Higher omega-3 DHA-plasmalogen phospholipid levels across early life mediate the benefits of maternal healthy diet and breastfeeding on infant neurocognition

Early-life lipid profiles may influence neurodevelopment, yet the underlying biochemical pathways are not well defined. Using serial lipidomic data from 1,074 mother-child pairs in the Barwon Infant Study, we examined associations between maternal and infant lipid networks and cognitive and language outcomes at two years. A shared lipid network enriched in DHA-carrying phosphatidylethanolamine plasmalogens (PEP-DHA) was associated with higher subsequent cognition and language at age two years. These findings were distinct from total DHA levels alone. Antenatally, maternal PEP-DHA partly mediated the relationship between prenatal diet quality and cognition and language. Postnatally, the beneficial effect of breastfeeding on neurocognition was substantially mediated by PEP-DHA levels in infant plasma at 6 months, while infant PEP-DHA mediated the effect of breastfeeding on receptive language. These findings suggest that DHA-containing plasmalogens may represent key lipid mediators linking early nutrition with optimal neurodevelopment.