n-3 long-chain polyunsaturated fatty acids (LCPUFA) for preterm and term infants
- Steven A Abrams, MD
Steven A Abrams, MD
- Section Editor — Neonatology
- Professor, Department of Pediatrics
- Dell Medical School at the University of Texas at Austin
- Section Editors
- Kathleen J Motil, MD, PhD
Kathleen J Motil, MD, PhD
- Section Editor — Pediatric Nutrition
- Professor of Pediatric Nutrition
- Baylor College of Medicine
- Richard Martin, MD
Richard Martin, MD
- Section Editor — Neonatology
- Professor, Pediatrics, Reproductive Biology, and Physiology & Biophysics
- Case Western Reserve University School of Medicine
Supplementation of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) has been proposed to improve outcome in infants, particularly neurodevelopmental outcome. However, it remains uncertain whether there is benefit in supplemental dietary n-3 LCPUFAs (also referred to as omega-3 LCPUFAs) for term and preterm infants.
This topic will review the evidence regarding whether or not dietary n-3 LCPUFAs supplementation for infants is beneficial. The risk and benefits of maternal intake of n-3 LCPUFAs through fish intake during pregnancy and the potential benefits of LCPUFAs consumed as dietary seafood or fish oil in adults are discussed separately. (See "Fish consumption and docosahexaenoic acid (DHA) supplementation in pregnancy" and "Fish oil and marine omega-3 fatty acids".)
Metabolism and function — LCPUFAs can be divided into n-6 and n-3 fatty acids (also referred to as omega-6 and omega-3 fatty acids, respectively). Arachidonic acid (AA) is an n-6 fatty acid because of the placement of its first double bond from the methyl end at the C6 position , whereas docosahexaenoic acid (DHA) is an n-3 fatty acid because of its first double bond at the third position . Both AA and DHA are biologically active end products of the essential fatty acids, linoleic (precursor for AA) and alpha-linolenic (precursor for DHA), which are exclusively attained from the diet. The LCPUFAs are synthesized in the liver endoplasmic reticulum and peroxisomes by a series of desaturase and elongase enzymes, and the n-6 and n-3 LCPUFAs compete for these enzymes in their biosynthesis (figure 1) [3,4]. Biosynthesis depends on precursor availability and enzyme activity, which may be limiting in ill or preterm newborns [5,6].
AA can be derived directly from meat sources, whereas DHA is derived from oily fish such as herring, tuna, and salmon, and vegetarian-fed chickens and their eggs . In the United States, the typical diet is higher in n-6 compared with n-3 LCPUFA, due to higher intake of meat over fish. This shift may have implications on the balance between proinflammatory (AA) and antiinflammatory prostaglandin (DHA and other n-3 LCPUFAs such as eicosapentaenoic acid) synthesis.
Docosahexaenoic acid — DHA is an integral component of the phospholipid membrane of brain and retinal cells, and also plays a role in antiinflammatory prostaglandin synthesis, signaling events, gene expression, and cytokine expression. It is preferentially incorporated into the rapidly developing brain and retina during the last trimester of pregnancy and the first six months of life, with ongoing accumulation into early childhood [8-11].
Subscribers log in hereLiterature review current through: Sep 2017. | This topic last updated: May 30, 2017.References
- Innis SM. Essential fatty acid transfer and fetal development. Placenta 2005; 26 Suppl A:S70.
- The nomenclature of lipids (recommendations 1976). IUPAC-IUB Commission on Biochemical Nomenclature. J Lipid Res 1978; 19:114.
- German JB, Dillard CJ. Composition, structure and absorption of milk lipids: a source of energy, fat-soluble nutrients and bioactive molecules. Crit Rev Food Sci Nutr 2006; 46:57.
- Valentine CJ. Maternal dietary DHA supplementation to improve inflammatory outcomes in the preterm infant. Adv Nutr 2012; 3:370.
- Clandinin MT, Chappell JE, Heim T, et al. Fatty acid utilization in perinatal de novo synthesis of tissues. Early Hum Dev 1981; 5:355.
- Mayes C, Burdge GC, Bingham A, et al. Variation in [U-13C] alpha linolenic acid absorption, beta-oxidation and conversion to docosahexaenoic acid in the pre-term infant fed a DHA-enriched formula. Pediatr Res 2006; 59:271.
- Souci SW, Fachmann W, Kraut H. Food Composition and Nutrition Tables, 7th ed, MedPharm Scientific Publishers, Stuttgart, Germany 2008.
- Kuipers RS, Luxwolda MF, Offringa PJ, et al. Fetal intrauterine whole body linoleic, arachidonic and docosahexaenoic acid contents and accretion rates. Prostaglandins Leukot Essent Fatty Acids 2012; 86:13.
- Innis SM. Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids. J Pediatr 2003; 143:S1.
- Martinez M. Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr 1992; 120:S129.
- Lewin GA, Schachter HM, Yuen D, et al. Effects of omega-3 fatty acids on child and maternal health. Evid Rep Technol Assess (Summ) 2005; :1.
- Cunnane SC, Francescutti V, Brenna JT, Crawford MA. Breast-fed infants achieve a higher rate of brain and whole body docosahexaenoate accumulation than formula-fed infants not consuming dietary docosahexaenoate. Lipids 2000; 35:105.
- Innis SM. Omega-3 Fatty acids and neural development to 2 years of age: do we know enough for dietary recommendations? J Pediatr Gastroenterol Nutr 2009; 48 Suppl 1:S16.
- Institute of Medicine of the National Academies. Dietary Reference Intakes (DRIs): For Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein and Amino Acids, The National Academies Press, Washington, DC 2005.
- Agostoni C, Buonocore G, Carnielli VP, et al. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr 2010; 50:85.
- Brenna JT, Varamini B, Jensen RG, et al. Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr 2007; 85:1457.
- Brenna JT. Animal studies of the functional consequences of suboptimal polyunsaturated fatty acid status during pregnancy, lactation and early post-natal life. Matern Child Nutr 2011; 7 Suppl 2:59.
- Jensen RG. Lipids in human milk. Lipids 1999; 34:1243.
- Valentine CJ, Morrow G, Morrow AL. Promoting Pasteurized Donor Human Milk Use in the Neonatal Intensive Care Unit (NICU) as an adjunct to care and to Prevent Necrotizing Enterocolitis and shorten length of stay, F. a. D. A. Division of Dockets Management (HFA-305) (Ed), Rockville, MD 2010.
- Valentine CJ, Morrow G, Fernandez S, et al. Docosahexaenoic Acid and Amino Acid Contents in Pasteurized Donor Milk are Low for Preterm Infants. J Pediatr 2010; 157:906.
- Baack ML, Norris AW, Yao J, Colaizy T. Long-chain polyunsaturated fatty acid levels in US donor human milk: meeting the needs of premature infants? J Perinatol 2012; 32:598.
- Makrides M, Neumann MA, Gibson RA. Effect of maternal docosahexaenoic acid (DHA) supplementation on breast milk composition. Eur J Clin Nutr 1996; 50:352.
- Lapillonne A, Eleni dit Trolli S, Kermorvant-Duchemin E. Postnatal docosahexaenoic acid deficiency is an inevitable consequence of current recommendations and practice in preterm infants. Neonatology 2010; 98:397.
- Quinn EA, Kuzawa CW. A dose-response relationship between fish consumption and human milk DHA content among Filipino women in Cebu City, Philippines. Acta Paediatr 2012; 101:e439.
- U.S. Environmental Protection Agency: Advisories and technical resources for fish and shellfish consumption. Available at: https://www.epa.gov/fish-tech (Accessed on February 16, 2017).
- Ponder DL, Innis SM, Benson JD, Siegman JS. Docosahexaenoic acid status of term infants fed breast milk or infant formula containing soy oil or corn oil. Pediatr Res 1992; 32:683.
- Putnam JC, Carlson SE, DeVoe PW, Barness LA. The effect of variations in dietary fatty acids on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidylethanolamine in human infants. Am J Clin Nutr 1982; 36:106.
- Makrides M, Neumann M, Simmer K, et al. Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Lancet 1995; 345:1463.
- Moon K, Rao SC, Schulzke SM, et al. Longchain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Syst Rev 2016; 12:CD000375.
- Makrides M, Gibson RA, McPhee AJ, et al. Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. JAMA 2009; 301:175.
- 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; 121:1137.
- Farquharson J, Jamieson EC, Abbasi KA, et al. Effect of diet on the fatty acid composition of the major phospholipids of infant cerebral cortex. Arch Dis Child 1995; 72:198.
- Qawasmi A, Landeros-Weisenberger A, Bloch MH. Meta-analysis of LCPUFA supplementation of infant formula and visual acuity. Pediatrics 2013; 131:e262.
- Newberry SJ, Chung M, Booth M, Maglione MA, Tang AM, O’Hanlon CE, Wang DD, Okunogbe A, Huang C, Motala A, Timmer M, Dudley W, Shanman R, Coker TR, Shekelle P. Omega-3 Fatty Acids and Maternal and Child Health: An Updated Systematic Review. Evidence Report/Technology Assessment No. 224. (Prepared by the RAND Southern California Evidence-based Practice Center under Contract No. 290-2012-00006-I.) AHRQ Publication No. 16(17)-E003-EF. Rockville, MD: Agency for Healthcare Research and Quality; October 2016. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm. (Accessed on October 31, 2016).
- Jasani B, Simmer K, Patole SK, Rao SC. Long chain polyunsaturated fatty acid supplementation in infants born at term. Cochrane Database Syst Rev 2017; 3:CD000376.
- Qawasmi A, Landeros-Weisenberger A, Leckman JF, Bloch MH. Meta-analysis of long-chain polyunsaturated fatty acid supplementation of formula and infant cognition. Pediatrics 2012; 129:1141.
- Beyerlein A, Hadders-Algra M, Kennedy K, et al. Infant formula supplementation with long-chain polyunsaturated fatty acids has no effect on Bayley developmental scores at 18 months of age--IPD meta-analysis of 4 large clinical trials. J Pediatr Gastroenterol Nutr 2010; 50:79.
- Smithers LG, Collins CT, Simmonds LA, et al. Feeding preterm infants milk with a higher dose of docosahexaenoic acid than that used in current practice does not influence language or behavior in early childhood: a follow-up study of a randomized controlled trial. Am J Clin Nutr 2010; 91:628.
- Isaacs EB, Ross S, Kennedy K, et al. 10-year cognition in preterms after random assignment to fatty acid supplementation in infancy. Pediatrics 2011; 128:e890.
- Westerberg AC, Schei R, Henriksen C, et al. Attention among very low birth weight infants following early supplementation with docosahexaenoic and arachidonic acid. Acta Paediatr 2011; 100:47.
- Almaas AN, Tamnes CK, Nakstad B, et al. Long-chain polyunsaturated fatty acids and cognition in VLBW infants at 8 years: an RCT. Pediatrics 2015; 135:972.
- Zhang P, Lavoie PM, Lacaze-Masmonteil T, et al. Omega-3 long-chain polyunsaturated fatty acids for extremely preterm infants: a systematic review. Pediatrics 2014; 134:120.
- Collins CT, Makrides M, McPhee AJ, et al. Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants. N Engl J Med 2017; 376:1245.
- Meldrum SJ, Smith MA, Prescott SL, et al. Achieving definitive results in long-chain polyunsaturated fatty acid supplementation trials of term infants: factors for consideration. Nutr Rev 2011; 69:205.
- Yeates AJ, Love TM, Engström K, et al. Genetic variation in FADS genes is associated with maternal long-chain PUFA status but not with cognitive development of infants in a high fish-eating observational study. Prostaglandins Leukot Essent Fatty Acids 2015; 102-103:13.
- Metabolism and function
- - Docosahexaenoic acid
- Suggested dietary requirements
- LCPUFA content in milk
- - Human milk
- - Infant formula
- OUR APPROACH
- RATIONALE FOR LCPUFA SUPPLEMENTATION
- CLINICAL TRIALS
- Term or preterm infants
- Very low birth weight infants
- KNOWLEDGE GAPS AND FUTURE RESEARCH
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS