Achieving definitive results in long-chain polyunsaturated fatty acid supplementation trials of term infants: Factors for consideration

Nutrition Reviews

Volumn 69, Issue 4, 2011, Pages 205-214

  Meldrum, Suzanne J ^a,b,d   Smith, Michael A ^b   Prescott, Susan L ^c   Hird, Kathryn ^b   Simmer, Karen ^a  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^c NORTHUMBRIA UNIVERSITY   (United Kingdom)

^d UNIVERSITY OF NOTRE DAME   (Australia)

Author keywords

Behavior; Dietary supplements; Fatty acids; Term infants

Indexed keywords

DOCOSAHEXAENOIC ACID; POLYUNSATURATED FATTY ACID;

ARTICLE; DIET SUPPLEMENTATION; FAT INTAKE; GENDER; GENETIC POLYMORPHISM; HUMAN; INFANT; INFANT NUTRITION; RANDOMIZED CONTROLLED TRIAL (TOPIC);

DIETARY SUPPLEMENTS; FATTY ACIDS, UNSATURATED; FEMALE; HUMANS; INFANT NUTRITIONAL PHYSIOLOGICAL PHENOMENA; INFANT, NEWBORN; MALE; OUTCOME ASSESSMENT (HEALTH CARE); POLYMORPHISM, GENETIC; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SEX FACTORS; TIME FACTORS;

EID: 79953266837     PISSN: 00296643     EISSN: 17534887     Source Type: Journal    
DOI: 10.1111/j.1753-4887.2011.00381.x     Document Type: Article

References (90)

1. Martinez M. Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr. 1992;120(Suppl):S129-S138.
2. Salem N Jr, Litman B, Kim HY, Gawrisch K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids. 2001;36:945-959.
3. Innis SM. Dietary (n-3) fatty acids and brain development. J Nutr. 2007;137:855-859.
4. Simopoulos AP. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr. 1991;54:438-463.
5. Uauy R, Mena P, Wegher B, Nieto S, Salem N Jr. Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth. Pediatr Res. 2000;47:127-135.
6. Elias SL, Innis SM. Infant plasma trans, conjugated linoleic, n-6 and n-3 fatty acids are related to maternal plasma fatty acids, length of gestation, birth weight and length. Am J Clin Nutr. 2001;73:807-814.
7. Innis SM. Polyunsaturated fatty acids in human milk: an essential role in infant development. Adv Exp Med Biol. 2004;554:27-43.
8. Makrides M. Outcomes for mothers and their babies: do n-3 long-chain polyunsaturated fatty acids and seafoods make a difference? J Am Diet Assoc. 2008;108:1622-1626.
9. Sastry PS. Lipids of nervous tissue: composition and metabolism. Prog Lipid Res. 1985;24:69-176.
10. Bouwstra H, Boersma ER, Boehm G, Dijick-Brouwer DA, Muskiet FA, Hadders-Algra M. Exclusive breastfeeding of healthy term infants for at least six weeks improves neurological condition. J Nutr. 2003;133:4243 -4245.
11. Agostoni C, Marangoni F, Lammardo AM, Giovannini M, Riva E, Galli C. Breastfeeding duration, milk fat composition and developmental indices at 1 year of life among breastfed infants. Prostaglandins Leukot Essent Fatty Acids. 2001;64:105-109.
12. Horwood LJ, Darlow BA, Mogridge N. Breast milk feeding and cognitive ability at 7-8 years. Arch Dis Child Fetal Neonatal Ed. 2001;84:F23-F27.
13. Oddy WH, Kendall GE, Blair E, etal. Breast feeding and cognitive development in children: a prospective birth cohort study. Pediatr Perinat Epidemiol. 2003;17:81-90.
14. Angelsen NK, Vik T, Jacobsen G, Bakketeig LS. Breast feeding and cognitive development at age 1 and 5 years. Arch Dis Child. 2001;85:183-188.
15. Fisher RJ. Formulas and milks for infants and children. Med Today. 2007;8:39-48.
16. Beyerlein A, Hadders-Algra M, Kennedy K, Fewtrell M, etal. 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;50:79-84.
17. Hoffman DR, Boettcher JA, Diersen-Schade DA. Toward optimizing vision and cognition in term infants by dietary docosahexaenoic and arachidonic acid supplementation: a review of randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids. 2009;81:151-158.
18. Lauritzen L, Hansen HS, Jorgensen MH, Michaelsen KF. The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res. 2001;40:1 -94.
19. McCann JC, Ames BN. Is docosahexanoic acid, an n-3 long-chain polyunsaturated fatty acid, required for the development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. Am J Clin Nutr. 2005;82:281-295.
20. Makrides M, Smithers LG, Gibson RA. Role of long-chain polyunsaturated fatty acids in neurodevelopment and growth. In: Lucas A, Makrides M, Ziegler EE, eds. Importance of Growth for Health and Development. Nestle Nutr Inst Workshop Ser Pediatr Program. Basel, Switzerland: Nestle Ltd, Vevey/S.Karger AG; 2010:123-136.
21. Simmer K, Patole SK, Rao SC. Longchain polyunsaturated fatty acid supplementation in infants born at term. Cochrane Database Syst Rev. 2008;1(CD000376).
22. Hoffman DR, Birch EE, Birch DG, etal. Impact of early dietary intake and blood lipid composition of long-chain polyunsaturated fatty acids on later visual development. J Pediatr Gastroenterol Nutr. 2000;31:540-553.
23. Makrides M, Neumann MA, Simmer K, Pater J, Gibson RA. Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Lancet. 1995;345:1463-1468.
24. Makrides M, Neumann MA, Simmer K, Gibson RA. A critical appraisal of the role of long-chain polyunsaturated fatty acids on neural indices of term infants: a randomized controlled trial. Pediatrics. 2000;150:32-38.
25. Ben XM, Zhou XY, Zhao WH, etal. Growth and development of term infants fed with milk with long-chain polyunsaturated fatty acid supplementation. Chin Med J. 2004;117:1268-1270.
26. Birch EE, Garfield S, Castenada Y, Hughbanks-Wheaton D, Uauy R, Hoffman D. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neurol. 2000;42:174-181.
27. Birch EE, Hoffman DR, Uauy R, Birch DG, Prestidge C. Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants. Pediatr Res. 1998;44:201-209.
28. Birch EE, Castaneda YS, Wheaton DH, Birch DG, Uauy RD, Hoffman DR. Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12mo. Am J Clin Nutr. 2005;81:871-879.
29. Lucas A, Stafford M, Morley R, etal. Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial. Lancet. 1999;354:1948-1954.
30. Carlson SE, Ford AJ, Werkman SH, Peeples JM, Koo WW. Visual acuity and fatty acid status of term infants fed human milk and formulas with and without docosahexaenoate and arachidonate from egg yolk lecithin. Pediatr Res. 1996;39:882-888.
31. Agostoni C, Trojan S, Bellu R, Riva E, Bruzzese MG, Giovannini M. Developmental quotient at 24 months and fatty acid composition of diet in early infancy: a follow up study. Arch Dis Child. 1997;76:421-424.
32. Agostoni C, Trojan S, Bellu R, Riva E, Giovannini M. Neurodevelopmental quotient of healthy term infants at 4 months and feeding practice: the role of long-chain polyunsaturated fatty acids. Pediatr Res. 1995;38:262-266.
33. Bouwstra H, Dijick-Brouwer DA, Boehm G, Boersma ER, Muskiet FA, Hadders-Algra M. Long-chain polyunsaturated fatty acids and neurological developmental outcome at 18 months in healthy term infants. Acta Paediatr. 2005;94:26-32.
34. Auestad N, Montalto MD, Hall RT, etal. Visual acuity, erythrocyte fatty acid composition and growth in term infants fed formulas with long-chain polyunsaturated fatty acids for one year. Pediatr Res. 1997;41:1-10.
35. Auestad N, Scott DT, Janowsky JS, etal. Visual, cognitive and language assessments at 39 months: a follow up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age. Pediatrics. 2003;112:e177-e183.
36. Scott DT, Janowsky JS, Carroll RE, Taylor JA, Auestad N, Montalto MB. Formula supplementation with long-chain polyunsaturated fatty acids: are there developmental benefits? Pediatrics. 1998;102:E59.
37. Auestad N, Halter R, Hall RT, Blatter M, etal. Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study. Pediatrics. 2001;108:372-381.
38. Willatts P, Forsyth JS, DiModugno MK, Varma S, Colvin M. Effect of long-chain polyunsaturated fatty acids in infant fomula on problem solving at 10 months of age. Lancet. 1998;352:688-691.
39. Drover J, Hoffman DR, Castenada YS, Morale SE, Birch EE. Three randomized controlled trials of early long-chain polyunsaturated fatty acid supplementation on means-end problem solving in 9-month olds. Child Dev. 2009;80:1376-1384.
40. de Jong C, Kikkert HK, Fidler V, Hadders-Algra M. The Groningen LCPUFA study: no effect on postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years. Br J Nutr. 2010;104:566-572.
41. Birch EE, Carlson SE, Hoffman DR, etal. The DIAMOND (DHA Intake And Measurement of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr. 2010;91:848-859.
42. Gibson RA, Neumann MA, Makrides M. Effect of increasing breast milk docosahexaenoic acid on plasma and erythrocyte phospholipid fatty acids and neural indices of exclusively breast fed infants. Eur J Clin Nutr. 1997;51:578-584.
43. Lauritzen L, Jorgensen MH, Olsen SF, Straarup EM, Michaelsen KF. Maternal fish oil supplementation in lactation: effect on developmental outcome in breast-fed infants. Reprod Nutr Dev. 2005;45:535-547.
44. Agostoni C, Zuccotti GV, Radaelli G, etal. Docosahexaenoic acid supplementation and time at achievement of gross motor milestones in healthy infants: a randomized, prospective, double-blind, placebo-controlled trial. Am J Clin Nutr. 2009;89:64-70.
45. Bayley N. Bayley Scales of Infant and Toddler Development, 3rd ed. San Antonio, TX: Harcourt Assessment; 2006.
46. Xie L, Innis SM. Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythtocyte phospholipids in women during pregnancy and in breast milk during lactation. J Nutr. 2008;138:2222-2228.
47. Rzehak P, Heinrich J, Klopp N, etal. Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desturase 2 (FADS1 FADS2) gene cluster and the fatty acid composition of erythrocyte membranes. Br J Nutr. 2009;101:20-26.
48. Schaeffer L, Gohlke H, Muller M, etal. Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet. 2006;15:1745-1756.
49. Dijck-Brouwer DAJ, Sanjabi B, van Goor SA, etal. The minor allele of the FADS1 gene polymorphism is associated with lower erythrocyte arachidonic acid (AA) in pregnant women and proves sensitive to AA status lowering by docosahexaenoic acid (DHA) supplementation [Abstract]. 8th International Congress of the International Society for the Study of Fatty Acids and Lipids, Kansas City, MO, USA, May 21, 2008.
50. Molto-Puigmarti C, Plat J, Mensink RP, etal. FADS1 FADS2 gene variants modify the association between fish intake and the docosahexaenoic acid proportions in human milk. Am J Clin Nutr. 2010;91:1368-1376.
51. Caspi A, Williams B, Kim-Cohen J, etal. Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism. Proc Natl Acad Sci USA. 2007;104:18860-18865.
52. Simopoulos AP. Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk. Exp Biol Med. 2010;235:785-795.
53. Fewtrell MS, Morley R, Abbott RA, etal. Double-blind, randomized trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants. Pediatrics. 2002;110:73-82.
54. Lucas A, Morley R, Cole TJ, Lister G, Leeson-Payne C. Breast milk and subsequent intelligence quotient in children born preterm. Lancet. 1992;339:261-264.
55. Makrides M, Gibson RA, McPhee AJ, etal. Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. JAMA. 2009;301:175-182.
56. Brenna JT, Varamini B, Jensen RG, Diersen-Schade DA, Boettcher JA, Arterburn JM. Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr. 2007;85:1457-1464.
57. Clandinin MT, Chappell JE, Leong S, Heim T, Swyer PR, Chance GW. Extrauterine fatty acid accretion in infant brain: implications for fatty acid requirements. Early Hum Dev. 1980;4:131-138.
58. Makrides M, Neumann MA, Byard RW, Simmer K, Gibson RA. Fatty acid composition of the brain, retina and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr. 1994;60:189-194.
59. Eilander A, Hundscheid DC, Osendarp SJ, Transler C, Zock PL. Effects of n-3 long chain polyunsaturated fatty acid supplementation on visual and cognitive development throughout childhood: a review of human studies. Prostaglandins Leukot Essent Fatty Acids. 2007;76:189-203.
60. 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):S16-S24.
61. Dunstan JA, Simmer K, Dixon G, Prescott SL. Cognitive assessment of children at age 2 (1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2008;10:F45-F50.
62. Innis SM, Gilley J, Werker J. Are human milk long-chain polyunsaturated fatty acids related to visual and neural development in breast-fed term infants? J Pediatr. 2001;139:532-538.
63. Makrides M, Neumann MA, Simmer K, Gibson RA. A critical appraisal of the role of dietary long-chain polyunsaturated fatty acids on neural indices of term infants: A randomized, controlled trial. Pediatrics. 2000;105:32-38.
64. National Health and Medical Research Council. NHMRC Dietary Guidelines for Children and Adolescents in Australia Incorporating the Infant Feeding Guidelines for Health Workers 2003. Retrieved from
65. Martinez M, Mougan I. Fatty acid composition of human brain phospholipids during normal development. J Neurochem. 1998;71:2528-2533.
66. Willett WC. Nutritional Epidemiology. New York: Oxford University Press; 1998.
67. Baylin A, Campos H. The use of fatty acid biomarkers to reflect dietary intake. Curr Opin Lipidol. 2006;17:22-27.
68. Fekete K, Marosvolgyi T, Jakobik V, Desci T. Methods of assessment of n-3 long-chain polyunsaturated fatty acid status in humans: a systematic review. Am J Clin Nutr. 2009;89(Suppl):S2070-S2084.
69. Kuratko CN, Salem N Jr. Biomarkers of DHA status. Prostaglandins Leukot Essent Fatty Acids. 2009;81:111-118.
70. Katan MB, Deslypere JP, van Birgelen AP, Penders M, Zegwaard M. Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes and adipose tissue: an 18 month controlled study. J Lipid Res. 1997;38:2012-2022.
71. Sun Q, Ma J, Campos H, Hankinson SE, Hu FB. Comparison between plasma and erythrocyte fatty acid content as biomarkers of fatty acid intake in US women. Am J Clin Nutr. 2007;86:74-81.
72. Sarkadi-Nagy E, Wijendran V, Diau GY, etal. Formula feeding potentiates docosehexaenoic and arachidonic acid biosynthesis in term and preterm baboon neonates. J Lipid Res. 2004;45:71-80.
73. Skeaff CM, Hodson L, McKenzie JE. Dietary-induced changes in fatty acid composition of human plasma, platelet, and erythrocyte lipids follow a similar time course. J Nutr. 2006;136:565-569.
74. Caldwell PH, Murphy SB, Butow PN, Craig JC. Clinical trials in children. Lancet. 2004;364:803-811.
75. Osendarp S, Baghurst KI, Bryan J, etal. Effect of a 12-mo micronutrient intervention on learning and memory in well-nourished and marginally nourished school-aged children: 2 parallel, randomized, placebo-controlled studies in Australia and Indonesia. Am J Clin Nutr. 2007;86:1082-1093.
76. McCall RB, Mash CW. Long-chain polyunsatured fatty acids and the measurement and prediction of intelligence (IQ). In: Dobbing J, ed. Developing Brain and Behaviour: The Role of Lipids in Infant Formula. New York, NY: Academic Press; 1997:295-338.
77. Cheatham CL, Colombo J, Carlson SE. N-3 fatty acids and cognitive and visual acuity development: methodologic and conceptual considerations. Am J Clin Nutr. 2006;83:(Suppl):S1458-S1466.
78. Carlson SE, Neuringer M. Polyunsaturated fatty acid status and neurodevelopment: a summary and critical analysis of the literature. Lipids. 1999;34:171-178.
79. Willatts P, Forsyth JS. The role of long-chain polyunsaturated fatty acids in infant cognitive development. Prostaglandins Leukot Essent Fatty Acids. 2000;63:95-100.
80. Colombo J. Recent advances in infant cognition: implications for long-chain polyunsaturated fatty acid supplementation studies. Lipids. 2001;36:919-926.
81. Hughes D, Bryan J. The assessment of cognitive performance in children: considerations for detecting nutritional influences. Nutr Rev. 2003;61:413-422.
82. Dijck-Brouwer DA, Hadders-Algra M, Bouwstra H, etal. Lower fetal status of docosahexaenoic acid, arachidonic acid and essential fatty acids is associated with less favourable neonatal neurological condition. Prostaglandins Leukot Essent Fatty Acids. 2005;72:21-28.
83. Prechtl H. The Neurological Examination of the Full-Term Newborn Infant. Clinics in Developmental Medicine. Vol. 63. London, UK: Spastics International Medical Publishers; 1977.
84. Largo RH, Graf S, Kundu S, Hunziker U, Molinari L. Predicting developmental outcome at school age from infant tests of normal, at-risk and retarded infants. Dev Med Child Neurol. 1990;32:30-45.
85. Dietrich KN, Eskenazi B, Schantz S, etal. Principles and practices of neurodevelopmental assessment in children: lessons learned from the centers for children's environmental health and disease prevention research. Environ Health Perspect. 2005;113:1437-1446.
86. Schuchardt JP, Huss M, Stauss-Grabo M, Hahn A. Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Eur J Pediatr. 2010;169:149-164.
87. Bouwstra H, Dijck-Brouwer DA, Wildeman JA, etal. Long-chain polyunsaturated fatty acids have a positive effect on the quality of general movements of healthy term infants. Am J Clin Nutr. 2003;78:313-318.
88. Kurlak LO, Stephenson TJ. Plausible explanations for effects of long chain polyunsaturated fatty acids (LCPUFA) on neonates. Arch Dis Child Fetal Neonatal Ed. 1999;80:F148-F154.
89. Lauritzen L, Jorgensen MH, Michaelsen FK. Test-restest reliability of swept visual evoked potential measurements of infant visual acuity and contrast sensitivity. Pediatr Res. 2004;55:701-708.
90. Prager TC, Zou YL, Jensen CL, Fraley JK, Anderson RE, Heird WC. Evaluation of methods for assessing visual function of infants. J AAPOS. 1999;3:275-282.