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Developmental changes in polyunsaturated fetal plasma phospholipids and feto-maternal plasma phospholipid ratios and their association with bronchopulmonary dysplasia

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Abstract

Background

Docosahexaenoic (C22:6) and arachidonic acid (C20:4) are long-chain polyunsaturated fatty acids (LC-PUFA), essential to fetal development, and preferentially transported by plasma phospholipids.

Objective

To characterize fetal and maternal plasma phospholipid changes during gestation, and to investigate whether LC-PUFA phospholipid profiles are associated with bronchopulmonary dysplasia (BPD).

Design

Cord plasma and parturient serum from N = 108 pregnancies [24–42 week postmenstrual age (PMA)] were collected. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were analyzed with tandem mass spectrometry. PMA-associated changes were quantified, and break point analyses served to describe nonlinear changes during gestation.

Results

PC and PE were lower in cord than in parturient samples. In parturients, PC decreased until 33 week PMA, but then re-increased, whereas in cord plasma, concentrations linearly decreased. Fetal PC and PC sub-group values correlated with maternal values. C20:4-PC was twofold higher in cord than in maternal samples throughout gestation. C22:6-PC values, however, exceeded maternal values only beyond 33 week PMA. Consequently, early preterm C20:4-PC-to-C22:6-PC ratio largely exceeded term infant values. In infants born before 28 week PMA, a low C20:4-PC-to-C22:6-PC ratio was associated with BPD severity.

Conclusions

Fetal plasma LC-PUFA–PC composition correlates with maternal values. Fetal C20:4-PC exceeds maternal values throughout gestation, whereas C22:6-PC exceeds maternal values only beyond 33 week PMA, resulting in a low fetal C20:4-PC/C22:6-PC ratio only toward end gestation. A low C20:4-PC/C22:6-PC ratio before 28 week PMA is associated with BPD severity. These data point to a concept of PMA-adjusted ARA and DHA supplementation and, potentially, cord plasma phospholipid analysis for BPD prediction.

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Abbreviations

C18:1:

Oleic acid

C18:2:

Linoleic acid

C18:3:

Alpha-linoleic acid

C20:4:

Arachidonic acid

C20:5:

Eicosapentaenoic acid

C22:4:

Docosatetraenoic acid

C22:6:

Docosahexaenoic acid

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 polyunsaturated fatty acid

LDL:

Low-density lipoproteins

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PEMT:

PE-N-methyltransferase

PMA:

Postmenstrual age

SRM:

Specific reaction monitoring

TIC:

Total ion count

VLDL:

Very low-density lipoproteins

w:

Week

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Acknowledgments

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.

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Authors and Affiliations

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

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

  2. Center for Pediatric Clinical Studies, Faculty of Medicine, Eberhard-Karls-University, Tübingen, Germany

    Axel R. Franz

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

    Harald Abele

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  1. Wolfgang Bernhard
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Correspondence to Wolfgang Bernhard.

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Bernhard, W., Raith, M., Koch, V. et al. Developmental changes in polyunsaturated fetal plasma phospholipids and feto-maternal plasma phospholipid ratios and their association with bronchopulmonary dysplasia. Eur J Nutr 55, 2265–2274 (2016). https://doi.org/10.1007/s00394-015-1036-5

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