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Human milk-derived fortifiers are linked with feed extension due to Hypoglycemia in infants <1250 g or <30 weeks: a matched retrospective chart review

Journal of Perinatology volume 43, pages 624–628 (2023)Cite this article

Subjects

Abstract

Objective

To investigate differences in hypoglycemia and extended feed prescriptions among premature infants provided bovine-derived human milk fortifiers (Bov-fort) with mother’s milk or formula vs human milk-derived human milk fortifiers (HM-fort) with mother’s milk or donor human milk.

Study design

This was a retrospective chart review (n = 98). Infants receiving HM-fort were matched with infants receiving Bov-fort. Blood glucose values and feed orders were retrieved from the electronic medical record.

Results

Prevalence of ever having blood glucose <60 mg/dL was 39.1% in the HM-fort group vs. 23.9% in the Bov-fort group (p = 0.09). Blood glucose ≤45 mg/dL occurred in 17.4% of HM-fort vs 4.3% in Bov-fort (p = 0.07). Feeds were extended for any reason in 55% of HM-fort vs. 20% of Bov-fort (p < 0.01). Feed extension due to hypoglycemia occurred in 24% of HM-fort vs. 0% of Bov-fort (p < 0.01).

Conclusion

Predominately HM-based feeds are associated with feed extension due to hypoglycemia. Prospective research is warranted to elucidate underlying mechanisms.

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Fig. 1: Percentage of infants requiring any feed extension.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Bhatia J. Human milk and the premature infant. Ann Nutr Metab. 2013;62:8–14.

    Article  CAS  PubMed  Google Scholar 

  2. Morales Y, Schanler RJ. Human milk and clinical outcomes in VLBW infants: how compelling is the evidence of benefit? Semin Perinatol. 2007;31:83–8.

    Article  PubMed  Google Scholar 

  3. Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Kiechl-Kohlendorfer U, et al. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr. 2010;156:562–7.e1.

    Article  CAS  PubMed  Google Scholar 

  4. Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R, Kiechl-Kohlendorfer U, et al. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr. 2013;163:1592–5.e1.

    Article  PubMed  Google Scholar 

  5. Wickland J, Wade C, Micetic B, Meredith K, Martin G. A retrospective analysis of the effects of an exclusively human milk protein diet on neonatal feeding tolerance. Am J Perinatol. 2020;39:995–1000.

  6. Assad M, Elliott MJ, Abraham JH. Decreased cost and improved feeding tolerance in VLBW infants fed an exclusive human milk diet. J Perinatol. 2016;36:216–20.

    Article  CAS  PubMed  Google Scholar 

  7. O’Connor DL, Kiss A, Tomlinson C, Bando N, Bayliss A, Campbell DM, et al. Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing <1250 g: a randomized clinical trial. Am J Clin Nutr. 2018;108:108–16.

    Article  PubMed  Google Scholar 

  8. 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.

    PubMed  Google Scholar 

  9. Sharma A, Davis A, Shekhawat PS. Hypoglycemia in the preterm neonate: etiopathogenesis, diagnosis, management and long-term outcomes. Transl Pediatr. 2017;6:335–48.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Staffler A, Klemme M, Mola-Schenzle E, Mittal R, Schulze A, Flemmer AW. Very low birth weight preterm infants are at risk for hypoglycemia once on total enteral nutrition. J Matern Fetal Neonatal Med. 2013;26:1337–41.

    Article  CAS  PubMed  Google Scholar 

  11. Amendoeira S, McNair C, Saini J, Habib S. Glucose homeostasis and the neonatal brain: a sweet relationship. Neonatal Netw. 2020;39:137–46.

    PubMed  Google Scholar 

  12. Barone G, Maggio L, Saracino A, Perri A, Romagnoli C, Zecca E. How to feed small for gestational age newborns. Ital J Pediatr. 2013;39:28.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Davis TA, Fiorotto ML, Suryawan A. Bolus vs. continuous feeding to optimize anabolism in neonates. Curr Opin Clin Nutr Metab Care. 2015;18:102–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bozzetti V, Paterlini G, De Lorenzo P, Gazzolo D, Valsecchi MG, Tagliabue PE. Impact of continuous vs bolus feeding on splanchnic perfusion in very low birth weight infants: a randomized trial. J Pediatr. 2016;176:86–92.e2.

    Article  PubMed  Google Scholar 

  15. Wang Y, Zhu W, Luo BR. Continuous feeding versus intermittent bolus feeding for premature infants with low birth weight: a meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2020;74:775–83.

    Article  PubMed  Google Scholar 

  16. Brooks C, Vickers AM, Aryal S. Comparison of lipid and calorie loss from donor human milk among 3 methods of simulated gavage feeding: one-hour, 2-hour, and intermittent gravity feedings. Adv Neonatal Care. 2013;13:131–8.

    Article  PubMed  Google Scholar 

  17. Castro M, Asbury M, Shama S, Stone D, Yoon EW, O’Connor DL, et al. Energy and fat intake for preterm infants fed donor milk is significantly impacted by enteral feeding method. JPEN J Parenter Enter Nutr. 2019;43:162–5.

    Article  CAS  Google Scholar 

  18. Rogers SP, Hicks PD, Hamzo M, Veit LE, Abrams SA. Continuous feedings of fortified human milk lead to nutrient losses of fat, calcium and phosphorous. Nutrients 2010;2:230–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Enfamil Human Milk Fortifer Powder: Mead Johnson & Company, LLC; Available from: https://www.hcp.meadjohnson.com/s/product/a4R4J000000PpQiUAK/enfamil-human-milk-fortifier-powder.

  20. Liquid Protein Fortifier: Abbot Nutrition; Available from: https://abbottnutrition.com/liquid-protein-fortifier.

  21. MCT oil Nestle Health Science Available from: https://www.nestlenutritionstore.com/mct-oilr.html.

  22. Thompson-Branch A, Havranek T. Neonatal hypoglycemia. Pediatr Rev. 2017;38:147–57.

    Article  PubMed  Google Scholar 

  23. Abramowski A, Ward R, Hamdan AH. Neonatal hypoglycemia. StatPearls. Treasure Island (FL, 2022).

  24. Mank E, van Toledo L, Heijboer AC, van den Akker CHP, van Goudoever JB. Insulin concentration in human milk in the first ten days postpartum: course and associated factors. J Pediatr Gastroenterol Nutr. 2021;73:e115–e9.

    Article  CAS  PubMed  Google Scholar 

  25. Rodel RL, Farabi SS, Hirsch NM, Rolloff KP, McNair B, Hernandez TL, et al. Human milk imparts higher insulin concentration in infants born to women with type 2 diabetes mellitus. J Matern Fetal Neonatal Med. 2022;35:7676–84.

    Article  CAS  PubMed  Google Scholar 

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Funding

Funding

This project was supported by the University of Rochester CTSA award number UL1 TR002001 from the National Center for Advancing Translational Sciences of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Danielle Ackley & Hongyue Wang

  2. Division of Neonatology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Carl T. D’Angio & Jeffrey Meyers

  3. Division of Pediatric Allergy and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Bridget E. Young

Authors
  1. Danielle Ackley
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  2. Hongyue Wang
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  3. Carl T. D’Angio
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  4. Jeffrey Meyers
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  5. Bridget E. Young
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Contributions

The following authors contributed significantly to the study conception and design: DA, CD, JM, BY; data collection: DA, BY; analysis and interpretation of results: DA, HW, BY; and draft manuscript preparation: DA, HW, BY. All authors reviewed the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Danielle Ackley.

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The authors declare no competing interests.

Ethics

This retrospective chart review was granted exempt status by the University of Rochester Institutional Review Board (study ID: STUDY00006172).

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Ackley, D., Wang, H., D’Angio, C.T. et al. Human milk-derived fortifiers are linked with feed extension due to Hypoglycemia in infants <1250 g or <30 weeks: a matched retrospective chart review. J Perinatol 43, 624–628 (2023). https://doi.org/10.1038/s41372-023-01654-z

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