Maternal BMI and infant obesity risk: a lipidomics perspective on the developmental origins of obesity
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Background Maternal obesity is a critical determinant of infant health, influencing birth weight and increasing the risk of obesity in early life. Plasma lipids are mechanistically linked to obesity and may mediate the intergenerational transfer. Using the Barwon Infant Study, a longitudinal birth cohort, we aimed to investigate the associations between maternal pre-pregnancy body mass index (pp-BMI), lipidomic profiles of mothers, human milk, and infants, and early life growth. We were particularly interested in ether lipids as they are higher in breastfed infants compared to formula-fed infants, are enriched in human milk compared to infant formula, and are involved in metabolic health and inflammation in adult populations. Methods Linear regression analyses assessed relationships between maternal pp-BMI and lipid profiles across all biospecimens, and infant BMI. A composite plasmalogen score, reflecting ether lipid metabolism, was developed due to its strong associations with maternal BMI and breastfeeding. Causal mediation analysis was performed to quantify the extent to which cord lipids mediated the effect of maternal pp-BMI on infant birth weight. Results Our findings revealed significant associations between maternal pp-BMI and both maternal and cord lipid profiles, as well as obesity risk indicators. Of the cord blood lipids, 6 of them mediated up to 18% of the effect of maternal pp-BMI on birth weight. Maternal plasmalogen score was negatively associated with pp-BMI and positively associated with plasmalogens in human milk and infant plasmalogen scores from birth to four years of age. Conclusions These findings position plasmalogens and ether lipids as potential biomarkers or intervention targets for reducing transmission of obesity from mother to infant. Optimising lipid profiles through reducing maternal pp-BMI and dietary or supplemental ether lipids may represent a novel strategy for mitigating early-life obesity risk.
