Parenteral Fish-Oil Lipid Emulsions in the Prevention of Severe Retinopathy of Prematurity: A Systematic Review and Meta-Analysis

Abstract

Objective Omega-3 fatty acids are vital for brain and retinal maturation. It is not clear if early use of ω-3 fatty acids in the form of fish-oil lipid emulsions (FLEs) prevents retinopathy of prematurity (ROP) in preterm infants. The aim of this meta-analysis is to evaluate whether early administration of parenteral FLEs reduces ROP requiring laser therapy or severe ROP ≥stage 3 in preterm infants.

Methods A literature search was performed to identify studies comparing parenteral FLEs with soybean-based lipid emulsions (SLEs) in preventing ROP. The main outcome was incidence of severe ROP or ROP requiring laser therapy.

Results Studies met the inclusion criteria (four RCTs and two observational studies). The pooled relative risk of ROP requiring laser therapy or severe ROP ≥ stage 3 in FLEs group was 0.47 [95% CI: 0.24–0.90] and 0.40 [95% CI: 0.22–0.76] in RCTs and observational studies, respectively. FLEs also reduced cholestasis; however, other secondary outcomes of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), and mortality were similar.

Conclusion The use of FLEs may reduce the incidence of severe ROP or need for laser therapy in preterm infants. A large multicenter RCT is required to confirm this.

Keywords

fish oil - prematurity - retinopathy of prematurity - total parenteral nutrition

Note

This study was presented as an oral presentation at the 39th AAP District-VIII Conference, 2015, in Victoria and as poster presentation at PAS, 2015, in San Diego and at the Canadian National Perinatal Research Meeting, 2015, at Montebello.

• References

• 1 Kong L, Fry M, Al-Samarraie M, Gilbert C, Steinkuller PG. An update on progress and the changing epidemiology of causes of childhood blindness worldwide. J AAPOS 2012; 16 (6) 501-507
• 2 Canadian Neonatal Network Annual Reports. http://wwwcanadianneonatalnetworkorg/Portal/LinkClickaspx?fileticket=lreR0871sjA%3d&tabid=39 2013
• 3 Vanek VW, Seidner DL, Allen P , et al; Novel Nutrient Task Force, Intravenous Fat Emulsions Workgroup; American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. A.S.P.E.N. position paper: clinical role for alternative intravenous fat emulsions. Nutr Clin Pract 2012; 27 (2) 150-192
• 4 SanGiovanni JP, Berkey CS, Dwyer JT, Colditz GA. Dietary essential fatty acids, long-chain polyunsaturated fatty acids, and visual resolution acuity in healthy fullterm infants: a systematic review. Early Hum Dev 2000; 57 (3) 165-188
• 5 Greenberg JA, Bell SJ, Ausdal WV. Omega-3 fatty acid supplementation during pregnancy. Rev Obstet Gynecol 2008; 1 (4) 162-169
• 6 Smithers LG, Gibson RA, McPhee A, Makrides M. Higher dose of docosahexaenoic acid in the neonatal period improves visual acuity of preterm infants: results of a randomized controlled trial. Am J Clin Nutr 2008; 88 (4) 1049-1056
• 7 Williams C, Birch EE, Emmett PM, Northstone K ; Avon Longitudinal Study of Pregnancy and Childhood Study Team. Stereoacuity at age 3.5 y in children born full-term is associated with prenatal and postnatal dietary factors: a report from a population-based cohort study. Am J Clin Nutr 2001; 73 (2) 316-322
• 8 Innis SM, Friesen RW. Essential n-3 fatty acids in pregnant women and early visual acuity maturation in term infants. Am J Clin Nutr 2008; 87 (3) 548-557
• 9 Lapillonne A, Jensen CL. Reevaluation of the DHA requirement for the premature infant. Prostaglandins Leukot Essent Fatty Acids 2009; 81 (2–3): 143-150
• 10 Baack ML, Puumala SE, Messier SE, Pritchett DK, Harris WS. What is the relationship between gestational age and docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels?. Prostaglandins Leukot Essent Fatty Acids 2015; 100: 5-11
• 11 Pawlik D, Lauterbach R, Turyk E. Fish-oil fat emulsion supplementation may reduce the risk of severe retinopathy in VLBW infants. Pediatrics 2011; 127 (2) 223-228
• 12 Martin CR, Dasilva DA, Cluette-Brown JE , et al. Decreased postnatal docosahexaenoic and arachidonic acid blood levels in premature infants are associated with neonatal morbidities. J Pediatr 2011; 159 (5) 743-749 .e1, 2
• 13 Henriksen C, Haugholt K, Lindgren M , et al. Improved cognitive development among preterm infants attributable to early supplementation of human milk with docosahexaenoic acid and arachidonic acid. Pediatrics 2008; 121 (6) 1137-1145
• 14 Dammann O. Inflammation and retinopathy of prematurity. Acta Paediatr 2010; 99 (7) 975-977
• 15 Bazan NG. Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection. Prostaglandins Leukot Essent Fatty Acids 2009; 81 (2–3): 205-211
• 16 Calder PC. Polyunsaturated fatty acids and inflammation. Prostaglandins Leukot Essent Fatty Acids 2006; 75 (3) 197-202
• 17 Connor KM, SanGiovanni JP, Lofqvist C , et al. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med 2007; 13 (7) 868-873
• 18 Sapieha P, Stahl A, Chen J , et al. 5-Lipoxygenase metabolite 4-HDHA is a mediator of the antiangiogenic effect of ω-3 polyunsaturated fatty acids. Sci Transl Med 2011; 3 (69) 69ra12
• 19 Fu Z, Lofqvist CA, Shao Z , et al. Dietary ω-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin. Am J Clin Nutr 2015; 101 (4) 879-888
• 20 The Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Arch Ophthalmol 1984; 102 (8) 1130-1134
• 21 Bell MJ, Ternberg JL, Feigin RD , et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187 (1) 1-7
• 22 Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics 1988; 82 (4) 527-532
• 23 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92 (4) 529-534
• 24 Fawaz R, Baumann U, Ekong U , et al. Guideline for the evaluation of cholestatic jaundice in infants: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr 2016;
• 25 Keffler S, Kelly DA, Powell JE, Green A. Population screening for neonatal liver disease: a feasibility study. J Pediatr Gastroenterol Nutr 1998; 27 (3) 306-311
• 26 Moyer V, Freese DK, Whitington PF , et al; North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2004; 39 (2) 115-128
• 27 Rosenthal P, Blanckaert N, Kabra PM, Thaler MM. Formation of bilirubin conjugates in human newborns. Pediatr Res 1986; 20 (10) 947-950
• 28 van Tulder M, Furlan A, Bombardier C, Bouter L ; Editorial Board of the Cochrane Collaboration Back Review Group. Updated method guidelines for systematic reviews in the cochrane collaboration back review group. Spine 2003; 28 (12) 1290-1299
• 29 Stroup DF, Berlin JA, Morton SC , et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283 (15) 2008-2012
• 30 Vlaardingerbroek H, Vermeulen MJ, Carnielli VP, Vaz FM, van den Akker CH, van Goudoever JB. Growth and fatty acid profiles of VLBW infants receiving a multicomponent lipid emulsion from birth. J Pediatr Gastroenterol Nutr 2014; 58 (4) 417-427
• 31 D'Ascenzo R, Savini S, Biagetti C , et al. Higher docosahexaenoic acid, lower arachidonic acid and reduced lipid tolerance with high doses of a lipid emulsion containing 15% fish oil: a randomized clinical trial. Clin Nutr 2014; 33 (6) 1002-1009
• 32 Beken S, Dilli D, Fettah ND, Kabataş EU, Zenciroğlu A, Okumuş N. The influence of fish-oil lipid emulsions on retinopathy of prematurity in very low birth weight infants: a randomized controlled trial. Early Hum Dev 2014; 90 (1) 27-31
• 33 Pawlik D, Lauterbach R, Walczak M, Hurkała J, Sherman MP. Fish-oil fat emulsion supplementation reduces the risk of retinopathy in very low birth weight infants: a prospective, randomized study. JPEN J Parenter Enteral Nutr 2014; 38 (6) 711-716
• 34 Pawlik D, Lauterbach R, Hurkała J. The efficacy of fish-oil based fat emulsion administered from the first day of life in very low birth weight newborns. Med Wieku Rozwoj 2011; 15 (3) 306-311
• 35 Tomsits E, Pataki M, Tölgyesi A, Fekete G, Rischak K, Szollár L. Safety and efficacy of a lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil: a randomised, double-blind clinical trial in premature infants requiring parenteral nutrition. J Pediatr Gastroenterol Nutr 2010; 51 (4) 514-521
• 36 Skouroliakou M, Konstantinou D, Agakidis C , et al. Cholestasis, bronchopulmonary dysplasia, and lipid profile in preterm infants receiving MCT/ω-3-PUFA-containing or soybean-based lipid emulsions. Nutr Clin Pract 2012; 27 (6) 817-824
• 37 Gura KM, Lee S, Valim C , et al. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics 2008; 121 (3) e678-e686
• 38 Kaufman SS, Loseke CA, Lupo JV , et al. Influence of bacterial overgrowth and intestinal inflammation on duration of parenteral nutrition in children with short bowel syndrome. J Pediatr 1997; 131 (3) 356-361
• 39 Jones A, Selby PJ, Viner C, Hobbs S, Gore ME, McElwain TJ. Tumour necrosis factor, cholestatic jaundice, and chronic liver disease. Gut 1990; 31 (8) 938-939
• 40 Goulet O, Antébi H, Wolf C , et al. A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr 2010; 34 (5) 485-495
• 41 D'Ascenzo R, D'Egidio S, Angelini L , et al. Parenteral nutrition of preterm infants with a lipid emulsion containing 10% fish oil: effect on plasma lipids and long-chain polyunsaturated fatty acids. J Pediatr 2011; 159 (1) 33-38.e1
• 42 Clayton PT, Whitfield P, Iyer K. The role of phytosterols in the pathogenesis of liver complications of pediatric parenteral nutrition. Nutrition 1998; 14 (1) 158-164
• 43 Puder M, Valim C, Meisel JA , et al. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg 2009; 250 (3) 395-402
• 44 Rayyan M, Devlieger H, Jochum F, Allegaert K. Short-term use of parenteral nutrition with a lipid emulsion containing a mixture of soybean oil, olive oil, medium-chain triglycerides, and fish oil: a randomized double-blind study in preterm infants. JPEN J Parenter Enteral Nutr 2012; 36 (1, Suppl): 81S-94S
• 45 Kapoor V, Glover R, Malviya MN. Alternative lipid emulsions versus pure soy oil based lipid emulsions for parenterally fed preterm infants. Cochrane Database Syst Rev 2015; (12) CD009172