Comparison of Growth of Healthy Term Infants Fed Extensively Hydrolyzed Protein- and Amino Acid-Based Infant Formulas

Abstract

The aim of this narrative review was to assess published growth data for healthy, term, infants consuming extensively hydrolyzed protein-based (EHF), or amino acid-based formulas (AAF). These data may be of use to clinicians managing infants with medical conditions consuming these products. A search was conducted using key terms: amino acid-based, hydrolysate, hydrolyzed, hydrolysed, infant formula, infant formulae or formulas, baby formula, or formulae or formulas, infant, infants, infantile, and growth. Seven controlled, randomized, prospective growth trials of healthy term infants fed EHFs or AAFs at similar time points during the first four months of age met these and other criteria, including that the trial was published in a peer-reviewed journal, subjects were enrolled by ≤14 days of age and were exclusively formula-fed at entry and throughout the duration of the trial, and infants were assessed at regular intervals with weight measures available ideally at 14 days, one, two, three, and four months of age. Results suggested that healthy infants receiving commonly available EHFs and AAFs do not appear to experience accelerated growth as reported for infants fed many standard formulas. Differences in growth patterns were observed with some formulas supporting normative growth patterns during the first four months but others appearing to support markedly lower growth patterns. These observations should be confirmed in well-designed prospective randomized trials. Until that time, it is recommended that EHFs and AAFs be chosen carefully with individual patient needs considered.

Keywords: elemental formula; extensively hydrolyzed protein-based formula; free amino acid-based formula; hydrolysate formula; infant growth.

Figure 1

Mean weight-for-age percentiles (World Health Organization (WHO)) of evaluable healthy term infants at 14 day, and one, two, three and four months of age fed extensively hydrolyzed protein-based (EHFs). (a) WHO weight-for-age percentiles of male infants; (b) WHO weight-for-age percentiles of female infants. Mean weight of infants fed EHF-A and EHF-B were not statistically significantly different during the first four months of life (p > 0.05) and were significantly greater than those fed EHF-C and EHF-D at 2 weeks and at 1, 2, 3, and 4 (EHF-C only) months of age (p < 0.05). Data source: EHF-A [15]; EHF-B [14]; EHF-C [17]; EHF-D [17].

Figure 2

Mean WHO weight-for-age z-scores of evaluable healthy term infants fed EHF-A, EHF-B, EHF-C, EHF-D and AAF-E at birth (ITT for EHF-C and EHF-D), 14, 28, 56, 84, and 112 days of age. Data source for EHF-A, EHF-B and AAF-E was from unpublished data from Borschel et al. [14] and Borschel et al. [15] and data source for EHF-C and EHF-D was Fields et al. [17]. An ad hoc analysis of change in mean WHO weight-for-age z-score for EHF-A, EHF-B and AAF-E from 14 to 112 days of age showed no statistically significant differences among formulas (p = 0.71). Differences in the WHO weight-for-age z-scores for EHF-C and EHF-D when compared to EHF-A, EHF-B, and AAF-E could not be determined from the published data.

Figure 3

Mean WHO weight-for-age percentiles of evaluable healthy term male infants fed EHF-B and AAF-E to 4 months of age. Data source was from unpublished data from the study of Borschel et al. [14].