Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Long-chain polyunsaturated fatty acids (LCPUFA) for preterm and term infants

Steven A Abrams, MD
Section Editors
Kathleen J Motil, MD, PhD
Richard Martin, MD
Deputy Editor
Alison G Hoppin, MD


Supplementation of non-human milk feedings with 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 feeding dietary LCPUFAs for term and preterm infants who receive non-human milk feedings.

This topic will review the evidence regarding whether or not dietary LCPUFAs supplementation of non-human milk feedings is beneficial. The risk and benefits of maternal intake of 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 are configured as n-6 and n-3 structures (also referred to as omega-6 and omega-3 fatty acids, respectively). In an n-6 fatty acid, the first double bond from the methyl end is at the C6 position [1]. In an n-3 fatty acid, the first double bond is at the C3 position [2].

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].

Docosahexaenoic acid (DHA) and other n-3 LCPUFAs — DHA is the biologically active end product of alpha-linolenic acid, which is an essential fatty acid because it is exclusively attained from the diet. DHA is primarily derived from fish, especially oily fish such as herring, tuna, and salmon, as well as omega-3-fed chickens and their eggs [7]. Eicosapentaenoic acid (EPA) is a precursor of DHA, and is metabolized to DHA in the liver.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Nov 07, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Innis SM. Essential fatty acid transfer and fetal development. Placenta 2005; 26 Suppl A:S70.
  2. The nomenclature of lipids (recommendations 1976). IUPAC-IUB Commission on Biochemical Nomenclature. J Lipid Res 1978; 19:114.
  3. 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.
  4. Valentine CJ. Maternal dietary DHA supplementation to improve inflammatory outcomes in the preterm infant. Adv Nutr 2012; 3:370.
  5. Clandinin MT, Chappell JE, Heim T, et al. Fatty acid utilization in perinatal de novo synthesis of tissues. Early Hum Dev 1981; 5:355.
  6. 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.
  7. Souci SW, Fachmann W, Kraut H. Food Composition and Nutrition Tables, 7th ed, MedPharm Scientific Publishers, Stuttgart, Germany 2008.
  8. 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.
  9. Innis SM. Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids. J Pediatr 2003; 143:S1.
  10. Martinez M. Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr 1992; 120:S129.
  11. 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.
  12. 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.
  13. Carlson SE, Colombo J. Docosahexaenoic Acid and Arachidonic Acid Nutrition in Early Development. Adv Pediatr 2016; 63:453.
  14. Lauritzen L, Brambilla P, Mazzocchi A, et al. DHA Effects in Brain Development and Function. Nutrients 2016; 8.
  15. 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.
  16. Fats and fatty acids in human nutrition: Report of an expert consultation. Available at: foris.fao.org/preview/25553-0ece4cb94ac52f9a25af77ca5cfba7a8c.pdf (Accessed on October 23, 2017).
  17. 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.
  18. 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.
  19. 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.
  20. Jensen RG. Lipids in human milk. Lipids 1999; 34:1243.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. Makrides M, Neumann MA, Gibson RA. Effect of maternal docosahexaenoic acid (DHA) supplementation on breast milk composition. Eur J Clin Nutr 1996; 50:352.
  26. 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.
  27. 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.
  28. 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).
  29. 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.
  30. 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.
  31. Makrides M, Neumann M, Simmer K, et al. Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Lancet 1995; 345:1463.
  32. Moon K, Rao SC, Schulzke SM, et al. Longchain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Syst Rev 2016; 12:CD000375.
  33. 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.
  34. 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.
  35. 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.
  36. 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).
  37. 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.
  38. Qawasmi A, Landeros-Weisenberger A, Bloch MH. Meta-analysis of LCPUFA supplementation of infant formula and visual acuity. Pediatrics 2013; 131:e262.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. Collins CT, Makrides M, McPhee AJ, et al. Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants. N Engl J Med 2017; 376:1245.
  47. 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.
  48. 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.