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.

Exclusive human milk diet reduces incidence of severe intraventricular hemorrhage in extremely low birth weight infants

Abstract

Objective

Compare the incidence of severe (grade III/IV) intraventricular hemorrhage (IVH) and/or periventricular leukomalacia (PVL) between two groups of ELBW infants based on diet until 34 weeks corrected gestational age (CGA): (1) Exclusive human milk (EHM)—mother’s own and/or pasteurized donor human milk, human milk-derived fortifier, and oral care with colostrum/human milk vs. (2) non-EHM—bovine formula or mother’s own milk with bovine-derived fortifier.

Study design

Retrospective observational study of two groups of ELBW infants based on diet until 34 weeks CGA.

Result

There were n = 306 infants, 127 EHM and 179 non-EHM. Demographics and morbidities were similar except higher antenatal steroids and NEC in EHM group. The rate of severe IVH/PVL was lower in EHM compared to non-EHM group (7 vs. 18%, p < 0.006).

Conclusion

EHM diet had an independent neuroprotective effect and was associated with decreased incidence of severe IVH/PVL, supporting the need of EHM in ELBW infants.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Incidence of IVH/PVL by type of EHM.

References

  1. 1.

    Quigley M, Embleton ND, McGuire W. Formula versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev. 2019;7:CD002971. https://doi.org/10.1002/14651858.CD002971.pub5.

    Article  PubMed  Google Scholar 

  2. 2.

    Hylander MA, Strobino DM, Pezzullo JC, Dhanireddy R. Association of human milk feedings with a reduction in retinopathy of prematurity among very low birth weight infants. J Perinatol. 2001;21:356–62. https://doi.org/10.1038/sj.jp.7210548.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Patel A, Johnson TJ, Robin B, Bigger HR, Buchanan A, Christian E, et al. Influence of own mother’s milk on bronchopulmonary dysplasia and costs. Arch Dis Child Fetal Neonatal Ed. 2017;102:F256–61. https://doi.org/10.1136/archdischild-2016-310898.

    Article  PubMed  Google Scholar 

  4. 4.

    Lechner BE, Vohr BR. Neurodevelopmental outcomes of preterm infants fed human milk: a systematic review. Clin Perinatol. 2017;44:69–83. https://doi.org/10.1016/j.clp.2016.11.004.

    Article  PubMed  Google Scholar 

  5. 5.

    Belfort MB. Human milk and preterm infant brain development. Breastfeed Med. 2018;13:S23–5. https://doi.org/10.1089/bfm.2018.29079.mbb.

    Article  PubMed  Google Scholar 

  6. 6.

    Vohr BR, Poindexter BB, Dusick AM, McKinley LT, Wright LL, Langer JC, et al. Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age. Pediatrics. 2006;118:e115–23. https://doi.org/10.1542/peds.2005-2382.

    Article  PubMed  Google Scholar 

  7. 7.

    Singhal A, Cole TJ, Lucas A. Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials. Lancet. 2001;357:413–9. https://doi.org/10.1016/S0140-6736(00)04004-6.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    American Academy of Pediatrics. Breastfeeding and the use of human milk. Pediatrics. 2012;129:e827–41. https://doi.org/10.1542/peds.2011-3552.

    Article  Google Scholar 

  9. 9.

    Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92:529–34. https://doi.org/10.1016/s0022-3476(78)80282-0.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010;126:443–56. https://doi.org/10.1542/peds.2009-2959.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Mercier CE, Dunn MS, Ferrelli KR, Howard DB, Soll RF. Vermont Oxford Network ELBW Infant Follow-Up Study Group. neurodevelopmental outcome of extremely low birth weight infants for the Vermont Oxford Network: 1998-2003. Neonatology. 2010;97:329–38. https://doi.org/10.1159/000260136.

    Article  PubMed  Google Scholar 

  12. 12.

    Vohr BR, Wright LL, Poole K, McDonald SA. Neurodevelopmental outcomes of extremely low birth weight infants <32 weeks’ gestation between 1993 and 1998. Pediatrics. 2005;116:635–43. https://doi.org/10.1542/peds.2004-2247.

    Article  PubMed  Google Scholar 

  13. 13.

    Schindler T, Koller-Smith L, Lui K, Bajuk B, Bolisetty S. Causes of death in very preterm infants cared for in neonatal intensive care units: a population-based retrospective cohort study. BMC Pediatr. 2017;17:59. https://doi.org/10.1186/s12887-017-0810-3.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Imamura T, Ariga H, Kaneko M, Watanabe M, Shibukawa Y, Fukuda Y, et al. Neurodevelopmental outcomes of children with periventricular leukomalacia. Pediatr Neonatol. 2013;54:367–72. https://doi.org/10.1016/j.pedneo.2013.04.006.

    Article  PubMed  Google Scholar 

  15. 15.

    Blesa M, Sullivan G, Anblagan D, Telford EJ, Quigley AJ, Sparrow SA, et al. Early breast milk exposure modifies brain connectivity in preterm infants. Neuroimage. 2019;184:431–9. https://doi.org/10.1016/j.neuroimage.2018.09.045.

    Article  PubMed  Google Scholar 

  16. 16.

    Ottolini KM, Andescavage N, Kapse K, Jacobs M, Limperopoulos C. Improved brain growth and microstructural development in breast milk-fed very low birth weight premature infants. Acta Paediatr. 2020;109:1580–7. https://doi.org/10.1111/apa.14156.

    Article  PubMed  Google Scholar 

  17. 17.

    Keller T, Körber F, Oberthuer A, Schafmeyer L, Mehler K, Kuhr K, et al. Intranasal breast milk for premature infants with severe intraventricular hemorrhage—an observation. Eur J Pediatr. 2019;178:199–206. https://doi.org/10.1007/s00431-018-3279-7.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:1–13. https://doi.org/10.1186/1471-2431-13-59.

    Article  Google Scholar 

  19. 19.

    Patel AL, Engstrom JL, Meier PP, Kimura RE. Calculating postnatal growth velocity in very low birth weight (VLBW) premature infants. J Perinatol. 2009;29:618–22. https://doi.org/10.1038/jp.2009.55.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Dohare P, Zia MT, Ahmed E, Ahmed A, Yadala V, Schober AL, et al. AMPA-kainate receptor inhibition promotes neurologic recovery in premature rabbits with intraventricular hemorrhage. J Neurosci. 2016;36:3363–77. https://doi.org/10.1523/JNEUROSCI.4329-15.2016.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Kim SE, Ko IG, Shin MS, Kim CJ, Ko YG, Cho H. Neuroprotective effects of bovine colostrum on intracerebral hemorrhage-induced apoptotic neuronal cell death in rats. Neural Reg Res. 2012;7:1715–21. https://doi.org/10.3969/j.issn.1673-5374.2012.22.006.

    Article  Google Scholar 

  22. 22.

    Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am. 2013;60:49–74. https://doi.org/10.1016/j.pcl.2012.10.002.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Gila-Diaz A, Arribas SM, Algara A, Martín-Cabrejas MA, López de Pablo AL, SáenzdePipaón M, et al. A review of bioactive factors in human breastmilk: a focus on prematurity. Nutrients. 2019;11:1307. https://doi.org/10.3390/nu11061307.

    CAS  Article  PubMed Central  Google Scholar 

  24. 24.

    Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis. 2004;16:1–13. https://doi.org/10.1016/j.nbd.2003.12.016.

    CAS  Article  Google Scholar 

  25. 25.

    Sweeney MD, Ayyadurai S, Zlokovic BV. Pericytes of the neurovascular unit: key functions and signaling pathways. Nat Neurosci. 2016;19:771–83. https://doi.org/10.1038/nn.4288.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Gale SM, Read LC, George-Nascimento C, Wallace JC, Ballard J. Is dietary epidermal growth factor absorbed by premature human infants? Biol Neonate. 1989;55:104–10. https://doi.org/10.1159/000242903.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Liu B, Neufeld AH. Activation of epidermal growth factor receptors in astrocytes: from development to neural injury. J Neurosci Res. 2007;85:3523–9. https://doi.org/10.1002/jnr.21364.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Ballabh P. Intraventricular hemorrhage in premature infants: Mechanism of disease. Pediatr Res. 2010;67:1–8. https://doi.org/10.1203/PDR.0b013e3181c1b176.

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Kornblum HI, Hussain R, Wiesen J, Miettinen P, Zurcher SD, Chow K, et al. Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor. J Neurosci Res. 1998;53:697–717. 10.1002/(SICI)1097-4547(19980915)53:6<697::AID-JNR8>3.0.CO;2-0.

    CAS  Article  Google Scholar 

  30. 30.

    Vinukonda G, Hu F, Mehdizadeh R, Dohare P, Kidwai A, Juneja A, et al. Epidermal growth factor preserves myelin and promotes astrogliosis after intraventricular hemorrhage. Glia. 2016;64:1987–2004. https://doi.org/10.1002/glia.23037.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Zhou Q, Li M, Wang X, Li Q, Wang T, Zhu Q, et al. Immune-related microRNAs are abundant in breast milk exosomes. Int J Biol Sci 2012;8:118–23. https://doi.org/10.7150/ijbs.8.118.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Alsaweed M, Lai CT, Hartmann PE, Geddes DT, Kakulas F. Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk. Sci Rep. 2016;6:20680. https://doi.org/10.1038/srep20680.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Golan-Gerstl R, Elbaum Shiff Y, Moshayoff V, Schecter D, Leshkowitz D, Reif S. Characterization and biological function of milk-derived miRNAs. Mol Nutr Food Res. 2017;61. https://doi.org/10.1002/mnfr.201700009.

  34. 34.

    Qiu J, Zhou XY, Zhou XG, Cheng R, Liu HY, Li Y. Neuroprotective effects of microRNA-210 on hypoxic-ischemic encephalopathy. Biomed Res Int. 2013;2013:350419. https://doi.org/10.1155/2013/350419.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Xi T, Jin F, Zhu Y, Wang J, Tang L, Wang Y, et al. miR-27a-3p protects against blood-brain barrier disruption and brain injury after intracerebral hemorrhage by targeting endothelial aquaporin-11. J Biol Chem. 2018;293:20041–50. https://doi.org/10.1074/jbc.RA118.001858.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Abrams SA, Landers S, Noble LM, Poindexter BB, Daniels S, Corkins M, et al. Donor human milk for the high-risk infant: preparation, safety, and usage options in the United States. Pediatrics. 2017;139:e20163440. https://doi.org/10.1542/peds.2016-3440.

    Article  Google Scholar 

  37. 37.

    Ewaschuk JB, Unger S, O’Connor DL, Stone D, Harvey S, Clandinin MT, et al. Effect of pasteurization on selected immune components of donated human breast milk. J Perinatol. 2011;31:593–8. https://doi.org/10.1038/jp.2010.209.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Peila C, Moro GE, Bertino E, Cavallarin L, Giribaldi M, Giuliani F, et al. The effect of holder pasteurization on nutrients and biologically-active components in donor human milk: a review. Nutrients. 2016;8:pii: E477. https://doi.org/10.3390/nu8080477.

    Article  Google Scholar 

  39. 39.

    Groer M, Duffy A, Morse S, Kane B, Zaritt J, Roberts S, et al. Cytokines, chemokines, and growth factors in banked human donor milk for preterm infants. J Hum Lact. 2014;30:317–23. https://doi.org/10.1177/0890334414527795.

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Wei JC, Catalano R, Profit J, Gould JB, Lee HC. Impact of antenatal steroids on intraventricular hemorrhage in very-low-birth-weight infants. J Perinatol. 2016;36:352–6. https://doi.org/10.1038/jp.2016.38.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Chawla S, Natarajan G, Shankaran S, Pappas A, Stoll BJ, Carlo WA, et al. Association of neurodevelopmental outcomes and neonatal morbidities of extremely premature infants with differential exposure to antenatal steroids. JAMA Pediatr. 2016;170:1164–72. https://doi.org/10.1001/jamapediatrics.2016.1936.

    Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Horbar JD, Carpenter JH, Bader GJ, Kenny MJ, Soll RF, Morrow KA, et al. Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009. Pediatrics. 2012;129:1019–26. https://doi.org/10.1542/peds.2011-3028.

    Article  PubMed  Google Scholar 

  43. 43.

    Garofalo NA, Caplan MS. Oropharyngeal mother’s milk: state of the science and influence on necrotizing enterocolitis. Clin Perinatol. 2019;46:77–88. https://doi.org/10.1016/j.clp.2018.09.005.

    Article  PubMed  Google Scholar 

  44. 44.

    Keunen K, van Elburg RM, van Bel F, Benders MJ. Impact of nutrition on brain development and its neuroprotective implications following preterm birth. Pediatr Res. 2015;77:148–55. https://doi.org/10.1038/pr.2014.171.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    American Academy of Pediatrics, Committee on Nutrition. Nutritional needs of low-birth-weight infants. Pediatrics. 1985;75:976–86.

    Google Scholar 

  46. 46.

    Hair AB, Hawthorne KM, Chetta KE, Abrams SA. Human milk feeding supports adequate growth in infants ≤1250 grams birth weight. BMC Res Notes. 2013;13:459. https://doi.org/10.1186/1756-0500-6-459.

    Article  Google Scholar 

  47. 47.

    Colaizy TT, Carlson S, Saftlas AF, Morriss FH. Growth in VLBW infants fed predominantly fortified maternal and donor human milk diets: a retrospective cohort study. BMC Pediatr. 2012;12:124. https://doi.org/10.1186/1471-2431-12-124.

    Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Brownell EA, Matson AP, Smith KC, Moore JE, Esposito PA, Lussier MM, et al. Dose-response relationship between donor human milk, mother’s own milk, preterm formula, and neonatal growth outcomes. J Pediatr Gastroenterol Nutr. 2018;67:90–6. https://doi.org/10.1097/MPG.0000000000001959.

    Article  PubMed  Google Scholar 

  49. 49.

    Neubauer V, Griesmaier E, Pehböck-Walser N, Pupp-Peglow U, Kiechl-Kohlendorf U. Poor postnatal head growth in very preterm infants is associated with impaired neurodevelopment outcome. Acta Paediatr. 2013;102:883–8. https://doi.org/10.1111/apa.12319.

    Article  PubMed  Google Scholar 

  50. 50.

    Harsha SS, Archana BR. SNAPPE-II (Score for Neonatal Acute Physiology With Perinatal Extension-II) in predicting mortality and morbidity in the NICU. J Clin Diagn Res. 2015;9:SC10–12. https://doi.org/10.7860/JCDR/2015/14848.6677.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

KC, AR, and BP contributed to the design of the experiment. KC and AR played a role in the acquisition of the data and KC, AR, and BP participated in the data analysis and interpretation. All coauthors played an active role in both the preparation and editing of this manuscript. All authors have read and agreed to the content of the manuscript.

Corresponding author

Correspondence to Amanda Rahman.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Carome, K., Rahman, A. & Parvez, B. Exclusive human milk diet reduces incidence of severe intraventricular hemorrhage in extremely low birth weight infants. J Perinatol 41, 535–543 (2021). https://doi.org/10.1038/s41372-020-00834-5

Download citation

Further reading

Search

Quick links