Human Milk Bioactive Components and Child Growth and Body Composition in the First 2 Years: A Systematic Review.

Human milk (HM) contains macronutrients, micronutrients, and a multitude of other bioactive factors, which can have a long-term impact on infant growth and development. We systematically searched MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. From 9992 abstracts screened, 141 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Bioactives including hormones, HM oligosaccharides (HMOs), and immunomodulatory components are reported here, based on 75 articles from 69 unique studies reporting observations from 9980 dyads. Research designs, milk collection strategies, sampling times, geographic and socioeconomic settings, reporting practices, and outcomes varied considerably. Meta-analyses were not possible because data collection times and reporting were inconsistent among the studies included. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only 5 studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n = 6773 dyads), compared with 13 (n = 2640 dyads) for HMOs and 12 (n = 1422 dyads) for immunomodulatory components. Two studies conducted untargeted metabolomics. Leptin and adiponectin demonstrated inverse associations with infant growth, although several studies found no associations. No consistent associations were found between individual HMOs and infant growth outcomes. Among immunomodulatory components in HM, IL-6 demonstrated inverse relationships with infant growth. Current research on HM bioactives is largely inconclusive and is insufficient to address the complex composition of HM. Future research should ideally capture HM intake, use biologically relevant anthropometrics, and integrate components across categories, embracing a systems biology approach to better understand how HM components work independently and synergistically to influence infant growth.

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Conflict of interest M(M)B, SMR, and MBA have contributed to online courses on breast milk and the infant microbiome produced by Microbiome Courses. SMR has also served as the scientific advisor for SimpliFed and as a consultant for TraverseScience®. She is a current employee of Prolacta Bioscience®; her contribution to this review occurred prior to this employment. JMM has received support from the Bill & Melinda Gates Foundation and serves on the Council on Research for the American Academy of Nutrition and Dietetics. DC is supported by a Canadian Nurses Foundation Scholarship. DTG is funded by an unrestricted research grant from Medela AG. She is also currently funded by Telethon Child Health Grants and the Australian National Health and Medical Research Council. LHA has research grants from the Bill & Melinda Gates Foundation. MBA is supported by a Canada Research Chair and is a CIFAR Fellow in the Humans and the Microbiome Program; she has consulted for DSM and is a scientific advisor to TinyHealth. LB is UC San Diego Chair of Collaborative Human Milk Research endowed by the Family Larsson-Rosenquist Foundation and also receives support from the USNational Institutes of Health and The Bill & Melinda Gates Foundation. AID, MG, RR, KKS, SM, PPP, CM, FJ, PK, DH, and KGE have no conflicts of interest.