Maternal obesity and the human milk metabolome: associations with infant body composition and postnatal weight gain

Abstract

Background: Maternal obesity is a risk factor for childhood obesity; this is a major public health concern given that ∼40% of pregnant women are either overweight or obese. Whether differences in milk composition in lean compared with obese women contribute to childhood obesity is unclear.

Objectives: We aimed to analyze relationships between maternal obesity and human milk metabolites, infant body composition, and postnatal weight gain.

Methods: This was a prospective study in which mothers intending to breastfeed exclusively, and their newborn infants, were enrolled at delivery (n = 35 mother-infant pairs). We excluded mothers with diabetes, other medical conditions, or pregnancy complications. Participants were grouped by maternal prepregnancy BMI <25 (lean) or ≥25 kg/m2 (overweight/obese). We analyzed infant body composition by dual-energy X-ray absorptiometry and used untargeted liquid chromatography-gas chromatography-mass spectrometry to measure the milk content of 275 metabolites at 1 and 6 mo postpartum.

Results: At 1 mo postpartum, 10 metabolites differed between overweight/obese and lean groups with nominal P < 0.05, but none was altered with a false discovery rate <0.25. Many differentially abundant metabolites belonged to the same chemical class; e.g., 4/10 metabolites were nucleotide derivatives, and 3/10 were human milk oligosaccharides. Milk adenine correlated positively with both continuously distributed maternal BMI and with infant adiposity and fat accrual. Analysis of milk composition at 6 mo postpartum revealed 20 differentially abundant metabolites (P < 0.05) in overweight/obese compared with lean women, including 6 metabolites with a false discovery rate of <0.25. At both 1 and 6 mo, human milk abundance of 1,5-anhydroglucitol, which has not previously been described in milk, was positively associated with maternal BMI.

Conclusions: Maternal obesity is associated with changes in the human milk metabolome. While only a subset of metabolites correlated with both maternal and infant weight, these point to potential milk-dependent mechanisms for mother-child transmission of obesity. This trial was registered at www.clinicaltrials.gov as NCT02535637.

Keywords: body composition; breast milk; human milk; human milk oligosaccharides; infant; maternal obesity; metabolomics.

© 2019 American Society for Nutrition.

Figures

FIGURE 1

Differentially abundant milk metabolites at 1 mo postpartum: selected top-ranking metabolites with levels differing significantly (P < 0.05, 2-sided t-test) between overweight or obese (“ov-ob”) compared with lean women, 1 mo postpartum, n = 15–16/group. (A) Human milk oligosaccharides. (B) Purine and pyrimidine derivatives. (C) Amino acids. (D) Alkaloids. AU, arbitrary units; LNFP, lacto-N-fucopentaose.

FIGURE 2

Differentially abundant milk metabolites at 6 mo postpartum: selected top-ranking metabolites with levels differing significantly (P < 0.05, 2-sided t-test) between overweight or obese compared with lean women, 6 mo postpartum, n = 12–14/group. (A) Acylcarnitines. (B) Monosaccharides and sugar alcohols. (C) Amino acids and metabolites. 1,5-AG, 1,5-anhydroglucitol.

FIGURE 3

Overlap between milk metabolites correlating with maternal weight status and those correlating with infant weight status at 1 mo postpartum. (A) Venn diagram depicting the overlap between breast milk metabolites at 1 mo postpartum that correlate with infant weight (assessed by weight for age and sex percentile at 1 mo) and metabolites correlating with maternal pre-pregnancy BMI, with all metabolites adjusted for gender, parity, and gestational age. (B) Venn diagram depicting the overlap between breast milk metabolites at 1 mo postpartum that correlate with infant adiposity (assessed by total fat % measured by dual-energy X-ray absorptiometry at 1 mo) and metabolites correlating with maternal prepregnancy BMI. All metabolites adjusted for gender, parity, and gestational age. Significant correlation defined as effect estimate with adjusted P < 0.05. (+) denotes positive correlation, and (–) denotes negative correlation. 1,5-AG, 1,5-anhydroglucitol; GPE, glycerylphosphorylethanolamine.