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Session: From the Womb to the World: Impact of Prenatal and Perinatal Exposures on Offspring Outcomes (Oral 21)

(OR21-06-23) Changes in Human Milk Composition Are Associated With Maternal BMI: An Untargeted Metabolomics Analysis of Milk Samples From the HAPIN Trial

Monday, July 24, 2023
5:00 PM – 5:12 PM ET
Location:  Constitution B
Disclosure(s):
Kasthuri Sivalogan, MS, MPH, BS: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Maternal overweight/obesity has been associated with poor lactation performance including delayed lactogenesis and reduced duration. However, the effect on breastmilk composition is less well understood. We evaluated the effect of maternal body mass index (BMI) on the human milk metabolome among breastfeeding Guatemalan mothers.

Methods: We used data from a subset of 75 Guatemalan mothers who participated in the Household Air Pollution Intervention Network trial. Maternal BMI was measured between 9- < 20 weeks gestation. Milk samples were collected at a single time point using aseptic collection, via breast pump or manual expression, from both breasts in the morning at six months postpartum and analyzed using high-resolution mass spectrometry. We identified perturbations in metabolic pathways and features associated with maternal BMI using an established untargeted metabolome-wise association study (MWAS) workflow, including pathway enrichment analysis and chemical annotation and confirmation. Two MWAS models were run using data from hydrophilic interaction (HILIC) and reverse phase (C18) liquid chromatography columns and adjusted for baseline maternal age, education, and dietary diversity.

Results: The mean age of participants at baseline was 23.62 ± 3.81 years and mean BMI was 24.27 ± 4.22 kg/m2. The final analyses included 19,199 metabolic features from the HILIC column and 11,594 from the C18 column. Of these, 1026 and 500 features were significantly associated with continuous maternal BMI (p < 0.05) from the HILIC and C18 columns respectively, representing 11 and 12 unique metabolic pathways. After adjusting for multiple comparisons using FDRBH < 0.2, 5 significant features were identified from the HILIC column and none from the C18 column. Chemical identification confirmed the identity of 24 and 12 metabolites, from HILIC and C18, significantly associated with continuous maternal BMI.

Conclusions: Findings from this untargeted MWAS indicate that maternal BMI is associated with metabolic perturbations of neurodevelopment-related pathways, including glutamate and tryptophan metabolism, and future cardiometabolic risk, including branched-chain amino acid metabolism.

Funding Sources: This research was supported by awards from NIEHS (T32 012870; P30ES019776).