Association Between Human Milk Oligosaccharides and Early Adiposity Rebound in Children: A Case-Control Study of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Background: Adiposity rebound (AR) is the point when the body mass index (BMI) begins to rise again during early childhood. Early AR (before age 5) is associated with a higher risk of lifelong obesity and metabolic disorders and may be influenced by breastfeeding. Although human milk oligosaccharides (HMOs) in breast milk are crucial for child growth, their association with AR status has not been studied.

Objective: To explore breast milk HMO compositions and molecules associated with AR status in children.

Methods: In this case-control study, we included 184 mother-child pairs from the Tohoku Medical Megabank Project Birth and Three-Generation (TMM BirThree) Cohort Study (93 AR cases, 91 controls). Breast milk was collected 1 month postpartum, and the concentration of 15 HMO molecules and alpha-diversity index (Inverse Simpson index) were quantified. Wilcoxon's rank-sum test and partial least squares-discriminant analysis (PLS-DA) identified candidate HMOs, and multivariable logistic regression analysis evaluated associations between candidate HMOs and AR status. Analyses were stratified by maternal secretor status (secretor or non-secretor).

Results: In secretor mothers, multivariable logistic regression showed that the Inverse Simpson index (OR, 0.54 [95% CI, 0.36-0.82]), sum of sialic acid-bound HMOs (0.61 [0.41-0.91]), and 3'-sialyllactose (0.67 [0.46-0.98]) were inversely associated with early AR in a fully adjusted model. A trend of interaction between sialyl-lacto-N-tetraose a (LSTa) and maternal secretor status on AR was observed in a fully adjusted model (P-value for interaction = 0.051).

Conclusions: Alpha diversity, sialic acid-bound HMOs, and 3'SL may be involved in inhibiting AR in children of secretor mothers, and a trend of interactive effect of LSTa among maternal secretor status on AR was indicated. These findings offer novel perspectives on the associations between breastfeeding and a child's adiposity as well as potential metabolic disorders later in life. REGISTRY NUMBER/WEBSITE: https://www.umin.ac.jp/ (trial registration number: UMIN000047160).