Download PDF
CC BY-NC-ND 4.0 · Am J Perinatol 2023; 40(02): 141-148
DOI: 10.1055/s-0042-1749166
Review Article

Acidified Feedings in Preterm Infants: A Historical and Physiological Perspective

Bridget Barrett-Reis
1   Abbott Nutrition, Columbus, Ohio
,
Fauzia Shakeel
2   Johns Hopkins All Children's Hospital, Maternal, Fetal and Neonatal Institute, Johns Hopkins University School of Medicine, St. Petersburg, Florida
,
Laura Dennis
3   Mercy San Juan Medical Center NICU, Carmichael, California
,
Geraldine Baggs
1   Abbott Nutrition, Columbus, Ohio
,
Marc L. Masor
4   M&M Arts and Science, LLP, Durango, Colorado
› Author Affiliations Funding None.
› Further Information
Also available at
   Permissions and Reprints

Abstract

The use of acidified milk for feeding infants has a long, interesting history that appears to have developed from the use of buttermilk in Holland as early as the late 19th century for feeding infants with diarrhea. Physicians in the early 20th century assumed that the observed benefits were from buttermilk's acidity leading to the practice of acidifying infant formula. The historical and physiological perspective on the use of acidified infant formula is now especially relevant with the emergence of an acidified liquid human milk fortifier for preterm infants. Here, we review that history, with a deeper dive into the contemporary research on the use of acidified human milk fortifiers, the consequences for preterm infants, and the underlying physiological mechanisms.

Key Points

  • In the late 19th and early 20th century acidified feedings were in common use for sick infants.

  • By the mid-20th century, acidified feedings tested in preterm infants resulted in acidic physiology and poor growth.

  • The current practice of acidifying feedings in preterm infants has been associated with metabolic acidosis, poor tolerance, and delayed growth.

Keywords

acidified feedings - human milk fortifier - infant formula - premature infant


Publication History

Received: 04 October 2021

Accepted: 28 March 2022

Article published online:
31 May 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Marriott WM, Davidson LT. Acidity of the gastric contents of infants. Am J Dis Child 1923; 26: 542-553
    PubMedGoogle Scholar
  • 2 Marriott WM, Davidson LT. Acidified whole milk as a routine infant food. JAMA 1923; 81 (24) 2007-2009
    CrossrefPubMedGoogle Scholar
  • 3 Marriott WM. Artificial feeding of athreptic infants. JAMA 1919; 73: 1173
    CrossrefPubMedGoogle Scholar
  • 4 Dunham BS. Acidification of milk with vinegar (acetic acid) in infant feeding. Am J Dis Child 1925; 29 (02) 200-205
    PubMedGoogle Scholar
  • 5 Gonce JE, Templeton HL. Citric acid milk in infant feeding. Am J Dis Child 1930; 39 (02) 265-276
    PubMedGoogle Scholar
  • 6 Faber HK. Hydrochloric acid milk in infant feeding. Am J Dis Child 1923; 26 (05) 401-410
    PubMedGoogle Scholar
  • 7 Anderson SA, Chinn HI, Fisher KD. History and current status of infant formulas. Am J Clin Nutr 1982; 35 (02) 381-397
    CrossrefPubMedGoogle Scholar
  • 8 Stevens EE, Patrick TE, Pickler R. A history of infant feeding. J Perinat Educ 2009; 18 (02) 32-39
    CrossrefPubMedGoogle Scholar
  • 9 Fomon S. Infant feeding in the 20th century: formula and beikost. J Nutr 2001; 131 (02) 409S-420S
    CrossrefPubMedGoogle Scholar
  • 10 Agostoni C, Goulet O, Kolacek S. et al; ESPGHAN Committee on Nutrition. Fermented infant formulae without live bacteria. J Pediatr Gastroenterol Nutr 2007; 44 (03) 392-397
    CrossrefPubMedGoogle Scholar
  • 11 Labuschagne IL, van Niekerk E, Lombard MJ. Acidified infant formula explained. S Afr Fam Pract 2013; 55 (04) 354-356
    CrossrefPubMedGoogle Scholar
  • 12 Zhu S, Schnell S, Fischer M. Growth inhibition of Cronobacter spp. strains in reconstituted powdered infant formula acidified with organic acids supported by natural stomach acidity. Food Microbiol 2013; 35 (02) 121-128
    CrossrefPubMedGoogle Scholar
  • 13 Karelitz S, Schell NB, Goldman HI. Lactic acid milk in the feeding of premature infants. J Pediatr 1959; 54 (06) 756-761
    CrossrefPubMedGoogle Scholar
  • 14 Goldman HI, Karelitz S, Seifter E, Acs H, Schell NB. Acidosis in premature infants due to lactic acid. Pediatrics 1961; 27: 921-930
    CrossrefPubMedGoogle Scholar
  • 15 Harrison VC, Peat G. Significance of milk pH in newborn infants. BMJ 1972; 4 (5839): 515-518
    CrossrefPubMedGoogle Scholar
  • 16 Moore A, Ansell C, Barrie H. Metabolic acidosis and infant feeding. BMJ 1977; 1 (6054): 129-131
    CrossrefPubMedGoogle Scholar
  • 17 Stolley H, Droese W. Lactic acid in milk formula, the influence on absorption of nutrients and the influence on the metabolism in young babies. Acta Paediatr Scand 1971; 60 (03) 367-368
    PubMedGoogle Scholar
  • 18 Ehrenkranz RA, Younes N, Lemons JA. et al. Longitudinal growth of hospitalized very low birth weight infants. Pediatrics 1999; 104 (2 Pt 1): 280-289
    CrossrefPubMedGoogle Scholar
  • 19 Clark RH, Wagner CL, Merritt RJ. et al. Nutrition in the neonatal intensive care unit: how do we reduce the incidence of extrauterine growth restriction?. J Perinatol 2003; a 23 (04) 337-344
    CrossrefPubMedGoogle Scholar
  • 20 Clark RH, Thomas P, Peabody J. Extrauterine growth restriction remains a serious problem in prematurely born neonates. Pediatrics 2003b111(5 Pt 1): 986-990
    PubMedGoogle Scholar
  • 21 Hack M, Breslau N, Weissman B, Aram D, Klein N, Borawski E. Effect of very low birth weight and subnormal head size on cognitive abilities at school age. N Engl J Med 1991; 325 (04) 231-237
    CrossrefPubMedGoogle Scholar
  • 22 Latal-Hajnal B, von Siebenthal K, Kovari H, Bucher HU, Largo RH. Postnatal growth in VLBW infants: significant association with neurodevelopmental outcome. J Pediatr 2003; 143 (02) 163-170
    CrossrefPubMedGoogle Scholar
  • 23 Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA, Poole WK. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 2006; 117 (04) 1253-1261
    Google Scholar
  • 24 Franz AR, Pohlandt F, Bode H. et al. Intrauterine, early neonatal, and postdischarge growth and neurodevelopmental outcome at 5.4 years in extremely preterm infants after intensive neonatal nutritional support. Pediatrics 2009; 123 (01) e101-e109
    CrossrefPubMedGoogle Scholar
  • 25 Ramel SE, Demerath EW, Gray HL, Younge N, Boys C, Georgieff MK. The relationship of poor linear growth velocity with neonatal illness and two-year neurodevelopment in preterm infants. Neonatology 2012; 102 (01) 19-24
    Google Scholar
  • 26 Stoll BJ, Hansen NI, Bell EF. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 (03) 443-456
    Google Scholar
  • 27 Lai KK. Enterobacter sakazakii infections among neonates, infants, children, and adults. Case reports and a review of the literature. Medicine (Baltimore) 2001; 80 (02) 113-122
    CrossrefPubMedGoogle Scholar
  • 28 Centers for Disease Control and Prevention (CDC). Enterobacter sakazakii infections associated with the use of powdered infant formula–Tennessee, 2001. MMWR Morb Mortal Wkly Rep 2002; 51 (14) 297-300
    PubMedGoogle Scholar
  • 29 Taylor CT. Health professionals letter on Enterobacter sakazakii infections associated with use of powdered (dry) infant formulas in neonatal intensive care units. Office of Nutritional Products, Labeling and Dietary Supplements Center for Food Safety and Applied Nutrition, USFDA;. Safety Alerts and Advisories, October 10, 2002
    PubMedGoogle Scholar
  • 30 Cristofalo EA, Schanler RJ, Blanco CL. et al. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr 2013; 163 (06) 1592-1595.e1
    CrossrefPubMedGoogle Scholar
  • 31 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 Pt 1): 1150-1157
    CrossrefPubMedGoogle Scholar
  • 32 Schanler RJ. Mother's own milk, donor human milk, and preterm formulas in the feeding of extremely premature infants. J Pediatr Gastroenterol Nutr 2007; 45 (Suppl. 03) S175-S177
    CrossrefPubMedGoogle Scholar
  • 33 Sancho-Madriz MF. Preservation of Food in Encyclopedia of Food Sciences and Nutrition. 2nd ed.. In: Caballero B. ed. Amsterdam, the Netherlands: Elsevier Science; 2003
    Google Scholar
  • 34 Featherstone S. Sanitary design and equipment requirements. In: A Complete Course in Canning and Related Processes. Volume 1 Fundamental Information on Canning (Woodhead Publishing Series in Food Science, Technology and Nutrition). 14th ed.. Sawston, United Kingdom: Woodhead Publishing; 2015: 95-105
    Google Scholar
  • 35 Caplice E, Fitzgerald GF. Food fermentations: role of microorganisms in food production and preservation. Int J Food Microbiol 1999; 50 (1–2): 131-149
    CrossrefPubMedGoogle Scholar
  • 36 Euber J, Solorio H, Batema R, Walsh K. (inventors). Acidified liquid human milk supplement. US patent 8,147,894 B2;. Original Assignee: Mead Johnson Nutrition Company. April 3, 2012
    PubMedGoogle Scholar
  • 37 Moya F, Sisk PM, Walsh KR, Berseth CL. A new liquid human milk fortifier and linear growth in preterm infants. Pediatrics 2012; 130 (04) e928-e935
    CrossrefPubMedGoogle Scholar
  • 38 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 (01) 261-275
    CrossrefPubMedGoogle Scholar
  • 39 Thoene M, Lyden E, Weishaar K. et al. Comparison of a powdered, acidified liquid, and non-acidified liquid human milk fortifier on clinical outcomes in premature infants. Nutrients 2016; 8 (08) 451
    CrossrefPubMedGoogle Scholar
  • 40 Cibulskis CC, Armbrecht ES. Association of metabolic acidosis with bovine milk-based human milk fortifiers. J Perinatol 2015; 35 (02) 115-119
    CrossrefPubMedGoogle Scholar
  • 41 Kumar N, Monga R, Sampath V, Ehrhart B. Prospective comparison of enfamil and similac liquid human milk fortifier on clinical outcomes in premature infants. Am J Perinatol 2017; 34 (14) 1411-1416
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Lainwala S, Kosyakova N, Spizzoucco AM, Herson V, Brownell EA. Clinical and nutritional outcomes of two liquid human milk fortifiers for premature infants. J Neonatal Perinatal Med 2017; 10 (04) 393-401
    CrossrefPubMedGoogle Scholar
  • 43 Schanler RJ, Groh-Wargo SL, Barrett-Reis B. et al. Improved outcomes in preterm infants fed a nonacidified liquid human milk fortifier: a prospective randomized clinical trial. J Pediatr 2018; 202: 31-37.e2
    CrossrefPubMedGoogle Scholar
  • 44 Darrow CJ, Bai-Tong SS, Kang EM, Thompson CL, Walsh MC. Use of acidified versus non-acidified liquid human milk fortifier in very low birth weight infants: A retrospective comparison of clinical outcomes. J Neonatal Perinatal Med 2020; 13 (01) 71-79
    CrossrefPubMedGoogle Scholar
  • 45 Cordova EG, Soldateli B, Rosner B. et al. Growth and clinical outcomes of very low-birth-weight infants receiving acidified vs nonacidified liquid human milk fortifiers. Nutr Clin Pract 2021; 36 (06) 1304-1311
    CrossrefPubMedGoogle Scholar
  • 46 Schünemann H, Brożek J, Guyatt G, Oxman A. eds. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group,. 2013. . April 22, 2022. at: guidelinedevelopment.org/handbook
    Google Scholar
  • 47 Ziegler EE. Meeting the nutritional needs of the low-birth-weight infant. Ann Nutr Metab 2011; 58 (Suppl. 01) 8-18
    CrossrefPubMedGoogle Scholar
  • 48 Miller J, Makrides M, Gibson RA. et al. Effect of increasing protein content of human milk fortifier on growth in preterm infants born at <31 wk gestation: a randomized controlled trial. Am J Clin Nutr 2012; 95 (03) 648-655
    CrossrefPubMedGoogle Scholar
  • 49 Brown LD, Hendrickson K, Masor ML, Hay Jr WW. High-protein formulas: evidence for use in preterm infants. Clin Perinatol 2014; 41 (02) 383-403
    CrossrefPubMedGoogle Scholar
  • 50 Ernst KD, Radmacher PG, Rafail ST, Adamkin DH. Postnatal malnutrition of extremely low birth-weight infants with catch-up growth postdischarge. J Perinatol 2003; 23 (06) 477-482
    CrossrefPubMedGoogle Scholar
  • 51 Stephens BE, Walden RV, Gargus RA. et al. First-week protein and energy intakes are associated with 18-month developmental outcomes in extremely low birth weight infants. Pediatrics 2009; 123 (05) 1337-1343
    CrossrefPubMedGoogle Scholar
  • 52 Thoene M, Anderson-Berry A. Response to Dr. Moya's Comments to Article by Thoene M et al., Nutrients 2016, 8, 451. Nutrients 2016; 8 (12) 822
    CrossrefPubMedGoogle Scholar
  • 53 Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol 2010; 6 (05) 274-285
    CrossrefPubMedGoogle Scholar
  • 54 Caso G, Garlick BA, Casella GA, Sasvary D, Garlick PJ. Acute metabolic acidosis inhibits muscle protein synthesis in rats. Am J Physiol Endocrinol Metab 2004; 287 (01) E90-E96
    CrossrefPubMedGoogle Scholar
  • 55 Reaich D, Channon SM, Scrimgeour CM, Goodship THJ. Ammonium chloride-induced acidosis increases protein breakdown and amino acid oxidation in humans. Am J Physiol 1992; 263 (4 Pt 1): E735-E739
    PubMedGoogle Scholar
  • 56 Ballmer PE, McNurlan MA, Hulter HN, Anderson SE, Garlick PJ, Krapf R. Chronic metabolic acidosis decreases albumin synthesis and induces negative nitrogen balance in humans. J Clin Invest 1995; 95 (01) 39-45
    CrossrefPubMedGoogle Scholar
  • 57 Kalhoff H, Diekmann L, Rudloff S, Manz F. Renal excretion of calcium and phosphorus in premature infants with incipient late metabolic acidosis. J Pediatr Gastroenterol Nutr 2001; 33 (05) 565-569
    CrossrefPubMedGoogle Scholar
  • 58 Rochow N, Jochum F, Redlich A. 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;. Clinical Nutrition 2011; 30: 99-105
    CrossrefPubMedGoogle Scholar
  • 59 Arnett TR. Extracellular pH regulates bone cell function. J Nutr 2008; 138 (02) 415S-418S
    CrossrefPubMedGoogle Scholar
  • 60 Aschner JL, Poland RL. Sodium bicarbonate: basically useless therapy. Pediatrics 2008; 122 (04) 831-835
    CrossrefPubMedGoogle Scholar
  • 61 Erickson T, Gill G, Chan GM. The effects of acidification on human milk's cellular and nutritional content. J Perinatol 2013; 33 (05) 371-373
    CrossrefPubMedGoogle Scholar
  • 62 Lönnerdal B. Nutritional and physiologic significance of human milk proteins. Am J Clin Nutr 2003; 77 (6, suppl): 1537S-1543S
    CrossrefPubMedGoogle Scholar
  • 63 Paul M, Partridge J, Barrett-Reis B. et al. Metabolic acidosis in preterm infants is associated with a longer length of stay in the neonatal intensive care unit. Pharmacoecon Open 2020; 4 (03) 541-547
    CrossrefPubMedGoogle Scholar