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.

  • Original Article
  • Published:

Association of metabolic acidosis with bovine milk-based human milk fortifiers

Journal of Perinatology volume 35, pages 115–119 (2015)Cite this article

Subjects

Abstract

Objective:

To compare the incidence of metabolic acidosis and feeding intolerance associated with powdered or acidified liquid human milk fortifier (HMF).

Study Design:

This retrospective study evaluated infants ⩽32 weeks gestational age or ⩽1500 g birth weight who received human milk with either powdered or acidified liquid HMF (50 consecutively born infants per group). Primary outcomes tracked were metabolic acidosis (base excess less than −4 mmol l−1 or bicarbonate less than 18 mmol l−1), feeding intolerance (gastric residual >50% feed volume, >3 loose stools or emesis per day, abdominal tenderness or distention), necrotizing enterocolitis, late-onset infection, death, length of hospital stay and ability to remain on HMF. Demographics, feeding practices, growth parameters and laboratory data were also collected.

Result:

Significantly more infants who received acidified liquid HMF developed metabolic acidosis (P<0.001). Base excess and bicarbonate were both significantly decreased after HMF addition in the liquid HMF group (base excess P=0.006, bicarbonate P<0.001). More infants were switched off liquid HMF due to metabolic acidosis or feeding intolerance than those on powdered HMF (P<0.001). Despite increased protein intake in the liquid HMF group (P=0.009), both groups had similar enteral caloric intakes with no difference in growth rates between the two groups. There was no significant difference in any of the other primary outcomes.

Conclusion:

Infants receiving acidified liquid human milk fortifier were more likely to develop metabolic acidosis and to be switched off HMF than those who received powdered HMF. Growth in the liquid HMF group was no different than the powdered group, despite higher protein intake.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

Similar content being viewed by others

References

  1. American Academy of Pediatrics Section on Breastfeeding. Policy statement: breastfeeding and the use of human milk. Pediatrics 2005; 115: 496–506.

    Article  Google Scholar 

  2. Hylander MA, Strobino DM, Dhanireddy R . Human milk feedings and infection among very low birth weight infants. Pediatrics 1998; 102: E38.

    Article  CAS  PubMed  Google Scholar 

  3. Schanler RJ, Shulman RJ, Lau C . Feeding strategies for premature infants: beneficial outcomes of feeding fortified human milk versus preterm formula. Pediatrics 1999; 103 (6): 1150–1157.

    Article  CAS  PubMed  Google Scholar 

  4. Narayanan I, Murthy NS, Prakash K, Gurjal VV . Randomised controlled trial of raw and Holder pasteurized human milk and of formula supplements on incidence of neonatal infection. Lancet 1984; 8412: 1111–1113.

    Article  Google Scholar 

  5. Sisk PM, Lovelady CA, Dillard RG, Gruber KJ, O’Shea TM . Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants. J Perinatol 2007; 27: 428–433.

    Article  CAS  PubMed  Google Scholar 

  6. Meinzen-Derr J, Poindexter B, Wrage L, Morrow AL, Stoll B, Donovan EF for the National Institute of Child Health and Human Development Neonatal Research Network. Role of human milk in extremely low birth weight infants’ risk of necrotizing enterocolitis or death. J Perinatol 2009; 29: 57–62.

    Article  CAS  PubMed  Google Scholar 

  7. Lucas A, Cole TJ . Breast milk and neonatal necrotising enterocolitis. Lancet 1990; 336: 1519–1523.

    Article  CAS  PubMed  Google Scholar 

  8. Lucchini R, Bizzarri B, Giampietro S, DeCurtis M . Feeding intolerance in preterm infants: how to understand the warning signs. J Matern Fetal Neonatal Med 2011; 24 (S1): 72–74.

    Article  PubMed  Google Scholar 

  9. 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 (1): e115–e123.

    Article  PubMed  Google Scholar 

  10. Horwood LJ, Darlow BA, Mogridge N . Breast milk feeding and cognitive ability at 7-8 years. ArchDis Child Fetal Neonatal Ed 2001; 84: F23–F27.

    Article  CAS  Google Scholar 

  11. Schanler RJ . The use of human milk for premature infants. Pediatr Clin N Amer 2001; 48: 207–219.

    Article  CAS  Google Scholar 

  12. Kashyap S, Schulze KF, Forsyth M, Dell RB, Ramakrishnan R, Heird WC . Growth, nutrient retention, and metabolic response of low-birth-weight infants fed supplemented and unsupplemented preterm human milk. Am J Clin Nutr 1990; 52: 254–262.

    Article  CAS  PubMed  Google Scholar 

  13. Wojcik KY, Rechtman DJ, Lee ML, Montoya A, Medo ET . Macronutrient analysis of a nationwide sample of donor breast milk. J Am Diet Assoc 2009; 109: 137–140.

    Article  PubMed  Google Scholar 

  14. 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: 121–126.

    Article  PubMed  Google Scholar 

  15. Centers for Disease Control and Prevention. Enterobacter sakazakii infections associated with the use of powdered infant formula—Tennessee, 2001. MMWR 2002; 51 (14): 298–300.

    Google Scholar 

  16. American Academy of Pediatrics. CDC, FDA advise against powdered formula in NICUs. AAP News 2002; 20: 219.

    Google Scholar 

  17. Kim Hae-Young . Statistical notes for clinical researchers: assessing normal distribution using skewness and kurtosis. Restor Dent Endod 2013; 38 (1): 52–54.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T et al. ESPGHAN Committee on Nutrition. Enteral nutrient supply for preterm infants: commentary from the European society for paediatric gastroenterology, hepatology, and nutrition committee on nutrition. JPGN 2010; 50 (1): 85–91.

    CAS  PubMed  Google Scholar 

  19. Abbott Nutrition, Abbott Laboratories. Similac Human Milk Fortifier—powdered unflavored (nutritional information on the internet, updated 12 December 2012). Available at http://abbottnutrition.com/brands/products/similac-human-milk-fortifier (last accessed 16 May 2014).

  20. Mead Johnson & Company, LLC. Enfamil Human Milk Fortifier Acidified Liquid—Enfamil (nutritional information on the internet, updated 20 October 2011. Available at http://www.enfamil.com/app/iwp/enf12/product.do?dm=enf&id=/Consumer_Home3/FeedingSolutions/EnfamilHumanMilkFortifier2&iwpst=B2C&ls=0&csred=1&r=3552909950 (last accessed 18 May 2012).

  21. Moya F, Sisk PM, Walsh KR, Berseth CL . A new liquid human milk fortifier and linear growth in preterm infants. Pediatrics 2012; 130 (4): e928–e935.

    Article  PubMed  Google Scholar 

  22. Erickson T, Gill G, Chan GM . The effects of acidification on human milk’s cellular and nutritional content. J Perinatol 2013; 33: 371–373.

    Article  CAS  PubMed  Google Scholar 

  23. Thoene M, Hanson C, Lyden E, Dugick L, Ruybal L, Anderson-Berry A . Comparison of the effect of two human milk fortifiers on clinical outcomes in premature infants. Nutrients 2014; 6: 261–275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Green J, Maor G . Effect of metabolic acidosis on the growth hormone/IGF-1 endocrine axis in skeletal growth centers. Kidney Int 2000; 57 (6): 2258–2267.

    Article  CAS  PubMed  Google Scholar 

  25. McSherry E, Morris RC Jr . Attainment and maintenance of normal stature with alkali therapy in infants and children with classic renal tubular acidosis. J Clin Invest 1978; 61: 509–527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rochow N, Jochum F, Redlich A, Korinekova Z, Linnemann K, Boehm G et al. Fortification of breast milk in VLBW infants: metabolic acidosis is linked to the composition of fortifiers and alters weight gain and bone mineralization. Clin Nutr 2011; 30: 99–105.

    Article  CAS  PubMed  Google Scholar 

  27. Kalhoff H, Manz F . Nutrition, acid-base status and growth in early childhood. Eur J Nutr 2001; 40 (5): 221–230.

    Article  CAS  PubMed  Google Scholar 

  28. Kalhoff H, Manz F, Diekmann L, Kunz C, Stock GJ, Weisser F . Decreased growth rate of low-birthweight infants with prolonged maximum renal acid stimulation. Acta Paediatr 1993; 82: 522–527.

    Article  CAS  PubMed  Google Scholar 

  29. Senger H, Boehm G, Beyreiss K, Braun W . Cholestasis in late metabolic acidosis of prematurely born infants. J Clin Chem Clin Biochem 1987; 25 (7): 413–418.

    CAS  PubMed  Google Scholar 

  30. Roberts D, Dalziel SR . Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006; ((3)) CD004454.

Download references

Acknowledgements

We gratefully acknowledge the assistance of Melissa Bowles, MSN, RN, PNP-BC, in collecting data. We also thank the staff involved in the maintenance of the neonatal database, Linda Breuer, LPN and Phyllis Anderson, RT and dietitian Rita Chrivia, RD, CSP, LD for assistance with calculations.

Author information

Authors and Affiliations

  1. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Saint Louis University, St Louis, MO, USA

    C C Cibulskis

  2. Saint Louis University Center for Outcomes Research, Saint Louis University, St Louis, MO, USA

    E S Armbrecht

Authors
  1. C C Cibulskis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E S Armbrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C C Cibulskis.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cibulskis, C., Armbrecht, E. Association of metabolic acidosis with bovine milk-based human milk fortifiers. J Perinatol 35, 115–119 (2015). https://doi.org/10.1038/jp.2014.143

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2014.143

This article is cited by

Search

Advanced search

Quick links