Human milk bioactive components and child growth and body composition in the first 2 years: a systematic review

Authors: BROCKWAY, MEREDITH - University Of Manitoba; DANIEL, ALLISON - Hospital For Sick Children (SICKKIDS); REYES, SARAH - University Of Manitoba; GAUGLITZ, JULIA - Sapient Bioanalytics; GRANGER, MATTHEW - University Of Manitoba; MCDERMID, JOANN - University Of Virginia; CHAN, DEBORAH - University Of Manitoba; REFVIK, REBECCA - University Of Manitoba; SIDHU, KARANBIR - University Of Manitoba; MUSSE, SUAD - University Of Manitoba; PATEL, POOJA - Tufts University; MONNIN, CAROLINE - University Of Manitoba; LOTOSKI, LARISA - University Of Manitoba; GEDDES, DONNA - The University Of Western Australia; JEHAN, FYEZAH - Aga Khan University; KOLSTEREN, PATRICK - Ghent University; BODE, LARS - University Of California, San Diego; ERIKSEN, KAMILLA - University Of Copenhagen; Allen, Lindsay - A; HAMPEL, DANIELA - University Of California, Davis; RODRIGUEZ, NATALIE - University Of Manitoba; AZAD, MEGHAN - University Of Manitoba

Submitted to: Advances in Nutrition
Publication Type: Literature Review
Publication Acceptance Date: 9/26/2023
Publication Date: 10/4/2023
Citation: Brockway, M., Daniel, A.I., Reyes, S.M., Gauglitz, J.M., Granger, M., Mcdermid, J.M., Chan, D., Refvik, R., Sidhu, K.K., Musse, S., Patel, P.P., Monnin, C., Lotoski, L., Geddes, D.T., Jehan, F., Kolsteren, P., Bode, L., Eriksen, K.G., Allen, L.H., Hampel, D., Rodriguez, N., Azad, M.B. 2023. Human milk bioactive components and child growth and body composition in the first 2 years: a systematic review. Advances in Nutrition. 15(1). https://doi.org/10.1016/j.advnut.2023.09.015.
DOI: https://doi.org/10.1016/j.advnut.2023.09.015

Interpretive Summary: Human milk (HM) contains many components which can have a long-term impact on infant growth and development. We systematically searched Medline, EMBASE, Cochrane Library, Scopus, and Web of Science for reports between 1980-2022 on HM components and anthropometry through 2 years of age among term-born infants. 9,992 abstracts were screened and 141 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Here, we are reporting on hormones, HM oligosaccharides (HMOs), and immunomodulatory components as so-called "bioactives" discussed in 75 articles from 69 unique studies reporting on 9,980 mother-infant pairs. We found great variation in research designs, milk collection strategies, sampling times, geographic and socioeconomic settings, reporting practices, and outcomes. Meta-analyses were not possible because data collection times and reporting were inconsistent amongst the studies. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only five studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n=6773 dyads), compared to 13 (n=2,640 dyads) for HMOs, and 12 (n=1422 dyads) for immunomodulatory components. Two studies conducted untargeted metabolomics. Leptin and adiponectin were inversely related to infant growth in some studies, while others found no associations. HMOs and infant growth could not be consistently linked to each other. Among immunomodulatory components in HM, interleukin-6 (IL-6) demonstrated inverse relationships with infant growth. Current research on HM bioactives is largely inconclusive and is not sufficient to address the composition of HM. Future research is needed to capture human milk intake, use biologically relevant anthropometrics, and integrate components across categories to better understand how HM components work and affect infant growth.

Technical Abstract: 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 1980-2022 on HM components and anthropometry through 2 years of age among term-born infants. From 9,992 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 9,980 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 amongst the studies included. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only five studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n=6773 dyads), compared to 13 (n=2,640 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, interleukin-6 (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 human milk 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.