Postdoctoral Fellow Indiana University-Bloomington Indianapolis, Indiana, United States
Background: Maternal weight status has been associated with alterations in the human milk metabolome and may impact infant growth. There is significant variability in how maternal weight changes following pregnancy, yet studies have not characterized this heterogeneity using milk metabolomics. Objective: Explore and characterize maternal weight change heterogeneity using milk metabolomics in exclusively breastfeeding mothers Design/Methods: A total of 348 mothers (M±SD, age 31.2±4.3 y, pre-pregnancy BMI 27.3±6.0 kg/m2, GDM 18%) who exclusively breastfed for at least 1 month were included. Maternal weight was collected at delivery and 1, 3, and 6 months postpartum. Breast milk samples were collected at 1 month. Untargeted metabolomics of milk samples was performed using liquid chromatography-gas chromatography-mass spectrometry to quantify relative metabolite abundances. Covariance pattern growth mixture models were used to identify distinct phenotypes of maternal postpartum weight change. If >1 phenotypes were identified, a one-way ANOVA was used to compare the relative abundances. P-values were adjusted for false discovery rate using the Benjamini-Hochberg procedure (q < 0.05 was considered significant). Results: Delivery maternal weight was 84.6±1.4 kg. Up to 6 months postpartum, 3 distinct maternal weight change phenotypes were identified and labeled by delivery weight: Low (LO, n=135), Middle (MID, n=200), and High (HI, n=13). LO (M±SE, -9±1 kg, p< 0.001) and MID (-7±2 kg, p=0.002) showed significant reductions in weight over time, whereas reductions in HI (-17±11 kg, p=0.115) did not reach significance. LO (36.8%) and MID (39.1%) had higher rates of excess gestational weight gain compared to HI (24.1%, p< 0.001). GDM rates were higher with increasing maternal weight (LO 9%, MID 18%, HI 39%, p=0.004) with no differences in gestational weight gain or infant sex. Out of 458 identified milk metabolites, abundance in asparagine (F=11.2, q=0.009), fumarate (F=8.8, q=0.03), and maleic acid (F=8.7, q=0.03) was significantly different across phenotypes. LO demonstrated significantly higher asparagine (vs MID) with lower fumarate and maleic acid (vs MID and HI).
Conclusion(s): A significant level of heterogeneity was observed in maternal postpartum weight changes and was characterized by altered milk metabolites, including asparagine, fumarate, and maleic acid. Determining whether these metabolites are involved in lactational programming of obesity and obesity-related disease risk among breastfed infants will inform future precision approaches.
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