Associations of human milk oligosaccharides and bioactive proteins with infant growth and development among Malawian mother-infant dyads

Abstract

Background Human milk oligosaccharides (HMOs) and bioactive breast milk proteins have many beneficial properties. Information is sparse regarding associations between these milk constituents and infant growth and development in lower-income countries. Objectives We aimed to examine associations of milk content of HMOs and bioactive proteins at 6 mo postpartum with infant growth and motor and cognitive development. These are secondary analyses of a randomized controlled trial in rural Malawi. Methods Breast milk samples were analyzed at 6 mo (n = 659) for general categories of HMOs (total HMOs, fucosylated HMOs, and sialylated HMOs), 51 individual HMOs, and 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of the relative abundances of HMOs and concentrations of bioactive proteins with infant growth from 6 to 12 mo [change in length-for-age (ΔLAZ), weight-for-age, weight-for-length, and head circumference z-scores] as well as ability to stand or walk alone at 12 mo, and motor and language skills, socioemotional development, executive function, and working memory at 18 mo. Analyses were adjusted for covariates and multiple hypothesis testing. Results Among all participants, there were inverse associations of IgA and lactoferrin concentrations with motor skills (P = 0.018 and P = 0.044), and a positive association of lactalbumin concentration with motor skills (P = 0.038). Among secretors only [fucosyltransferase 2 gene (FUT2) positive], there were positive associations of absolute abundance of HMOs with ΔLAZ (P = 0.035), and relative abundance of fucosylated and sialylated HMOs with language at 18 mo (P < 0.001 and P = 0.033, respectively), and inverse associations of osteopontin with standing and walking at 12 mo (P = 0.007 and 0.002, respectively). Relative abundances of several individual HMOs were associated with growth and development, mostly among secretors. Conclusions Certain bioactive breast milk proteins and HMOs are associated with infant growth and motor and cognitive development. Further studies are needed to determine if a causal relation exists. This trial was registered at clinicaltrials.gov as NCT01239693.

Comprehensive Human Milk Patterns Are Related to Infant Growth and Allergy in the CHMP Study

“…In general, current evidence on HMO in relation to infant growth is inconclusive, with substantial variations being observed across geographic locations. [26][27][28][29] Interestingly, however, two studies reported negative association between 6'SL content and infant growth, which is in agreement with our results. [27,28] It has been proposed that those variations may be partly due to the differing composition of gut microbiota as HMO might interact differently according to the intestine microbiome profile.…”

“…[26][27][28][29] Interestingly, however, two studies reported negative association between 6'SL content and infant growth, which is in agreement with our results. [27,28] It has been proposed that those variations may be partly due to the differing composition of gut microbiota as HMO might interact differently according to the intestine microbiome profile. [28] Future studies are needed to take microbiota profile into account when exploring association between HMO content and infant growth.…”

Associations of Human Milk Oligosaccharides and Bioactive Proteins with Infant Morbidity and Inflammation in Malawian Mother-Infant Dyads

“…There were several significant associations of the bioactive breast milk proteins with the other bioactive proteins, groups of HMOs, or individual HMOs ( Supplemental Table 1 ) as described previously ( 22 ).…”

“…All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc.). We first examined whether median values of HMOs and proteins differed between women with the secretor phenotype [positive for the functional enzyme encoded by the fucosyltransferase 2 ( FUT2 ) gene, as determined by >6% α1-2-linked fucosylated HMOs, as described previously ( 22 )] and nonsecretors using the nonparametric Kruskal–Wallis test. Covariate adjusted regression models were examined separately in secretors and in nonsecretors for those HMOs that differed between secretors and nonsecretors, and also when the interaction between secretor status and the predictor variable was significant.…”

Longitudinal Changes in the Concentration of Major Human Milk Proteins in the First Six Months of Lactation and Their Effects on Infant Growth

“…α-lactalbumin is the predominant whey protein in HM. The concentrations of α-lactalbumin in milk from different populations have been reported, including Switzerland [ 9 ], the United States [ 19 ], Malawi [ 42 ], and China [ 13 , 36 ]. The present study found the concentration of α-lactalbumin remained relatively consistent in the first two weeks of lactation and then decreased slightly in the first month postpartum.…”