Abstract
BACKGROUND: Gestational diabetes mellitus (GDM) increases offspring obesity risk, but whether this occurs via changes in human milk composition, including alterations in human milk oligosaccharides (HMOs), is unknown. OBJECTIVES: This study aimed to identify differences in HMO concentrations in mothers with and without GDM and test whether GDM-associated HMOs are associated with infant growth, body composition, and fecal microbiome characteristics over the first 6-mo of life. METHODS: Human milk was collected at 1-mo postpartum from 337 females (49 with GDM) who fed their infants breastmilk exclusively. HMOs were quantified by high-performance liquid chromatography and multivariate regression models were used to test differences in HMO concentrations by GDM status (false discovery rate adjustment for multiple testing set at q < 0.05). HMOs associated with GDM were then tested for associations with infant growth, body composition, and 1 and 6-mo infant fecal microbial abundances measured by metagenomic whole-genome sequencing. RESULTS: Participants with GDM had ∼1 SD higher milk 6'sialyllactose (6'SL) {[β (95% confidence interval): 0.58 (0.20, 0.96)] and lacto-N-fucopentaose III (LNFP III) III [95% CI: 0.55 (0.16, 0.94)]} compared with those without GDM and 6'SL concentration was also positively associated with weight and length gain. Although infants of mothers with GDM had lower 1-mo fecal α-diversity and altered abundances of 6 of 56 microbial species detected compared with those without GDM, microbial features were not associated with the concentration of either 6'SL or LNFP III and evidence for mediation of GDM-growth and GDM-microbiome by HMOs was not found. CONCLUSIONS: Mothers with a GDM diagnosis had higher milk concentrations of LNFP III and 6'SL, and 6'SL was in turn associated with increased infant growth rate, but neither HMO was associated with differential infant gut microbial abundances. The results suggest that the link between 6'SL and faster infant growth, if causal, occurs via mechanisms independent of the infant gut microbiome. This study was registered at clinicaltrials.gov as NCT03301753.