Growth and tolerance of healthy, term infants fed lower protein extensively hydrolyzed or amino acid-based formula: double-blind, randomized, controlled trial

Craig B Adams, William H Johnston, Harold Deulofeut, Joseph Leader, Robbie Rhodes, Michael Yeiser, Cheryl L Harris, Jennifer L Wampler, Rebecca J Hill, Timothy Cooper, Craig B Adams, William H Johnston, Harold Deulofeut, Joseph Leader, Robbie Rhodes, Michael Yeiser, Cheryl L Harris, Jennifer L Wampler, Rebecca J Hill, Timothy Cooper

Abstract

Background: Optimal protein level in hypoallergenic infant formulas is an area of ongoing investigation. The aim was to evaluate growth of healthy term infants who received extensively hydrolyzed (EH) or amino acid (AA)-based formulas with reduced protein.

Methods: In this prospective, multi-center, double-blind, controlled, parallel group study, infants were randomized to receive a marketed EH casein infant formula at 2.8 g protein/100 kcal (Control) or one of two investigational formulas: EH casein formula at 2.4 g protein/100 kcal (EHF) or AA-based formula at 2.4 g total protein equivalents/100 kcal (AAF). Control and EHF each had 2 × 107 CFU Lactobacillus rhamnosus GG/100 kcal. Anthropometrics were measured and recall of formula intake, tolerance, and stool characteristics was collected at 14, 30, 60, 90, 120 days of age. Primary outcome was weight growth rate (g/day) between 14 and 120 days of age (analyzed by ANOVA). Medically confirmed adverse events were recorded throughout the study.

Results: No group differences in weight or length growth rate from 14 to 120 days were detected. With the exception of significant differences at several study time points for males, no group differences were detected in mean head circumference growth rates. However, mean achieved weight, length, and head circumference demonstrated normal growth throughout the study period. No group differences in achieved weight or length (males and females) and head circumference (females) were detected and means were within the WHO growth 25th and 75th percentiles from 14 to 120 days of age. With the exception of Day 90, there were no statistically significant group differences in achieved head circumference for males; means remained between the WHO 50th and 75th percentiles for growth at Days 14, 30, and 60 and continued along the 75th percentile through Day 120. No differences in study discontinuation due to formula were detected. The number of participants for whom at least one adverse event was reported was similar among groups.

Conclusions: This study demonstrated hypoallergenic infant formulas at 2.4 g protein/100 kcal were safe, well-tolerated, and associated with appropriate growth in healthy term infants from 14 to 120 days of age.

Trial registration: ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT01354366 . Registered 13 May 2011.

Keywords: Amino acid; Extensively hydrolyzed protein; Infant formula; Lactobacillus rhamnosus GG.

Conflict of interest statement

CBA, WHJ, HD, JL, RR and MY have received support for study site coordination and data collection from Mead Johnson Nutrition. CLH and JLW work in the Department of Medical Affairs and RH works in Nutrition Science at Mead Johnson Nutrition. TC was previously employed by Mead Johnson Nutrition.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Flow of study participants
Fig. 2
Fig. 2
a Mean achieved weight for male participants with World Health Organization (WHO) percentiles (2nd to 98th) from 14 to 120 days of age. Control, stars; EHF, circles; AAF, diamonds. b Mean achieved weight for female participants with World Health Organization (WHO) percentiles (2nd to 98th) from 14 to 120 days of age. Control, stars; EHF, circles; AAF, diamonds
Fig. 3
Fig. 3
a Mean achieved length for male participants with World Health Organization (WHO) percentiles (2nd to 98th) from 14 to 120 days of age. Control, stars; EHF, circles; AAF, diamonds. b Mean achieved length for female participants with World Health Organization (WHO) percentiles (2nd to 98th) from 14 to 120 days of age. Control, stars; EHF, circles; AAF, diamonds
Fig. 4
Fig. 4
a Mean achieved head circumference for male participants with World Health Organization (WHO) percentiles (2nd to 98th) from 14 to 120 days of age. Control, stars; EHF, circles; AAF, diamonds. b Mean achieved head circumference for female participants with World Health Organization (WHO) percentiles (2nd to 98th) from 14 to 120 days of age. Control, stars; EHF, circles; AAF, diamonds

References

    1. Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol. 2007;120(3):638–46. 10.1016/j.jaci.2007.05.026.
    1. Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. J Am Acad Dermatol. 2011;64(1):175–92. 10.1016/j.jaad.2010.11.020.
    1. Savage J, Johns CB. Food allergy: epidemiology and natural history. Immunol Allergy Clin N Am. 2015;35(1):45–59. doi: 10.1016/j.iac.2014.09.004.
    1. Dunlop JH, Keet CA. Epidemiology of food allergy. Immunol Allergy Clin N Am. 2018;38(1):13–25. doi: 10.1016/j.iac.2017.09.002.
    1. Flom JD, Sicherer SH. Epidemiology of cow's milk allergy. Nutrients. 2019;11(5).
    1. Meyer R, Groetch M, Venter C. When should infants with cow's milk protein allergy use an amino acid formula? A practical guide. J Allergy Clin Immunol Pract. 2018;6(2):383–399. doi: 10.1016/j.jaip.2017.09.003.
    1. Lönnerdal B. Nutritional and physiologic significance of human milk proteins. Am J Clin Nutr. 2003;77(6):1537S–1543S. doi: 10.1093/ajcn/77.6.1537S.
    1. Lien EL. Infant formulas with increased concentrations of α-lactalbumin. Am J Clin Nutr. 2003;77(6):1555S–1558S. doi: 10.1093/ajcn/77.6.1555S.
    1. Rudloff S, Kunz C. Protein and nonprotein nitrogen components in human milk, bovine milk, and infant formula: quantitative and qualitative aspects in infant nutrition. J Pediatr Gastroenterol Nutr. 1997;24(3):328–344. doi: 10.1097/00005176-199703000-00017.
    1. Koletzko B, von Kries R, Closa R, Escribano J, Scaglioni S, Giovannini M, et al. Lower protein in infant formula is associated with lower weight up to age 2 y: a randomized clinical trial. Am J Clin Nutr. 2009;89(6):1836–45. 10.3945/ajcn.2008.27091.
    1. Kramer MS, Guo T, Platt RW, Vanilovich I, Sevkovskaya Z, Dzikovich I, et al. Feeding effects on growth during infancy. J Pediatr. 2004;145(5):600–5. 10.1016/j.jpeds.2004.06.069.
    1. EFSA NDA Panel (EFSA Panel on Dietetic Products Nutrition and Allergies). Scientific Opinion on the essential composition of infant and follow-on formulae. EFSA J. 2014;12(7):3760. 10.2903/j.efsa.2014.3760
    1. EU Commission E. Commission delegated regulation (EU) 2016/127 of 25 September 2015 supplementing regulation (EU) no 609/2013 of the European Parliament and of the council as regards the specific compositional and information requirements for infant formula and follow-on formula and as regards requirements on information relating to infant and young child feeding. OJ. 2016;59:1–29.
    1. Burks W, Jones SM, Berseth CL, Harris C, Sampson HA, Scalabrin DMF. Hypoallergenicity and effects on growth and tolerance of a new amino acid-based formula with docosahexaenoic acid and arachidonic acid. J Pediatr. 2008;153(2):266–271. doi: 10.1016/j.jpeds.2008.02.043.
    1. US FDA: Title 21 Food and Drugs §106 Infant formula requirements pertaining to current Good Manufacturing Practice, Quality Control Procedures, Quality Factors, Recordsand Reports, and Notifications. US Congress .
    1. US FDA: Title 21 Food and Drugs §107 Infant Formula: General provisions, labeling, exempt infant formulas, nutrient requirements, and infant formula recalls. US Congress .
    1. Ashley C, JohnstonWH, Harris CL, Stolz SI, Wampler JL, Berseth CL. Growth and tolerance ofinfants fed formula supplemented with polydextrose (PDX) and/or galactooligosaccharides(GOS): double-blind, randomized, controlled trial. Nutr J. 2012;11:38. 10.1186/1475-2891-11-38.
    1. Yeiser M, Harris CL, Kirchoff AL, Patterson AC, Wampler JL, ZissmanEN, Berseth CL: Growth and tolerance of infants fed formula with a new algalsource of docosahexaenoic acid: Double-blind, randomized, controlled trial.Prostaglandins Leukot Essent Fatty Acids. 2016;115:89-96. 10.1016/j.plefa.2016.09.001.
    1. Hoffman D, Ziegler E, Mitmesser SH, Harris CL, Diersen-Schade DA.Soy-based infant formula supplemented with DHA and ARA supports growth andincreases circulating levels of these fatty acids in infants. Lipids. 2008;43(1):29-35. 10.1007/s11745-007-3116-7.
    1. Hoffman DR, HarrisCL, Wampler JL, Patterson AC, Berseth CL. Growth, tolerance, and DHA and ARAstatus of healthy term infants receiving formula with two different ARAconcentrations: Double-blind, randomized, controlled trial. ProstaglandinsLeukot Essent Fatty Acids. 2019;146:19-27. 10.1016/j.plefa.2019.04.007.
    1. Johnston WH, Ashley C, Yeiser M, Harris CL, Stolz SI, Wampler JL,Wittke A, Cooper TR. Growth and tolerance of formula with lactoferrin ininfants through one year of age: double-blind, randomized, controlled trial.BMC Pediatr. 2015;15:173. 10.1186/s12887-015-0488-3.
    1. AAP Task Force on Clinical Testing of Infant Formulas, Committee onNutrition (Finberg L, Bell EF, Cooke RJ, Fomon SJ, Kleinman RE, Pencharz PB,Reynolds JW, Schanler RJ, Forbes AL) Report: Clinical testing of infantformulas with respect to nutritional suitability for term infants. Foodand Drug Administration, Center for Food Safety and Applied Nutrition.1-16. .
    1. WHO Multicentre Growth Reference Study Group, WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006;450:76-85. 10.1111/j.1651-2227.2006.tb02378.x.
    1. Department of Nutrition for Health and Development, World Health Organization; WHO child growth standards: Length/height-for-age,weight-for-age, weight-for-length, weight-for-height and body massindex-for-age--Methods and development. Geneva: World Health Organization;2006. .
    1. Scalabrin DM, Johnston WH, Hoffman DR, P'Pool VL, Harris CL,Mitmesser SH: Growth and tolerance of healthy term infants receiving hydrolyzedinfant formulas supplemented with Lactobacillus rhamnosus GG. randomized, double-blind, controlled trial. Clin Pediatr(Phila). 2009;48(7):734-44. 10.1177/0009922809332682.
    1. Kleinman RE, Greer FR(eds.). AAP Committee on Nutrition. Pediatric Nutrition, 8th edn: American Academy of Pediatrics; 2019.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit