Gestational Age and the Cord Blood Lipidomic Profile in Late Preterm and Term Infants

McCloskey, Kate; Livera, Alysha M De; Collier, Fiona; Ponsonby, Anne–Louise; Vuillermin, Peter; Mellett, Natalie A.; Jayawardana, Kaushala S.; Weir, Jacqueline M; Blangero, John; Curran, Joanne E.; Burgner, David; Meikle, Peter J.

doi:10.1159/000487506

Cited by 5 publications

(4 citation statements)

References 24 publications

(31 reference statements)

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“…In our study, we found di- and triacylglycerols were positively associated with gestational age, which reflect an evolutionary adaptation in preparation for the metabolic stress of labour, a period of high energy expenditure ( Ghaemi et al, 2014 ; McCloskey et al, 2018a ). A concomitant increase in branched-chain fatty acids and corresponding phospholipids, a downstream product of the mitochondrial catabolism of branched-chain amino acids along with elevated levels of acylcarnitines, both suggest increased mitochondrial activity in babies with greater gestational age ( Bjørndal et al, 2018 ).…”

Section: Discussionsupporting

confidence: 61%

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

Burugupalli

Smith

Oshlensky

et al. 2022

eLife

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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).

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Section: Discussionsupporting

confidence: 61%

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

Burugupalli

Smith

Oshlensky

et al. 2022

eLife

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“…Serum lipid composition is known to depend on GA at birth [ 28 ] and GA is an established confounder for the later development of ROP. Therefore, S1P association to ROP was tested with mixed models for repeated measures with postnatal days as time scale and adjusted for GA at birth and weight SDS change from birth over the study period ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…There is little longitudinal data on sphingolipids for full-term infants with which to compare our data. In a study comparing lipid profiles in cord blood from late preterm and term infants, the abundance of 39% of the analyzed lipid species was found to depend on GA at birth [ 28 ]. However, in the study by McCloskey et al, none of the analyzed sphingolipid classes (Cer, gangliosides, HexCer, and SM) were associated with GA at birth after adjusting for birth weight, gender, and labor.…”

Section: Discussionmentioning

confidence: 99%

Sphingolipidomics of serum in extremely preterm infants: Association between low sphingosine-1-phosphate levels and severe retinopathy of prematurity

Nilsson

Andersson

Sjöbom

et al. 2021

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Background: Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP) that can cause impaired vision or blindness. Changes in blood lipids have been associated with ROP. This study aimed to monitor longitudinal changes in the serum sphingolipidome of extremely preterm infants and investigate the relationship to development of severe ROP. Methods: This is a prospective study that included 47 infants born <28 gestational weeks. Serum samples were collected from cord blood and at postnatal days 1, 7, 14, and 28, and at postmenstrual weeks (PMW) 32, 36, and 40. Serum sphingolipids and phosphatidylcholines were extracted and analyzed by LC-MS/MS. Associations between sphingolipid species and ROP were assessed using mixed models for repeated measures. Results: The serum concentration of all investigated lipid classes, including ceramide, mono- di- and trihexosylceramide, sphingomyelin, and phosphatidylcholine displayed distinct temporal patterns between birth and PMW40. There were also substantial changes in the lipid species composition within each class. Among the analyzed sphingolipid species, sphingosine-1-phosphate showed the strongest association with severe ROP, and this association was independent of gestational age at birth and weight standard deviation score change. Conclusions: The serum phospho- and sphingolipidome undergoes significant remodeling during the first weeks of the preterm infant’s life. Low postnatal levels of the signaling lipid sphingosine-1-phosphate are associated with the development of severe ROP.

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“…In this study, we examined the association of gestational age, birthweight, and mode of birth with cord serum lipid concentrations. Di- and tri-acylglycerols were positively associated with gestational age, which may reflect an evolutionary adaptation in preparation for the metabolic stress of labor, a period of high energy expenditure [16] [17]. A concomitant increase in branched chain fatty acids and corresponding phospholipids, a downstream product of the mitochondrial catabolism of branched chain amino acids and elevated levels of acylcarnitines, both suggest increased mitochondrial activity in babies with greater gestational age [18].…”

Section: Discussionmentioning

confidence: 99%

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

Burugupalli

Smith

Olshansky

et al. 2021

Preprint

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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).

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Gestational Age and the Cord Blood Lipidomic Profile in Late Preterm and Term Infants

Cited by 5 publications

References 24 publications

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

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

Sphingolipidomics of serum in extremely preterm infants: Association between low sphingosine-1-phosphate levels and severe retinopathy of prematurity

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

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