The protective effect of L-carnitine supplementation on retinopathy of prematurity: A retrospective cohort study

Öz

Background/Aim: Retinopathy of prematurity (ROP) is important morbidity in premature infants and is the most common preventable cause of blindness in childhood. Carnitine is a key molecule in energy metabolism and in oxidation of fatty acids, which are the main structural component of phospholipid membrane of the brain and retinal cells. Premature babies are born with insufficient carnitine pools. This study aimed to evaluate the effect of carnitine replacement on ROP in premature infants aged < 34 gestational weeks. Methods: Premature infant records between 2014 and 2019 were retrospectively examined. All premature infants at gestational ages < 34 weeks were included. Data from the two groups who received/did not receive carnitine supplementation in total parenteral nutrition (TPN) over two consecutive time periods and whose ROP examination was complete were recorded retrospectively. Fifty-eight out of 125 infants were in the carnitine group, and 67 formed the non-carnitine group (CG and NCG, respectively). The morbidity data from subjects, especially those with ROP, who received (CG) and did not receive carnitine (NCG), were compared. Results: Of the 125 infants enrolled, no significant differences in gestational age (P = 0.323) or birth weight (P = 0.597) between the groups was found. The Cox regression analysis revealed that carnitine replacement in the premature infant was a protective factor for ROP (P=0.045, B= −0.933, hazard ratio 0.393, 95% confidence interval 0.158–0.978). Conclusion: Carnitine supplementation may offer protection from developing ROP during exposure to oxygen in premature infants.

Anahtar Kelimeler

• Premature retinopathy
• L-carnitine
• Morbidities

Kaynakça

1. 1. Coats DK, Miller AM, Hussein MA, McCreery KM, Holz E, Paysse EA. Involution of retinopathy of prematurity after laser treatment: factors associated with development of retinal detachment. Am J Ophthalmol. 2005 Aug;140(2):214-22. doi: 10.1016/j.ajo.2004.12.106. PMID: 16086945.
2. 2. Domanico R, Davis DK, Coleman F, Davis BO. Documenting the NICU design dilemma: comparative patient progress in open-ward and single family room units. J Perinatol. 2011 Apr;31(4):281-8. doi: 10.1038/jp.2010.120. Epub 2010 Nov 11. PMID: 21072040; PMCID: PMC3070087.
3. 3. Azad R, Chandra P. Retinopathy of prematurity. J Indian Med Assoc. 2005 Jul;103(7):370-2. PMID: 16366189.
4. 4. Kim TI, Sohn J, Pi SY, Yoon YH. Postnatal risk factors of retinopathy of prematurity. Paediatr Perinat Epidemiol. 2004 Mar;18(2):130-4. doi: 10.1111/j.1365-3016.2003.00545.x. PMID: 14996252.
5. 5. Souci SW, Fachmann W, Kraut H. Food Composition and Nutrition Tables, 7th ed, MedPharm Scientific Publishers, Stuttgart, Germany, 2008.
6. 6. Kuipers RS, Luxwolda MF, Offringa PJ, Boersma ER, Dijck-Brouwer DA, Muskiet FA. Fetal intrauterine whole body linoleic, arachidonic and docosahexaenoic acid contents and accretion rates. Prostaglandins LeukotEssent Fatty Acids. 2012 Jan-Feb;86(1-2):13-20. doi: 10.1016/j.plefa.2011.10.012. Epub 2011 Nov 23. PMID: 22115845.
7. 7. Lewin GA, Schachter HM, Yuen D, Merchant P, Mamaladze V, Tsertsvadze A. Effects of omega-3 fatty acids on child and maternal health. Evid Rep Technol Assess (Summ). 2005 Aug;(118):1-11. PMID: 16194124; PMCID: PMC4781637.
8. 8. Martinez M. Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr. 1992 Apr;120(4 Pt 2):S129-38. doi: 10.1016/s0022-3476(05)81247-8. PMID: 1532827.

9. 9. Innis SM. Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids. J Pediatr. 2003 Oct;143(4 Suppl):S1-8. doi: 10.1067/s0022-3476(03)00396-2. PMID: 14597908.
10. 10. Bonner CM, DeBrie KL, Hug G, Landrigan E, Taylor BJ. Effects of parenteral L-carnitine supplementation on fat metabolism and nutrition in premature neonates. J Pediatr. 1995 Feb;126(2):287-92. doi: 10.1016/s0022-3476(95)70562-7. PMID: 7844680.
11. 11. Cairns PA, Stalker DJ. Carnitine supplementation of parenterally fed neonates. Cochrane Database Syst Rev. 2000;2000(4):CD000950. doi: 10.1002/14651858.CD000950. PMID: 11034690; PMCID: PMC7061355.
12. 12. Section on Ophthalmology American Academy of Pediatrics; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2006 Feb;117(2):572-6. doi: 10.1542/peds.2005-2749. Erratum in: Pediatrics. 2006 Sep;118(3):1324. PMID: 16452383
13. 13. Darlow BA, Gilbert C. Retinopathy of prematurity - A world update. Semin Perinatol. 2019 Oct;43(6):315-316. doi: 10.1053/j.semperi.2019.05.001. Epub 2019 May 10. PMID: 31151777.
14. 14. Pekala J, Patkowska-Sokoła B, Bodkowski R, Jamroz D, Nowakowski P, Lochyński S, et al.L-carnitine--metabolic functions and meaning in humans life. Curr Drug Metab. 2011 Sep;12(7):667-78. doi: 10.2174/138920011796504536. PMID: 21561431.
15. 15. Cairns PA, Stalker DJ. Carnitine supplementation of parenterally fed neonates. Cochrane Database Syst Rev. 2000;2000(4):CD000950. doi: 10.1002/14651858.CD000950. PMID: 11034690; PMCID: PMC7061355.
16. 16. Ozturk MA, Kardas Z, Kardas F, Gunes T, Kurtoglu S. Effects of L-carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: A single blind randomized controlled trial. ExpTher Med. 2016 Mar;11(3):1123-1127. doi: 10.3892/etm.2015.2964. Epub 2015 Dec 29. PMID: 26998047; PMCID: PMC4774440.
17. 17. Korkmaz A, Tekinalp G, Coskun T, Yigit S, Yurdakok M. Plasma carnitine levels in preterm infants with respiratory distress syndrome. Pediatr Int. 2005 Feb;47(1):49-52. doi: 10.1111/j.1442-200x.2005.01998.x. PMID: 15693866.
18. 18. Keleş S, Caner İ, Ateş O, Çakici Ö, Saruhan F, Mumcu UY, et al. Protective effect of L-carnitine in a rat model of retinopathy of prematurity. Turk J Med Sci. 2014;44(3):471-5. doi: 10.3906/sag-1301-9. PMID: 25558651.
19. 19. Schoors S, Bruning U, Missiaen R, Queiroz KC, Borgers G, Elia I, et al. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature. 2015 Apr 9;520(7546):192-197. doi: 10.1038/nature14362. Epub 2015 Apr 1. Erratum in: Nature. 2015 Oct 1;526(7571):144. PMID: 25830893; PMCID: PMC4413024.
20. 20. Spiekerkoetter U, Lindner M, Santer R, Grotzke M, Baumgartner MR, Boehles H, et al. Management and outcome in 75 individuals with long-chain fatty acid oxidation defects: results from a workshop. J Inherit Metab Dis. 2009 Aug;32(4):488-97. doi: 10.1007/s10545-009-1125-9. Epub 2009 Apr 29. PMID: 19399638.
21. 21. Yang Y, Wu Z, Li S, Yang M, Xiao X, Lian C, et al. Targeted Blood Metabolomic Study on Retinopathy of Prematurity. Invest Ophthalmol Vis Sci. 2020 Feb 7;61(2):12. doi: 10.1167/iovs.61.2.12. PMID: 32049343; PMCID: PMC7326483.
22. 22. SalgueroOlid A, Blanco Sánchez G, Alonso Ojembarrena A. A systematic review about prophylactic L-carnitine administration in parenteral nutrition of extremely preterm infants. Farm Hosp. 2018 Jul 1;42(4):168-173. English. doi: 10.7399/fh.10976. PMID: 29959842.
23. 23. Pooyandjoo M, Nouhi M, Shab-Bidar S, Djafarian K, Olyaeemanesh A. The effect of (L-)carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2016 Oct;17(10):970-6. doi: 10.1111/obr.12436. Epub 2016 Jun 22. PMID: 27335245.
24. 24. Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. 1988 Apr;106(4):471-9. doi: 10.1001/archopht.1988.01060130517027. PMID: 2895630.
25. 25. Löfqvist C, Hansen-Pupp I, Andersson E, Holm K, Smith LE, Ley D, et al. Validation of a new retinopathy of prematurity screening method monitoring longitudinal postnatal weight and insulin like growth factor I. Arch Ophthalmol. 2009 May;127(5):622-7. doi: 10.1001/archophthalmol.2009.69. PMID: 19433710.
26. 26. Hellström A, Smith LE, Dammann O. Retinopathy of prematurity. Lancet. 2013 Oct 26;382(9902):1445-57. doi: 10.1016/S0140-6736(13)60178-6. Epub 2013 Jun 17. PMID: 23782686; PMCID: PMC4389630.
27. 27. Binenbaum G. Algorithms for the prediction of retinopathy of prematurity based on postnatal weight gain. ClinPerinatol. 2013 Jun;40(2):261-70. doi: 10.1016/j.clp.2013.02.004. PMID: 23719309; PMCID: PMC3692738.
28. 28. Hellström A, Engström E, Hård AL, Albertsson-Wikland K, Carlsson B, Niklasson A, et al. Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth. Pediatrics. 2003 Nov;112(5):1016-20. doi: 10.1542/peds.112.5.1016. PMID: 14595040.