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Choline concentrations are lower in postnatal plasma of preterm infants than in cord plasma

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Abstract

Background

Choline is essential to human development, particularly of the brain in the form of phosphatidylcholine, sphingomyelin and acetylcholine, for bile and lipoprotein formation, and as a methyl group donator. Choline is actively transported into the fetus, and maternal supply correlates with cognitive outcome. Interruption of placental supply may therefore impair choline homeostasis in preterm infants.

Objective

Determination of postnatal plasma concentrations of choline and its derivatives betaine and dimethylglycine (DMG) in preterm infants compared to cord and maternal blood matched for postmenstrual age (PMA).

Design

We collected plasma of very low-birth-weight infants undergoing neonatal intensive care (n = 162), cord plasma of term and preterm infants (n = 176, 24–42-week PMA), serum of parturients (n = 36), and plasma of healthy premenopausal women (n = 40). Target metabolites were analyzed with tandem mass spectrometry and reported as median (25th/75th percentiles).

Results

Cord plasma choline concentration was 41.4 (31.8–51.2) µmol/L and inversely correlated with PMA. In term but not in preterm infants, cord plasma choline was lower in girls than in boys. Prenatal glucocorticoid treatment did not affect choline levels in cord plasma, whereas betaine was decreased and DMG increased. In parturients and non-pregnant women, choline concentrations were 14.1 (10.3–16.9) and 8.8 (5.7–11.2) µmol/L, respectively, whereas betaine was lowest in parturients. After delivery, preterm infant plasma choline decreased to 20.8 (16.0–27.6) µmol/L within 48 h. Betaine and DMG correlated with plasma choline in all groups.

Conclusions

In preterm infants, plasma choline decreases to 50 % of cord plasma concentrations, reflecting choline undernourishment and postnatal metabolic adaptation, and potentially contributing to impaired outcome.

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Abbreviations

AI:

Adequate intake

BHMT:

Betaine homocysteine methyltransferase

D:

Deuterium

DHA:

Docosahexaenoic acid

DMG:

Dimethylglycine

EDTA:

Ethylene diamine tetraacetate

H-ESI:

Heated electrospray ionization interface

HPLC:

High performance liquid chromatography

LC–ESI–MS/MS:

Liquid chromatography–electrospray ionization interface tandem mass spectrometry

LC–PUFA:

Long-chain poly-unsaturated fatty acid

NICU:

Neonatal intensive care unit

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PEMT:

PE-N-methyltransferase

PMA:

Postmenstrual age

SAM:

S-adenosylmethionine

SM:

Sphingomyelin

SRM:

Specific reaction monitoring

TIC:

Total ion count

VLDL:

Very low-density lipoproteins

w:

Week

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Acknowledgements

This study was supported by an institutional grant (Project No. E.1100008) of the ZEM—Zentrum Ernährungsmedizin of the Medical Faculty of the University of Tuebingen and the University of Hohenheim. The authors have no financial relationships relevant to this article to disclose. This study was funded by an internal grant of the Eberhard-Karls-University, Tübingen, and the University of Hohenheim, Stuttgart, Germany (ZEM 4A II-08).

Conflict of interest

The authors have no conflict of interests to disclose.

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Authors and Affiliations

  1. Department of Neonatology, Faculty of Medicine, Eberhard-Karls-University, Calwer Straße 7, 72076, Tūbingen, Germany

    Wolfgang Bernhard, Marco Raith, Rebecca Kunze, Vera Koch, Christoph Maas, Christian F. Poets & Axel R. Franz

  2. Department of Internal Medicine IV, Faculty of Medicine, Eberhard-Karls-University, Tūbingen, Germany

    Martin Heni

  3. Department of Gynecology, Faculty of Medicine, Eberhard-Karls-University, Tūbingen, Germany

    Harald Abele

  4. Center for Pediatric Clinical Studies, Faculty of Medicine, Eberhard-Karls-University, Tūbingen, Germany

    Axel R. Franz

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  1. Wolfgang Bernhard
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  2. Marco Raith
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  4. Vera Koch
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  9. Axel R. Franz
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Correspondence to Wolfgang Bernhard.

Additional information

Study registration: This study was registered at www.clinicaltrials.gov. Identifier: NCT02027584.

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Bernhard, W., Raith, M., Kunze, R. et al. Choline concentrations are lower in postnatal plasma of preterm infants than in cord plasma. Eur J Nutr 54, 733–741 (2015). https://doi.org/10.1007/s00394-014-0751-7

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  • DOI: https://doi.org/10.1007/s00394-014-0751-7

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