Ontogeny of circulating lipid metabolism in pregnancy and early childhood: a longitudinal population study
- Baker Heart and Diabetes Institute, Australia
- National University of Singapore, Singapore
- Singapore Institute for Clinical Sciences, A*STAR, Singapore
- Deakin University, Australia
- Murdoch Children's Research Institute, Australia
- The Florey Institute of Neuroscience and Mental Health, Australia
- Murdoch Children's Research Institute, Australia
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 four 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 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 child's age. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. Alkenylphosphatidylethanolamine species containing LC-PUFAs increased with child's age, whereas the corresponding lysophospholipids and triglycerides decreased. 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 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. Breastfeeding had a significant impact on the plasma lipidome in the first year of life, with upto 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 Statement: This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
Data availability
Due to the consent obtained during recruitment process, it is not possible to make all data publicly available. Access to BIS data including all data used in this paper may be requested through the BIS Steering Committee by contacting the corresponding author. Requests to access cohort data are considered on scientific and ethical grounds and, if approved, provided under collaborative research agreements. Deidentified cohort data can be provided in Stata or CSV format. All statistical methods used are referenced within the methods section. Data that is not subject to data-sharing restrictions can be found in Supplementary File 1. Additional project information, including cohort data description and access procedures, is available at the project's website https://www.barwoninfantstudy.org.au
Article and author information
Author details
Anne-Louise Ponsonby
Funding
National Health and Medical Research Council (A*STAR-NHMRC joint call funding (1711624031).)
- Peter Meikle
National Health and Medical Research Council (A*STAR-NHMRC joint call funding (1711624031).)
- Markus R Wenk
- Neerja Karnani
- Fiona Collier
- Richard Saffery
- Peter Vuillermin
- Anne-Louise Ponsonby
- David Burgner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The original study was granted by the Barwon Health Human Research and Ethics Committee (HREC 10/24).
Copyright
© 2022, Burugupalli et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Ontogeny of circulating lipid metabolism in pregnancy and early childhood: a longitudinal population study
eLife 11:e72779.
https://doi.org/10.7554/eLife.72779
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