Ontogeny of circulating lipid metabolism in pregnancy and early childhood – a longitudinal population study

Author:

Burugupalli Satvika1ORCID,Smith Adam Alexander T1,Oshlensky Gavriel1,Huynh Kevin1,Giles Corey1,Wang Tingting1,George Alexandra1ORCID,Paul Sudip1,Nguyen Anh1,Duong Thy1,Mellett Natalie1,Cinel Michelle1,Mir Sartaj Ahmad23,Chen Li24,Wenk Markus R23,Karnani Neerja34,Collier Fiona56ORCID,Saffery Richard78,Vuillermin Peter567,Ponsonby Anne-Louise79ORCID,Burgner David78ORCID,Meikle Peter1ORCID,

Affiliation:

1. Metabolomics Laboratory, Baker Heart and Diabetes Institute

2. Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore

3. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore

4. Singapore Institute for Clinical Sciences, A*STAR

5. School of Medicine, Deakin University

6. Child Health Research Unit, Barwon Health

7. Murdoch Children's Research Institute, Royal Children’s Hospital

8. Dept of Paediatrics, University of Melbourne

9. The Florey Institute of Neuroscience and Mental Health

Abstract

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).

Funder

National Health and Medical Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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