Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Sudip Paul
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Anh Nguyen
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Thy Duong
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Natalie Mellett
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Michelle Cinel
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
Sartaj Ahmad Mir
Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Li Chen
Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Singapore Institute for Clinical Sciences, A*STAR, Singapore, Singapore
Markus R Wenk
Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Neerja Karnani
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Singapore Institute for Clinical Sciences, A*STAR, Singapore, Singapore
School of Medicine, Deakin University, Melbourne, Australia; Child Health Research Unit, Barwon Health, Geelong, Australia
Richard Saffery
Murdoch Children's Research Institute, Royal Children’s Hospital, Melbourne, Australia; Dept of Paediatrics, University of Melbourne, Parkville, Australia
Peter Vuillermin
School of Medicine, Deakin University, Melbourne, Australia; Child Health Research Unit, Barwon Health, Geelong, Australia; Murdoch Children's Research Institute, Royal Children’s Hospital, Melbourne, Australia
Murdoch Children's Research Institute, Royal Children’s Hospital, Melbourne, Australia; The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia
Murdoch Children's Research Institute, Royal Children’s Hospital, Melbourne, Australia; Dept of Paediatrics, University of Melbourne, Parkville, Australia
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. We studied the effect of antenatal factors such as gestational age, birth weight, and mode of birth on lipid metabolism at birth; changes in the circulating lipidome in the first 4 years of life and the effect of breastfeeding in the first year of life. From this study, we aim to generate a framework for deeper understanding into factors effecting lipid metabolism in early life, to provide early interventions for those at risk of developing metabolic disorders including cardiovascular diseases. Methods: 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 features across 39 lipid classes using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). 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 6, 12 months, and 4 years, respectively. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. We performed regression analyses to investigate the associations of cord serum lipid species with antenatal factors: gestational age, birth weight, mode of birth and duration of labour. Results: The lipidome differed between mother and newborn and changed markedly with increasing child’s age. Alkenylphosphatidylethanolamine species containing LC-PUFAs increased with child’s age, whereas the corresponding lysophospholipids and triglycerides decreased. 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. Breastfeeding had a significant impact on the plasma lipidome in the first year of life, with up to 17-fold increases in a few species of alkyldiaclylglycerols at 6 months of age. Conclusions: 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: This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
