Growth of Infants Fed Formula with Evolving  Nutrition Composition: A Single‐Arm Non‐Inferiority Study

Abstract

The nutritional composition of human milk evolves over the course of lactation, to match the changing needs of infants. This single-arm, non-inferiority study evaluated growth against the WHO standards in the first year of life, in infants consecutively fed four age-based formulas with compositions tailored to infants’ nutritional needs during the 1st, 2nd, 3rd–6th, and 7th–12th months of age. Healthy full-term formula-fed infants (n = 32) were enrolled at ≤14 days of age and exclusively fed study formulas from enrollment, to the age of four months. Powdered study formulas were provided in single-serving capsules that were reconstituted using a dedicated automated preparation system, to ensure precise, hygienic preparation. The primary outcome was the weight-for-age z-score (WAZ) at the age of four months (vs. non-inferiority margin of −0.5 SD). Mean (95% CI) z-scores for the WAZ (0.12 (−0.15, 0.39)), as well as for the length-for-age (0.05 (−0.19, 0.30)), weight-for-length (0.16 (−0.16, 0.48)), BMI-for-age (0.11 (−0.20, 0.43)), and head circumference-for-age (0.41 (0.16, 0.65)) at the age of four months, were non-inferior. Throughout the study, anthropometric z-scores tracked closely against the WHO standards (within ±1 SD). In sum, a four-stage, age-based infant formula system with nutritional compositions tailored to infants’ evolving needs, supports healthy growth consistent with WHO standards, for the first year of life.

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

“…After two months of age, growth accelerated matching the growth of breastfed infants at four months of age and then exceeded the growth of breastfed infants from 4 to 12 months of age [ 23 ]. This growth pattern for the FF infants studied by Spalinger et al [ 24 ] was similar to that described by Dewey et al [ 1 ].…”

“…In the current narrative review, weight of healthy term infants fed some formulas (EHF-A, EHF-B, AAF-E, AAF-G) appeared to track quite closely and in a normative fashion with that of breastfed infants throughout the first 4 months of life, whereas the growth of infants on other formulas (EHF-C, EHF-D, AAF-F, AAF-H, and AAF-I) was markedly different. For the latter group of formulas, the mean weights of infants dropped below the means of breastfed infants by 14 days of age and unlike the formula-fed infants reported by Spalinger et al [ 24 ], remained considerably lower than the breastfed infant and those of infants fed formulas EHF-A, EHF-B, AAF-E, and AAF-G during the first four months of life. It should be noted that although growth for an individual infant may be interpreted as “normal” if the infant tracks between the 25th and 75th percentiles, when means of a larger group of healthy term infants track consistently lower, and more specifically in the 20th and 30th percentiles, some individual infants would be tracking considerably less than this.…”

“…Thus, it was surprising that commonly available EHFs and AAFs did not all support growth of these infants closer to the 50th percentile during the first 4 months of life and did not display growth patterns previously reported for FF infants [ 1 ]. It has been recently reported [ 24 ] that compared to breastfed infants included in the WHO Growth Reference Study [ 5 ], infants fed intact whey predominant protein-based formula containing no more than 15.1 g protein/L displayed somewhat lower growth during the first two months of life. After two months of age, growth accelerated matching the growth of breastfed infants at four months of age and then exceeded the growth of breastfed infants from 4 to 12 months of age [ 23 ].…”

“…Failure to thrive is a frequently used term for infants with weight-for-age below the 5th percentile [ 25 , 26 ] and a concern for pediatric health care professionals. Thus, although it has been suggested that mean growth of groups of infants fed specific formulas is adequate when above −1 SD of the reference standard [ 24 ], it appeared when this standard was used, some individual infants fed EHF-C and EHF-D may have displayed suboptimal growth. In addition to WHO mean weight-for age z -scores, mean weight-for-age percentiles were available for infants fed EHF-C.…”

The Pregnant Surgeon

“…A study of exclusively formula-fed infants using age-based formulas from 14 days through 4 months demonstrated noninferiority for growth metrics when compared with WHO standards. 31 There are multiple strategies for low milk supply, including pumping more frequently, increasing rest, fluid intake, and adding various foods such as oatmeal, almonds, or fenugreek seeds. By contrast, if desired, to facilitate a gradual wean from breastfeeding, certain herbs (parsley, peppermint, sage, oregano), topical application of cabbage leaves, antihistamines, and gradually eliminating pumping can accelerate the process while minimizing discomfort associated with engorgement.…”