Human Milk Composition Is Associated with Maternal Body Mass Index in a Cross-Sectional, Untargeted Metabolomics Analysis of Human Milk from Guatemalan Mothers

Background: Maternal overweight and obesity has been associated with poor lactation performance including delayed lactogenesis and reduced duration. However, the effect on human milk composition is less well understood. Objectives: We evaluated the relationship of maternal BMI on the human milk metabolome among Guatemalan mothers. Methods: We used data from 75 Guatemalan mothers who participated in the Household Air Pollution Intervention Network trial. Maternal BMI was measured between 9 and < 20 weeks of gestation. Milk samples were collected at a single time point using aseptic collection from one breast at 6 mo postpartum and analyzed using high -resolution mass spectrometry. A cross-sectional untargeted high -resolution metabolomics analysis was performed by coupling hydrophilic interaction liquid chromatography (HILIC) and reverse phase C18 chromatography with mass spectrometry. Metabolic features associated with maternal BMI were determined by a metabolome-wide association study (MWAS), adjusting for baseline maternal age, education, and dietary diversity, and perturbations in metabolic pathways were identi fi ed by pathway enrichment analysis. Results: The mean age of participants at baseline was 23.62 +/- 3.81 y, and mean BMI was 24.27 +/- 4.22 kg/m 2 . Of the total metabolic features detected by HILIC column (19,199 features) and by C18 column (11,594 features), BMI was associated with 1026 HILIC and 500 C18 features. Enriched pathways represented amino acid metabolism, galactose metabolism, and xenobiotic metabolic metabolism. However, no signi fi cant features were identi fi ed after adjusting for multiple comparisons using the Benjamini - Hochberg false discovery rate procedure (FDR BH < 0.2). Conclusions: Findings from this untargeted MWAS indicate that maternal BMI is associated with metabolic perturbations of galactose metabolism, xenobiotic metabolism, and xenobiotic metabolism by cytochrome p450 and biosynthesis of amino acid pathways. Signi fi cant metabolic pathway alterations detected in human milk were associated with energy metabolism-related pathways including carbohydrate and amino acid metabolism. This trial was registered at clinicaltrials.gov as NCT02944682.