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Human milk is a dynamic, complex fluid that offers much more than nutrition to infants. The macronutrient content of human milk has been well characterized and described. However, human milk is not a simple matrix of protein, carbohydrate, fat, and micronutrients. The National Institutes of Health have defined bioactives in food as elements that "affect biological processes or substrates and hence have an impact on body function or condition and ultimately health." Bioactives are cells, anti-infectious and anti-inflammatory agents, growth factors, and prebiotics that are naturally present in human milk. They may explain the differences in health outcomes observed between breastfed and non-breastfed infants. They influence the development of the immune and gastrointestinal systems, gut microbiota, neurodevelopment, metabolic health, and protection against infection. Human milk oligosaccharides are one bioactive that have been an increasingly popular area of research. This review provides a broad overview of some bioactive components that positively affect the immune system and touches on certain well-known growth factors present in human milk. Future research will look at the interplay of the multitude of bioactive components in human milk as a biological system and beyond singular compounds., (© 2022 S. Karger AG, Basel.)

Background: For infants who are partially or exclusively fed infant formula, many options exist with compositional differences between formulas making choices difficult for caregivers and healthcare professionals. The protein in routine infant formulas differs by the source, fraction of cow's milk protein used, and degree of hydrolysis. All commercially available regulated infant formulas support growth and development, but different stool patterns have been observed based on formula composition. A pooled analysis of seven clinical trials was conducted to examine growth, stool consistency, and stool frequency of infants fed an intact cow's milk-based formula (CMF) or a partially hydrolyzed whey formula (PHF-W) from a single manufacturer. Method s. Individual subject data from seven infant formula growth studies (3 CMF, 4 PHF-W) were pooled and analyzed. All studies included healthy, full-term, formula-fed infants enrolled at 14 days of age with outcomes assessed over 4 months. Gains in weight and length to 4 months were analyzed using linear regression accounting for clustering within study. Outcomes of caregiver-reported stool consistency and frequency were analyzed using a longitudinal multinomial model., Results: Data from 511 infants were included (197 CMF, 314 PHF-W). There were no differences in weight gain between groups. There was no difference in length gain in girls fed PHF-W while boys fed PHF-W had a significant difference of +0.016 cm/month compared to boys fed CMF. Infants fed PHF-W had a significantly higher probability of soft and lower probability of hard stools as compared to infants fed CMF at each time point (p<0.001). Stool frequency was similar between groups., Conclusions: Infants fed CMF and PHF-W exhibit appropriate growth with comparable gains in weight and length through 4 months. More soft and fewer hard stools are observed in infants fed PHF-W compared to CMF. This difference could help to inform decision-making when choosing an infant formula.

Objective: This study's primary aim was to compare the growth (daily weight gain) of infants consuming a new (Test) amino acid-based formula (AAF) or a commercially available AAF (Control)., Methods: Healthy infants were randomized to Test or Control from 14 to 112 days of age. Anthropometric measurements were taken at 14, 28, 56, 84, and 112 days of age. Tolerance records were completed prior to each visit. Serum albumin and plasma amino acids were ascertained in a subset of infants at 84 days of age., Results: A total of 119 subjects completed the study per protocol. Mean daily weight gains were 27.26 ± 4.92 g/day for Control and 27.42 ± 6.37 g/day for Test (P = 0.8812). There were no significant differences between groups in formula intake, adverse events, flatulence, spit-up/vomiting, mood, or sleep. Albumin and plasma amino acids were within normal limits for both groups., Conclusions: Infants fed the new AAF had similar daily weight gains as infants fed a commercially available AAF.

Background: Lactobacillus reuteri has been studied for its safety and beneficial effects in infants. This study assessed growth of infants fed a partially hydrolyzed whey formula with L reuteri., Methods: Healthy term infants were randomized to 1 of 2 formulas (partially hydrolyzed whey formula with (PRO) or without (CON) L reuteri from 14 to 112 days of age. Anthropometric measures were assessed at 14, 28, 56, 84, and 112 days of age. Tolerance records were completed 2 days prior to each visit., Results: A total of 122 subjects completed study per protocol (60 PRO, 62 CON). No differences were seen in daily weight gain, length, or head circumference. Overall, between groups, there were no significant differences in formula intake, stool frequency, color, consistency, flatulence, frequency of spit-up/vomiting, mood, sleep, or incidence of adverse events., Conclusion: Infants fed probiotic formula had similar growth to infants fed control formula. Both formulas were well tolerated., (© The Author(s) 2015.)

Objective: To estimate the health and economic impact of feeding partially hydrolyzed formula-whey (PHF-W) instead of standard cow's milk formula (CMF) for the first 4 months of life among US infants at high risk for developing atopic dermatitis (AD)., Study Design: A Markov model was developed integrating published data, a survey of US pediatricians, costing sources and market data, and expert opinion. Key modeled outcomes included reduction in AD risk, time spent post AD diagnosis, days without AD flare, and AD-related costs. Costs and clinical consequences were discounted at 3% annually., Results: An estimated absolute 14-percentage point reduction in AD risk was calculated with the use of PHF-W compared with CMF (95% CI for difference, 3%-22%). Relative to CMF, PHF-W decreased the time spent post-AD diagnosis by 8.3 months (95% CI, 2.78-13.31) per child and increased days without AD flare by 39 days (95% CI, 13-63) per child. The AD-related, 6-year total cost estimate was $495 less (95% CI, -$813 to -$157) per child with PHF-W ($724 per child; 95% CI, $385-$1269) compared with CMF ($1219 per child; 95% CI, $741-$1824)., Conclusion: Utilization of PHF-W in place of CMF as the initial infant formula administered to high-risk US infants not exclusively breastfed during the first 4 months of life may reduce the incidence and economic burden of AD. Broad implementation of this strategy could result in a minimum savings of $355 million per year to society., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Unlabelled: The American Academy of Pediatrics (AAP) defined a formula as hypoallergenic if it ensures with 95% confidence that 90% of infants with confirmed cow's milk allergy (CMA) will not react with defined symptoms under double-blind, placebo-controlled conditions. This study's objective was to determine whether a new amino acid-based formula (AAF) meets the AAP hypoallergenicity criteria., Methods: Children with CMA were randomized to double-blind placebo-controlled food challenges (DBPCFC) with a new AAF and a commercial AAF in crossover fashion followed by an at-home open challenge with the new AAF. Allergic reactions were assessed using a scoring system., Results: Thirty-three subjects completed DBPCFCs with both formulas without acute allergic reactions. The lower bound 95% confidence interval for hypoallergenicity was 91.3%. No unusual stool patterns, allergic symptoms, or signs of intolerance were reported during the open challenge., Conclusion: . The new AAF meets AAP hypoallergenicity criteria and can be recommended for the management of CMA., (© The Author(s) 2014.)

Objective: To describe atopic dermatitis (AD) management patterns in children ≤36 months old as reported by pediatricians, dermatologists, and allergists in the US., Study Design: A nationally-representative survey was administered to pediatricians (n = 101), dermatologists (n = 26), and allergists (n = 26). Main outcomes included referrals to health care professionals, suggested/ordered laboratory tests, management approach (dietary, pharmacologic, or combination of both) by age, AD location, and severity., Results: Significant differences were observed in referrals to healthcare professionals (P < .001). Pediatricians more frequently referred to dermatologists than allergists in mild (52.4% vs 32.0%) and moderate/severe (60.6% vs 38.1%) cases. Dermatologists referred to allergists less frequently for mild (9.1%) than moderate/severe (40.7%) AD cases. Pediatricians (59%), allergists (61.5%), and dermatologists (26.9%) reported treating at least some of their patients with AD with dietary management (infant formula change) alone (with or without emollients). Soy-based formulas were often used. For mild AD, the most commonly reported first-line pharmacologic treatments included topical emollients, topical corticosteroids, and barrier repair topical therapy/medical devices. Over 80% of physicians used a dietary and pharmacologic combination approach. Dermatologists were most likely to manage AD symptoms with a pharmacologic-only approach. AD lesion location influenced pharmacologic treatment in >80% of physicians., Conclusions: Significant and distinct differences in AD treatment approach exist among physicians surveyed. Most pediatricians and allergists use formula change as a management strategy in some patients, whereas dermatologists favor a pharmacologic approach. This diversity may result from inadequate evidence for a standard approach. Consistent methods for managing AD are needed., (Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.)