonatal variables pose sex-specific risks. Acta Paediatr 2015; 104 (5): 14–21.

    Article  Google Scholar 

  25. Ginovart G, Gich I, Verd S . Human milk feeding protects very low-birth-weight infants from retinopathy of prematurity: a pre-post cohort analysis. J Matern Fetal Neonatal Med 2016; 26: 1–6 .

    Google Scholar 

  26. Hair AB, Peluso AM, Hawthorne KM, Perez J, Smith DP, Khan JY et al. Beyond necrotizing enterocolitis prevention: improving outcomes with an exclusive human milk-based diet. Breastfeed Med 2016; 11 (2): 70–74.

    Article  Google Scholar 

  27. Schanler RJ, Lau C, Hurst NM, Smith EO . Randomized trial of donor human milk versus preterm formula as substitutes for mothers' own milk in the feeding of extremely premature infants. Pediatrics 2005; 116 (2): 400–406.

    Article  Google Scholar 

  28. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M et al The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Canada: Department of Epidemiology and community Medicine, University of Ottawa; 2009. Available at http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm.

  29. Likis FE, Andrews JC, Fonnesbeck CJ, Hartmann KE, Jerome RN, Potter SA et al. Smoking cessation interventions in pregnancy and postpartum care. Appendix F, Thresholds for Quality Assessment. Agency for Healthcare Research and Quality: Rockville, MD, USA, 2014. Available at. http://www.ncbi.nlm.nih.gov/books/NBK190490/.

  30. Patel AL, Meier PP, Engstrom JL . The evidence for use of human milk in very low-birthweight preterm infants. Neoreviews 2007; 8 (11): e459–e466.

    Article  Google Scholar 

  31. Friel JK, Martin SM, Langdon M, Herzberg GR, Buettner GR . Milk from mothers of both premature and full-term infants provides better antioxidant protection than does infant formula. Pediatr Res 2002; 51 (5): 612–618.

    Article  Google Scholar 

  32. Katz ML, Robison WG . Autoxidative damage to the retina: potential role in retinopathy of prematurity. Birth Defects Orig Artic Ser 1988; 24 (1): 237–248.

    CAS  PubMed  Google Scholar 

  33. Manzoni P, Guardian R, Bonetti P, Priolo C, Maestri A, Caterina M et al. Lutein and zeaxanthin supplementation in preterm infants in NICU: preliminary data from a multi center RCT. Early Hum Dev 2009; 85 (10 Supplement): S93–S94.

    CAS  Google Scholar 

  34. Lindmark-Månsson H, Akesson B . Antioxidative factors in milk. Br J Nutr 2000; 84 (Suppl 1): S103–S110.

    PubMed  Google Scholar 

  35. Spierer A, Rabinowitz R, Pri-Chen S, Rosner M . An increase in superoxide dismutase ameliorates oxygen-induced retinopathy in transgenic mice. Eye (Lond) 2005; 19 (1): 86–91.

    Article  CAS  Google Scholar 

  36. Shoji H, Shimizu T, Shinohara K, Oguchi S, Shiga S, Yamashiro Y . Suppressive effects of breast milk on oxidative DNA damage in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2004; 89 (2): F136–F138.

    Article  CAS  Google Scholar 

  37. Raju TN, Langenberg P, Bhutani V, Quinn GE . Vitamin E prophylaxis to reduce retinopathy of prematurity: a reappraisal of published trials. J Pediatr 1997; 131 (6): 844–850.

    Article  CAS  Google Scholar 

  38. Birch E, Birch D, Hoffman D, Hale L, Everett M, Uauy R . Breast-feeding and optimal visual development. J Pediatr Ophthalmol Strabismus 1993; 30 (1): 33–38.

    CAS  PubMed  Google Scholar 

  39. Pawlik D, Lauterbach R, Turyk E . Fish-oil fat emulsion supplementation may reduce the risk of severe retinopathy in VLBW infants. Pediatrics 2011; 127 (2): 223–228.

    Article  Google Scholar 

  40. SanGiovanni JP, Chew EY . The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res 2005; 24 (1): 87–138.

    Article  CAS  Google Scholar 

  41. Hellström A, Carlsson B, Niklasson A, Segnestam K, Boguszewski M, de Lacerda L et al. IGF-I is critical for normal vascularization of the human retina. J Clin Endocrinol Metab 2002; 87 (7): 3413–3416.

    Article  Google Scholar 

  42. Nissenkorn I, Yassur Y, Mashkowski D, Sherf I, Ben-Sira I . Myopia in premature babies with and without retinopathy of prematurity. Br J Ophthalmol 1983; 67 (3): 170–173.

    Article  CAS  Google Scholar 

  43. Kushner BJ . Long-term follow-up of regressed retinopathy of prematurity. Birth Defects Orig Artic Ser 1988; 24 (1): 193–199.

    CAS  PubMed  Google Scholar 

  44. Burns PB, Rohrich RJ, Chung KC . The levels of evidence and their role in evidence-based medicine. Plast Reconstr 2011; 128 (1): 305–310.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to profusely thank the following for their help in this project: Peter J. Porcelli, MD; Professor, Department of Pediatrics, Wake Forest University, Winston-Salem, NC 27157, United States for sharing summary data from his study. Jessica Bennett, MSHS, RD, LD, CNSC, Neonatal Dietitian & Clinical Manager, The Woman’s Hospital of Texas, Houston, TX 77054.

Author contributions

Reproducible literature search strategy: BFG, SKB and RD. Collection and assembly of the data: SKB, SSB, SSB and RD. Analysis and interpretation of the data: SKB, JCP, SSB, SSB and RD. Conception and design, drafting of the article, critical revision of the article for important intellectual content and final approval of the article: SKB, BFG, JCP, SSB, SSB and RD.

Author information

Authors and Affiliations

  1. Neonatologist, Pediatrix Medical Group and The Womans Hospital of Texas, Houston, TX, USA

    S K Bharwani

  2. Head of Education, Research and Clinical Services, Biomedical Libraries, Dartmouth College, Hanover, NH, USA

    B F Green

  3. Department of Medicine, Georgetown University, Washington,, DC, USA

    J C Pezzullo

  4. Emory University, Atlanta, GA, USA

    S S Bharwani & S S Bharwani

  5. Department of Pediatrics, Division of Neonatology, University of Tennessee Health Science Center, E201 Rout Center for Women and Newborns, Memphis, TN, USA

    R Dhanireddy

Authors
  1. S K Bharwani
    View author publications

    Search author on:PubMed Google Scholar

  2. B F Green
    View author publications

    Search author on:PubMed Google Scholar

  3. J C Pezzullo
    View author publications

    Search author on:PubMed Google Scholar

  4. S S Bharwani
    View author publications

    Search author on:PubMed Google Scholar

  5. S S Bharwani
    View author publications

    Search author on:PubMed Google Scholar

  6. R Dhanireddy
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to R Dhanireddy.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Journal of Perinatology website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bharwani, S., Green, B., Pezzullo, J. et al. Systematic review and meta-analysis of human milk intake and retinopathy of prematurity: a significant update. J Perinatol 36, 913–920 (2016). https://doi.org/10.1038/jp.2016.98

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/jp.2016.98

This article is cited by

Search

Advanced search

Quick links