Ontogeny of plasma lipid metabolism in pregnancy and early childhood: a longitudinal population study

Background: There is mounting evidence that in utero and early life exposures may predispose an individual to metabolic disorders in later life; and dysregulation of lipid metabolism is critical in such outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. In this study, we aim to understand the lipid metabolism in pregnancy, and from birth to four years. Methods and findings: We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population based pre-birth cohort and measured 776 distinct lipid species across 42 lipid classes using ultra high-performance liquid chromatography (UHPLC). We measured lipids in 1032 maternal serum samples at 28 weeks gestation, 893 cord serum samples at birth, 793, 735, and 511 plasma samples at six, twelve months, and four years, respectively. The lipidome differed between mother and newborn and changed markedly with increasing postnatal age. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. Alkenyl-phosphatidylethanolamine species containing LC-PUFAs increased with postnatal age, whereas the corresponding lysophospholipids and triglycerides decreased. We performed regression analyses to investigate the associations of cord serum lipid species with birth factors: gestational age, birth weight, mode of birth and duration of labor. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids. Conclusions: There were marked changes in the plasma lipidome over the first four years of life. This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood. Funding Statement: This work was supported by the A*STAR-NHMRC joint call funding (1711624031).