Sphingolipidomics of Serum in Extremely Preterm Infants: Association Between Low Sphingosine-1-phosphate Levels and Severe Retinopathy of Prematurity

Overview

Journal Biochim Biophys Acta Mol Cell Biol Lipids

Publisher Elsevier

Specialties Biochemistry
Biophysics
Cell Biology

Date 2021 Apr 16

PMID 33862236

Citations 9

Authors

Anders K Nilsson

Mats X Andersson

Ulrika Sjobom

Gunnel Hellgren

Pia Lundgren

Aldina Pivodic

Lois E H Smith

Ann Hellstrom

Affiliations

Soon will be listed here.

Abstract

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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References

Najm S, Lofqvist C, Hellgren G, Engstrom E, Lundgren P, Hard A . Effects of a lipid emulsion containing fish oil on polyunsaturated fatty acid profiles, growth and morbidities in extremely premature infants: A randomized controlled trial. Clin Nutr ESPEN. 2017; 20:17-23. PMC: 5784264. DOI: 10.1016/j.clnesp.2017.04.004. View

Grip T, Dyrlund T, Ahonen L, Domellof M, Hernell O, Hyotylainen T . Serum, plasma and erythrocyte membrane lipidomes in infants fed formula supplemented with bovine milk fat globule membranes. Pediatr Res. 2018; 84(5):726-732. DOI: 10.1038/s41390-018-0130-9. View

Rodriguez-Cuenca S, Barbarroja N, Vidal-Puig A . Dihydroceramide desaturase 1, the gatekeeper of ceramide induced lipotoxicity. Biochim Biophys Acta. 2014; 1851(1):40-50. DOI: 10.1016/j.bbalip.2014.09.021. View

Sun K, Zhang Y, DAlessandro A, Nemkov T, Song A, Wu H . Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia. Nat Commun. 2016; 7:12086. PMC: 4947158. DOI: 10.1038/ncomms12086. View

. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005; 123(7):991-9. DOI: 10.1001/archopht.123.7.991. View

Lundgren P, Nilsson A, Hellgren G, Pivodic A, Smith L, Hellstrom A . Association between low fatty acid levels and platelet count in infants with Retinopathy of Prematurity. Acta Paediatr. 2020; 109(12):2547-2548. PMC: 8637217. DOI: 10.1111/apa.15406. View

Gaengel K, Niaudet C, Hagikura K, Lavina B, Siemsen B, Muhl L . The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Dev Cell. 2012; 23(3):587-99. DOI: 10.1016/j.devcel.2012.08.005. View

Eresch J, Stumpf M, Koch A, Vutukuri R, Ferreiros N, Schreiber Y . Sphingosine Kinase 2 Modulates Retinal Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy. Invest Ophthalmol Vis Sci. 2018; 59(2):653-661. DOI: 10.1167/iovs.17-22544. View

Crilly C, Haneuse S, Litt J . Predicting the outcomes of preterm neonates beyond the neonatal intensive care unit: What are we missing?. Pediatr Res. 2020; 89(3):426-445. PMC: 7276948. DOI: 10.1038/s41390-020-0968-5. View

10.

OReilly H, Johnson S, Ni Y, Wolke D, Marlow N . Neuropsychological Outcomes at 19 Years of Age Following Extremely Preterm Birth. Pediatrics. 2020; 145(2). DOI: 10.1542/peds.2019-2087. View

11.

Reardon H, Hsieh A, Park W, Kothapalli K, Anthony J, Nathanielsz P . Dietary long-chain polyunsaturated fatty acids upregulate expression of FADS3 transcripts. Prostaglandins Leukot Essent Fatty Acids. 2012; 88(1):15-9. PMC: 3386357. DOI: 10.1016/j.plefa.2012.02.003. View

12.

Tanaka K, Hosozawa M, Kudo N, Yoshikawa N, Hisata K, Shoji H . The pilot study: sphingomyelin-fortified milk has a positive association with the neurobehavioural development of very low birth weight infants during infancy, randomized control trial. Brain Dev. 2012; 35(1):45-52. DOI: 10.1016/j.braindev.2012.03.004. View

13.

Nilsson A . Role of Sphingolipids in Infant Gut Health and Immunity. J Pediatr. 2016; 173 Suppl:S53-9. DOI: 10.1016/j.jpeds.2016.02.076. View

14.

Quinn G . Retinopathy of prematurity blindness worldwide: phenotypes in the third epidemic. Eye Brain. 2017; 8:31-36. PMC: 5398741. DOI: 10.2147/EB.S94436. View

15.

Miranda G, Abrahan C, Politi L, Rotstein N . Sphingosine-1-phosphate is a key regulator of proliferation and differentiation in retina photoreceptors. Invest Ophthalmol Vis Sci. 2009; 50(9):4416-28. DOI: 10.1167/iovs.09-3388. View

16.

Lofgren L, Stahlman M, Forsberg G, Saarinen S, Nilsson R, Hansson G . The BUME method: a novel automated chloroform-free 96-well total lipid extraction method for blood plasma. J Lipid Res. 2012; 53(8):1690-700. PMC: 3540853. DOI: 10.1194/jlr.D023036. View

17.

Anderson J, Baer R, Partridge J, Kuppermann M, Franck L, Rand L . Survival and Major Morbidity of Extremely Preterm Infants: A Population-Based Study. Pediatrics. 2016; 138(1). DOI: 10.1542/peds.2015-4434. View

18.

Lane D, McConathy W . Changes in the serum lipids and apolipoproteins in the first four weeks of life. Pediatr Res. 1986; 20(4):332-7. DOI: 10.1203/00006450-198604000-00011. View

19.

Rabinowitz S, Dzakpasu P, Piecuch S, Leblanc P, Valencia G, Kornecki E . Platelet-activating factor in infants at risk for necrotizing enterocolitis. J Pediatr. 2001; 138(1):81-6. DOI: 10.1067/mpd.2001.110132. View

20.

Bernhard W, Maas C, Shunova A, Mathes M, Bockmann K, Bleeker C . Transport of long-chain polyunsaturated fatty acids in preterm infant plasma is dominated by phosphatidylcholine. Eur J Nutr. 2017; 57(6):2105-2112. DOI: 10.1007/s00394-017-1484-1. View