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Characterization of lipoproteins and associated lipidome in very preterm infants: a pilot study

Abstract

Background

Preterm birth is associated with higher risks of suboptimal neurodevelopment and cardiometabolic disease later in life. Altered maternal–fetal lipid supply could play a role in such risks. Our hypothesis was that very preterm infants born with very low birth weight (VLBW) have altered lipidome and apolipoprotein profiles, compared with term infants.

Methods

Seven mothers of VLBW infants born at <32 GA and 8 full-term mother–infant dyads were included. Cholesterol and triglycerides in lipoproteins were determined in maternal plasma and in the two blood vessels of the umbilical cord (vein (UV) and artery (UA)) following FPLC isolation. Apolipoprotein concentrations in lipoproteins and plasma lipidomic analysis were performed by LC-MS/MS.

Results

We found higher cholesterol and VLDL-cholesterol in UV and UA and lower apolipoprotein A-I in HDL2 in UV in preterm neonates. Phosphatidylcholine (PC) containing saturated and monounsaturated fatty acids and specific sphingomyelin species were increased in UV and UA, whereas PC containing docosahexaenoic acid (DHA) was reduced in UV of VLBW neonates.

Conclusions

Lower DHA-PC suggests a lower DHA bioavailability and may contribute to the impaired neurodevelopment. Altered HDL-2, VLDL, and sphingomyelin profile reflect an atherogenic risk and increased metabolic risk at adulthood in infants born prematurely.

Impact

  • Lower ApoA-I in HDL2, and increased specific sphingomyelin and phosphatidylcholine containing saturated and monounsaturated fatty acid could explain the accumulation of cholesterol in umbilical vein in VLBW preterm neonates.

  • Decreased phosphatidylcholine containing DHA suggest a reduced DHA availability for brain development in VLBW preterm infants.

  • Characterization of alterations in fetal lipid plasma and lipoprotein profiles may help to explain at least in part the causes of the elevated cardiovascular risk known in people born prematurely and may suggest that a targeted nutritional strategy based on the composition of fatty acids carried by phosphatidylcholine may be promising in infants born very early.

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Fig. 1: Plasma cholesterol concentration increased in preterm neonates.
Fig. 2: Lipoprotein profile in mother-infant dyads at full term and preterm.
Fig. 3: Higher cholesterol/HDL-c ratio and lower ApoA-1 concentration in HDL2 in preterm neonates.

Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

The authors are grateful to the staff of the Mère-Enfant Clinical Investigation Centre of University Hospital in Nantes for their invaluable help in the management of the blood collection. The authors thank Caroline Mallier for her technical assistance. Lipidomic analysis and apolipoprotein quantification were performed in the Mass Spectrometry Core Facility of CRNH Ouest, Biogenouest Corsaire and SFR F. Bonamy UMS 016 at the University of Nantes.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Contributions

A.K. designed the study protocol and provided the human samples. M.C. quantified apolipoprotein in the lipoprotein fractions. D.D. and K.O. supervised the experiments. V.F.-R. conducted the lipidomic analysis, analyzed the results, supervised the experiments, and wrote the manuscript. T.M. supervised the statistical analyses. All authors discussed the results, edited the manuscript, and approved the final version.

Corresponding author

Correspondence to Véronique Ferchaud-Roucher.

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A written informed consent was obtained from every woman included in this clinical pilot study.

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Küster, A., Croyal, M., Moyon, T. et al. Characterization of lipoproteins and associated lipidome in very preterm infants: a pilot study. Pediatr Res (2022). https://doi.org/10.1038/s41390-022-02159-9

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