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Дополнительное введение полиненасыщенной жирной кислоты в младенческом возрасте для профилактики аллергии.

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Referencias

References to studies included in this review

Birch 2005 {published data only}

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 12 mo. American Journal of Clinical Nutrition 2005;81(4):871‐9. [PUBMED: 15817866]CENTRAL
Birch EE, Khoury JC, Berseth CL, Castaneda YS, Couch JM, Bean J, et al. The impact of early nutrition on incidence of allergic manifestations and common respiratory illnesses in children. Journal of Pediatrics 2010;156(6):902‐6, 906.e1. [PUBMED: 20227721]CENTRAL
Drover J, Hoffman DR, Castaneda 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 Development 2009;80(5):1376‐84. [PUBMED: 19765006]CENTRAL
Drover JR, Felius J, Hoffman DR, Castaneda YS, Garfield S, Wheaton DH, et al. A randomized trial of DHA intake during infancy: school readiness and receptive vocabulary at 2‐3.5 years of age. Early Human Development 2012;88(11):885‐91. [PUBMED: 22835597]CENTRAL
Morale SE, Hoffman DR, Castaneda YS, Wheaton DH, Burns RA, Birch EE. Duration of long‐chain polyunsaturated fatty acids availability in the diet and visual acuity. Early Human Development 2005;81(2):197‐203. [PUBMED: 15748975]CENTRAL

Damsgaard 2006 {published data only}

Damsgaard CT, Lauritzen L, Kjaer TM, Holm PM, Fruekilde MB, Michaelsen KF, et al. Fish oil supplementation modulates immune function in healthy infants. Journal of Nutrition 2007;137(4):1031‐6. [PUBMED: 17374672]CENTRAL
Damsgaard CT, Schack‐Nielsen L, Michaelsen KF, Fruekilde MB, Hels O, Lauritzen L. Fish oil affects blood pressure and the plasma lipid profile in healthy Danish infants. Journal of Nutrition 2006;136(1):94‐9. [PUBMED: 16365065]CENTRAL
Harbild HL, Harslof LB, Christensen JH, Kannass KN, Lauritzen L. Fish oil‐supplementation from 9 to 12 months of age affects infant attention in a free‐play test and is related to change in blood pressure. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2013;89(5):327‐33. [PUBMED: 24045099]CENTRAL
Lauritzen L, Christensen JH, Damsgaard CT, Michaelsen KF. The effect of fish oil supplementation on heart rate in healthy Danish infants. Pediatric Research 2008;64(6):610‐4. [PUBMED: 18679165]CENTRAL
Nielsen S, Nielsen DS, Lauritzen L, Jakobsen M, Michaelsen KF. Impact of diet on the intestinal microbiota in 10‐month‐old infants. Journal of Pediatric Gastroenterology and Nutrition 2007;44(5):613‐8. [PUBMED: 17460496]CENTRAL

Fewtrell 2004 {published data only}

Fewtrell MS, Abbott RA, Kennedy K, Singhal A, Morley R, Caine E, et al. Randomized, double‐blind trial of long‐chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. Journal of Pediatrics 2004;144(4):471‐9. [PUBMED: 15069395]CENTRAL
Isaacs EB, Ross S, Kennedy K, Weaver LT, Lucas A, Fewtrell MS. 10‐year cognition in preterms after random assignment to fatty acid supplementation in infancy. Pediatrics 2011;128(4):e890‐8. [PUBMED: 21930549]CENTRAL
Kennedy K, Ross S, Isaacs EB, Weaver LT, Singhal A, Lucas A, Fewtrell MS. The 10‐year follow‐up of a randomised trial of long‐chain polyunsaturated fatty acid supplementation in preterm infants: effects on growth and blood pressure. Archives of Disease in Childhood 2010;95(8):588‐95. [PUBMED: 20515959]CENTRAL

Furuhjelm 2009 {published data only}

Furuhjelm C, Jenmalm MC, Falth‐Magnusson K, Duchen K. Th1 and Th2 chemokines, vaccine‐induced immunity, and allergic disease in infants after maternal omega‐3 fatty acid supplementation during pregnancy and lactation. Pediatric Research 2011;69(3):259‐64. [PUBMED: 21099447]CENTRAL
Furuhjelm C, Warstedt K, Fageras M, Falth‐Magnusson K, Larsson J, Fredriksson M, et al. Allergic disease in infants up to 2 years of age in relation to plasma omega‐3 fatty acids and maternal fish oil supplementation in pregnancy and lactation. Pediatric Allergy and Immunology 2011;22(5):505‐14. [PUBMED: 21332799]CENTRAL
Furuhjelm C, Warstedt K, Larsson J, Fredriksson M, Bottcher MF, Falth‐Magnusson K, et al. Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy. Acta Paediatrica 2009;98(9):1461‐7. [PUBMED: 19489765]CENTRAL

Hayes 1992 {published data only}

Hayes KC, Pronczuk A, Wood RA, Guy DG. Modulation of infant formula fat profile alters the low‐density lipoprotein/high‐density lipoprotein ratio and plasma fatty acid distribution relative to those with breast‐feeding. Journal of Pediatrics 1992;120(4 Pt 2):S109‐16. [PUBMED: 1560323]CENTRAL

Hoffman 2008 {published data only}

Hoffman D, Ziegler E, Mitmesser SH, Harris CL, Diersen‐Schade DA. Soy‐based infant formula supplemented with DHA and ARA supports growth and increases circulating levels of these fatty acids in infants. Lipids 2008;43(1):29‐35. [PUBMED: 17912568]CENTRAL

Kitz 2006 {published data only}

Kitz R, Rose MA, Schonborn H, Zielen S, Bohles HJ. Impact of early dietary gamma‐linolenic acid supplementation on atopic eczema in infancy. Pediatric Allergy and Immunology 2006;17(2):112‐7. [PUBMED: 16618360]CENTRAL

Lauritzen 2004 {published data only}

Asserhoj M, Nehammer S, Matthiessen J, Michaelsen KF, Lauritzen L. Maternal fish oil supplementation during lactation may adversely affect long‐term blood pressure, energy intake, and physical activity of 7‐year‐old boys. Journal of Nutrition 2009;139(2):298‐304. [PUBMED: 19091800]CENTRAL
Cheatham CL, Nerhammer AS, Asserhoj M, Michaelsen KF, Lauritzen L. Fish oil supplementation during lactation: effects on cognition and behavior at 7 years of age. Lipids 2011;46(7):637‐45. [PUBMED: 21512889]CENTRAL
Larnkjaer A, Christensen JH, Michaelsen KF, Lauritzen L. Maternal fish oil supplementation during lactation does not affect blood pressure, pulse wave velocity, or heart rate variability in 2.5‐y‐old children. Journal of Nutrition 2006;136(6):1539‐44. [PUBMED: 16702318]CENTRAL
Lauritzen L, Hoppe C, Straarup EM, Michaelsen KF. Maternal fish oil supplementation in lactation and growth during the first 2.5 years of life. Pediatric Research 2005;58(2):235‐42. [PUBMED: 16006428]CENTRAL
Lauritzen L, Jorgensen MH, Mikkelsen TB, Skovgaard lM, Straarup EM, Olsen SF, et al. Maternal fish oil supplementation in lactation: effect on visual acuity and n‐3 fatty acid content of infant erythrocytes. Lipids 2004;39(3):195‐206. [PUBMED: 15233397]CENTRAL
Lauritzen L, Jorgensen MH, Olsen SF, Straarup EM, Michaelsen KF. Maternal fish oil supplementation in lactation: effect on developmental outcome in breast‐fed infants. Reproduction, Nutrition, Development 2005;45(5):535‐47. [PUBMED: 16188206]CENTRAL
Lauritzen L, Kjaer TM, Fruekilde MB, Michaelsen KF, Frokiaer H. Fish oil supplementation of lactating mothers affects cytokine production in 2 1/2‐year‐old children. Lipids 2005;40(7):669‐76. [PUBMED: 16196417]CENTRAL

Linnamaa 2010 {published data only}

Linnamaa P, Nieminen K, Koulu L, Tuomasjukka S, Kallio H, Yang B, et al. Black currant seed oil supplementation of mothers enhances IFN‐gamma and suppresses IL‐4 production in breast milk. Pediatric Allergy and Immunology 2013;24(6):562‐6. [PUBMED: 23980846]CENTRAL
Linnamaa P, Savolainen J, Koulu L, Tuomasjukka S, Kallio H, Yang B, et al. Blackcurrant seed oil for prevention of atopic dermatitis in newborns: a randomized, double‐blind, placebo‐controlled trial. Clinical and Experimental Allergy 2010;40(8):1247‐55. [PUBMED: 20545710]CENTRAL

Lucas 1999 {published data only}

Lucas A, Stafford M, Morley R, Abbott R, Stephenson T, MacFadyen U, et al. Efficacy and safety of long‐chain polyunsaturated fatty acid supplementation of infant‐formula milk: a randomised trial. Lancet 1999;354(9194):1948‐54. [PUBMED: 10622297]CENTRAL
Singhal A, Morley R, Cole TJ, Kennedy K, Sonksen P, Isaacs E, et al. Infant nutrition and stereoacuity at age 4‐6 y. American Journal of Clinical Nutrition 2007;85(1):152‐9. [PUBMED: 17209191]CENTRAL

Makrides 2002 {published data only}

Makrides M, Hawkes JS, Neumann MA, Gibson RA. Nutritional effect of including egg yolk in the weaning diet of breast‐fed and formula‐fed infants: a randomized controlled trial. American Journal of Clinical Nutrition 2002;75(6):1084‐92. [PUBMED: 12036817]CENTRAL

Meldrum 2011 {published data only}

D'Vaz N, Meldrum SJ, Dunstan JA, Lee‐Pullen TF, Metcalfe J, Holt BJ, et al. Fish oil supplementation in early infancy modulates developing infant immune responses. Clinical and Experimental Allergy 2012;42(8):1206‐16. [PUBMED: 22805468]CENTRAL
D'Vaz N, Meldrum SJ, Dunstan JA, Martino D, McCarthy S, Metcalfe J, et al. Postnatal fish oil supplementation in high‐risk infants to prevent allergy: randomized controlled trial. Pediatrics 2012;130(4):674‐82. [PUBMED: 22945403]CENTRAL
Meldrum SJ, D'Vaz N, Casadio Y, Dunstan JA, Niels Krogsgaard‐Larsen N, Simmer K, et al. Determinants of DHA levels in early infancy: differential effects of breast milk and direct fish oil supplementation. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2012;86(6):233‐9. [PUBMED: 22572105]CENTRAL
Meldrum SJ, D'Vaz N, Dunstan J, Mori TA, Prescott SL. The Infant Fish Oil Supplementation Study (IFOS): design and research protocol of a double‐blind, randomised controlled n‐3 LCPUFA intervention trial in term infants. Contemporary Clinical Trials 2011;32(5):771‐8. [PUBMED: 21718804]CENTRAL
Meldrum SJ, D'Vaz N, Simmer K, Dunstan JA, Hird K, Prescott SL. Effects of high‐dose fish oil supplementation during early infancy on neurodevelopment and language: a randomised controlled trial. British Journal of Nutrition 2012;108(8):1443‐54. [PUBMED: 22348468]CENTRAL

Mihrshahi 2003 {published data only}

Almqvist C, Garden F, Xuan W, Mihrshahi S, Leeder SR, Oddy W, et al. Omega‐3 and omega‐6 fatty acid exposure from early life does not affect atopy and asthma at age 5 years. Journal of Clinical Immunology 2007;119(6):1438‐44. [PUBMED: 17379291]CENTRAL
Ayer JG, Harmer JA, Xuan W, Toelle B, Webb K, Almqvist C, et al. Dietary supplementation with n‐3 polyunsaturated fatty acids in early childhood: effects on blood pressure and arterial structure and function at age 8 y. American Journal of Clinical Nutrition 2009;90(2):438‐46. [PUBMED: 19515739]CENTRAL
Hoyos C, Almqvist C, Garden F, Xuan W, Oddy WH, Marks GB, et al. Effect of omega 3 and omega 6 fatty acid intakes from diet and supplements on plasma fatty acid levels in the first 3 years of life. Asia Pacific Journal of Clinical Nutrition 2008;17(4):552‐7. [PUBMED: 19114389]CENTRAL
Marks GB, Mihrshahi S, Kemp AS, Tovey ER, Webb K, Almqvist C, et al. Prevention of asthma during the first 5 years of life: a randomized controlled trial. Journal of Allergy and Clinical Immunology 2006;118(1):53‐61. [PUBMED: 16815138]CENTRAL
Mihrshahi S, Peat JK, Marks GB, Mellis CM, Tovey ER, Webb K, et al. Eighteen‐month outcomes of house dust mite avoidance and dietary fatty acid modification in the Childhood Asthma Prevention Study (CAPS). Journal of Allergy and Clinical Immunology 2003;111(1):162‐8. [PUBMED: 12532113]CENTRAL
Mihrshahi S, Peat JK, Webb K, Oddy W, Marks GB, Mellis CM, CAPS Team. Effect of omega‐3 fatty acid concentrations in plasma on symptoms of asthma at 18 months of age. Pediatric Allergy and Immunology 2004;15(6):517‐22. [PUBMED: 15610365]CENTRAL
Peat JK, Mihrshahi S, Kemp AS, Marks GB, Tovey ER, Webb K, et al. Three‐year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study. Journal of Allergy and Clinical Immunology 2004;114(4):807‐13. [PUBMED: 15480319]CENTRAL
Skilton MR, Ayer JG, Harmer JA, Webb K, Leeder SR, Marks GB, et al. Impaired fetal growth and arterial wall thickening: a randomized trial of omega‐3 supplementation. Pediatrics 2012;129(3):e698‐703. [PUBMED: 22351892]CENTRAL

Morris 2000 {published data only}

Morris G, Moorcraft J, Mountjoy A, Wells JC. A novel infant formula milk with added long‐chain polyunsaturated fatty acids from single‐cell sources: a study of growth, satisfaction and health. European Journal of Clinical Nutrition 2000;54(12):883‐6. [PUBMED: 11114686]CENTRAL

O'Connor 2001 {published data only}

O'Connor DL, Hall R, Adamkin D, Auestad N, Castillo M, Connor WE, et al. Growth and development in preterm infants fed long‐chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Pediatrics 2001;108(2):359‐71. [PUBMED: 11483801]CENTRAL
O'Connor DL, Jacobs J, Hall R, Adamkin D, Auestad N, Castillo M, et al. Growth and development of premature infants fed predominantly human milk, predominantly premature infant formula, or a combination of human milk and premature formula. Journal of Pediatric Gastroenterology and Nutrition 2003;37(4):437‐46. [PUBMED: 14508214]CENTRAL

Smithers 2008 {published data only}

Atwell K, Collins CT, Sullivan TR, Ryan P, Gibson RA, Makrides M, et al. Respiratory hospitalisation of infants supplemented with docosahexaenoic acid as preterm neonates. Journal of Paediatrics and Child Health 2013;49(1):E17‐22. [PUBMED: 23279074]CENTRAL
Collins CT, Gibson RA, Anderson PJ, McPhee AJ, Sullivan TR, Gould JF, et al. Neurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high‐dose docosahexaenoic acid to term equivalent: a follow‐up of a randomised controlled trial. BMJ Open 2015;5(3):e007314. [PUBMED: 25787990]CENTRAL
Collins CT, Makrides M, Gibson RA, McPhee AJ, Davis PG, Doyle LW, et al. Pre‐ and post‐term growth in pre‐term infants supplemented with higher‐dose DHA: a randomised controlled trial. British Journal of Nutrition 2011;105(11):1635‐43. [PUBMED: 21443815]CENTRAL
Makrides M, Gibson RA, McPhee AJ, Collins CT, Davis PG, Doyle LW, et al. Neurodevelopmental outcomes of preterm infants fed high‐dose docosahexaenoic acid: a randomized controlled trial. JAMA 2009;301(2):175‐82. [PUBMED: 19141765]CENTRAL
Manley BJ, Makrides M, Collins CT, McPhee AJ, Gibson RA, Ryan P, et al. High‐dose docosahexaenoic acid supplementation of preterm infants: respiratory and allergy outcomes. Pediatrics 2011;128(1):e71‐7. [PUBMED: 21708809]CENTRAL
Smithers LG, Collins CT, Simmonds LA, Gibson RA, McPhee A, Makrides M. 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. American Journal of Clinical Nutrition 2010;91(3):628‐34. [PUBMED: 20053878]CENTRAL
Smithers LG, Gibson RA, McPhee A, Makrides M. Effect of long‐chain polyunsaturated fatty acid supplementation of preterm infants on disease risk and neurodevelopment: a systematic review of randomized controlled trials. American Journal of Clinical Nutrition 2008;87(4):912‐20. [PUBMED: 18400714]CENTRAL
Smithers LG, Gibson RA, McPhee A, Makrides M. Effect of two doses of docosahexaenoic acid (DHA) in the diet of preterm infants on infant fatty acid status: results from the DINO trial. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2008;79(3‐5):141‐6. [PUBMED: 18951004]CENTRAL
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. American Journal of Clinical Nutrition 2008;88(4):1049‐56. [PUBMED: 18842793]CENTRAL

van Gool 2003 {published data only}

van Gool CJ, Thijs C, Henquet CJ, van Houwelingen AC, Dagnelie PC, Schrander J, et al. Gamma‐linolenic acid supplementation for prophylaxis of atopic dermatitis ‐ a randomized controlled trial in infants at high familial risk. American Journal of Clinical Nutrition 2003;77(4):943‐51. [PUBMED: 12663296]CENTRAL

References to studies excluded from this review

Agostoni 1994 {published data only}

Agostoni C, Riva E, Bellu R, Trojan S, Luotti D, Giovannini M. Effects of diet on the lipid and fatty acid status of full‐term infants at 4 months. Journal of the American College of Nutrition 1994;13(6):658‐64. [PUBMED: 7706601]CENTRAL
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. Archives of Disease in Childhood 1997;76(5):421‐4. [PUBMED: 9196357]CENTRAL
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. Pediatric Research 1995;38(2):262‐6. [PUBMED: 7478826]CENTRAL
Forsyth JS, Varma S, Colvin M. A randomised controlled study of the effect of long chain polyunsaturated fatty acid supplementation on stool hardness during formula feeding. Archives of Disease in Childhood 1999;81(3):253‐6. [PUBMED: 10451400]CENTRAL
Forsyth JS, Willatts P, Agostoni C, Bissenden J, Casaer P, Boehm G. Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial. BMJ 2003;326(7396):953. [PUBMED: 12727766]CENTRAL
Willatts P, Forsyth JS, DiModugno MK, Varma S, Colvin M. Effect of long‐chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age. Lancet 1998;352(9129):688‐91. [PUBMED: 9728984]CENTRAL
Willatts P, Forsyth JS, DiModugno MK, Varma S, Colvin M. Influence of long‐chain polyunsaturated fatty acids on infant cognitive function. Lipids 1998;33(10):973‐80. [PUBMED: 9832076]CENTRAL
Willatts P, Forsyth S, Agostoni C, Casaer P, Riva E, Boehm G. Effects of long‐chain PUFA supplementation in infant formula on cognitive function in later childhood. American Journal of Clinical Nutrition 2013;98(2):536S‐42S. [PUBMED: 23783296]CENTRAL

Agostoni 2009 {published data only}

Agostoni C, Zuccotti G V, Radaelli G, Besana R, Podesta A, Sterpa A, et al. Docosahexaenoic acid supplementation and time at achievement of gross motor milestones in healthy infants: a randomized, prospective, double‐blind, placebo‐controlled trial. American Journal of Clinical Nutrition 2009;89(1):64‐70. [PUBMED: 19056592]CENTRAL

Alam 2010 {published data only}

Alam DS, van Raaij JM, Hautvast JG, Yunus M, Wahed MA, Fuchs GJ. Effect of dietary fat supplementation during late pregnancy and first six months of lactation on maternal and infant vitamin A status in rural Bangladesh. Journal of Health, Population & Nutrition 2010;28(4):333‐42. [PUBMED: 20824976]CENTRAL

Amesz 2010 {published data only}

Amesz EM, Schaafsma A, Cranendonk A, Lafeber HN. Optimal growth and lower fat mass in preterm infants fed a protein‐enriched postdischarge formula. Journal of Pediatric Gastroenterology and Nutrition 2010;50(2):200‐7. CENTRAL
van de Lagemaat M, Rotteveel J, Muskiet FA, Schaafsma A, Lafeber HN. Post term dietary‐induced changes in DHA and AA status relate to gains in weight, length, and head circumference in preterm infants. Prostaglandins Leukotrienes & Essential Fatty Acids 2011;85(6):311‐6. CENTRAL

Andersen 2011 {published data only}

Andersen AD, Michaelsen KF, Hellgren LI, Trolle E, Lauritzen L. A randomized controlled intervention with fish oil versus sunflower oil from 9 to 18 months of age: exploring changes in growth and skinfold thicknesses. Pediatric Research 2011;70(4):368‐74. [PUBMED: 21691253]CENTRAL
Andersen AD, Molbak L, Michaelsen KF, Lauritzen L. Molecular fingerprints of the human fecal microbiota from 9 to 18 months old and the effect of fish oil supplementation. Journal of Pediatric Gastroenterology and Nutrition 2011;53(3):303‐9. [PUBMED: 21865979]CENTRAL
Harslof LB, Damsgaard CT, Andersen AD, Aakjaer DL, Michaelsen KF, Hellgren LI, et al. Reduced ex vivo stimulated IL‐6 response in infants randomized to fish oil from 9 to 18 months, especially among PPARG2 and COX2 wild types. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2015;94:21‐7. [PUBMED: 25498245]CENTRAL
Harslof LB, Damsgaard CT, Hellgren LI, Andersen AD, Vogel U, Lauritzen L. Effects on metabolic markers are modified by PPARG2 and COX2 polymorphisms in infants randomized to fish oil. Genes & Nutrition 2014;9(3):396. [PUBMED: 24643342]CENTRAL

Auestad 1997 {published data only}

Auestad N, Montalto MB, Hall RT, Fitzgerald KM, Wheeler RE, Connor WE, et al. Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Ross Pediatric Lipid Study. Pediatric Research 1997;41(1):1‐10. [PUBMED: 8979282]CENTRAL
Auestad N, Scott DT, Janowsky JS, Jacobsen C, Carroll RE, Montalto MB, et al. 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(3 Pt 1):e177‐83. CENTRAL
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(5):E59. CENTRAL

Auestad 2001 {published data only}

Auestad N, Halter R, Hall RT, Blatter M, Bogle M L, Burks W, et al. Growth and development in term infants fed long‐chain polyunsaturated fatty acids: a double‐masked, randomized, parallel, prospective, multivariate study. Pediatrics 2001;108(2):372‐81. CENTRAL

Ben 2004 {published data only}

Ben XM, Zhou XY, Zhao WH, Yu WL, Pan W, Zhang WL, et al. Growth and development of term infants fed with milk with long‐chain polyunsaturated fatty acid supplementation. Chinese Medical Journal 2004;117(8):1268‐70. [PUBMED: 15361309]CENTRAL

Benito Fernandez 2002 {published data only}

Benito Fernandez J, Ruiz Sanz JI, Aquino Farina L, Pijoan Zubizarreta JI, Sasieta Altuna M, Sanjurjo Crespo P. The influence of human milk and various artificial formulae commercially available in Spain on the fatty acid status of infants in the first two months of life. Anales Espanoles de Pediatria 2002;57(2):163‐9. [PUBMED: 12139873]CENTRAL

Bergmann 2008 {published data only}

Bergmann RL, Haschke‐Becher E, Klassen‐Wigger P, Bergmann KE, Richter R, Dudenhausen JW, et al. Supplementation with 200 mg/day docosahexaenoic acid from mid‐pregnancy through lactation improves the docosahexaenoic acid status of mothers with a habitually low fish intake and of their infants. Annals of Nutrition & Metabolism 2008;52(2):157‐66. [PUBMED: 18446020]CENTRAL

Berseth 2014 {published data only}

Berseth CL, Harris CL, Wampler JL, Hoffman DR, Diersen‐Schade DA. Liquid human milk fortifier significantly improves docosahexaenoic and arachidonic acid status in preterm infants. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2014;91(3):97‐103. CENTRAL
Moya F, Sisk PM, Walsh KR, Berseth CL. A new liquid human milk fortifier and linear growth in preterm infants. Pediatrics 2012;130(4):e928‐35. CENTRAL

Billeaud 1996 {published data only}

Babin F, Rodriguez A, Sarda P, Vandeputte B, Mendy F, Descomps B. Alpha linolenic acid in cholesterol esters: a marker of alphalinolenic acid intake in newborns. European Journal of Clinical Nutrition 2000;54(11):840‐3. [PUBMED: 11114678]CENTRAL
Billeaud C, Bougle D, Sarda P, Combe N, Mazette S, Babin F, et al. Effects of preterm infant formula supplementation with alpha‐linolenic acid with a linoleate/alpha‐linolenate ratio of 6: a multicentric study. European Journal of Clinical Nutrition 1997;51(8):520‐6. [PUBMED: 11248877]CENTRAL
Bougle D, Nouvelot A, Billeaud C, Sarda P, Entressangles B, Descomps B, et al. Relationships between red blood cell vitamin E and polyunsaturated fatty acid in the premature infant. Annals of Nutrition & Metabolism 1996;40(6):325‐30. [PUBMED: 9087310]CENTRAL

Birch 1992 {published data only}

Birch DG, Birch EE, Hoffman DR, Uauy RD. Retinal development in very‐low‐birth‐weight infants fed diets differing in omega‐3 fatty acids. Investigative Ophthalmology & Visual Science 1992;33(8):2365‐76. [PUBMED: 1386065]CENTRAL
Birch EE, Birch DG, Hoffman DR, Uauy R. Dietary essential fatty acid supply and visual acuity development. Investigative Ophthalmology & Visual Science 1992;33(11):3242‐53. [PUBMED: 1399429]CENTRAL

Birch 1998 {published data only}

Birch EE, Garfield S, Castaneda Y, Hughbanks‐Wheaton D, Uauy R, Hoffman D. Visual acuity and cognitive outcomes at 4 years of age in a double‐blind, randomized trial of long‐chain polyunsaturated fatty acid‐supplemented infant formula. Early Human Development 2007;83(5):279‐84. [PUBMED: 17240089]CENTRAL
Birch EE, Garfield S, Hoffman DR, Uauy R, Birch DG. A randomized controlled trial of early dietary supply of long‐chain polyunsaturated fatty acids and mental development in term infants. Developmental Medicine and Child Neurology 2000;42(3):174‐81. [PUBMED: 10755457]CENTRAL
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. Pediatric Research 1998;44(2):201‐9. [PUBMED: 9702915]CENTRAL
Hoffman DR, Birch EE, Birch DG, Uauy R, Castaneda YS, Lapus MG, et al. Impact of early dietary intake and blood lipid composition of long‐chain polyunsaturated fatty acids on later visual development. Journal of Pediatric Gastroenterology and Nutrition 2000;31(5):540‐53. [PUBMED: 11144440]CENTRAL
Morale SE, Hoffman DR, Castaneda YS, Wheaton DH, Burns RA, Birch EE. Duration of long‐chain polyunsaturated fatty acids availability in the diet and visual acuity. Early Human Development 2005;81(2):197‐203. [PUBMED: 15748975]CENTRAL

Birch 2002 {published data only}

Birch EE, Hoffman DR, Castaneda YS, Fawcett SL, Birch DG, Uauy RD. A randomized controlled trial of long‐chain polyunsaturated fatty acid supplementation of formula in term infants after weaning at 6 wk of age. American Journal of Clinical Nutrition 2002;75(3):570‐80. [PUBMED: 11864865]CENTRAL
Drover J, Hoffman DR, Castaneda 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 Development 2009;80(5):1376‐84. [PUBMED: 19765006]CENTRAL
Morale SE, Hoffman DR, Castaneda YS, Wheaton DH, Burns RA, Birch EE. Duration of long‐chain polyunsaturated fatty acids availability in the diet and visual acuity. Early Human Development 2005;81(2):197‐203. [PUBMED: 15748975]CENTRAL

Birch 2010 {published data only}

Birch EE, Carlson SE, Hoffman DR, Fitzgerald‐Gustafson KM, Fu VL, Drover JR, et al. 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. American Journal of Clinical Nutrition 2010;91(4):848‐59. [PUBMED: 20130095]CENTRAL
Colombo J, Carlson SE, Cheatham CL, Fitzgerald‐Gustafson KM, Kepler A, Doty T. Long‐chain polyunsaturated fatty acid supplementation in infancy reduces heart rate and positively affects distribution of attention. Pediatric Research 2011;70(4):406‐10. [PUBMED: 21705959]CENTRAL
Colombo J, Carlson SE, Cheatham CL, Shaddy DJ, Kerling EH, Thodosoff JM, et al. Long‐term effects of LCPUFA supplementation on childhood cognitive outcomes. American Journal of Clinical Nutrition 2013;98(2):403‐12. [PUBMED: 23803884]CENTRAL
Drover JR, Felius J, Hoffman DR, Castaneda YS, Garfield S, Wheaton DH, et al. A randomized trial of DHA intake during infancy: school readiness and receptive vocabulary at 2‐3.5 years of age. Early Human Development 2012;88(11):885‐91. [PUBMED: 22835597]CENTRAL
Drover JR, Hoffman DR, Castaneda YS, Morale SE, Garfield S, Wheaton DH, et al. Cognitive function in 18‐month‐old term infants of the DIAMOND study: a randomized, controlled clinical trial with multiple dietary levels of docosahexaenoic acid. Early Human Development 2011;87(3):223‐30. [PUBMED: 21295417]CENTRAL

Boehm 1996 {published data only}

Boehm G, Borte M, Bohles HJ, Muller H, Kohn G, Moro G. Docosahexaenoic and arachidonic acid content of serum and red blood cell membrane phospholipids of preterm infants fed breast milk, standard formula or formula supplemented with n‐3 and n‐6 long‐chain polyunsaturated fatty acids. European Journal of Pediatrics 1996;155(5):410‐6. [PUBMED: 8741041]CENTRAL

Boehm 1997 {published data only}

Boehm G, Muller H, Kohn G, Moro G, Minoli I, Bohles HJ. Docosahexaenoic and arachidonic acid absorption in preterm infants fed LCP‐free or LCP‐supplemented formula in comparison to infants fed fortified breast milk. Annals of Nutrition & Metabolism 1997;41(4):235‐41. CENTRAL

Bondia‐Martinez 1998 {published data only}

Bondia‐Martinez E, Lopez‐Sabater MC, Castellote‐Bargallo AI, Rodriguez‐Palmero M, Gonzalez‐Corbella MJ, Rivero‐Urgell M, et al. Fatty acid composition of plasma and erythrocytes in term infants fed human milk and formulae with and without docosahexaenoic and arachidonic acids from egg yolk lecithin. Early Human Development 1998;53(Suppl):S109‐19. [PUBMED: 10102659]CENTRAL

Bougle 1999 {published data only}

Bougle D, Denise P, Vimard F, Nouvelot A, Penneillo MJ, Guillois B. Early neurological and neuropsychological development of the preterm infant and polyunsaturated fatty acids supply. Clinical Neurophysiology 1999;110(8):1363‐70. [PUBMED: 10454271]CENTRAL

Bouwstra 2003 {published data only}

Bouwstra H, Dijck‐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 Paediatrica 2005;94(1):26‐32. [PUBMED: 15858956]CENTRAL
Bouwstra H, Dijck‐Brouwer DA, Wildeman JA, Tjoonk HM, van der Heide JC, Boersma ER, et al. Long‐chain polyunsaturated fatty acids have a positive effect on the quality of general movements of healthy term infants. American Journal of Clinical Nutrition 2003;78(2):313‐8. [PUBMED: 12885715]CENTRAL
de Jong C, Boehm G, Kikkert HK, Hadders‐Algra M. The Groningen LCPUFA study: no effect of short‐term postnatal long‐chain polyunsaturated fatty acids in healthy term infants on cardiovascular and anthropometric development at 9 years. Pediatric Research 2011;70(4):411‐6. [PUBMED: 21705958]CENTRAL
de Jong C, Kikkert HK, Fidler V, Hadders‐Algra M. Effects of long‐chain polyunsaturated fatty acid supplementation of infant formula on cognition and behaviour at 9 years of age. Developmental Medicine & Child Neurology 2012;54(12):1102‐8. [PUBMED: 23066842]CENTRAL
de Jong C, Kikkert HK, Fidler V, Hadders‐Algra M. The Groningen LCPUFA study: no effect of postnatal long‐chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years. British Journal of Nutrition 2010;104(4):566‐72. [PUBMED: 20370943]CENTRAL

Carlson 1987 {published data only}

Carlson SE, Cooke RJ, Rhodes PG, Peeples JM, Werkman SH. Effect of vegetable and marine oils in preterm infant formulas on blood arachidonic and docosahexaenoic acids. Journal of Pediatrics 1992;120(4 Pt 2):S159‐67. [PUBMED: 1532828]CENTRAL
Carlson SE, Rhodes PG, Rao VS, Goldgar DE. Effect of fish oil supplementation on the n‐3 fatty acid content of red blood cell membranes in preterm infants. Pediatric Research 1987;21(5):507‐10. [PUBMED: 2954026]CENTRAL

Carlson 1991a {published data only}

Carlson SE, Cooke RJ, Rhodes PG, Peeples JM, Werkman SH. Effect of vegetable and marine oils in preterm infant formulas on blood arachidonic and docosahexaenoic acids. Journal of Pediatrics 1992;120(4 Pt 2):S159‐67. [PUBMED: 1532828]CENTRAL
Carlson SE, Cooke RJ, Rhodes PG, Peeples JM, Werkman SH, Tolley EA. Long‐term feeding of formulas high in linolenic acid and marine oil to very low birth weight infants: phospholipid fatty acids. Pediatric Research 1991;30(5):404‐12. [PUBMED: 1684416]CENTRAL

Carlson 1991b {published data only}

Carlson SE, Cooke RJ, Rhodes PG, Peeples JM, Werkman SH, Tolley EA. Long‐term feeding of formulas high in linolenic acid and marine oil to very low birth weight infants: phospholipid fatty acids. Pediatric Research 1991;30(5):404‐12. [PUBMED: 1684416]CENTRAL
Carlson SE, Werkman SH, Rhodes PG, Tolley EA. Visual‐acuity development in healthy preterm infants: effect of marine‐oil supplementation. American Journal of Clinical Nutrition 1993;58(1):35‐42. [PUBMED: 8317386]CENTRAL
Werkman SH, Carlson SE. A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until nine months. Lipids 1996;31(1):91‐7. [PUBMED: 8649241]CENTRAL

Carlson 1996a {published data only}

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. Pediatric Research 1996;39(5):882‐8. [PUBMED: 8726246]CENTRAL

Carlson 1996b {published data only}

Carlson SE, Werkman SH. A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until two months. Lipids 1996;31(1):85‐90. [PUBMED: 8649239]CENTRAL
Carlson SE, Werkman SH, Tolley EA. Effect of long‐chain n‐3 fatty acid supplementation on visual acuity and growth of preterm infants with and without bronchopulmonary dysplasia. American Journal of Clinical Nutrition 1996;63(5):687‐97. [PUBMED: 8615350]CENTRAL

Carlson 1998 {published data only}

Carlson SE, Montalto MB, Ponder DL, Werkman SH, Korones SB. Lower incidence of necrotizing enterocolitis in infants fed a preterm formula with egg phospholipids. Pediatric Research 1998;44(4):491‐8. [PUBMED: 9773836]CENTRAL

Carnielli 1998 {published data only}

Carnielli VP, Simonato M, Verlato G, Luijendijk I, De Curtis M, Sauer PJ, et al. Synthesis of long‐chain polyunsaturated fatty acids in preterm newborns fed formula with long‐chain polyunsaturated fatty acids. American Journal of Clinical Nutrition 2007;86(5):1323‐30. [PUBMED: 17991642]CENTRAL
Carnielli VP, Verlato G, Pederzini F, Luijendijk I, Boerlage A, Pedrotti D, et al. Intestinal absorption of long‐chain polyunsaturated fatty acids in preterm infants fed breast milk or formula. American Journal of Clinical Nutrition 1998;67(1):97‐103. [PUBMED: 9440382]CENTRAL

Clandinin 1992 {published data only}

Clandinin MT, Garg ML, Parrott A, Van Aerde J, Hervada A, Lien E. Addition of long‐chain polyunsaturated fatty acids to formula for very low birth weight infants. Lipids 1992;27(11):896‐900. [PUBMED: 1491607]CENTRAL
Clandinin MT, Parrott A, Van Aerde JE, Hervada AR, Lien E. Feeding preterm infants a formula containing C20 and C22 fatty acids simulates plasma phospholipid fatty acid composition of infants fed human milk. Early Human Development 1992;31(1):41‐51. [PUBMED: 1486817]CENTRAL

Clandinin 1997 {published data only}

Clandinin MT, Van Aerde JE, Parrott A, Field CJ, Euler AR, Lien E. Assessment of feeding different amounts of arachidonic and docosahexaenoic acids in preterm infant formulas on the fatty acid content of lipoprotein lipids. Acta Paediatrica 1999;88(8):890‐6. [PUBMED: 10503691]CENTRAL
Clandinin MT, Van Aerde JE, Parrott A, Field CJ, Euler AR, Lien EL. Assessment of the efficacious dose of arachidonic and docosahexaenoic acids in preterm infant formulas: fatty acid composition of erythrocyte membrane lipids. Pediatric Research 1997;42(6):819‐25. [PUBMED: 9396564]CENTRAL

Clandinin 2005 {published data only}

Clandinin MT, Van Aerde JE, Merkel KL, Harris CL, Springer MA, Hansen JW, et al. Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. Journal of Pediatrics 2005;146(4):461‐8. [PUBMED: 15812447]CENTRAL

Clark 1992 {published data only}

Clark KJ, Makrides M, Neumann MA, Gibson RA. Determination of the optimal ratio of linoleic acid to alpha‐linolenic acid in infant formulas. Journal of Pediatrics 1992;120(4 Pt 2):S151‐8. [PUBMED: 1348533]CENTRAL
Gibson RA, Makrides M, Clark KJ, Neumann MA, Lines DR. Long chain omega 3 polyunsaturates in formula‐fed term infants. Advances in Experimental Medicine and Biology 1992;318:341‐5. [PUBMED: 1353286]CENTRAL

Decsi 1995 {published data only}

Decsi T, Koletzko B. Growth, fatty acid composition of plasma lipid classes, and plasma retinol and alpha‐tocopherol concentrations in full‐term infants fed formula enriched with omega‐6 and omega‐3 long‐chain polyunsaturated fatty acids. Acta Paediatrica 1995;84(7):725‐32. [PUBMED: 7549287]CENTRAL
Decsi T, Szasz M, Sarkany I, Botykai A, Berthold K. Effect of long‐chain polyunsaturated fatty acids on arachidonate and docosahexaeonic acid in healthy infants in the first four months of life. Orvosi hetilap 1996;137(38):2089‐92. [PUBMED: 8966026]CENTRAL
Koletzko B, Decsi T, Sawatzki G. Vitamin E status of low birthweight infants fed formula enriched with long‐chain polyunsaturated fatty acids. International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift fur Vitamin‐ und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition 1995;65(2):101‐4. [PUBMED: 7591527]CENTRAL

Decsi 1997 {published data only}

Decsi T, Burus I, Koletzko B. Effects of dietary long‐chain polyunsaturated fatty acids on plasma amino acids and indices of protein metabolism in infants: results from a randomized clinical trial. Annals of Nutrition & Metabolism 1998;42(4):195‐201. [PUBMED: 9745105]CENTRAL
Decsi T, Fekete M, Koletzko B. Plasma lipid and apolipoprotein concentrations in full term infants fed formula supplemented with long‐chain polyunsaturated fatty acids and cholesterol. European Journal of Pediatrics 1997;156(5):397‐400. [PUBMED: 9177986]CENTRAL

Demmelmair 2001 {published data only}

Demmelmair H, Feldl F, Horvath I, Niederland T, Ruszinko V, Raederstorff D, et al. Influence of formulas with borage oil or borage oil plus fish oil on the arachidonic acid status in premature infants. Lipids 2001;36(6):555‐66. [PUBMED: 11485158]CENTRAL

Dotterud 2013 {published data only}

Dotterud CK, Storro O, Simpson MR, Johnsen R, Oien T. The impact of pre‐ and postnatal exposures on allergy related diseases in childhood: a controlled multicentre intervention study in primary health care. BMC Public Health 2013;13:123. CENTRAL

Faldella 1996 {published data only}

Faldella G, Govoni M, Alessandroni R, Marchiani E, Salvioli GP, Biagi PL, et al. Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 1996;75(2):F108‐12. [PUBMED: 8949693]CENTRAL

Fang 2005 {published data only}

Fang PC, Kuo HK, Huang CB, Ko TY, Chen CC, Chung MY. The effect of supplementation of docosahexaenoic acid and arachidonic acid on visual acuity and neurodevelopment in larger preterm infants. Chang Gung Medical Journal 2005;28(10):708‐15. [PUBMED: 16382755]CENTRAL

Fewtrell 2002 {published data only}

Fewtrell MS, Morley R, Abbott RA, Singhal A, Isaacs EB, Stephenson T, et al. Double‐blind, randomized trial of long‐chain polyunsaturated fatty acid supplementation in formula fed to preterm infants. Pediatrics 2002;110(1 Pt 1):73‐82. [PUBMED: 12093949]CENTRAL

Fidler 2000 {published data only}

Fidler N, Sauerwald T, Pohl A, Demmelmair H, Koletzko B. Docosahexaenoic acid transfer into human milk after dietary supplementation: a randomized clinical trial. Journal of Lipid Research 2000;41(9):1376‐83. CENTRAL

Field 2000 {published data only}

Field CJ, Thomson CA, Van Aerde JE, Parrott A, Euler A, Lien E, et al. Lower proportion of CD45R0+ cells and deficient interleukin‐10 production by formula‐fed infants, compared with human‐fed, is corrected with supplementation of long‐chain polyunsaturated fatty acids. Journal of Pediatric Gastroenterology and Nutrition 2000;31(3):291‐9. [PUBMED: 10997375]CENTRAL

Field 2008 {published data only}

Field CJ, Van Aerde JE, Goruk S, Clandinin MT. Effect of feeding a formula supplemented with long‐chain polyunsaturated fatty acids for 14 weeks improves the ex vivo response to a mitogen and reduces the response to a soy protein in infants at low risk for allergy. Journal of Pediatric Gastroenterology and Nutrition 2010;50(6):661‐9. [PUBMED: 20386325]CENTRAL
Field CJ, Van Aerde JE, Robinson LE, Clandinin MT. Effect of providing a formula supplemented with long‐chain polyunsaturated fatty acids on immunity in full‐term neonates. British Journal of Nutrition 2008;99(1):91‐9. [PUBMED: 17640422]CENTRAL
Field CJ, Van Aerde JE, Robinson LE, Clandinin MT. Feeding a formula supplemented with long chain polyunsaturated fatty acids modifies the "ex vivo" cytokine responses to food proteins in infants at low risk for allergy. Pediatric Research 2008;64(4):411‐7. [PUBMED: 18552712]CENTRAL

Fleddermann 2014 {published data only}

Fleddermann M, Demmelmair H, Grote V, Nikolic T, Trisic B, Koletzko B. Infant formula composition affects energetic efficiency for growth: the BeMIM study, a randomized controlled trial. Clinical Nutrition 2014;33(4):588‐95. CENTRAL

Foreman‐van Drongelen 1995 {published data only}

Foreman‐van Drongelen MM, Houwelingen AC, Kester AD, de Jong AE, Blanco CE, Hasaart TH, et al. Long‐chain polyene status of preterm infants with regard to the fatty acid composition of their diet: comparison between absolute and relative fatty acid levels in plasma and erythrocyte phospholipids. British Journal of Nutrition 1995;73(3):405‐22. [PUBMED: 7766564]CENTRAL
Foreman‐van Drongelen MM, van Houwelingen AC, Kester AD, Blanco CE, Hasaart TH, Hornstra G. Influence of feeding artificial‐formula milks containing docosahexaenoic and arachidonic acids on the postnatal long‐chain polyunsaturated fatty acid status of healthy preterm infants. British Journal of Nutrition 1996;76(5):649‐67. [PUBMED: 8958000]CENTRAL

Ghebremeskel 1995 {published data only}

Ghebremeskel K, Leighfield M, Leaf A, Costeloe K, Crawford M. Fatty acid composition of plasma and red cell phospholipids of preterm babies fed on breast milk and formulae. European Journal of Pediatrics 1995;154(1):46‐52. [PUBMED: 7895755]CENTRAL

Gibson 1997 {published data only}

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. European Journal of Clinical Nutrition 1997;51(9):578‐84. CENTRAL

Gibson 2009 {published data only}

Gibson RA, Barclay D, Marshall H, Moulin J, Maire JC, Makrides M. Safety of supplementing infant formula with long‐chain polyunsaturated fatty acids and Bifidobacterium lactis in term infants: a randomised controlled trial. British Journal of Nutrition 2009;101(11):1706‐13. CENTRAL

Granot 2011 {published data only}

Granot E, Jakobovich E, Rabinowitz R, Levy P, Schlesinger M. DHA supplementation during pregnancy and lactation affects infants' cellular but not humoral immune response. Mediators of Inflammation 2011;2011:493925. [PUBMED: 21941411]CENTRAL

Groh‐Wargo 2005 {published data only}

Groh‐Wargo S, Jacobs J, Auestad N, O'Connor DL, Moore JJ, Lerner E. Body composition in preterm infants who are fed long‐chain polyunsaturated fatty acids: a prospective, randomized, controlled trial. Pediatric Research 2005;57(5 Pt 1):712‐8. [PUBMED: 15718356]CENTRAL

Hauner 2012 {published data only}

Brunner S, Schmid D, Huttinger K, Much D, Bruderl M, Sedlmeier EM, et al. Effect of reducing the n‐6/n‐3 fatty acid ratio on the maternal and fetal leptin axis in relation to infant body composition. Obesity 2014;22(1):217‐24. [PUBMED: 23596009]CENTRAL
Hauner H, Much D, Vollhardt C, Brunner S, Schmid D, Sedlmeier EM, et al. Effect of reducing the n‐6:n‐3 long‐chain PUFA ratio during pregnancy and lactation on infant adipose tissue growth within the first year of life: an open‐label randomized controlled trial. American Journal of Clinical Nutrition 2012;95(2):383‐94. [PUBMED: 22205307]CENTRAL
Much D, Brunner S, Vollhardt C, Schmid D, Sedlmeier EM, Bruderl M, et al. Breast milk fatty acid profile in relation to infant growth and body composition: results from the INFAT study. Pediatric Research 2013;74(2):230‐7. [PUBMED: 23715519]CENTRAL
Much D, Brunner S, Vollhardt C, Schmid D, Sedlmeier EM, Bruderl M, et al. Effect of dietary intervention to reduce the n‐6/n‐3 fatty acid ratio on maternal and fetal fatty acid profile and its relation to offspring growth and body composition at 1 year of age. European Journal of Clinical Nutrition 2013;67(3):282‐8. [PUBMED: 23340492]CENTRAL

Hawkes 2001 {published data only}

Hawkes JS, Bryan DL, Makrides M, Neumann MA, Gibson RA. A randomized trial of supplementation with docosahexaenoic acid‐rich tuna oil and its effects on the human milk cytokines interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha. American Journal of Clinical Nutrition 2002;75(4):754‐60. [PUBMED: 11916764]CENTRAL
Hawkes JS, Bryan DL, Neumann MA, Makrides M, Gibson RA. Transforming growth factor beta in human milk does not change in response to modest intakes of docosahexaenoic acid. Lipids 2001;36(10):1179‐81. [PUBMED: 11768164]CENTRAL

Helland 1998 {published data only}

Helland IB, Saarem K, Saugstad OD, Drevon CA. Fatty acid composition in maternal milk and plasma during supplementation with cod liver oil. European Journal of Clinical Nutrition 1998;52(11):839‐45. CENTRAL

Helland 2001 {published data only}

Helland IB, Saugstad OD, Saarem K, Van Houwelingen AC, Nylander G, Drevon CA. Supplementation of n‐3 fatty acids during pregnancy and lactation reduces maternal plasma lipid levels and provides DHA to the infants. Journal of Maternal‐fetal & Neonatal Medicine 2006;19(7):397‐406. [PUBMED: 16923694]CENTRAL
Helland IB, Saugstad OD, Smith L, Saarem K, Solvoll K, Ganes T, et al. Similar effects on infants of n‐3 and n‐6 fatty acids supplementation to pregnant and lactating women. Pediatrics 2001;108(5):E82. [PUBMED: 11694666]CENTRAL
Helland IB, Smith L, Blomen B, Saarem K, Saugstad OD, Drevon CA. Effect of supplementing pregnant and lactating mothers with n‐3 very‐long‐chain fatty acids on children's IQ and body mass index at 7 years of age. Pediatrics 2008;122(2):e472‐9. [PUBMED: 18676533]CENTRAL
Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal supplementation with very‐long‐chain n‐3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics 2003;111(1):e39‐44. [PUBMED: 12509593]CENTRAL

Henriksen 2008 {published data only}

Henriksen C, Haugholt K, Lindgren M, Aurvag AK, Ronnestad A, Gronn 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):1137‐45. [PUBMED: 18519483]CENTRAL
Henriksen C, Westerberg AC, Ronnestad A, Nakstad B, Veierod MB, Drevon CA, et al. Growth and nutrient intake among very‐low‐birth‐weight infants fed fortified human milk during hospitalisation. British Journal of Nutrition 2009;102(8):1179‐86. [PUBMED: 19445820]CENTRAL
Westerberg AC, Henriksen C, Ellingvag A, Veierod MB, Juliusson PB, Nakstad B, et al. First year growth among very low birth weight infants. Acta Paediatrica 2010;99(4):556‐62. [PUBMED: 20096031]CENTRAL
Westerberg AC, Schei R, Henriksen C, Smith L, Veierod MB, Drevon CA, et al. Attention among very low birth weight infants following early supplementation with docosahexaenoic and arachidonic acid. Acta Paediatrica 2011;100(1):47‐52. [PUBMED: 20624152]CENTRAL

Hoffman 2003 {published data only}

Drover J, Hoffman DR, Castaneda 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 Development 2009;80(5):1376‐84. [PUBMED: 19765006]CENTRAL
Hoffman DR, Birch EE, Castaneda YS, Fawcett SL, Wheaton DH, Birch DG, et al. Visual function in breast‐fed term infants weaned to formula with or without long‐chain polyunsaturates at 4 to 6 months: a randomized clinical trial. Journal of Pediatrics 2003;142(6):669‐77. [PUBMED: 12838196]CENTRAL
Morale SE, Hoffman DR, Castaneda YS, Wheaton DH, Burns RA, Birch EE. Duration of long‐chain polyunsaturated fatty acids availability in the diet and visual acuity. Early Human Development 2005;81(2):197‐203. [PUBMED: 15748975]CENTRAL

Hoffman 2004 {published data only}

Hoffman DR, Theuer RC, Castaneda YS, Wheaton DH, Bosworth RG, O'Connor AR, et al. Maturation of visual acuity is accelerated in breast‐fed term infants fed baby food containing DHA‐enriched egg yolk. Journal of Nutrition 2004;134(9):2307‐13. [PUBMED: 15333721]CENTRAL

Hoffman 2006 {published data only}

Hoffman DR, Wheaton DK, James KJ, Tuazon M, Diersen‐Schade DA, Harris CL, et al. Docosahexaenoic acid in red blood cells of term infants receiving two levels of long‐chain polyunsaturated fatty acids. Journal of Pediatric Gastroenterology and Nutrition 2006;42(3):287‐92. [PUBMED: 16540798]CENTRAL

Horby Jorgensen 1998 {published data only}

Horby Jorgensen M, Holmer G, Lund P, Hernell O, Michaelsen KF. Effect of formula supplemented with docosahexaenoic acid and gamma‐linolenic acid on fatty acid status and visual acuity in term infants. Journal of Pediatric Gastroenterology and Nutrition 1998;26(4):412‐21. [PUBMED: 9552137]CENTRAL

Innis 1996 {published data only}

Innis SM, Auestad N, Siegman JS. Blood lipid docosahexaenoic and arachidonic acid in term gestation infants fed formulas with high docosahexaenoic acid, low eicosapentaenoic acid fish oil. Lipids 1996;31(6):617‐25. [PUBMED: 8784742]CENTRAL

Innis 2002 {published data only}

Innis SM, Adamkin DH, Hall RT, Kalhan SC, Lair C, Lim M, et al. Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula. Journal of Pediatrics 2002;140(5):547‐54. [PUBMED: 12032520]CENTRAL

Jensen 1996 {published data only}

Jensen CL, Chen H, Fraley JK, Anderson RE, Heird WC. Biochemical effects of dietary linoleic/alpha‐linolenic acid ratio in term infants. Lipids 1996;31(1):107‐13. [PUBMED: 8649227]CENTRAL
Jensen CL, Prager TC, Fraley JK, Chen H, Anderson RE, Heird WC. Effect of dietary linoleic/alpha‐linolenic acid ratio on growth and visual function of term infants. Journal of Pediatrics 1997;131(2):200‐9. [PUBMED: 9290604]CENTRAL
Voigt RG, Jensen CL, Fraley JK, Rozelle JC, Brown FR, Heird WC. Relationship between omega3 long‐chain polyunsaturated fatty acid status during early infancy and neurodevelopmental status at 1 year of age. Journal of Human Nutrition and Dietetics 2002;15(2):111‐20. [PUBMED: 11972740]CENTRAL

Jensen 2000 {published data only}

Jensen CL, Maude M, Anderson RE, Heird WC. Effect of docosahexaenoic acid supplementation of lactating women on the fatty acid composition of breast milk lipids and maternal and infant plasma phospholipids. American Journal of Clinical Nutrition 2000;71(1 Suppl):292S‐9S. [PUBMED: 10617985]CENTRAL

Kaempf‐Rotzoll 2003 {published data only}

Kaempf‐Rotzoll DE, Hellstern G, Linderkamp O. Influence of long‐chain polyunsaturated fatty acid formula feeds on vitamin E status in preterm infants. International Journal for Vitamin and Nutrition Research 2003;73(5):377‐87. [PUBMED: 14639802]CENTRAL

Kohn 1994 {published data only}

Kohn G, Sawatzki G, van Biervliet JP, Rosseneu M. Diet and the essential fatty acid status of term infants. Acta Paediatrica Supplement 1994;402:69‐74. [PUBMED: 7841626]CENTRAL

Koletzko 1989 {published data only}

Koletzko B, Schmidt E, Bremer HJ, Haug M, Harzer G. Effects of dietary long‐chain polyunsaturated fatty acids on the essential fatty acid status of premature infants. European Journal of Pediatrics 1989;148(7):669‐75. CENTRAL

Koletzko 1995 {published data only}

Koletzko B, Edenhofer S, Lipowsky G, Reinhardt D. Effects of a low birthweight infant formula containing human milk levels of docosahexaenoic and arachidonic acids. Journal of Pediatric Gastroenterology and Nutrition 1995;21(2):200‐8. CENTRAL

Koletzko 2003 {published data only}

Koletzko B, Sauerwald U, Keicher U, Saule H, Wawatschek S, Bohles H, et al. Fatty acid profiles, antioxidant status, and growth of preterm infants fed diets without or with long‐chain polyunsaturated fatty acids. A randomized clinical trial. European Journal of Nutrition 2003;42(5):243‐53. [PUBMED: 14569405]CENTRAL

Lapillonne 2000a {published data only}

Lapillonne A, Brossard N, Claris O, Reygrobellet B, Salle BL. Erythrocyte fatty acid composition in term infants fed human milk or a formula enriched with a low eicosapentanoic acid fish oil for 4 months. European Journal of Pediatrics 2000;159(1‐2):49‐53. [PUBMED: 10653329]CENTRAL

Lapillonne 2000b {published data only}

Lapillonne A, Picaud JC, Chirouze V, Goudable J, Reygrobellet B, Claris O, et al. The use of low‐EPA fish oil for long‐chain polyunsaturated fatty acid supplementation of preterm infants. Pediatric Research 2000;48(6):835‐41. [PUBMED: 11102555]CENTRAL

Leite 2013 {published data only}

Leite M E, Lasekan J, Baggs G, Ribeiro T, Menezes‐Filho J, Pontes M, et al. Calcium and fat metabolic balance, and gastrointestinal tolerance in term infants fed milk‐based formulas with and without palm olein and palm kernel oils: a randomized blinded crossover study. BMC Pediatrics 2013;13:215. CENTRAL

Liu 1987 {published data only}

Carlson SE, Cooke RJ, Rhodes PG, Peeples JM, Werkman SH. Effect of vegetable and marine oils in preterm infant formulas on blood arachidonic and docosahexaenoic acids. Journal of Pediatrics 1992;120(4 Pt 2):S159‐67. CENTRAL
Liu CC, Carlson SE, Rhodes PG, Rao VS, Meydrech EF. Increase in plasma phospholipid docosahexaenoic and eicosapentaenoic acids as a reflection of their intake and mode of administration. Pediatric Research 1987;22(3):292‐6. CENTRAL

Llorente 2003 {published data only}

Jensen CL, Voigt RG, Prager TC, Zou YL, Fraley JK, Rozelle JC, et al. Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed term infants. American Journal of Clinical Nutrition 2005;82(1):125‐32. [PUBMED: 16002810]CENTRAL
Llorente AM, Jensen CL, Voigt RG, Fraley JK, Berretta MC, Heird WC. Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing. American Journal of Obstetrics and Gynecology 2003;188(5):1348‐53. [PUBMED: 12748510]CENTRAL

Lopez‐Alarcon 2006 {published data only}

Lopez‐Alarcon M, Bernabe‐Garcia M, Del Prado M, Rivera D, Ruiz G, Maldonado J, et al. Docosahexaenoic acid administered in the acute phase protects the nutritional status of septic neonates. Nutrition 2006;22(7‐8):731‐7. CENTRAL
Lopez‐Alarcon M, Bernabe‐Garcia M, del Valle O, Gonzalez‐Moreno G, Martinez‐Basilea A, Villegas R. Oral administration of docosahexaenoic acid attenuates interleukin‐1beta response and clinical course of septic neonates. Nutrition 2012;28(4):384‐90. CENTRAL

Lucia Bergmann 2007 {published data only}

Lucia Bergmann R, Bergmann KE, Haschke‐Becher E, Richter R, Dudenhausen JW, Barclay D, et al. Does maternal docosahexaenoic acid supplementation during pregnancy and lactation lower BMI in late infancy?. Journal of Perinatal Medicine 2007;35(4):295‐300. [PUBMED: 17547539]CENTRAL

Makrides 1995 {published data only}

Makrides M, Neumann M, Simmer K, Pater J, Gibson R. Are long‐chain polyunsaturated fatty acids essential nutrients in infancy?. Lancet 1995;345(8963):1463‐8. [PUBMED: 7769900]CENTRAL
Makrides M, Neumann MA, Simmer K, Gibson RA. Erythrocyte fatty acids of term infants fed either breast milk, standard formula, or formula supplemented with long‐chain polyunsaturates. Lipids 1995;30(10):941‐8. [PUBMED: 8538382]CENTRAL

Makrides 1999 {published data only}

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(1 Pt 1):32‐8. [PUBMED: 10617701]CENTRAL
Makrides M, Neumann MA, Simmer K, Gibson RA. Dietary long‐chain polyunsaturated fatty acids do not influence growth of term infants: a randomized clinical trial. Pediatrics 1999;104(3 Pt 1):468‐75. [PUBMED: 10469771]CENTRAL

Makrides 2000 {published data only}

Makrides M, Neumann MA, Jeffrey B, Lien EL, Gibson RA. A randomized trial of different ratios of linoleic to alpha‐linolenic acid in the diet of term infants: effects on visual function and growth. American Journal of Clinical Nutrition 2000;71(1):120‐9. [PUBMED: 10617956]CENTRAL

Martinez 2002 {published data only}

Martinez FE, Sieber VM, Jorge SM, Ferlin ML, Mussi‐Pinhata MM. Effect of supplementation of preterm formula with long chain polyunsaturated fatty acids on mineral balance in preterm infants. Journal of Pediatric Gastroenterology & Nutrition 2002;35(4):503‐7. [PUBMED: 12394374]CENTRAL

Maurage 1998 {published data only}

Guesnet P, Pugo‐Gunsam P, Maurage C, Pinault M, Giraudeau B, Alessandri JM, et al. Blood lipid concentrations of docosahexaenoic and arachidonic acids at birth determine their relative postnatal changes in term infants fed breast milk or formula. American Journal of Clinical Nutrition 1999;70(2):292‐8. [PUBMED: 10426708]CENTRAL
Maurage C, Guesnet P, Pinault M, Rochette de Lempdes J, Durand G, Antoine J, et al. Effect of two types of fish oil supplementation on plasma and erythrocyte phospholipids in formula‐fed term infants. Biology of the Neonate 1998;74(6):416‐29. [PUBMED: 9784633]CENTRAL

Mize 1995 {published data only}

Mize CE, Uauy R, Kramer R, Benser M, Allen S, Grundy SM. Lipoprotein‐cholesterol responses in healthy infants fed defined diets from ages 1 to 12 months: comparison of diets predominant in oleic acid versus linoleic acid, with parallel observations in infants fed a human milk‐based diet. Journal of Lipid Research 1995;36(6):1178‐87. [PUBMED: 7665996]CENTRAL

Moltu 2013 {published data only}

Moltu SJ, Blakstad EW, Strommen K, Almaas AN, Nakstad B, Ronnestad A, et al. Enhanced feeding and diminished postnatal growth failure in very‐low‐birth‐weight infants. Journal of Pediatric Gastroenterology and Nutrition 2014;58:344‐51. CENTRAL
Moltu SJ, Sachse D, Blakstad EW, Strommen K, Nakstad B, Almaas AN, et al. Urinary metabolite profiles in premature infants show early postnatal metabolic adaptation and maturation. Nutrients 2014;6:1913‐30. CENTRAL
Moltu SJ, Strommen K, Blakstad EW, Almaas AN, Westerberg AC, Braekke K, et al. Enhanced feeding in very‐low‐birth‐weight infants may cause electrolyte disturbances and septicemia ‐ a randomized, controlled trial. Clinical Nutrition 2013;32:207‐12. CENTRAL
Strommen K, Blakstad EW, Moltu SJ, Almaas AN, Westerberg AC, Amlien IK, et al. Enhanced nutrient supply to very low birth weight infants is associated with improved white matter maturation and head growth. Neonatology 2015;107:68‐75. CENTRAL

Morgan 1998a {published data only}

Morgan C, Stammers J, Colley J, Spencer S A, Hull D. Fatty acid balance studies in preterm infants fed formula milk containing long‐chain polyunsaturated fatty acids (LCP) II. Acta Paediatrica 1998;87:318‐24. CENTRAL

Morgan 1998b {published data only}

Morgan C, Davies L, Corcoran F, Stammers J, Colley J, Spencer SA, et al. Fatty acid balance studies in term infants fed formula milk containing long‐chain polyunsaturated fatty acids. Acta Paediatrica 1998;87:136‐42. CENTRAL

Moya 2001 {published data only}

Moya M, Cortes E, Juste M, De Dios JG, Vera A. Fatty acid absorption in preterms on formulas with and without long‐chain polyunsaturated fatty acids and in terms on formulas without these added. European Journal of Clinical Nutrition 2001;55:755‐62. CENTRAL

Ponder 1992 {published data only}

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. Pediatric Research 1992;32(6):683‐8. [PUBMED: 1287559]CENTRAL

Ramirez 2001 {published data only}

Ramirez M, Gallardo EM, Souto AS, Weissheimer C, Gil A. Plasma fatty‐acid composition and antioxidant capacity in low birth‐weight infants fed formula enriched with n‐6 and n‐3 long‐chain polyunsaturated fatty acids from purified phospholipids. Clinical Nutrition 2001;20(1):69‐76. [PUBMED: 11161546]CENTRAL

Rodriguez 2003 {published data only}

Rodriguez M, Funke S, Fink M, Demmelmair H, Turini M, Crozier G, et al. Plasma fatty acids and [13C]linoleic acid metabolism in preterm infants fed a formula with medium‐chain triglycerides. Journal of Lipid Research 2003;44:41‐8. CENTRAL

Ryan 1999 {published data only}

Ryan AS, Montalto MB, Groh‐Wargo S, Mimouni F, Sentipal‐Walerius J, Doyle J, et al. Effect of DHA‐containing formula on growth of preterm infants to 59 weeks postmenstrual age. American Journal of Human Biology 1999;11(4):457‐67. [PUBMED: 11533965]CENTRAL

Sauerwald 2012 {published data only}

Sauerwald UC, Fink MM, Demmelmair H, Schoenaich PV, Rauh‐Pfeiffer AA, Koletzko B. Effect of different levels of docosahexaenoic acid supply on fatty acid status and linoleic and alpha‐linolenic acid conversion in preterm infants. Journal of Pediatric Gastroenterology & Nutrition 2012;54(3):353‐63. [PUBMED: 22008957]CENTRAL

Schwartz 2009 {published data only}

Schwartz J, Drossard C, Dube K, Kannenberg F, Kunz C, Kalhoff H, et al. Dietary intake and plasma concentrations of PUFA and LC‐PUFA in breastfed and formula fed infants under real‐life conditions. European Journal of Nutrition 2010;49(3):189‐95. [PUBMED: 19851802]CENTRAL
Schwartz J, Dube K, Alexy U, Kalhoff H, Kersting M. PUFA and LC‐PUFA intake during the first year of life: can dietary practice achieve a guideline diet?. European Journal of Clinical Nutrition 2010;64(2):124‐30. [PUBMED: 19935821]CENTRAL
Schwartz J, Dube K, Sichert‐Hellert W, Kannenberg F, Kunz C, Kalhoff H, et al. Modification of dietary polyunsaturated fatty acids via complementary food enhances n‐3 long‐chain polyunsaturated fatty acid synthesis in healthy infants: a double blinded randomised controlled trial. Archives of Disease in Childhood 2009;94(11):876‐82. [PUBMED: 19193660]CENTRAL

Siahanidou 2007 {published data only}

Siahanidou T, Lazaropoulou C, Michalakakou K, Papassotiriou I, Bacoula C, Mandyla H. Oxidative stress in preterm infants fed a formula containing long‐chain polyunsaturated fatty acids (LCPUFA). American Journal of Perinatology 2007;24(8):475‐9. [PUBMED: 17992715]CENTRAL
Siahanidou T, Margeli A, Kappis A, Papassotiriou I, Mandyla H. Circulating visfatin levels in healthy preterm infants are independently associated with high‐density lipoprotein cholesterol levels and dietary long‐chain polyunsaturated fatty acids. Metabolism 2011;60(3):389‐93. [PUBMED: 20359723]CENTRAL
Siahanidou T, Margeli A, Lazaropoulou C, Karavitakis E, Papassotiriou I, Mandyla H. Circulating adiponectin in preterm infants fed long‐chain polyunsaturated fatty acids (LCPUFA)‐supplemented formula ‐ a randomized controlled study. Pediatric Research 2008;63(4):428‐32. [PUBMED: 18356752]CENTRAL

Smit 2000a {published data only}

Smit EN, Oelen EA, Seerat E, Boersma ER, Muskiet FA. Fish oil supplementation improves docosahexaenoic acid status of malnourished infants. Archives of Disease in Childhood 2000;82(5):366‐9. [PUBMED: 10799425]CENTRAL

Smit 2000b {published data only}

Smit EN, Koopmann M, Boersma ER, Muskiet FA. Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2000;62:335‐40. CENTRAL

Socha 2002 {published data only}

Socha P, Koletzko B, Jankowska I, Pawlowska J, Demmelmair H, Stolarczyk A, et al. Long‐chain PUFA supplementation improves PUFA profile in infants with cholestasis. Lipids 2002;37:953‐7. CENTRAL

Stier 1997 {published data only}

Stier C, Hess M, Watzer B, Schweer H, Seyberth H W, Leonhardt A. Prostanoid formation during feeding of a preterm formula with long‐chain polyunsaturated fatty acids in healthy preterm infants during the first weeks of life. Pediatric Research 1997;42:509‐13. CENTRAL

Uauy 1990 {published data only}

Hoffman DR, Uauy R. Essentiality of dietary omega 3 fatty acids for premature infants: plasma and red blood cell fatty acid composition. Lipids 1992;27(11):886‐95. [PUBMED: 1362792]CENTRAL
Uauy R, Hoffman DR, Birch EE, Birch DG, Jameson DM, Tyson J. Safety and efficacy of omega‐3 fatty acids in the nutrition of very low birth weight infants: soy oil and marine oil supplementation of formula. Journal of Pediatrics 1994;124(4):612‐20. [PUBMED: 7908693]CENTRAL
Uauy RD, Birch DG, Birch EE, Tyson JE, Hoffman DR. Effect of dietary omega‐3 fatty acids on retinal function of very‐low‐birth‐weight neonates. Pediatric Research 1990;28(5):485‐92. [PUBMED: 2255573]CENTRAL
Uauy‐Dagach R, Mena P, Hoffman DR. Essential fatty acid metabolism and requirements for LBW infants. Acta Paediatrica Supplement 1994;405:78‐85. [PUBMED: 7734797]CENTRAL

Unay 2004 {published data only}

Unay B, Sarici SU, Ulas UH, Akin R, Alpay F, Gokcay E. Nutritional effects on auditory brainstem maturation in healthy term infants. Archives of Disease in Childhood Fetal & Neonatal Edition 2004;89(2):F177‐9. [PUBMED: 14977907]CENTRAL

Van Biervliet 1986 {published data only}

Van Biervliet JP, Rosseneu M, Caster H. Influence of dietary factors on the plasma lipoprotein composition and content in neonates. European Journal of Pediatrics 1986;144(5):489‐93. [PUBMED: 3456892]CENTRAL

Van Biervliet 1992 {published data only}

Van Biervliet JP, Vinaimont N, Vercaemst R, Rosseneu M. Serum cholesterol, cholesteryl ester, and high‐density lipoprotein development in newborn infants: response to formulas supplemented with cholesterol and gamma‐linolenic acid. Journal of Pediatrics 1992;120(4 Pt 2):S101‐8. [PUBMED: 1313864]CENTRAL

Vanderhoof 1999 {published data only}

Vanderhoof J, Gross S, Hegyi T. A multicenter long‐term safety and efficacy trial of preterm formula supplemented with long‐chain polyunsaturated fatty acids. Journal of Pediatric Gastroenterology and Nutrition 2000;31(2):121‐7. [PUBMED: 10941962]CENTRAL
Vanderhoof J, Gross S, Hegyi T, Clandinin T, Porcelli P, DeCristofaro J, et al. Evaluation of a long‐chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age. Journal of Pediatric Gastroenterology & Nutrition 1999;29(3):318‐26. [PUBMED: 10467999]CENTRAL

van der Merwe 2013 {published data only}

van der Merwe LF, Moore SE, Fulford AJ, Halliday KE, Drammeh S, Young S, et al. Long‐chain PUFA supplementation in rural African infants: a randomized controlled trial of effects on gut integrity, growth, and cognitive development. American Journal of Clinical Nutrition 2013;97(1):45‐57. [PUBMED: 23221579]CENTRAL

van Goor 2009 {published data only}

Doornbos B, van Goor SA, Dijck‐Brouwer DA, Schaafsma A, Korf J, Muskiet FA. Supplementation of a low dose of DHA or DHA+AA does not prevent peripartum depressive symptoms in a small population based sample. Progress in Neuro‐psychopharmacology & Biological Psychiatry 2009;33(1):49‐52. [PUBMED: 18955102]CENTRAL
van Goor SA, Dijck‐Brouwer DA, Doornbos B, Erwich JJ, Schaafsma A, Muskiet FA, et al. Supplementation of DHA but not DHA with arachidonic acid during pregnancy and lactation influences general movement quality in 12‐week‐old term infants. British Journal of Nutrition 2010;103(2):235‐42. [PUBMED: 19703327]CENTRAL
van Goor SA, Dijck‐Brouwer DA, Erwich JJ, Schaafsma A, Hadders‐Algra M. The influence of supplemental docosahexaenoic and arachidonic acids during pregnancy and lactation on neurodevelopment at eighteen months. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2011;84(5‐6):139‐46. [PUBMED: 21316208]CENTRAL
van Goor SA, Dijck‐Brouwer DA, Hadders‐Algra M, Doornbos B, Erwich JJ, Schaafsma A, et al. Human milk arachidonic acid and docosahexaenoic acid contents increase following supplementation during pregnancy and lactation. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2009;80(1):65‐9. [PUBMED: 19118992]CENTRAL

van Wezel‐Meijler 2002 {published data only}

van Wezel‐Meijler G, van der Knaap MS, Huisman J, Jonkman EJ, Valk J, Lafeber HN. Dietary supplementation of long‐chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation. Acta Paediatrica 2002;91(9):942‐50. [PUBMED: 12412870]CENTRAL

Weizman 1998 {published data only}

Weizman Z, Brutman E, Leader D, Zegerman C. Evaluation of a local infant formula enriched with polyunsaturated fatty acids produced in Israel. Harefuah 1998;134(9):686‐90, 751. [PUBMED: 10909613]CENTRAL

Yang 2013 {published data only}

Yang Q, Ayers K, Chen Y, Helderman J, Welch CD, O'Shea TM. Early enteral fat supplement and fish oil increases fat absorption in the premature infant with an enterostomy. Journal of Pediatrics 2013;163(2):429‐34. [PUBMED: 23453547]CENTRAL
Yang Q, Ayers K, Welch CD, O'Shea TM. Randomized controlled trial of early enteral fat supplement and fish oil to promote intestinal adaptation in premature infants with an enterostomy. Journal of Pediatrics 2014;165(2):274‐9.e1. [PUBMED: 24630347]CENTRAL

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Osborn 2007b

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RevMan 2014 [Computer program]

The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Romieu 2007

Romieu I, Torrent M, Garcia‐Esteban R, Ferrer C, Ribas‐Fito N, Anto JM, et al. Maternal fish intake during pregnancy and atopy and asthma in infancy. Clinical and Experimental Allergy 2007;37(4):518‐25.

Schachter 2004

Schachter HM, Reisman J, Tran K, Dales B, Kourad K, Barnes D, et al. Health effects of omega‐3 fatty acids on asthma. Evidence Report/technology Assessment (Summary) 2004;91:1‐7.

Schwartz 2010

Schwartz J, Dube K, Alexy U, Kalhoff H, Kersting M. PUFA and LC‐PUFA intake during the first year of life: can dietary practice achieve a guideline diet?. European Journal of Clinical Nutrition 2010;64(2):124‐30.

Schünemann 2013

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Suarez‐Varela 2010

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Birch 2005

Methods

Multicentre, double‐blind RCT in USA

Participants

2 cohorts from previously completed RCTs (cohort A and B)

Inclusion criteria: infants (not selected for risk of allergy); gestation 37 to 40 weeks; birth weight appropriate for gestational age; singleton birth; exclusively formula fed

Exclusion criteria: family history of milk protein allergy or genetic or familial eye disease; maternal vegetarian or vegan dietary patterns; maternal metabolic disease, anaemia or infection; congenital malformation or infection; jaundice, perinatal asphyxia or meconium aspiration; neonatal intensive care unit admission

Interventions

Infants randomised to AA + DHA supplement for first year of life

Control (n = 90): Enfamil formula with iron (LA 8.5 g/L, α‐LA 0.9 g/L) (n‐3:n‐6 ratio = 1:9)

Intervention: control formula with added AA/DHA formula (n = 89): (LA 8.4 g/L, AA 0.4 g/L, α‐LA 0.9 g/L, DHA 0.2 g/L) (n‐3:n‐6 ratio = 1:8)

Control group intermediate‐high PUFA intake, intervention group high PUFA intake

Co‐interventions: none reported

Outcomes

Primary outcome (cohort A): visual cortex maturity as assessed by sweep visual evoked potential acuity

Primary outcome (cohort B): metabolic parameters including lipoprotein profile, antioxidant status and hydroelectrolytic balance

Outcome assessed: incidence of respiratory infections and allergic disease in first 3 years of life (infant allergy incidence)

Notes

Supported by Mead Johnson Nutrition

Co‐authors employees of Mead Johnson Nutrition

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Cohort A: all infants were randomly assigned with the use of a single randomisation schedule at a central location. The randomisation schedule had random length blocks (block length varied from 6 to 12) and was provided in individual sealed envelopes to the study site

Cohort B: method not reported

Allocation concealment (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Cohort A: each diet masked by colour and number code

Cohort B: reported to be "double blind" but details not reported

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Incomplete outcome data (attrition bias)
All outcomes

High risk

90/179 (50%) no outcome data

Selective reporting (reporting bias)

High risk

Allergy not prespecified but reported

Other bias

Low risk

Groups well balanced after allocation

Damsgaard 2006

Methods

Multicentre 2 x 2 factorial RCT in Denmark May to October 2003

Participants

Singleton term infants supplemented from 9 to 12 months with a birth weight > 2500 g and above the 5th percentile for gestational age, a 5‐minute Apgar score ≥ 7, no major complications at birth or in fetal life, and no chronic diseases, with a daily consumption of cow's milk or infant formula

Interventions

Infants supplemented from 9 to 12 months

Intervention (n = 45): fish oil 5 mL/day (high PUFA intake) (LCPUFA 352 g/L n‐3 60% EPA and 40% DHA and cholesterol 3 g/L; mean fish oil consumption 3.3 mL/day n‐3 LCPUFA 924 mg/day)

Control (n = 49): no fish oil (intermediate PUFA intake)

Infants were also randomly assigned to drink either cow's milk or standard infant formula (no LCPUFA 18:2(n‐6) and 18:3(n‐3) in a ratio of 8:1)

Outcomes

Blood pressure, FA profile, growth up to 12 months

Allergy: at the end of the intervention period of 3 months, parents were interviewed about infant diet, growth and allergy diagnoses using questions validated for atopic dermatitis. Only reported allergic tendencies (itchy rash, wheezing or food allergy) as verified by a doctor

Notes

Allergy data only reported at baseline

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method not reported. Randomisation done within clusters of 12 by drawing notes from 1 envelope for each intervention

Allocation concealment (selection bias)

Low risk

Parents who agreed to the principle of randomisations and whose infants met the inclusion criteria were invited to an individual introduction visit

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Unmasked

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Incomplete outcome data (attrition bias)
All outcomes

High risk

11/91 (12%) lost at 12 months

Selective reporting (reporting bias)

High risk

Allergy not a stated primary outcome but reported

Other bias

High risk

Baseline differences between groups

Fewtrell 2004

Methods

Multicentre RCT in UK April 1995 and July 1997

Participants

Preterm neonates birth weight ≤ 2000 g supplemented until 9 months' corrected age (formula fed)

Interventions

Intervention (n = 122): fish oil LCPUFA supplemented formula (EPA 0.1%; γ‐LA 0.9%; AA 0.04%; DHA 0.5%) (intermediate‐high PUFA intake)

Control (n = 116): borage oil supplemented formula (no EPA; γ‐LA; AA; DHA) (intermediate PUFA intake)

Outcomes

Growth, development up to 18 months

Prevalence of asthma, eczema recorded but not reported

Notes

Did not report allergy

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random permuted block allocation with assignments kept in sealed opaque envelopes and opened at the point of randomisation

Allocation concealment (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Trial formulas were identical in appearance and smell. Blinding was maintained until

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Incomplete outcome data (attrition bias)
All outcomes

High risk

121/238 (51%) lost at 18 months; 131/238 (55%) lost at 10 years

Selective reporting (reporting bias)

High risk

Allergy not prespecified, recorded but not reported

Other bias

Unclear risk

Some baseline imbalances between groups

Furuhjelm 2009

Methods

Multicentre, double‐blind RCT in Sweden March 2003 to June 2005

Participants

Pregnant women with at least 1 first‐degree relative with current or previous allergic symptoms (i.e. bronchial asthma, eczema, allergic food reactions, itching and running eyes and nose at exposure to pollen, pets or other known allergens)

Exclusion criteria: allergy to soy or fish; treatment with anticoagulants or n‐3 FA supplements

Interventions

Mothers randomised to n‐3 FA supplement from 25th week of gestation until cessation of breastfeeding mean 3 to 4 months

Control (n = 75): supplemented with soy bean oil (LA 2.5 g, α‐LA 0.2 g; n‐3:n‐6 ratio = 1:9)

Intervention (n = 70): supplemented with DHA 1.1 g + EPA 1.6 g (n‐3:n‐6 ratio: n‐3 only)

Control group intermediate‐high PUFA intake, intervention group high PUFA intake

Outcomes

Primary outcome: allergic sensitisation and disease in first 2 years

Paediatric allergy research nurses examined children at 3, 6 and 12 months

In case of eczema or a food reaction a paediatrician also examined the child

Food allergy was defined as: gastrointestinal symptoms, hives, aggravated eczema or wheeze following ingestion of egg or milk in the presence of detectable IgE antibodies or a positive SPT to the particular food. Recovery from symptoms after elimination of the particular food from the diet and reoccurrence after ingestion of the food was required for the diagnosis

IgE‐associated eczema: reoccurring and itching eczematous, lichenified or nummular dermatitis according to the criteria modified by Oranje in 1995 (Oranje 1995) in the presence of detectable IgE antibodies or positive SPT towards egg, milk or wheat

Notes

Supported by GlaxoSmithKline, Sweden

Note: childhood prevalence reported at 24 months

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Producer performed block randomisation. Method not reported

Allocation concealment (selection bias)

Low risk

Recruited ... then accepted participation in a randomised study

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Mothers and study personnel blinded to group allocation. Capsules could not be distinguished from each other

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Incomplete outcome data (attrition bias)
All outcomes

High risk

29/145 (20%) no outcome data

Selective reporting (reporting bias)

Low risk

Primary outcome: allergic sensitisation and disease during the first year of life

Other bias

Low risk

Groups similar at baseline

Hayes 1992

Methods

Single centre RCT in USA before 1992

Participants

Term neonates fed fat‐modified formulas until 4 months of age (formula fed)

Interventions

Control (n = 15): coconut oil/soybean oil formula (LA 25%, α‐LA 2.5%) (intermediate PUFA intake)

Intervention (n = 15): corn oil/soybean oil formula (LA 58.5%, α‐LA 2.0%) (intermediate‐high PUFA intake)

Outcomes

FA profile, growth up to 4 months of age. Parents recorded a diary before each visit including formula acceptance and tolerance

Notes

Did not report allergy

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method not reported

Allocation concealment (selection bias)

Unclear risk

Details not reported

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Method not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Method not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up

Selective reporting (reporting bias)

High risk

The parent reported diarrhoea, vomiting, spitting up, prolonged crying (colic), rash, runny nose, wheezing, constipation, appetite changes or other notable conditions

Other bias

Unclear risk

Baseline characteristics not reported

Hoffman 2008

Methods

Multicentre RCT in USA before 2008

Participants

Term neonates with birth weight > 2500 g supplemented until 4 months of age (formula fed)

Exclusion criteria: history of underlying disease or malformation that could interfere with growth and development; large‐for‐gestational‐age infants whose mothers had diabetes; breastfeeding within 24 hours prior to randomisation; evidence of formula intolerance or poor intake at time of randomisation; weight at randomisation < 98% of birth weight; enlarged liver or spleen; or plans to move outside area

Interventions

Intervention (n = 124): soy formula with DHA 17 mg/100 kcal + AA 34 mg/100 kcal (intermediate PUFA intake)

Control (n = 120): soy formula without DHA + AA (intermediate PUFA intake)

Outcomes

FA profile, growth up to 4 months of age. Used SCORAD assessment of atopic dermatitis. Recorded adverse events

Notes

Reported atopic dermatitis severity but not incidence

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method not reported

Allocation concealment (selection bias)

Unclear risk

Details not reported

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Method not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Method not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

62/244 (25%) did not complete study

Selective reporting (reporting bias)

High risk

Atopic dermatitis assessed using SCORAD indices prespecified but incidence not reported

Other bias

Unclear risk

Some baseline differences

Kitz 2006

Methods

Multicentre, double‐blind RCT in Germany before 2006

Participants

Inclusion criteria: full term infants; at least 1 first‐degree relative with atopic disease

Exclusion criteria: newborns unable to be fed orally; severe concurrent disease

Interventions

Infants randomised to γ‐LA supplement for first 5 months of life

Stratification into 3 groups based on maternal decision whether to breastfeed within the first 2 days of life

Exclusively breastfed infants (n = 58)

Control 1 (n = 37): whey hydrolysate

Intervention 1 (n = 21): whey hydrolysate + γ‐LA 0.1 g (n‐3:n‐6 ratio: n‐6 only) (γ‐LA supplement)

Both groups intermediate PUFA intake

Breast and formula fed infants (n = 53)

Control 2 (n = 31): maternal whey or whey formula (γ‐LA <0.1 g)

Intervention 2 (n = 22): maternal whey + γ‐LA 0.1 g or whey formula + γ‐LA 0.2 g (n‐3:n‐6 ratio: n‐6 only) (γ‐LA supplement)

Both groups intermediate‐high PUFA intake

Exclusively formula fed infants (n = 20)

Control 3 intervention (n = 8): whey formula (γ‐LA < 0.1 g)

Intervention 3 (n = 12): whey formula + γ‐LA 0.2 g (n‐3:n‐6 ratio: n‐6 only) (γ‐LA supplement)

Both groups high PUFA intake

Co‐interventions: none reported

Outcomes

Primary outcome: atopic dermatitis in first 12 months of life

Secondary outcome: serum IgE level at 12 months

Study participants seen at 1 week, 4 and 12 months. Skin atopy score of atopic dermatitis (SCORAD) used. Diagnosis of atopic eczema was made by the criteria of Hanifin (Hanifin 1980)

Total serum IgE determined at birth, age of 4 and 12 months

Notes

No conflict of interest declared

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method not reported

Allocation concealment (selection bias)

Unclear risk

Method not reported

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Reported to be "double‐blind" but details not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Reported to be "double‐blind" but details not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

6/137 (4%) not followed due to non‐compliance

Selective reporting (reporting bias)

Unclear risk

No primary outcome stated. Eczema reported at 3 time points

Other bias

Unclear risk

Baseline characteristics not reported

Lauritzen 2004

Methods

Multicentre, double‐blind RCT with parallel reference group in Denmark December 1998 to November 1999

Participants

Maternal inclusion criteria: pregnant women; fish intake below population median (n‐3 LCPUFA < 0.4 g/day); uncomplicated pregnancy; pre‐pregnancy BMI < 30 kg/m2; no metabolic disorders; intention to breastfeed for at least 4 months of age

Infant inclusion criteria: healthy; term; singleton; birth weight appropriate for gestational age; Apgar score > 7; able to start supplements within 2 weeks of birth (not selected for risk of allergy)

Interventions

Breastfeeding mothers randomised to supplement for the first 4 months of life

Control (n = 60): olive oil (predominantly n‐9) (intermediate PUFA intake)

Intervention (n = 62): supplemented with fish oil 4 g/day (n‐3 LCPUFA 1.5 g; n‐3:n‐6 ratio = n‐3 only) (high PUFA intake)

Co‐interventions: none reported

Outcomes

Primary outcomes: breast milk FA composition; n‐3 PUFA levels in infant erythrocytes; infant development during the first year of life

Secondary outcomes: immune function as assessed by cytokine responses

Allergy: parent interviews about allergy diagnoses in the child, signs of allergic tendencies, and family history of allergy using validated questionnaire for atopic dermatitis at 2.5 years. Allergic tendencies (itchy rash, wheezing or food allergy) verified by a doctor

Notes

No conflict of interest declared

Allergic tendencies verified by doctor used for review

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random block‐wise allocation to the supplement groups was applied in blocks of 2 in 5 strata according to mean parental education

Allocation concealment (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Investigators and families blinded to randomisation throughout the first year of life

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Incomplete outcome data (attrition bias)
All outcomes

High risk

68/122 (56%) no follow‐up data

Selective reporting (reporting bias)

High risk

Allergy not prespecified. Time point for assessment not prespecified

Other bias

Low risk

Groups well balanced after allocation

Linnamaa 2010

Methods

Multicentre, double‐blind RCT in Finland 2004 to 2008

Participants

Inclusion criteria: pregnant women (not selected for risk of allergy); <16 weeks' gestation; preterm and sick infants excluded after randomisation

Interventions

Mothers randomised to blackcurrant seed oil supplement from 8 to 16 weeks' gestation through exclusive breastfeeding period. Infants supplemented with same oil 1 mL/day after exclusive breastfeeding period until 2 years

Control (n = 162): supplemented with placebo = olive oil 3 g/day (LA 9%; no γ‐LA or α‐LA or stearidonic acid; predominantly oleic acid 73%: n‐9). Infants 1 mL/day to 2 years (intermediate PUFA intake)

Intervention (n = 151): supplemented with blackcurrant seed oil 3 g/day (LA 48%, γ‐LA 13%, α‐LA 14%, stearidonic acid 3%; oleic acid 14%) (n‐3:n‐6 ratio 1:4). Infants 1 mL/day to 2 years (high PUFA intake)

Co‐interventions: none reported

Outcomes

Primary outcome: atopic dermatitis in first 12 months

Secondary outcomes: atopic dermatitis in first 2 years; serum IgE level and SPT during first 2 years; FA analysis

A specialist in dermatology evaluated the skin of each child at each visit. Atopic dermatitis was defined as a chronic or relapsing itchy dermatitis with a characteristic morphology and distribution. The SCORAD index used to assess dermatitis severity

Skin tests were carried out at 3‐, 12‐ and 24‐month visits

Notes

No conflict of interest declared

Note: data for eczema calculated from percentages in paper

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Assigned by a random number list .... immediately after the mother was enrolled

Allocation concealment (selection bias)

Low risk

Randomisation performed by personnel not involved in recruitment or subsequent assessment

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Oils could not be distinguished from each other

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Randomisation performed by personnel not involved in recruitment or subsequent assessment

Incomplete outcome data (attrition bias)
All outcomes

High risk

145/322 (45%) lost to follow‐up

Selective reporting (reporting bias)

Low risk

Prespecified atopic dermatitis by the age of 12 months as primary outcome

Other bias

Low risk

Groups similar at baseline

Lucas 1999

Methods

Multicentre RCT in UK 1993 to 1995

Participants

Women giving birth to healthy singletons of appropriate size for gestational age and > 37 weeks' gestation supplemented until 6 months of age (formula fed)

Interventions

Intervention (n = 154): LCPUFA supplemented formula (AA 0.30% and DHA 0.32% obtained from purified egg phospholipid and triglyceride fractions) (intermediate PUFA intake)

Control (n = 155): unsupplemented formula (intermediate PUFA intake)

Outcomes

Primary outcome: 'explore efficacy and safety outcomes'

Other outcomes: development, growth, safety data until 18 months. History of eczema (coded as none, possibly some, small patches, small areas requiring regular use of steroid cream or widespread eczema with itching and scratching; the latter 3 categories were considered as eczema), wheeze, and asthma recorded. Summary of reports of infection and atopy compared at 9 months

Notes

Nestec Ltd (Switzerland) for collaboration, funding and supply of trial diets

Allergy outcomes reported as odds ratios (95% CI)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random permuted block design stratified by centre and gender concealed by sealed opaque envelopes

Allocation concealment (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Mothers and study personnel were unaware of the dietary allocations ‐ differences between the coded formulas were not evident by observation

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Incomplete outcome data (attrition bias)
All outcomes

High risk

69/309 (22%) lost or excluded at 9 months

Selective reporting (reporting bias)

High risk

Multiple allergy endpoints measured

Other bias

Unclear risk

Similar at baseline. Substantial withdrawals with differences between groups in numbers lost at 9 months

Makrides 2002

Methods

Single centre RCT in Australia before 2001

Participants

Healthy 6‐month‐old infants born at term (> 37 weeks' gestation) with birth weights > 2500 g. Supplemented diet of weaning infants between 6 and 12 months of age with 4 eggs per week

Interventions

Breastfed infants

Intervention (n = 27): n‐3 eggs x 4 per week (intermediate‐high PUFA intake)

Control 1 (n = 27): regular eggs x 4 per week (intermediate PUFA intake)

Control 2 (n = 28): no egg supplement (intermediate PUFA intake)

Formula fed infants

Intervention (n = 26): n‐3 eggs x 4 per week (intermediate‐high PUFA intake)

Control 1 (n = 26): regular eggs x 4 per week (intermediate PUFA intake)

Control 2 (n = 27): no egg supplement (intermediate PUFA intake)

Outcomes

Primary outcome measures included erythrocyte DHA concentrations, infant iron status and plasma cholesterol concentrations. Secondary outcomes included growth and plasma indexes of atopy (egg yolk and egg white RAST)

Notes

Did not report clinical allergy

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer generated randomisation schedule. Breastfed and formula fed infants were allocated by using separate schedules

Allocation concealment (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Eggs were supplied in plain cartons coded A or B. Note second control group received no eggs

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Incomplete outcome data (attrition bias)
All outcomes

High risk

23/161 (14%) lost

Selective reporting (reporting bias)

Low risk

Allergy not prespecified or reported

Other bias

Unclear risk

Some baseline differences

Meldrum 2011

Methods

Single centre, double‐blind RCT in Australia June 2005 and October 2008

Participants

Inclusion criteria: infants; maternal history of doctor diagnosed asthma or allergic rhinitis; maternal SPT positive to at least 1 allergen

Exclusion criteria: maternal smoking; autoimmune disease; pre‐existing medical conditions other than asthma; high‐risk pregnancy; seafood allergy; fish eaten > 3 times per week; fish oil supplementation already taken (in excess of 1000 mg/day); pre‐term delivery < 36 week; infant with congenital abnormalities or significant disease not related to intervention

Interventions

Infants (mixed feeding, mostly breastfed) randomised to fish oil supplement for first 6 months of life

Control (n = 202): supplemented with olive oil 650 mg (66.6% n‐9 oleic acid)

Intervention (n = 218): supplemented with fish oil 650 mg (DHA 0.28 g, EPA 0.11 g) (n‐3:n‐6 ratio n‐3 only)

Control group intermediate PUFA intake, intervention group high PUFA intake

Co‐interventions: none reported

Outcomes

Primary outcomes:

1. Infant FA status
2. Immune development as determined by adaptive (T cell) and innate in vitro immune responses using samples collected at 6 months and at 1 year of age
3. Allergic outcomes (food allergy, eczema, asthma, wheezing and allergen sensitisation) at 12, 30 and 60 months of age determined through clinical history, allergen SPT and clinical examination
4. Infant neurodevelopment and language as determined by the Bayley Scales of Infant Development III, the Achenbach Child Behaviour Checklist, and the Macarthur Communicative Development Inventory. Further assessments are proposed at 6 years of age

Notes

No conflict of interest declared. 12‐month assessments reported to date

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation based on computer software (Excel) generation and stratified by block randomisation according to maternal allergy (asthma versus other allergy), parity (first child versus second or more child) and paternal allergy (allergic versus non‐allergic)

Allocation concealment (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Placebo capsules used

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Research scientists involved in the assessments will remain blind to the interventions for the duration of the study, until after the completion of the 6‐year clinical visits

Incomplete outcome data (attrition bias)
All outcomes

High risk

97/420 (23%) lost to follow‐up at 12 months

Selective reporting (reporting bias)

Low risk

Prespecified allergy outcomes

Other bias

Low risk

Groups similar at baseline

Mihrshahi 2003

Methods

Multicentre, parallel‐group RCT in Australia with completion of recruitment January 2000

Participants

Inclusion criteria: ≥ 1 parent or sibling with symptoms of asthma as assessed by screening questionnaire; reasonable fluency in English; telephone at home; reside within 30 km from centre of recruitment; any method of feeding

Exclusion criteria: pet cat at home; families on strict vegetarian diet; multiple births; babies born < 36 weeks' gestation

Withdrawal criteria: birth weight < 2.5 kg; babies requiring surgery; babies requiring hospitalisation for > 1 week; babies with significant neonatal disease; babies with congenital malformations

Interventions

Pregnant women randomised at 36 weeks' gestation to dietary FA modification for mother and infant for at least 5 years

Control (n = 304): supplemented with Sunola (sunflower) oil 500 mg (n‐3 PUFA < 0.1 g; n‐6 PUFA < 0.1 g) administered to infant when formula introduced, or at 6 months (n‐3:n‐6 ratio = 1:23); family provided with polyunsaturated oils for cooking (intermediate PUFA intake)

Intervention (n = 312): supplemented with tuna fish oil 500 mg (n‐3 PUFA 0.2 g, n‐6 PUFA < 0.1 g) administered to infant when formula introduced or at 6 months (n‐3:n‐6 ratio = 6:1); families provided with canola‐based (high n‐3) oils for cooking (high PUFA intake).

Co‐interventions: parallel (factorial) randomisation to active house dust mite avoidance

Outcomes

Primary outcomes: asthma symptoms at 18 months; wheeze frequency; physician diagnosed asthma at 18 months; asthma at 3 to 5 years

Secondary outcomes: eczema using validated questionnaire; nocturnal cough; allergic symptoms

SPT at 18 months

Notes

Contributions of goods and services Allergopharma Joachim Ganzer KG Germany, John Sands Australia, Nu‐Mega Ingredients Pty Ltd. Co‐author consultant arrangements with Merck Sharp & Dohme, Altana Pharma

Note: groups with house dust mite avoidance measures were included in the review

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomised in blocks of 4 sealed in sequentially numbered sealed envelopes

Allocation concealment (selection bias)

Low risk

Informed consent 34 to 37 weeks' gestation, randomisation at 36‐week home visit

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Placebo supplemented although active supplements had a slight fishy smell

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Research personnel undertaking outcome assessments blinded to group allocation of participants

Incomplete outcome data (attrition bias)
All outcomes

High risk

62/616 (10%) at 18 months; 90/616 (15%) at 3 years; 100/616 (16%) no 5‐year outcome data

Selective reporting (reporting bias)

Low risk

The primary aim in children at high risk of allergic disease was the incidence of allergy and asthma at age 5 years

Other bias

Low risk

Groups similar at baseline

Morris 2000

Methods

Single centre RCT in UK before 2000

Participants

Term neonates supplemented until 12 weeks (formula fed). Participants (n = 140) (numbers per group not specified)

Interventions

Intervention: LCPUFA supplemented formula (AA 0.4% + DHA 0.2%) (intermediate PUFA intake)

Control: standard formula (no AA or DHA) (intermediate PUFA intake)

Outcomes

Growth up to 12 months

Notes

Allergic symptoms measured but not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Following recruitment each participant was block randomised in a double‐blind fashion. Method not reported

Allocation concealment (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Coded milk

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Incomplete outcome data (attrition bias)
All outcomes

High risk

31/140 (22%) withdrawn

Selective reporting (reporting bias)

High risk

Measured 'allergic symptoms' but did not report data

Other bias

High risk

Differences between groups at baseline

O'Connor 2001

Methods

Multicentre RCT in USA October 1996 and January 1998

Participants

Preterm infants (< 33 weeks' gestation) with birth weight 750 g to 1805 g supplemented until 12 months' corrected age (formula fed)

Interventions

Intervention 1 (n = 283): AA + DHA supplemented formula (fish/fungal oil) (in hospital formula: AA 0.43% + EPA 0.08% + DHA 0.27%; postdischarge preterm formula: AA 0.43% + no EPA + DHA 0.16%) (intermediate‐high PUFA intake)

Intervention 2 (n = 283): AA + DHA supplemented formula (egg‐derived triglyceride/fish oil) (in hospital formula: AA 0.41% + no EPA + DHA 0.24%; postdischarge preterm formula: AA 0.41% + no EPA + DHA 0.15%) (intermediate‐high PUFA intake)

Control (n = 144): standard formula (no AA or EPA or DHA) (intermediate PUFA intake)

Outcomes

Hospital morbidity, serious adverse events, FA profile, visual acuity, growth, development up to 12 months' corrected age

Notes

Serious adverse events including asthma and wheezing measured but not reported separately

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Centrally computer generated randomisation schedule was stratified for site, gender and birth weight stratum (750 to 1250 g and 1251 to 1800 g) using a random permuted blocks algorithm

Allocation concealment (selection bias)

Low risk

'After informed written consent ... infants were randomized to 1 of 3 study formula groups'

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

94/470 (20%) did not complete study

Selective reporting (reporting bias)

High risk

Serious adverse events including asthma and wheezing measured but not reported separately

Other bias

Low risk

Groups similar at baseline

Smithers 2008

Methods

Multicentre, double‐blind RCT in Australia April 2001 and September 2003

Participants

Inclusion criteria: infants born before 33 weeks' gestation (not selected for risk of allergy); within 5 days of receiving any enteral feeds

Exclusion criteria: major congenital or chromosomal abnormalities; multiple birth where not all live‐born infants were eligible; enrolled in other trials of FA supplementation; lactating mothers in whom tuna oil was contraindicated

Interventions

Randomised to intervention within 5 days of birth until infants reached their estimated due date

Intervention: DHA‐rich tuna oil supplement (n = 322): mothers randomised to DHA‐rich tuna oil until expected date of delivery 3 g/day (DHA ˜ 1.3 g; n‐3:n‐6 ratio = n‐3 only). If supplementary formula was required, infants were given a high‐DHA preterm formula (DHA 1% + AA 0.6%) (high PUFA intake)

Control (n = 335): maternal soy oil 3 g/day (LA ˜ 1.5 g, α‐LA ˜ 0.2 g) (n‐3:n‐6 ratio = 1:8). If supplementary formula was required, infants were given a standard preterm formula (DHA 0.35%, AA 0.6%) (intermediate PUFA intake)

Co‐interventions: none reported

Outcomes

Primary outcomes: neurodevelopment at 18 months; intellectual ability at 7 years

Secondary outcomes: growth; safety; cognitive function; educational progress; behaviour; quality of life; symptoms of asthma and allergy; anthropometrics; blood pressure

Parental recall of subsequent hospitalisations and diagnoses were sought at the ages of term, 4, 12 and 18 months' corrected age

Structured parental interviews at 12 and 18 months allowed parents to report medical attention for, or the treatment of, hay fever, eczema, asthma or food allergy

Notes

Co‐authors on scientific advisory boards for Nestle, Fonterra and Nutricia with associated honoraria

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Mother‐infant pairs were randomly assigned a unique study number through a computer‐driven telephone randomisation service according to an independently generated randomisation schedule. Stratification was by centre, birth weight and infant sex

Allocation concealment (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

To facilitate blinding, each treatment group was separately colour‐coded into 2 groups. All capsules were similar in size, shape and colour. If formula was required in the pilot phase, 2 drops of oil from capsules in matching colour‐coded containers were added to each 90 mL jar of formula. For the remainder of the trial, ready‐to‐feed preterm formula to trial specifications and packaged the formula according to the colour codes were manufactured

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Parents, clinicians and all research personnel blinded to participant study group

Incomplete outcome data (attrition bias)
All outcomes

Low risk

54/657 (8%) incomplete outcome data at 18 months

Selective reporting (reporting bias)

Low risk

Structured parental interviews at 12 and 18 months allowed parents to report medical attention for, or the treatment of, hay fever, eczema, asthma or food allergy

Other bias

Low risk

Groups well balanced after allocation

van Gool 2003

Methods

Multicentre, double‐blind RCT in Netherlands October 1997 and April 2000

Participants

Formula fed infants (n = 121) with a maternal history of atopic disease: gestational age ≥ 38 weeks, birth weight > 2500 g, an uncomplicated perinatal period and exclusive formula‐feeding from 2 weeks age

Maternal inclusion criteria: maternal history of allergic asthma or allergic rhinoconjunctivitis related to aeroallergen exposure or atopic dermatitis or a positive allergen test or improvement of asthma or rhinoconjunctivitis with the use of antihistamine or anti‐asthma drugs

Maternal exclusion criteria: diabetes treated with medication or diet, or both; pre‐eclampsia; metabolic disease

Interventions

Infants randomised to supplement for first 6 months of life

Control (n = 60): supplemented with sunflower oil 446 mg (LA 0.2 g; n‐3:n‐6 ratio = n‐6 only)

Intervention (n = 61): supplemented with borage oil 446 mg (LA 0.2 g; γ‐LA 103 mg/day; n‐3:n‐6 ratio = n‐6 only)

Both groups intermediate PUFA intake

Co‐interventions: none reported

Outcomes

Primary outcome: atopic dermatitis at 12 months by dermatologist using the criteria of the UK Working Party

Secondary outcome: total IgE and specific IgE for common aero‐ and food allergens at age 1 year (UniCAP)

Severity of dermatitis scored by dermatologist using SCORAD

Notes

Supported by F Hoffmann‐La Roche (Basel, Switzerland), Friesland Coberco Dairy Foods (Leeuwarden, Netherlands)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Block randomisation in blocks of 4. Method not reported

Allocation concealment (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Powders packaged in low‐oxygen sachets to blind the investigators and parents to possible differences in smell and appearance

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3/121 (2%) lost to follow‐up

Selective reporting (reporting bias)

Low risk

Primary outcome atopic dermatitis at 12 months

Other bias

Low risk

Groups similar at baseline

AA: arachidonic acid; BMI: body mass index; CI: confidence interval; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; FA: fatty acid; IgE: immunoglobulin E; LA: linoleic acid; LCPUFA: long chain polyunsaturated fatty acid; n: number of participants; PUFA: polyunsaturated fatty acid; RAST: radioallergosorbent test; RCT: randomised controlled trial; SCORAD: SCORing Atopic Dermatitis; SPT: skin prick test.

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Agostoni 1994

Excluded as allergy not prespecified or reported

Multicentre (n = 6) randomised controlled trial in Italy and Ireland in 1992

Term neonates supplemented from birth until 4 months (formula fed)

Intervention (n = 111): LCPUFA supplemented formula (LA 11.5% to 12.8% of fat; α‐LA 0.6% to 0.65%; AA 0.3% to 0.4%; DHA 0.15% to 0.25%) (intermediate PUFA intake)

Control (n = 126): standard formula (LA 11.4% of fat; α‐LA 0.7%; AA < 0.1%; DHA 0%) (low PUFA intake)

Outcome: neurodevelopment at 4 months; blood pressure in childhood; growth and developmental quotient at 4, 12, 18 and 24 months; 24 months Brunet‐Lézine's scale of development; at age 6 years intelligence quotient, attention control (Day‐Night Test), and speed of processing on the Matching Familiar Figures Test

Agostoni 2009

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Italy May 2005 and June 2005

Term neonates supplemented from hospital discharge until 12 months (mixed feeding, mostly breastfed)

Intervention (n = 580): DHA 20 mg supplement (intermediate PUFA intake) + vitamin D3 400 IU

Control (n = 580): placebo (intermediate PUFA intake) = vitamin D3 400 IU

Outcome: achievement of gross motor milestones in first year of life

Alam 2010

Excluded as allergy not prespecified or reported

Multicentre cluster (16 villages) randomised controlled trial in Bangladesh November 1995 to October 1997

Pregnant women recruited at 5 to 7 months of gestation and treated until 6 months' postpartum (infants mostly breastfed)

Intervention (n = 341): soybean oil 20 mL (high PUFA intake)

Control (n = 335): no supplement (intermediate PUFA intake)

Outcome: plasma vitamin A status at 6 months

PUFA intake not reported

Amesz 2010

Excluded as used co‐interventions that differed between treatment and control groups

Single centre randomised controlled trial in Netherlands

Participants: 102 preterm infants born at gestational age ≤ 32 weeks or birth weights ≤ 1500 g supplemented until 6 months' corrected age (formula fed)

Intervention (n = 52): postdischarge formula with AA 0.5% to 0.6% + DHA 0.4% to 0.5% supplemented formula (intermediate‐high PUFA intake). The postdischarge formula provided the same quantity of energy but a higher level of protein and a lower level of carbohydrates, higher levels of some minerals, vitamins, and LCPUFA

Control (n = 50): standard term formula (intermediate PUFA intake)

Outcomes: fatty acid profile, growth up to 6 months' corrected age

Did not report allergy

Andersen 2011

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Denmark January 2008 to March 2009

Infants supplemented from 9 to 18 months of age (mixed feeding)

Intervention (n = 75): fish oil 5 mL daily (EPA + DHA 1.6 g/day) (high PUFA intake; high n‐3)

Control (n = 79): sunflower oil 5 mL daily (LA 3.1 g/day) (intermediate‐high PUFA intake; high n‐6)

Outcome: growth up to 18 months

Auestad 1997

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 1997

Formula fed term neonates supplemented from before 9 days to until 12 months if formula fed

Formula groups (oil blend consisted of high oleic safflower, coconut and soy oils)

Intervention 1 (n = 59): AA 0.43% + DHA 0.12% supplemented formula (egg derived phospholipid) (intermediate PUFA intake)

Intervention 2 (n = 61): DHA 0.23% supplemented formula (fish oil derived) (intermediate PUFA intake)

Control (n = 63): standard formula (intermediate PUFA intake; no DHA or AA)

Outcome: visual acuity at 12 months

Auestad 2001

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 2001

Term neonates supplemented until 12 months (formula fed and breastfed groups)

Formula fed infants

Intervention 1 (n = 80): AA 0.45% + DHA 0.14% supplemented formulas (egg derived) (intermediate‐high PUFA intake)

Intervention 2 (n = 82): AA 0.46% + DHA 0.13% supplemented formulas (fish/fungal derived) (intermediate‐high PUFA intake)

Control 1 (n = 77): standard formula (intermediate‐high PUFA intake; no AA or DHA)

Breastfed infants (supplemented after 3 months)

Intervention (n = 83): AA + DHA supplemented formula (egg derived) (intermediate‐high PUFA intake)

Control 2 (n = 82): standard formula (intermediate‐high PUFA intake)

Outcome: multiple measures of infant development up to 14 months

Ben 2004

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in China 2001 to 2002

Term neonates supplemented until 6 months of age (formula fed)

Intervention (n = 69): AA + DHA supplemented formulas (intermediate PUFA intake) (LA 435 mg; α‐LA 62 mg; AA 6.9 mg; and DHA 6.9 mg per 100 mL)

Control (n = 52): standard formula (intermediate PUFA intake) (LA 440 mg; α‐LA 44 mg; no AA or DHA per 100 mL)

Outcome: growth, development and infections up to 6 months

Benito Fernandez 2002

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Spain before June 2001

Term neonates (n = 37) supplemented until 2 months (formula fed)

Intervention/control (numbers per group not specified): 1 of 4 formulas (standard (low‐intermediate), n‐3 supplemented (intermediate), n‐3 + n‐6 supplemented (intermediate), nucleotide supplemented (intermediate‐high))

Outcome: fatty acid profile, growth up to 2 months

Written in Spanish; English abstract

Bergmann 2008

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Germany October 2000 to August 2002

Pregnant women supplemented from 21 to 37 weeks' gestation; and then from 2 weeks' to 3 months' postpartum

Intervention (n = 48): maternal DHA 200 mg supplement (intermediate PUFA intake) (fish oil derived)

Control (n = 48): no maternal DHA supplement (intermediate PUFA intake)

Outcome: growth up to 21 months

Berseth 2014

Excluded as used co‐interventions that differed between treatment and control groups

Multicentre randomised controlled trial in USA

Participants: 150 preterm infants born at gestational age ≤ 30 + 3/7 weeks or birth weights ≤ 1250 g supplemented for 28 days, until hospital discharge or discontinuation of breast milk (breast milk fed)

Intervention (n = 75): concentrated human milk fortifier enriched with LCPUFA (intermediate‐high PUFA intake)

Control (n = 75): standard milk fortifier (intermediate PUFA intake)

Outcomes: fatty acid profile, growth, adverse events up to 28 days

Did not report allergy

Billeaud 1996

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in France before 1996

Preterm neonates < 34 weeks' gestation supplemented until 37 weeks' corrected gestation (formula fed)

Intervention (n = 31): α‐LA 1.95% supplemented formula (intermediate PUFA intake)

Control (n = 32): standard formula with α‐LA 0.55% (low‐intermediate PUFA intake)

Outcome: fatty acid profile, growth up to 37 weeks' corrected gestation

Birch 1992

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA before 1992

73 healthy preterm infants born at 27 to 33 weeks' postconception

Formula groups fed from 10 days postnatal to 57 weeks' postconception

Control: corn oil that provided solely linoleic acid

Intervention 1: soy oil that provided LA and α‐LA or

Intervention 2: soy/marine oil that was similar to the soy oil formula but also provided DHA 0.46%

Outcome: visual evoked potentials at 57 weeks

Birch 1998

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA

Term neonates supplemented until 17 weeks (formula fed)

Intervention 1 (n = 27): AA 0.72% + DHA 0.36% supplemented formula (intermediate PUFA intake)

Intervention 2 (n = 26): DHA 0.35% supplemented formula (intermediate PUFA intake)

Control (n = 26): standard formula (intermediate PUFA intake; no AA or DHA)

Outcome: fatty acid profile, visual acuity, growth up to 12 months

Birch 2002

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 2001

Term neonates supplemented from 6 weeks to 12 months (formula fed)

Intervention (n = 32): AA 0.72% + DHA 0.36% supplemented formula

Control (n = 33): standard formula

Outcome: visual acuity up to 12 months

Birch 2010

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 1998

Participants: term neonates supplemented from birth to 12 months (formula fed)

Intervention 1 (n = 84): DHA 0.32% + 0.64% AA (34 mg/100 kcal) formula

Intervention 2 (n = 85): DHA 0.64% (34 mg/100 kcal) + AA 0.64% (34 mg/100 kcal) formula

Intervention 3 (n = 88): DHA 0.96% (51 mg/100 kcal) + AA 0.64% (34 mg/100 kcal) formula

Control (n = 86): standard formula with no DHA or AA

Outcome: visual acuity up to 12 months

Boehm 1996

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Germany before 1996

Very‐low‐birth‐weight infants appropriate for gestational age from 2nd week to discharge

When breast milk was not available the infants were randomly assigned to be fed either:

Control: standard preterm formula (n = 11), virtually LCPUFA free (LA 11.3%, α‐LA 0.56%)

Intervention: LCPUFA supplemented formula (n = 12). (LA 12.75%, α‐LA 0.82%; DHA 0.15%; AA 0.25%)

Changed to identical fatty acid term formulas at 34 to 36 weeks' postconceptual age

Outcome: fatty acid composition of serum and red blood cell membrane phospholipids

Boehm 1997

Excluded as intervention < 1 month

Single centre randomised controlled trial in Germany

Participants: 39 very‐low‐birth‐weight infants appropriate for gestational age over 10‐day feeding period

Intervention: LCPUFA‐supplemented formula (n = 11) (DHA: 50.2 ± 4.2 mg/72 hours; AA: 30.2 ± 2.7 mg/72 hours) (intermediate‐high PUFA intake)

Control: LCPUFA‐free formula (n = 11) (intermediate PUFA intake)

Outcome: DHA and AA absorption

Did not report allergy

Bondia‐Martinez 1998

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Spain before 1998

Term neonates supplemented until 3 months (formula fed)

Intervention (n = 18): AA 0.30% + DHA 0.15% supplemented formula (intermediate PUFA intake)

Control (n = 15): standard formula (intermediate PUFA intake)

Outcome: fatty acid profile at 3 months

Bougle 1999

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in France before 1999

Preterm neonates < 34 weeks' gestation supplemented for at least 30 days until 37 weeks' corrected gestation (formula fed)

Intervention (n = 14): LCPUFA enriched formula (LA 17.7%, α‐LA 1.2%; DHA 0.6%; EPA 0.1%, AA 0.1%) (intermediate PUFA intake)

Control (n = 11): standard formula with no LCPUFA (LA 14.1%, α‐LA 1.3%) (intermediate PUFA intake)

Outcome: fatty acid profile, auditory and visual evoked potentials, nerve conduction velocity, growth up to 37 weeks' corrected gestation

Bouwstra 2003

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Netherlands February 1997 until October 1999

Term neonates supplemented until 2 months (formula fed)

Intervention (n = 145): AA 0.45% + DHA 0.3% supplemented formula (intermediate PUFA intake)

Control (n = 167): standard formula (intermediate PUFA intake)

Outcome: general movements at 3 months

Carlson 1987

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA May 1985 and January 1986

Infants born at < 1500 g (range 600 g to 1440 g)

Intervention (n = 30): preterm formula with the fish oil supplement (750 mg/kg/day). (Provided approximately 6 times as much DHA as would have been received by infants fed preterm human milk)

Control (n = 31): preterm formula (no DHA)

Outcome: red blood cell membrane docosahexaenoic acid

Carlson 1991a

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA November 1987 and 1989

Preterm infants (600 to 1270 g birth weight) when tolerated preterm formulas at intakes > 462 to 504 kJ/kg/day for 5 to 7 days

Randomised to receive 1 of 3 formulas for 4 weeks

Intervention 1 (n = 8): preterm formula contained EPA 0.3% and DHA 0.2% from marine oil

Intervention 2 (n = 7): preterm formula contained EPA 0.7% and DHA 0.4% from marine oil

Control (n = 6): preterm formula did not contain marine oil and was free of EPA and DHA

Outcome: fatty acid profiles up to 12 months' corrected age

Carlson 1991b

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA November 1987 and 1989

Infants weighed 748 to 1398 g at birth and were eligible for the study when they were receiving > 462 kJ/kg/day of a preterm formula

Randomised (n = 79; group numbers unclear) to receive 1 of 2 formulas to discharge and then term formula with or without marine oil postdischarge until 79 weeks' postconceptual age

Control: preterm formula without marine oil during hospital stay; then term formula without marine oil post discharge to 79 weeks' postconceptual age

Intervention 2: preterm formula contained EPA 0.3% and DHA 0.2% from marine oil during hospital stay; then term formula with marine oil post discharge to 79 weeks' postconceptual age

Outcome: fatty acid profiles up to 12 months' corrected age. Visual acuity as measured by the Teller Acuity Card procedure

Carlson 1996a

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA before 1996

Term neonates supplemented until 12 months (formula fed)

Intervention (n = 28): AA 0.43% + DHA 0.1% supplemented formula (added egg phospholipid) (intermediate PUFA intake)

Control (n = 31): standard formula (intermediate PUFA intake) (no DHA or AA)

Outcome: fatty acid profile, visual acuity up to 12 months

Carlson 1996b

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA before 1996

Participants (n = 94) (numbers per group not specified): preterm neonates supplemented until 2 months' corrected age (formula fed)

Intervention: marine oil supplemented formula (high PUFA intake)

Control: standard formula (high PUFA intake)

Outcome: fatty acid profile, visual acuity, growth up to 12 months

Carlson 1998

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA September 1992 to March 1997

Participants (n = 120) (numbers per group not specified): preterm neonates supplemented until 4 months' corrected age (formula fed)

Intervention: egg phospholipid supplemented formula AA 0.41%; DHA 0.13%; no γ‐LA (intermediate‐high PUFA intake; high n‐3; low n‐6)

Control: standard formula (no AA or DHA; γ‐LA 2.24%) (intermediate PUFA intake; no n‐3; high n‐6)

Outcome: hospital morbidity, fatty acid profile, growth up to 4 months

Carnielli 1998

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Italy 1992 to 1995

Preterm infants fed exclusively with study formulas until ≥ 5 weeks old. Report control and treatment 2 groups continued on formulas until 7 months of age

Control (n = 19): preterm formula without LCPUFAs added. (No AA or DHA; no n‐3 or n‐6)

Intervention 1 (n = 19): preterm formulas supplemented with LCPUFAs derived from egg phospholipids. (AA 0.35%; DHA 0.24%; n‐3 0.55%; n‐3 0.45%)

Intervention 2 (n = 19): preterm formula with LCPUFAs from triacylglycerols derived from unicellular organisms. (AA 0.84%; DHA 0.64%; n‐3 0.97%; n‐3 0.64%)

Outcome: dietary intakes, fecal excretion and intestinal absorption of LCPUFAs. Fatty acid profile up to 7 months

Clandinin 1992

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Canada before April 1990

Preterm neonates supplemented from first week of life for four weeks (formula fed)

Intervention (n = 12): preterm formula with LCPUFA supplementation (intermediate‐high PUFA intake)

Control (n = 10): standard preterm formula (intermediate PUFA intake)

Outcome: fatty acid profile after 4 weeks

Clandinin 1997

Excluded as allergy not prespecified or reported

Single centre controlled trial in USA before April 1997

Stable preterm infants appropriate weight for gestational age (n = 72)

4 formulas contain the same nutrient composition but provided increasing levels of AA (0%, 0.32%, 0.49% and 1.1%) and DHA (0%, 0.24%, 0.35% and 0.75%) for 6 weeks

Outcome: erythrocyte membrane phospholipid content and lipoprotein content up to 6 weeks

Clandinin 2005

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Canada

Preterm neonates gestational age was ≤ 35 weeks' postmenstrual age and they had received < 10 total days of enteral feedings of > 30 mL/kg/day

Preterm neonates supplemented until 6 months (formula fed)

Intervention 1 (n = 112): AA + DHA supplemented formulas (intermediate PUFA intake) (DHA 17 mg/100 kcal from algal oil and AA 34 mg/100 kcal from fungal oil; DHA 0.3% and AA 0.6%)

Intervention 2 (n = 130): AA + DHA supplemented formulas (high PUFA intake) (DHA 17 mg/100 kcal from tuna fish oil and AA 34 mg/100 kcal from fungal oil; DHA 0.3% and AA 0.6%)

Control (n = 119): standard formula (intermediate PUFA intake)

Outcome: growth, development up to 18 months

Clark 1992

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Australia before 1992

Healthy term infants whose mothers had decided not to breastfeed were enrolled in the study at birth

Infants were randomly allocated to 1 of 3 formulas for a total of 10 weeks

Intervention 1 (n = 10): formula with a high ratio of LA to α‐LA 19:1 (LA 14%; α‐LA 0.7%)

Intervention 2 (n = 11): formula contained LA:α‐LA ratio 4:1 reduced by increasing α‐LA (LA 13%; α‐LA 3.3%) or

Intervention 2 (n = 8): formula contained LA:α‐LA ratio 3:1 reduced by decreasing LA (LA 3.5%; α‐LA 1.1%).

Outcome: incorporation of n‐3 and n‐6 C20 and C22 fatty acids into erythrocyte membranes

Decsi 1995

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Hungary before 1995

Healthy, full‐term, appropriate‐for‐gestational age infants fed formula were enrolled at 5 days of age supplemented until 4 months (formula fed)

Intervention (n = 12): LCPUFA 1.1% supplemented formula (intermediate PUFA intake) (AA 0.5%; α‐LA 0.2%; EPA 0.03%; DHA 0.3%)

Control (n = 10): standard formula with low LCPUFA intake 0.1% (no AA or α‐LA or EPA or DHA)

Outcome: fatty acid profile up to 4 months

Decsi 1997

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Hungary prior to March 1996

Full term infants whose parents decided not to breastfeed, formula fed for 1 month

Randomly assigned to:

Control (n = 10): conventional cow's milk protein formula based on and vegetable fat (No AA; α‐LA 1.0; No DHA; LCPUFA 0.1%)

Intervention (n = 12): same formula supplemented with egg lipids and evening primrose oil (AA 0.4%; α‐LA 0.6; DHA 0.2%; LCPUFA 0.9%)

Outcome: lipid profiles to 30 days

Demmelmair 2001

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Hungary December 1994 to May 1997

Preterm neonates supplemented for 28 days (formula fed)

Intervention 1 (n = 13): borage oil supplemented formula (intermediate PUFA intake) (0.6% γ‐LA)

Intervention 2 (n = 13): borage oil + low fish oil supplemented formula (intermediate PUFA intake) (γ‐LA 0.6%; DHA 0.3%; EPA 0.06%)

Intervention 3 (n = 14): borage oil + high fish oil supplemented formula (intermediate‐high PUFA intake) (γ‐LA 0.6%; DHA 0.3%; EPA 0.2%)

Control (n = 13): standard formula (intermediate PUFA intake)

Outcome: fatty acid profile up to 4 months

Dotterud 2013

Excluded as non‐randomised and used co‐interventions that differed between treatment and control groups

Multicentre non‐randomised controlled clinical trial in Norway

A multiple life‐style intervention programme was introduced as a primary healthcare intervention involving increased maternal and infant dietary n‐3 PUFA intake, reduced tobacco smoke exposure and reduced indoor dampness in homes. Pregnant women and children up to 2 years of age were recruited to participate in a before‐and‐after study

Intervention (n = 2860): increased n‐3 PUFA intake as part of intervention programme (unknown PUFA intake)

Control (n = 4780): recruited before initiation of intervention programme (unknown PUFA intake)

Outcome: prevalence of parentally reported allergy related diseases at 2 years of age

Faldella 1996

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Italy before 1996

Preterm neonates < 33 weeks of gestational age, appropriate weight and with no malformation supplemented until 12 weeks' corrected age (formula fed)

Intervention (n = 23): LCPUFA supplemented formula (AA 0.01%; DHA 0.3%; n‐6 4.3%) (intermediate PUFA intake)

Control (n = 26): standard formula (no AA or DHA) (low‐intermediate PUFA intake)

Outcome: visual evoked potentials, growth up to 12 weeks' corrected age

Fang 2005

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Taiwan before 2005

Preterm neonates 30 to 37 weeks' gestation, > 2000 g, over 32 weeks and on full feeds supplemented for 6 months (formula fed)

Intervention (n = 16): AA + DHA supplemented formula (unclear PUFA intake)

Control (n = 11): standard formula (unclear PUFA intake)

Outcome: visual acuity, growth, development up to 12 months

Fewtrell 2002

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in UK before 2002

Preterm neonates < 1750 g supplemented until hospital discharge (formula fed minimum 3 weeks)

Intervention (n = 95): LCPUFA supplemented formula (EPA 0.04%; AA 0.31%; DHA 0.17%; cholesterol 7.73%) (intermediate PUFA intake)

Control (n = 100): standard formula (no EPA or AA or DHA or cholesterol) (low PUFA intake)

Outcome: hospital morbidity, growth, development up to 18 months

Fidler 2000

Excluded as intervention < 1 month

Single centre randomised controlled trial in Germany

Participants: healthy breastfeeding women with healthy single, full‐term newborns. The infants were exclusively breastfed during the duration of the study. At 4 weeks' postpartum, mothers were randomly assigned to receive 2 DHA capsules per day for 14 days

Intervention: DHA capsule twice daily (intermediate‐high PUFA intake)

Control: placebo oil (intermediate PUFA intake)

Outcome: effect on human milk fatty acid composition

Did not report allergy

Field 2000

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Canada before 2000

Stable preterm infants gestational age 27 and 36 weeks appropriate for gestational age and receive 100% of requirements enterally by day 14

Groups received formula from before day 8 to day 42 of postnatal life

Control (n = 12): standard preterm formula (no AA or DHA)

Intervention (n = 15): same formula supplemented with AA 0.49% and DHA 0.35%

Outcome: immune cell types and the antigenic maturity of T cells

Field 2008

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Canada before 2007

Mothers who had chosen to switch from breastfeeding to formula before 14 days age

Randomised to feeding from 14 days to 16 weeks age

Control (n = 14): standard term infant formula

Intervention (n = 16): same formula supplemented with AA 0.34% and DHA 0.2%

Outcome: immune cell phenotypes and the ability of peripheral blood cells to proliferate and produce cytokines in vitro

Fleddermann 2014

Excluded as used co‐interventions that differed between treatment and control groups

Single centre randomised controlled trial in Serbia

Participants: 213 term infants born at 37 to 41 weeks' gestation, appropriate for gestational age given modified infant formula for 4 months (formula fed)

Intervention (n = 107): reduced protein formula enriched with α‐lactalbumin and LCPUFA (intermediate‐high PUFA intake)

Control (n = 106): standard term formula (intermediate PUFA intake)

Outcomes: fatty acid profile, growth, tolerance up to 4 months

Did not report allergy

Foreman‐van Drongelen 1995

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Netherlands before 1994

Preterm neonates < 37 weeks' gestation appropriate for gestational age supplemented until 3 months' corrected age (formula fed)

Randomised to formula (preterm to 2000 g then term formula)

Intervention (n = 15): dihomo‐γ‐linolenic acid 0.06% + AA 0.61% + DHA 0.30% supplemented formulas (intermediate PUFA intake)

Control (n = 16): standard formula (intermediate PUFA intake) (no dihomo‐γ‐linolenic acid or AA or DHA)

Outcome: fatty acid profile at 3 months' corrected age

Ghebremeskel 1995

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in UK before 1994

Preterm neonates supplemented until term corrected age (formula fed). Participants (n = 63): numbers per group not specified; includes breast milk fed controls

Intervention: AA 0.12% + DHA 0.51% supplemented formula (intermediate PUFA intake)

Control: standard formula AA 0.04% + No DHA (low PUFA intake)

Outcome: fatty acid profile at term corrected age

Gibson 1997

Excluded as used co‐interventions that differed between treatment and control groups

Single centre randomised controlled trial in Australia

Participants: mothers of term infants (> 37 weeks' gestation) who intended to breastfeed for at least 12 weeks

Mothers were randomised to receive 1 of 5 doses (0.2, 0.4, 0.9 or 1.3 g DHA/day) of a DHA‐rich algal oil between day 5 and week 12 postpartum. The oil contained 43% DHA, 1% n‐6 PUFA, 38% saturates and 18% monounsaturates

Intervention 1 (n = 10): DHA 0.35% of fatty acids in breast milk

Intervention 2 (n = 12): DHA 0.46%

Intervention 3 (n = 10): DHA 0.86%

Intervention 4 (n = 8): DHA 1.13%

Control (n = 12): no DHA supplement (DHA 0.21%: intermediate PUFA intake)

Outcomes: fatty acid profile, visual evoked potentials, growth, development up to 2 years. Adverse events were assessed at each visit by a nurse

Did not report allergy

Gibson 2009

Excluded as used co‐interventions that differed between treatment and control groups

Single centre randomised controlled trial in Australia

Participants: 142 term infants > 36 weeks, < 11 days old assigned to 1 of 2 formulas for 4 months (formula fed)

Intervention (n = 72): formula with LCPUFA and probiotics supplements (intermediate PUFA intake)

Control (n = 70): standard term formula (intermediate PUFA intake)

Outcomes: fatty acid profile, growth, tolerance, adverse events up to 4 months

Did not report allergy

Granot 2011

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Israel before 2011

60 pregnant women aged 20 to 35 years in their 3rd pregnancy supplemented from 12 weeks' gestation until 4 months postpartum

Intervention (n = 30): DHA 400 mg/day from 12 weeks' gestation until 4 months' postpartum (high PUFA intake)

Control (n = 30): no DHA supplement (intermediate PUFA intake)

Outcome: infant immune cell profile at 4 months

Groh‐Wargo 2005

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA September 1997 and September 1998

Preterm neonates with birth weight 750 to 1800 g and gestational age < 33 weeks supplemented until 12 months (formula fed)

Intervention 1 (n = 20): DHA 0.26% + AA 0.42% from fish/fungal oil supplemented formula to 40 weeks' corrected age; and DHA 0.26% + AA 0.42% from 40 weeks' corrected age

Intervention 2 (n = 18): DHA 0.26% + AA 0.42% from egg/fish oil supplemented formula; and DHA 0.26% + AA 0.42% from 40 weeks' corrected age

Control (n = 22): standard formula

Outcome: growth and body composition up to 12 months' corrected age

Note: 20 of 60 infants also enrolled in O'Connor 2001

Hauner 2012

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Germany July 2006 and May 2009

Healthy pregnant women before the 15th week of gestation

Women supplemented from 15th week of gestation to 4 months postpartum:

Intervention (n = 104): LCPUFA supplement (high PUFA intake) (fish oil supplement as capsules containing n‐3 LCPUFAs 1200 mg (DHA 1020 mg and EPA 180 mg) and 9 mg vitamin E per day)

Control (n = 104): no LCPUFA supplement (intermediate PUFA intake)

Outcome: infant fat mass up to 12 months

Hawkes 2001

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Australia before 2001

Healthy women aged ≥ 18 years who delivered full‐term singleton infants and intended to breastfeed for ≥ 12 weeks

Randomly allocated from day 3 postpartum until the end of their 12th postpartum week

Control (n = 40): 4 x 500 mg placebo oil capsules

Intervention 1 (n = 40): DHA 300 mg/day and EPA 70 mg/day (2 x 500 mg tuna oil capsules + 2 x 500 mg placebo oil capsules)

Intervention 2 (n = 40): DHA 600 mg/day and EPA 140 mg/day (4 x 500 mg tuna oil capsules)

Outcome: maternal immune profile at 5 weeks

Helland 1998

Excluded as supplementation period < 1 month

Single centre randomised controlled trial in Norway

Participants: 22 healthy, lactating women recruited at child healthcare centres 3 ± 8 weeks after they had given birth

Supplementation period was 14 days, between 3 and 8 weeks' postpartum

Intervention 1: cod liver oil 2.5 mL/day (intermediate‐high PUFA intake)

Intervention 2: cod liver oil 5 mL/day (intermediate‐high PUFA intake)

Intervention 3: cod liver oil 10 mL/day (intermediate‐high PUFA intake)

Control: no supplementation (intermediate PUFA intake)

Cod liver oil contained EPA 7.7 g, DHA 10.2 g and total n‐3 fatty acids 22.9 g per 100 mL

Outcome: amount of essential fatty acids in mothers' breast milk

Did not report allergy

Helland 2001

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Norway December 1994 and October 1996

Healthy women with single pregnancies aged 19 to 35 years, and nulli‐ or primipara and intending to breastfeed

Supplemented from 17 to 19 weeks' gestation until 3 months' postpartum

Intervention (n = 301): cod liver oil 10 mL/day (DHA 1183 mg/10 mL, EPA 803 mg/10 mL; n‐3 PUFAs 2494 mg/10 mL) (high PUFA intake)

Control (n = 289): corn oil 10 mL/day (LA 4747 mg/10 mL and α‐LA 92 mg/10 mL) (intermediate PUFA intake)

Outcome: growth and development up to 12 months

Henriksen 2008

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Norway December 2003 and November 2005

Very low birth weight neonates supplemented until discharge (breast milk fed)

Intervention (n = 68): LA 18.8% + DHA 6.9% + AA 6.7% + α‐LA 2.3% supplemented feeds (high PUFA intake)

Control (n = 73): unsupplemented feeds: LA 27.1% + α‐LA 3.4% + no DHA or AA (intermediate PUFA intake)

Outcome: fatty acid profile, growth, development up to 18 months

Hoffman 2003

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 2003

Infants supplemented from 4 to 6 months until 12 months of age (breastfed until enrolment)

Intervention (n = 33): dihomo‐γ‐linolenic acid 0.05% + AA 0.72% + DHA 0.36% supplemented formula (intermediate‐high PUFA intake)

Control (n = 35): standard formula (no dihomo‐γ‐linolenic acid or AA or DHA) (intermediate PUFA intake)

Outcome: fatty acid profile, visual evoked potentials, growth up to 12 months

Hoffman 2004

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA

Infants supplemented from 6 to 12 months (breastfed until enrolment)

Intervention (n = 28): egg yolk enriched baby foods with α‐LA 0.366% + AA 0.078% + DHA 0.115% (n‐6 1.18%; n‐3 0.51%; n‐6:n‐3 PUFA ratio 2.3) (intermediate PUFA intake)

Control (n = 27): no supplement α‐LA 0.011% + AA 0.001% + no DHA (n‐6 0.12%; n‐3 0.01%; n‐6:n‐3 PUFA ratio 9.8) (intermediate PUFA intake)

Outcome: fatty acid profile, visual evoked potentials, growth up to 12 months

Hoffman 2006

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 2005

Term neonates 38 to 42 weeks' gestation with birth weight > 2500 g supplemented until 4 months of age (formula fed)

Intervention (n = 39): high LCPUFA formula (LA 17.2% + α‐LA 1.65% + AA 0.64% + DHA 0.32%) (intermediate PUFA intake)

Control (n = 27): low LCPUFA formula (LA 19.5% + α‐LA 2.1% + AA 0.4% + DHA 0.15%) (intermediate PUFA intake)

Outcome: fatty acid profile, growth up to 4 months

Horby Jorgensen 1998

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Denmark began in October 1993

Uncomplicated pregnancy, term delivery (gestational age 37 to 42 weeks), birth weight 2700 to 4500 g, Apgar > 7 after 5 minutes, and no neonatal diseases; supplemented until 4 months (formula fed). Participants: (n = 39) (numbers per group not specified)

Intervention 1 (n = 14): LCPUFA supplemented formula (DHA 0.3% + EPA 0.4% in fish oil) (intermediate PUFA intake)

Intervention 2 (n = 12): LCPUFA supplemented formula (DHA 0.3% + EPA 0.4% + γ‐LA 0.5% in borage oil) (intermediate PUFA intake)

Control (n = 11): standard formula (no LCPUFA supplement) (intermediate PUFA intake)

Outcome: fatty acid profile, visual evoked potentials, growth up to 4 months

Innis 1996

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA before 1996

Term gestation infants formula fed to 16 weeks of age

3 formulas contained soy and coconut oil and were relatively low in 18:1, but high in 18:2n‐6 and 18:3n‐3 (high 18:2n‐6 formulas)

Intervention 1 (n = 16 + losses): high LA 34.2% + DHA 0%

Intervention 2 (n = 18 + losses): high LA 32.2% + DHA 0.10%

Intervention 3 (n = 17 + losses): high LA 31.9% + DHA 0.22%

3 formulas contained high‐oleic safflower, soy and coconut oil, and were high in 18:1 lower in 18:2n‐6 and 18:3n‐3 (low 18:2n‐6 formulas)

Intervention 4 (n = 21 + losses): low LA 20.5% + DHA 0%

Intervention 5 (n = 17 + losses): low LA 20.0% + DHA 0.11%

Intervention 6 (n = 16 + losses): low LA 20.4% + DHA 0.24%

Outcome: plasma and erythrocyte phospholipid fatty acids and growth

Innis 2002

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 2002

Very low birth weight (846 to 1560 g) infants fed formula until discharge

Intervention 1 (n = 66): DHA 0.34% supplemented formula (intermediate‐high PUFA intake)

Intervention 2 (n = 66): AA 0.60% + DHA 0.33% supplemented formula (intermediate‐high PUFA intake)

Control (n = 62): standard formula (intermediate‐high PUFA intake)

Outcome: fatty acid profile, visual acuity, growth up to 4 months

Jensen 1996

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 1996

Healthy term infants whose mothers had elected not to breastfeed supplemented until 4 months (formula fed)

Intervention 1 (n = 20): α‐LA 3.24% supplemented formulas (intermediate to intermediate‐high PUFA intake)

Intervention 2 (n = 20): α‐LA 1.7% supplemented formulas (intermediate to intermediate‐high PUFA intake)

Intervention 3 (n = 20): α‐LA 0.95% supplemented formulas (intermediate to intermediate‐high PUFA intake)

Control (n = 20): low α‐LA 0.4% formula (low‐intermediate PUFA intake)

Outcome: fatty acid profile, visual evoked potentials, growth up to 4 months, neurodevelopment at 12 months

Jensen 2000

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 2000

Breastfeeding mothers of term neonates supplemented from 2 to 8 weeks' postpartum

Intervention 1 (n = 7): algae‐produced triacylglycerol with a high DHA content supplement (intermediate to intermediate‐high PUFA intake)

Intervention 2 (n = 7): eggs 2/day with a high DHA content supplement (intermediate to intermediate‐high PUFA intake)

Intervention 3 (n = 6): low‐EPA, high‐DHA fish oil supplement (intermediate to intermediate‐high PUFA intake)

Control (n = 7): regular eggs 2/day with no DHA supplement (intermediate PUFA intake)

Outcome: fatty acid profile at 8 weeks

Kaempf‐Rotzoll 2003

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Germany before 2003

Preterm neonates 28 to 32 weeks' gestation supplemented from birth until 6 weeks (formula fed)

Intervention (n = 9 + losses): LCPUFA‐enriched formula + vitamin E supplementation (LA 14.8%, AA 0.37%, α‐LA 0.9%, DHA 0.2%) (intermediate PUFA intake)

Control (n = 11 + losses): standard formula + vitamin E supplementation (LA 15.5%, AA 0%, α‐LA 0.85%, DHA 0%) (intermediate PUFA intake)

Outcome: fatty acid profile, growth and neurodevelopment to 24 months

Kohn 1994

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Belgium before 1994

Healthy, term infants with gestational age of 38.5 to 41.5 weeks and a birth weight 2800 to 4000 g supplemented until 3 months (formula fed)

Intervention: α‐LA 0.28% + AA 0.25% + DHA 0.18% supplemented formula (intermediate PUFA intake)

Control: standard formula (no α‐LA + AA 0.02% + no DHA) (low‐intermediate PUFA intake)

Outcome: fatty acid profile, growth up to 3 months

Koletzko 1989

Excluded as supplementation period < 1 month

Single centre randomised controlled trial in Germany

Participants: premature infants with a birth weight of ≥ 1300 g. Infants fed from day 4 to 21 of life

Intervention (n = 8): AA 0.2% and DHA 0.1% (intermediate PUFA intake)

Control (n = 10): adapted formula (no AA or DHA) (low PUFA intake)

Outcome: composition of plasma lipids

Did not report allergy

Koletzko 1995

Excluded as supplementation period < 1 month, allergy not prespecified or reported

Single centre randomised controlled trial in Germany

Participants: premature infants with a birth weight of ≥ 1300 g. Infants fed from day 4 to 21 of life

Intervention (n = 9): α‐LA (n‐6: 0.2%; n‐3 0.8%) + EPA 0.03% + AA 0.5% + DHA 0.3% from egg and evening primrose oil (intermediate PUFA intake)

Control (n = 10): adapted formula (AA 0.05%; α‐LA (n‐6: 0%; n‐3: 0.4%); no EPA or DHA) (low PUFA intake)

Outcome: composition of plasma lipids

Did not report allergy

Koletzko 2003

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Germany before 2003

Preterm neonates born < 1800 g supplemented for 4 weeks (formula fed)

Intervention (n = 15): LCPUFA supplemented formula with LA 0.5% + α‐LA 0.8% + AA 0.4% + DHA 0.57% (intermediate PUFA intake)

Control (n = 15): standard formula AA 0.04% + no DHA (intermediate PUFA intake)

Outcome: fatty acid profile, growth up to 4 weeks

Lapillonne 2000a

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in France before 2000

Term infants appropriate for gestational age and born with a birth weight > 280 g supplemented until 4 months (formula fed)

Infants who had a history of maternal cocaine or alcohol abuse, or born to mothers with a history of diabetes, hyperlipidaemia, abnormal dietary patterns (strict vegetarian or vegan diets) were ineligible for participation

Intervention (n = 12): LCPUFA supplemented formula (LA 17.62%, AA 0.03%, α‐LA 1.07%, DHA 0.31%, EPA 0.08%) (intermediate PUFA intake)

Control (n = 12): standard formula (LA 17.35%, α‐LA 1.59%) (intermediate PUFA intake)

Outcome: fatty acid profile, growth up to 4 months

Lapillonne 2000b

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in France before 2000

Preterm infants appropriate for gestational age 700 to 1500 g supplemented until 4 months' corrected age (formula fed)

Exclusion criteria included major neonatal morbidity; postnatal age > 21 days, requirement for supplemental oxygen or treatments (e.g. diuretics and corticosteroids) that could influence growth and development; failure to achieve full enteral feeding of 150 mL/kg/day by a postnatal age of 21 days; and maternal history of cocaine/alcohol abuse, diabetes, hyperlipidaemia or abnormal dietary patterns (strict vegetarian diets)

Intervention (n = 11): LCPUFA supplemented formula (LA 17.78%, AA 0.02%, α‐LA 1.1%, DHA 0.37%, EPA 0.05%) (intermediate PUFA intake)

Control (n = 12): standard formula (LA 17.95%, α‐LA 1.6%) (intermediate PUFA intake)

Outcome: fatty acid profile, growth up to 6 months' corrected age

Leite 2013

Excluded as supplementation period < 1 month and PUFA content comparable between treatment and control groups

Single centre randomised controlled crossover trial in Brazil

Participants: 33 term infants aged 84 to 156 ± 3 days fed 1 of 2 formulas with crossover after 14 days (formula fed)

Intervention 1: standard term formula containing palm oils (intermediate PUFA intake)

Intervention 2: standard term formula not containing palm oils (intermediate PUFA intake)

Outcomes: metabolic parameters, growth, tolerance up to 36 days

Did not report allergy

Liu 1987

Excluded as supplementation period < 1 month, allergy not prespecified or reported

Single centre randomised controlled trial in USA

Participants: 17 Infants < 1500 g at birth (range 560 to 1440 g) randomly allocated to formulas for 2 weeks

Intervention: similac Special Care with 100 or 250 μL MaxEPA (DHA 0.2% or 0.5%) per 4‐ounce bottle (intermediate PUFA intake)

Control: similac Special Care with soybean oil 250 μL (no DHA) (low PUFA intake)

Outcome: plasma phospholipid AA and DHA

Did not report allergy

Llorente 2003

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA before 2003

Pregnant women who planned to breastfeed their infants exclusively for at least 4 months

Breastfeeding women (n = 138) allocated within 1 week of delivery for 4 months

Intervention (n = 51 reported): algae‐derived triglyceride capsule 200 mg DHA/day

Control (n = 50 reported): placebo capsule

Infant outcomes not reported

Lopez‐Alarcon 2006

Excluded as supplementation period < 1 month, allergy not prespecified or reported

Single centre randomised controlled trial in Mexico

Participants: 27 preterm and term infants with sepsis after a surgical procedure given DHA or placebo for 2 weeks

Intervention: DHA supplement 100 mg (intermediate PUFA intake)

Control: olive oil 100 mg (intermediate PUFA intake)

Outcomes: fatty acid profile, growth, illness severity after 2 weeks

Did not report allergy

Lucia Bergmann 2007

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Germany October 2000 to August 2002

Pregnant women supplemented until 3 months' postpartum (n = 144) (numbers per group not specified)

Exclusion criteria for prospective mothers were increased risk of premature delivery or multiple pregnancy, allergy to cow's milk protein, lactose intolerance, diabetes, smoking, consumption of alcohol (> 20 g/week), or participation in another study. Infants were excluded from the study if they were premature at birth (< 37 weeks’ gestation), had any major malformations or were hospitalised for more than 1 week

Intervention: DHA supplement 200 mg/day + prebiotic (intermediate PUFA intake)

Control: no DHA supplement (intermediate PUFA intake) (2 control groups, prebiotic in 1 group)

Outcome: growth up to 21 months

Makrides 1995

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Australia before 1995

Women giving birth to healthy infants of 37 to 42 weeks' gestation, supplemented until 30 weeks age (formula fed). Participants (n = 89) (numbers per group not specified, includes breast milk fed controls)

Intervention: LCPUFA supplemented formula using fish and evening primrose oil (γ‐LA 0.27% + AA 0.01% + EPA 0.58% + DHA 0.36%) (intermediate‐high PUFA intake)

Control: standard formula (γ‐LA 0.05% + no AA or EPA or DHA) (intermediate PUFA intake)

Outcome: fatty acid profile, visual evoked potentials, growth up to 30 weeks

Makrides 1999

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Australia December 1993 and November 1994

Healthy, white, term infants supplemented until 12 months (formula fed)

Intervention 1 (n = 27): DHA 0.35% supplemented formula from tuna oil (intermediate PUFA intake)

Intervention 2 (n = 28): AA 0.34% + DHA 0.34% supplemented formula from egg phospholipid (intermediate PUFA intake)

Control (n = 28): standard formula (intermediate PUFA intake)

Outcome: fatty acid profile, growth up to 2 years

Makrides 2000

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Australia November 1994 and June 1995

Healthy, white, term infants supplemented from birth to 34 weeks (formula fed)

Intervention: LA:α‐LA 16.6%:3.3% (5:1) (total n‐6 = 16.9%; total n‐3 = 3.3%)

Control: LA:α‐LA of 16.9%:1.7% (10:1) (total n‐6 = 17.0%; total n‐3 = 1.7%)

Outcome: fatty acid profiles, growth and visual evoked potential acuity

Martinez 2002

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Brazil before 2002

Preterm very‐low‐birth‐weight infants on full enteral feeding for 2 days, gestational age 28 to 34 weeks; birth weight 900 to 1500 g supplemented for 30 days (formula fed)

Intervention (n = 20): egg lipid extracts 0.9 g/100 kcal = 0.63% and evening primrose oil supplemented formula (α‐LA 0.2% + EPA 0.03% + AA 0.5% + DHA 0.3%; n‐3 0.8%) (intermediate PUFA intake)

Control (n = 20): standard formula (AA 0.05%; no α‐LA or EPA or DHA; n‐3 = 0.4%) (intermediate PUFA intake)

Outcome: fatty acid profile, growth at 30 days

Maurage 1998

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in France before 1998

Term neonates supplemented for 6 weeks (formula fed). Participants (n = 98) (numbers per group not specified, includes breast milk fed controls)

Intervention 1 (high EPA): fish oil supplemented formulas (no AA; EPA 0.35% + DHA 0.45%) (intermediate PUFA intake)

Intervention 2 (low EPA): fish oil supplemented formulas (no AA; EPA 0.10% + DHA 0.45%) (intermediate PUFA intake)

Control: standard formula (no AA; EPA 0.10% + DHA 0.45%) (intermediate PUFA intake)

Outcome: fatty acid profile at 6 weeks

Mize 1995

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA before 1995

Full term newborn infants appropriate for gestational age with gestational age 37 to 41 weeks supplemented until 12 months (formula fed)

Intervention (n = 22): LCPUFA supplemented formula (PUFA 16.3%) (high PUFA intake)

Control (n = 20): high monounsaturated fatty acid formula (PUFA 7.1%) (intermediate PUFA intake)

Outcome: fatty acid profile, growth up to 12 months

Moltu 2013

Excluded as used co‐interventions that differed between treatment and control groups, allergy not prespecified or reported

Multicentre randomised controlled trial in Norway

Participants: very‐low‐birth‐weight infants within 24 hours after birth

Intervention group (n = 24): received significantly higher amounts of energy, protein, lipids, vitamin A, AA and DHA in parenteral and enteral nutrition (intermediate‐high PUFA intake)

Control group (n = 26): lower amounts of energy, protein, lipids, vitamin A, AA and DHA in parenteral and enteral nutrition (intermediate PUFA intake)

Outcomes: postnatal growth and clinical outcome during neonatal hospitalisation, urinary metabolite profiles

Did not report allergy

Morgan 1998a

Excluded as supplementation period < 1 month, allergy not prespecified or reported

Single centre randomised controlled trial in UK

Participants: 20 preterm infants < 32 weeks, birth weight 1000 to 1500 g randomly allocated to formulas for 6 days (formula fed)

Intervention (n = 10): preterm formula with LCPUFA supplement (intermediate‐high PUFA intake)

Control (n = 10): preterm formula without LCPUFA supplement (intermediate PUFA intake)

Outcome: fatty acid profile, fat excretion at 6 days

Did not report allergy

Morgan 1998b

Excluded as supplementation period < 1 month, allergy not prespecified or reported

Single centre randomised controlled trial in UK

Participants: 20 term infants 37 to 42 weeks, birth weight 2500 to 4500 g randomly allocated to formulas for 6 days (formula fed)

Intervention (n = 10): term formula with LCPUFA supplement (intermediate‐high PUFA intake)

Control (n = 10): term formula without LCPUFA supplement (intermediate PUFA intake)

Outcome: fatty acid profile, fat excretion at 6 days

Did not report allergy

Moya 2001

Excluded as supplementation period < 1 month, allergy not prespecified or reported

Single centre randomised controlled trial in Spain

Participants: 31 preterm infants (mean gestation 34 weeks) fed 1 of 3 formulas for 20 days

Control (n = 9): preterm formula with no LCPUFA (intermediate PUFA intake)

Intervention 2 + 3 (n = 21): preterm formula with LCPUFA (intermediate PUFA intake)

Outcome: metabolic parameters, tolerance up to 20 days

Did not report allergy

Ponder 1992

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 1992

Full‐term 37 to 42 weeks' gestation with weight, length and head circumference 5th to 95th percentile supplemented until 8 weeks (formula fed)

Intervention (n = 11: losses not reported): soy oil based formula (60% soy oil and 40% coconut oil: LA 34.2%; α‐LA 4.8%) (high PUFA intake)

Control (n = 14: losses not reported): corn oil based formula (50% corn oil and 50% coconut oil: LA 31.4%; α‐LA 0.8%) (intermediate PUFA intake)

Outcome: fatty acid profile, growth, development up to 8 weeks

Ramirez 2001

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Brazil before 2001

Preterm neonates supplemented for 30 days (formula fed)

Intervention (n = 17): LCPUFA supplemented formula (EA 0.18% + AA 0.34% + adrenic acid 0.16% + DHA 0.23%) (intermediate PUFA intake)

Control (n = 17): standard formula (no EA or AA or Adrenic acid or DHA) (intermediate PUFA intake)

Outcome: fatty acid profile, growth at 30 days. Tolerance recorded

Rodriguez 2003

Excluded as supplementation period < 1 month

Single centre randomised controlled trial in Hungary

Participants: preterm infants (gestational age < 37 weeks), birth weight 1000 to 2000 g, weight appropriate for gestational age, exclusive formula feeding with a minimal daily ingestion of 100 mL/kg

Randomised to formula for 7 days

Intervention: 40% medium‐chain triglycerides (total n‐6 PUFA 11.98%; n‐3 PUFA 1.13%) (intermediate PUFA intake)

Control: minimal medium chain fatty acids (total n‐6 PUFA 13.28%; n‐3 PUFA 1.03%) (intermediate PUFA intake)

Outcome: fatty acid metabolism

Did not report allergy

Ryan 1999

Excluded as allergy not prespecified or reported

2 centre randomised controlled trial in USA May 1993 and September 1994

Healthy low‐birth‐weight infants 940 to 2250 g beginning at 7 to 10 days prior to hospital discharge to 59 weeks' postmenstrual age

Intervention (n = 46): DHA 0.2% from fish oil (EPA 0.04% + AA 0.1% + DHA 0.2%)

Control (n = 44): control formula (no EPA or AA or DHA)

Outcome: growth and body composition to 59 weeks' postmenstrual age. Sudden infant death syndrome

Sauerwald 2012

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Germany before 2012

Preterm neonates birth weight 1000 to 2200 g exclusively (80% of total energy intake) fed formula or human milk supplemented for 28 days

Intervention 1 (n = 13): DHA supplemented formula (DHA 0.33%) (intermediate to intermediate‐high PUFA intake; total PUFA = 18.42%; total n‐6 LC‐PUFA = 0.16%; total n‐3 LC‐PUFA = 0.41%).

Intervention 2 (n = 15): DHA supplemented formula (DHA 0.52%) (intermediate to intermediate‐high PUFA intake; total PUFA = 19.01%; total n‐6 LC‐PUFA = 0.20%; total n‐3 LC‐PUFA = 0.65%).

Control (n = 14): low DHA formula (DHA 0.04%) (intermediate PUFA intake; total PUFA = 18.21%; total n‐6 LC‐PUFA = 0.12%; total n‐3 LC‐PUFA = 0.05%)

Outcome: fatty acid profile, growth up to 28 days

Schwartz 2009

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Germany September 2005 and July 2006

Healthy term newborn infants (gestational age > 37 weeks, birth weight > 2500 g); German speaking mother; intention to breastfeed

Randomly allocated to complementary food (commercial vegetable‐potato‐meat meals in jars) from 4 to 6 months of age until 10 months

Intervention (n = 66): rapeseed oil complementary feeds (LA 20%; α‐LA 9%; LA/α‐LA = 2.2) (intermediate PUFA intake)

Control (n = 66): corn oil complementary feeds (LA 55%; α‐LA 1%; LA/α‐LA = 55) (intermediate PUFA intake)

Outcome: fatty acid profile at 10 months

Siahanidou 2007

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Greece before 2007

Preterm neonates (n = 140) gestational age ≥ 28 weeks, birth weight ≥ 1000 g, no family history of hyper‐ or hypolipidaemias, no congenital malformation and mothers who elected formula feeding supplemented for 1 month

Intervention (n = 50 excluding losses): LCPUFA supplemented formula (AA 12.0 mg/100 mL and DHA 7.1 mg/100 mL) (unclear PUFA intake)

Control (n = 54 excluding losses): unsupplemented formula (no AA or DHA) (unclear PUFA intake)

Outcome: lipid peroxidation in serum after 1 month; adiponectin levels; visfatin levels; neonatal morbidity to discharge

Smit 2000a

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Pakistan before 2000

Malnourished infants (8 to 30 months) supplemented for 9 weeks (mixed feeding)

Intervention (n = 10): fish oil supplement (AA 10 mg/day; EPA 190 mg/day; DHA 112 mg/day) (intermediate‐high PUFA intake)

Control (n = 7): no fish oil supplement (low‐intermediate PUFA intake)

Outcome: fatty acid profile, growth after 9 weeks

Smit 2000b

Excluded as supplementation period < 1 month, allergy not prespecified or reported

Single centre randomised controlled trial in Netherlands

Participants: 29 mothers who were breastfeeding 3 to 10 months supplemented for 7 days

Intervention 1 (n = 10): AA oil 0.8 mL (intermediate PUFA intake)

Intervention 2 (n = 9): AA oil 0.8 mL + DHA oil 1.7 mL (intermediate‐high PUFA intake)

Control (n = 10): unsupplemented (intermediate PUFA intake)

Outcome: breast milk fatty acid composition

Did not report allergy

Socha 2002

Excluded as infants with cholestasis, allergy not prespecified or reported

Single centre randomised controlled trial in Poland

Participants: infants with cholestasis (2 to 5 months) supplemented for 1 month (formula fed)

Intervention (n = 11): LCPUFA supplemented formula (intermediate PUFA intake)

Control (n = 12): standard formula (low‐intermediate PUFA intake)

Outcome: fatty acid profile, growth after 1 month

Did not report allergy

Stier 1997

Excluded as supplementation period < 1 month, allergy not prespecified or reported

Single centre randomised controlled trial in Germany

Participants: 20 preterm infants < 32 weeks, birth weight < 2000 g randomly allocated to formulas for 3 weeks

Intervention (n = 10): preterm formula with LCPUFA supplement (intermediate PUFA intake)

Control (n = 10): preterm formula without LCPUFA supplement (intermediate PUFA intake)

Outcome: urine prostanoids, growth up to 3 weeks

Did not report allergy

Uauy 1990

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA before 1990

Preterm neonates birth weight 1000 to 1500 g; appropriate for gestational age, enteral feedings 70 to 120 kcal/kg and free of major neonatal morbidity by day 10. Supplemented until 36 weeks' corrected gestational age (formula fed)

Control (n = 10): formula medium‐chain triglyceride/coconut/corn oil blend (predominant n‐6 PUFA: oleic acid 11.8%; LA 24.2%; α‐LA 0.5%; n‐6 > C18 none; n‐3 > C18 none) (low‐intermediate PUFA intake)

Intervention 1 (n = 10): formula medium‐chain triglyceride/coconut/soy blend (high n‐3 PUFA: oleic acid 10.3%; LA 20.8%; α‐LA 2.7; n‐6 > C18 none; n‐3 > C18 none) (intermediate‐high PUFA intake)

Intervention 2 (n = 12): formula medium‐chain triglyceride/ coconut/ soy/marine oil blend (high n‐3 PUFA: oleic acid 10.7%; LA 20.4%; α‐LA 1.4; n‐6 > C18 0.1%; n‐3 > C18 1.0%) (intermediate‐high PUFA intake)

Outcome: fatty acid profile, visual evoked potentials, growth at 36 weeks' corrected gestational age. Growth, clinical tolerance, coagulation test results, changes in erythrocyte membrane fluidity and plasma concentrations of vitamins A and E from 30 to 57 weeks' postmenstrual age

Unay 2004

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Turkey November 2000 and September 2001

Healthy, full term newborns appropriate size for gestational age who were not going to be breastfed supplemented until 16 weeks (formula fed)

Intervention (n = 28): DHA supplemented formula (oleic acid 50.8%; LA 9.7%; α‐LA 1.2% DHA 0.5%) (intermediate PUFA intake)

Control (n = 26): unsupplemented formula (oleic acid 44.9%; LA 11.2%; α‐LA 2.2%: no DHA) (intermediate PUFA intake)

Outcome: auditory evoked potentials at 16 weeks

Van Biervliet 1986

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Belgium before 1986

Healthy full‐term infants fed formula for 30 days

Control (n = 10): 80% derived from milk‐fat, 20% from corn oil (C16:1 3.6%; C18:1 32.4%; C18:2 12.8%; C18:3 1.0%; C20:4 0.8%)

Intervention (n = 10): vegetable origin (73% palm olein, 20% coconut oil, 7% corn oil) (C16:1 0.2%; C18:1 37.5%; C18:2 15.1%; C18:3 0.3%; C20:4 0.3%)

Outcome: plasma lipoprotein composition

Van Biervliet 1992

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Belgium before 1992

Healthy term newborn infants supplemented until 30 days (formula fed)

Intervention (n = 10): α‐LA supplemented formula (C18:2n‐6 14.8%; C18:3n‐6 0.7%; C20:2n‐6 0.1%; C18:3n‐3 0.6%; cholesterol 4.0%) (low‐intermediate PUFA intake)

Control (n = 10): unsupplemented formula (C18:2n‐6 13.4%; C18:3n‐3 0.1%; cholesterol 10.0%) (low‐intermediate PUFA intake)

Outcome: fatty acid profile at 30 days

van der Merwe 2013

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Gambia May 2007 to October 2008

172 rural Gambian infants aged 3 to 9 months (mixed feeding)

Intervention (n = 92): fish oil supplement (EPA 300 mg/day + DHA 200 mg/day) (intermediate‐high PUFA intake)

Control (n = 91): olive oil supplement (intermediate PUFA intake)

Outcome: gut integrity, morbidity, growth, development up to 12 months

van Goor 2009

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in Netherlands December 2004 to December 2006

Women supplemented from enrolment 12 to 20th weeks' pregnancy until 12 weeks' postpartum

Intervention 1 (n = 63): DHA 220 mg supplement + 1 capsule soy bean oil (intermediate‐high PUFA intake)

Intervention 2 (n = 58): AA 220 mg + DHA 220 mg supplement (intermediate‐high PUFA intake)

Control (n = 62): placebo 2 capsules soy bean oil (intermediate PUFA intake)

Outcome: human milk AA + DHA content; general movements assessment at 12 weeks; neurodevelopment at 18 months; depressive symptoms

van Wezel‐Meijler 2002

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Netherlands September 1993 and January 1996

Preterm neonates < 34 weeks' gestation, birth weight < 1750 g and normal neurological examination throughout the neonatal period. Supplemented until 6 months' corrected age (formula fed)

Intervention (n = 28): AA 0.70% + DHA 0.34% supplemented formula (unclear PUFA intake)

Control (n = 27): standard formula (low‐intermediate PUFA intake)

Outcome: magnetic resonance imaging, visual acuity and development up to 2 years' corrected age

Vanderhoof 1999

Excluded as allergy not prespecified or reported

Multicentre randomised controlled trial in USA before 1999

Preterm neonates medically stable, < 28 days old, had received enteral feedings for < 24 hours, birth weight 750 to 2000 g and appropriate for gestational age. Supplemented until 8 weeks' corrected age (formula fed)

Intervention (n = 77): LCPUFA supplemented formula (AA 0.50% + DHA 0.35%) (unclear PUFA intake)

Control (n = 78): standard formula (no AA or DHA) (unclear PUFA intake)

Outcome: fatty acid profile, growth up to 8 weeks' corrected age

Weizman 1998

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in Israel before 1998

Term neonates supplemented for 30 days (formula fed)

Intervention (n = 25): PUFA supplemented formula (LA 24.2%, α‐LA 0.25%) (unclear PUFA intake)

Control (n = 25): standard formula (unclear PUFA intake)

Outcome: growth, development up to 3 months. Reported safety and efficacy

Written in Hebrew; English abstract

Yang 2013

Excluded as allergy not prespecified or reported

Single centre randomised controlled trial in USA before 2013

Preterm neonates with enterostomies supplemented postoperatively until reanastomosis (2 to 10 weeks) (mixed feeding)

Intervention (n = 18): fish oil supplement (infants < 1000 g: 0.2 g every 12 hours; infants > 1000 g: 0.25 g every 12 hours; maximum 0.5 g every 6 hours) (DHA dose range 50 to < 315 mg/day) (high PUFA intake)

Control (n = 78): no fish oil supplement (intermediate PUFA intake)

Outcome: fat absorption, growth until reanastomosis

AA: arachidonic acid; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; IU: international unit; LA: linoleic acid; LCPUFA: long chain polyunsaturated fatty acid; PUFA: polyunsaturated fatty acid.

Characteristics of ongoing studies [ordered by study ID]

Caplan 2013

Trial name or title

PUFA Supplementation in Premature Infants

Methods

Multicentre, randomised, placebo controlled, double blind trial

Participants

Inclusion criteria: premature infant born at gestational age < 34 weeks; birth weight < 1000 g; legally authorised representative is able to provide written informed consent within the first 72 hours of life, prior to the performance of a protocol‐specified evaluations or procedures

Exclusion criteria: infants with known metabolic disorder or known congenital gastrointestinal anomaly. Infants who are deemed to be inappropriate for enrolment per attending neonatologist

Interventions

2 doses of PUFA will be compared to placebo ‐ a "high" dose and a "low" dose

Outcomes

LCPUFA levels measured at 2 and 8 weeks of life

Resolvin, a metabolite of LCPUFA, measured at 2 and 8 weeks of life

Starting date

Contact information

Notes

ClinicalTrials.gov Identifier: NCT01955044

Collins 2012

Trial name or title

Can Omega 3 Fatty Acids Improve Respiratory Outcomes in Preterm Infants?

Methods

Randomised controlled trial

Participants

Inclusion criteria: born at < 29 weeks' gestational age; within 3 days of commencing enteral feeds; has a legally acceptable representative capable of understanding the informed consent document and providing consent on the infant's behalf

Exclusion criteria: infants who have a major congenital or chromosomal abnormality; women providing breast milk who are taking supplements providing DHA > 250 mg/day and do not wish to stop taking supplements; infants participating in another fatty acid study; infants receiving intravenous lipid emulsions containing fish oil given as early lipid parenteral nutrition support

Interventions

Intervention: tuna oil emulsion containing DHA 120 mg/mL to provide DHA 60 mg/kg/day (0.17 mL/kg 3 times a day). Intervention given enterally within 72 hours of the first enteral feed and continued until 36 weeks' postmenstrual age or discharge home (whichever occurs first)

Control: soy oil emulsion with no additional DHA given at 0.17 mL/kg 3 times a day. Control given enterally within 72 hours of the first enteral feed and continued until 36 weeks' postmenstrual age or discharge home (whichever occurs first)

Outcomes

Bronchopulmonary dysplasia at 36 weeks' postmenstrual age; safety and tolerability; length of hospital stay; growth rate; grade of intraventricular haemorrhage; confirmed sepsis; confirmed necrotising enterocolitis; grade of retinopathy of prematurity and death

Attention (ability to resist distraction) to 2 years' corrected age

Starting date

2012

Contact information

Notes

ACTRN12612000503820

Gianni 2012

Trial name or title

The Influence of a Formula Supplemented with Dairy Lipids and Plant Oils on the Erythrocyte Membrane Omega‐3 Fatty Acid Profile in Healthy Full‐Term Infants

Methods

Double‐blind controlled randomised trial

Participants

75 healthy full‐term infants

Inclusion criteria: gestational age 37 to 42 weeks, birth weight > 2500 g, healthy newborns from normal pregnancy, aged up to 3 weeks when entering the study

Exclusion criteria: newborns whose parents have planned to move within 6 months after birth, newborns with a positive family history of allergy to milk proteins, newborns with known congenital or postnatal diseases which could interfere with the study

Interventions

4 months of formula feeding

Control: formula supplemented with a mixture of dairy lipids and plant oils or a formula containing only plant oils

Intervention: formula containing plant oils supplemented with arachidonic acid and DHA

Outcomes

Erythrocyte membrane omega‐3 fatty acid profile, LCPUFAs and the other fatty acids content, plasma lipid profile and insulin‐growth factor 1 level measured after 4 months

Gastrointestinal tolerance, the changes in blood fatty acids content, in growth and body composition

Adverse events and serious adverse events

Starting date

2012

Contact information

Notes

ClinicalTrials.gov Identifier NCT01611649

Liu 2013

Trial name or title

The Effects of Polyunsaturated Fatty Acids (PUFA) on Allergic/Atopic Dermatitis

Methods

Randomised double blind controlled trial

Participants

Inclusion criteria: woman pregnant between 16 and 20 weeks, mother delivers after 36 weeks, mother is willing to breastfeed for 4 months, mother has potential to deliver a child with increased risk of atopic dermatitis, signed informed consent

Exclusion criteria: mother is smoking, disease with influence on breastfeeding, complicated pregnancy, allergic to seafood, allergic to soy, allergic to marine fish, mother has > 2 salmon or tuna meals per week, mother is undergoing treatment with anticoagulants

Interventions

PUFA supplementation during pregnancy and lactation period

Outcomes

Fatty acid composition in human milk and plasma of the mothers and the clinical outcome of atopic dermatitis in infants at increased risk

Starting date

April 2015 (postponed)

Contact information

Notes

ClinicalTrials.gov Identifier: NCT01936194

Millett 2010

Trial name or title

Effect of Docosahexaenoic Acid (DHA)‐Enriched Human Milk in Premature Newborns (DHARMA)

Methods

Randomised double blind controlled trial

Participants

Inclusion criteria: childbirth between 34 and 35 weeks' gestational age, breastfeeding, Caucasian, affiliation to social security, obtained consent from mother and parents for the child, mother with balanced diet, no allergy to eggs, single pregnancy

Exclusion criteria: allergy to egg, unbalanced diet, diabetes, known digestive disease, contraindication with breastfeeding, smoker (> 5 cigarettes/day), alcoholism (daily consumption of alcohol), multiple pregnancy

Interventions

Lactating mothers and their newborn with mothers

Supplemented with DHA

Glycerophospholipid enriched in docosahexaenoic acid

No supplementation

Outcomes

PUFA status and infant survey at 6 months

Starting date

February 2010

Contact information

Notes

This study has been terminated (difficulties of recruitment)

DHA: docosahexaenoic acid; LCPUFA: long chain polyunsaturated fatty acid; PUFA: polyunsaturated fatty acid.

Data and analyses

Open in table viewer
Comparison 1. Higher versus lower PUFA intake

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.1

Comparison 1 Higher versus lower PUFA intake, Outcome 1 All allergic disease.

Comparison 1 Higher versus lower PUFA intake, Outcome 1 All allergic disease.

1.1 Infant incidence

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

1.2 Childhood incidence

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.47, 1.02]

1.3 Childhood prevalence

2

633

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.81, 1.19]

2 Asthma Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.2

Comparison 1 Higher versus lower PUFA intake, Outcome 2 Asthma.

Comparison 1 Higher versus lower PUFA intake, Outcome 2 Asthma.

2.1 Infant incidence

3

1162

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.80, 1.35]

2.2 Childhood incidence

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

2.3 Childhood prevalence

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.82, 1.53]

3 Dermatitis/eczema Show forest plot

9

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.3

Comparison 1 Higher versus lower PUFA intake, Outcome 3 Dermatitis/eczema.

Comparison 1 Higher versus lower PUFA intake, Outcome 3 Dermatitis/eczema.

3.1 Infant incidence

7

1906

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.82, 1.06]

3.2 Childhood incidence

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.34, 1.24]

3.3 Childhood prevalence

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.59, 1.09]

4 Allergic rhinitis Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.4

Comparison 1 Higher versus lower PUFA intake, Outcome 4 Allergic rhinitis.

Comparison 1 Higher versus lower PUFA intake, Outcome 4 Allergic rhinitis.

4.1 Infant incidence

2

594

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.23, 0.96]

4.2 Childhood prevalence

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.25]

5 Food allergy Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.5

Comparison 1 Higher versus lower PUFA intake, Outcome 5 Food allergy.

Comparison 1 Higher versus lower PUFA intake, Outcome 5 Food allergy.

5.1 Infant incidence

3

915

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.56, 1.19]

5.2 Childhood incidence

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

5.3 Childhood prevalence

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Open in table viewer
Comparison 2. Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease ‐ infant incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.1

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 1 All allergic disease ‐ infant incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 1 All allergic disease ‐ infant incidence.

1.1 Infant supplementation

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

2 All allergic disease ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.2

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 2 All allergic disease ‐ childhood incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 2 All allergic disease ‐ childhood incidence.

2.1 Infant supplementation

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.34, 0.92]

2.2 Maternal supplementation

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.51, 1.91]

3 All allergic disease ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.3

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 3 All allergic disease ‐ childhood prevalence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 3 All allergic disease ‐ childhood prevalence.

3.1 Infant supplementation

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.83, 1.25]

3.2 Maternal supplementation

1

117

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.44, 1.38]

4 Asthma ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.4

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 4 Asthma ‐ infant incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 4 Asthma ‐ infant incidence.

4.1 Infant supplementation

1

554

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.78, 1.81]

4.2 Maternal supplementation

2

608

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.69, 1.33]

5 Asthma ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.5

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 5 Asthma ‐ childhood incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 5 Asthma ‐ childhood incidence.

5.1 Infant supplementation

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

6 Asthma ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.6

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 6 Asthma ‐ childhood prevalence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 6 Asthma ‐ childhood prevalence.

6.1 Infant supplementation

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.82, 1.57]

6.2 Maternal supplementation

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.41, 2.72]

7 Dermatitis/eczema ‐ infant incidence Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.7

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 7 Dermatitis/eczema ‐ infant incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 7 Dermatitis/eczema ‐ infant incidence.

7.1 Infant supplementation

5

1245

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.82, 1.11]

7.2 Maternal supplementation

3

661

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.68, 1.15]

8 Dermatitis/eczema ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.8

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

8.1 Infant supplementation

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.25, 1.20]

8.2 Maternal supplementation

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.28, 3.20]

9 Dermatitis/eczema ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.9

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

9.1 Infant supplementation

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.62, 1.18]

9.2 Maternal supplementation

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.23, 1.36]

10 Allergic rhinitis ‐ infant incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.10

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 10 Allergic rhinitis ‐ infant incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 10 Allergic rhinitis ‐ infant incidence.

10.1 Maternal supplementation

2

594

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.23, 0.96]

11 Allergic rhinitis ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.11

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

11.1 Infant supplementation

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.83, 1.25]

11.2 Maternal supplementation

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.18, 8.26]

12 Food allergy ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.12

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 12 Food allergy ‐ infant incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 12 Food allergy ‐ infant incidence.

12.1 Infant supplementation

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.47, 1.42]

12.2 Maternal supplementation

2

592

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.48, 1.37]

13 Food allergy ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.13

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 13 Food allergy ‐ childhood incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 13 Food allergy ‐ childhood incidence.

13.1 Maternal supplementation

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

14 Food allergy ‐ childhood prevalence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.14

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 14 Food allergy ‐ childhood prevalence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 14 Food allergy ‐ childhood prevalence.

14.1 Maternal supplementation

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Open in table viewer
Comparison 3. Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease ‐ infant incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.1

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 1 All allergic disease ‐ infant incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 1 All allergic disease ‐ infant incidence.

1.1 n‐3 supplementation

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

2 All allergic disease ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.2

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 2 All allergic disease ‐ childhood incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 2 All allergic disease ‐ childhood incidence.

2.1 n‐3 supplementation

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.47, 1.02]

3 All allergic disease ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.3

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 3 All allergic disease ‐ childhood prevalence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 3 All allergic disease ‐ childhood prevalence.

3.1 n‐3 supplementation

2

633

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.81, 1.19]

4 Asthma ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.4

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 4 Asthma ‐ infant incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 4 Asthma ‐ infant incidence.

4.1 n‐3 supplementation

3

1162

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.80, 1.35]

5 Asthma ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.5

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 5 Asthma ‐ childhood incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 5 Asthma ‐ childhood incidence.

5.1 n‐3 supplementation

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

6 Asthma ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.6

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 6 Asthma ‐ childhood prevalence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 6 Asthma ‐ childhood prevalence.

6.1 n‐3 supplementation

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.82, 1.53]

7 Dermatitis/eczema ‐ infant incidence Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.7

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 7 Dermatitis/eczema ‐ infant incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 7 Dermatitis/eczema ‐ infant incidence.

7.1 n‐3 supplementation

5

1657

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.82, 1.09]

7.2 n‐6 supplementation

2

249

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.59, 1.23]

8 Dermatitis/eczema ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.8

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

8.1 n‐3 supplementation

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.34, 1.24]

9 Dermatitis/eczema ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.9

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

9.1 n‐3 supplementation

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.59, 1.09]

10 Allergic rhinitis ‐ infant incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.10

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 10 Allergic rhinitis ‐ infant incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 10 Allergic rhinitis ‐ infant incidence.

10.1 n‐3 supplementation

2

594

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.23, 0.96]

11 Allergic rhinitis ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.11

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

11.1 n‐3 supplementation

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.25]

12 Food allergy ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.12

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 12 Food allergy ‐ infant incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 12 Food allergy ‐ infant incidence.

12.1 n‐3 supplementation

3

915

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.56, 1.19]

13 Food allergy ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.13

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 13 Food allergy ‐ childhood incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 13 Food allergy ‐ childhood incidence.

13.1 n‐3 supplementation

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

14 Food allergy ‐ childhood prevalence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 3.14

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 14 Food allergy ‐ childhood prevalence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 14 Food allergy ‐ childhood prevalence.

14.1 n‐3 supplementation

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Open in table viewer
Comparison 4. Higher versus lower PUFA intake: subgrouped by method of infant feeding

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease ‐ infant incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.1

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 1 All allergic disease ‐ infant incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 1 All allergic disease ‐ infant incidence.

1.1 Human milk fed infants

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

2 All allergic disease ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.2

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 2 All allergic disease ‐ childhood incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 2 All allergic disease ‐ childhood incidence.

2.1 Human milk fed infants

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.51, 1.91]

2.2 Formula fed infants

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.34, 0.92]

3 All allergic disease ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.3

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 3 All allergic disease ‐ childhood prevalence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 3 All allergic disease ‐ childhood prevalence.

3.1 Human milk fed infants

2

633

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.81, 1.19]

4 Asthma ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.4

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 4 Asthma ‐ infant incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 4 Asthma ‐ infant incidence.

5 Asthma ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.5

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 5 Asthma ‐ childhood incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 5 Asthma ‐ childhood incidence.

5.1 Formula fed infants

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

6 Asthma ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.6

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 6 Asthma ‐ childhood prevalence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 6 Asthma ‐ childhood prevalence.

6.1 Human milk fed infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.82, 1.53]

7 Dermatitis/eczema ‐ infant incidence Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.7

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 7 Dermatitis/eczema ‐ infant incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 7 Dermatitis/eczema ‐ infant incidence.

7.1 Human milk fed infants

6

1715

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.82, 1.09]

7.2 Formula fed infants

2

191

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.57, 1.23]

8 Dermatitis/eczema ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.8

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

8.1 Human milk fed infants

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.28, 3.20]

8.2 Formula fed infants

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.25, 1.20]

9 Dermatitis/eczema ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.9

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

9.1 Human milk fed infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.59, 1.09]

10 Allergic rhinitis ‐ infant incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.10

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 10 Allergic rhinitis ‐ infant incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 10 Allergic rhinitis ‐ infant incidence.

10.1 Human milk fed infants

2

594

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.23, 0.96]

11 Allergic rhinitis ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.11

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

11.1 Human milk fed infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.25]

12 Food allergy ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.12

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 12 Food allergy ‐ infant incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 12 Food allergy ‐ infant incidence.

12.1 Human milk fed infants

3

915

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.56, 1.19]

13 Food allergy ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.13

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 13 Food allergy ‐ childhood incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 13 Food allergy ‐ childhood incidence.

13.1 Human milk fed infants

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

14 Food allergy ‐ childhood prevalence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 4.14

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 14 Food allergy ‐ childhood prevalence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 14 Food allergy ‐ childhood prevalence.

14.1 Human milk fed infants

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Open in table viewer
Comparison 5. Higher versus lower PUFA intake: subgrouped by infant heredity for allergy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease ‐ infant incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.1

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 1 All allergic disease ‐ infant incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 1 All allergic disease ‐ infant incidence.

1.1 High risk for allergy

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

2 All allergic disease ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.2

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 2 All allergic disease ‐ childhood incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 2 All allergic disease ‐ childhood incidence.

2.1 Risk for allergy not selected

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.47, 1.02]

3 All allergic disease ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.3

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 3 All allergic disease ‐ childhood prevalence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 3 All allergic disease ‐ childhood prevalence.

3.1 High risk for allergy

2

633

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.81, 1.19]

4 Asthma ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.4

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 4 Asthma ‐ infant incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 4 Asthma ‐ infant incidence.

4.1 High risk for allergy

2

673

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.79, 1.71]

4.2 Risk for allergy not selected

1

489

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.66, 1.34]

5 Asthma ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.5

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 5 Asthma ‐ childhood incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 5 Asthma ‐ childhood incidence.

5.1 Risk for allergy not selected

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

6 Asthma ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.6

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 6 Asthma ‐ childhood prevalence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 6 Asthma ‐ childhood prevalence.

6.1 High risk for allergy

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.82, 1.53]

7 Dermatitis/eczema ‐ infant incidence Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.7

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 7 Dermatitis/eczema ‐ infant incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 7 Dermatitis/eczema ‐ infant incidence.

7.1 High risk for allergy

5

1245

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.81, 1.12]

7.2 Risk for allergy not selected

2

661

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.71, 1.12]

8 Dermatitis/eczema ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.8

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

8.1 Risk for allergy not selected

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.34, 1.24]

9 Dermatitis/eczema ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.9

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

9.1 High risk for allergy

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.59, 1.09]

10 Allergic rhinitis ‐ infant incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.10

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 10 Allergic rhinitis ‐ infant incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 10 Allergic rhinitis ‐ infant incidence.

10.1 High risk for allergy

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.18, 8.26]

10.2 Risk for allergy not selected

1

475

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.18, 0.89]

11 Allergic rhinitis ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.11

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

11.1 High risk for allergy

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.25]

12 Food allergy ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.12

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 12 Food allergy ‐ infant incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 12 Food allergy ‐ infant incidence.

12.1 High risk for allergy

2

442

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.38, 1.02]

12.2 Risk for allergy not selected

1

473

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.67, 2.31]

13 Food allergy ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.13

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 13 Food allergy ‐ childhood incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 13 Food allergy ‐ childhood incidence.

13.1 Risk for allergy not selected

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

14 Food allergy ‐ childhood prevalence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.14

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 14 Food allergy ‐ childhood prevalence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 14 Food allergy ‐ childhood prevalence.

14.1 High risk for allergy

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Open in table viewer
Comparison 6. Higher versus lower PUFA intake: subgrouped by gestational age at birth

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease ‐ infant incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.1

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 1 All allergic disease ‐ infant incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 1 All allergic disease ‐ infant incidence.

1.1 Term infants

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

2 All allergic disease ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.2

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 2 All allergic disease ‐ childhood incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 2 All allergic disease ‐ childhood incidence.

2.1 Term infants

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.47, 1.02]

3 All allergic disease ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.3

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 3 All allergic disease ‐ childhood prevalence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 3 All allergic disease ‐ childhood prevalence.

3.1 Term infants

2

633

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.81, 1.19]

4 Asthma ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.4

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 4 Asthma ‐ infant incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 4 Asthma ‐ infant incidence.

4.1 Term infants

2

673

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.79, 1.71]

4.2 Preterm infants

1

489

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.66, 1.34]

5 Asthma ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.5

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 5 Asthma ‐ childhood incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 5 Asthma ‐ childhood incidence.

5.1 Term infants

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

6 Asthma ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.6

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 6 Asthma ‐ childhood prevalence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 6 Asthma ‐ childhood prevalence.

6.1 Term infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.82, 1.53]

7 Dermatitis/eczema ‐ infant incidence Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.7

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 7 Dermatitis/eczema ‐ infant incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 7 Dermatitis/eczema ‐ infant incidence.

7.1 Term infants

6

1422

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.80, 1.07]

7.2 Preterm infants

1

484

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.71, 1.29]

8 Dermatitis/eczema ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.8

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

8.1 Term infants

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.34, 1.24]

9 Dermatitis/eczema ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.9

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

9.1 Term infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.59, 1.09]

10 Allergic rhinitis ‐ infant incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.10

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 10 Allergic rhinitis ‐ infant incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 10 Allergic rhinitis ‐ infant incidence.

10.1 Term infants

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.18, 8.26]

10.2 Preterm infants

1

475

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.18, 0.89]

11 Allergic rhinitis ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.11

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

11.1 Term infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.25]

12 Food allergy ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.12

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 12 Food allergy ‐ infant incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 12 Food allergy ‐ infant incidence.

12.1 Term infants

2

442

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.38, 1.02]

12.2 Preterm infants

1

473

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.67, 2.31]

13 Food allergy ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.13

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 13 Food allergy ‐ childhood incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 13 Food allergy ‐ childhood incidence.

13.1 Term infants

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

14 Food allergy ‐ childhood prevalence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 6.14

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 14 Food allergy ‐ childhood prevalence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 14 Food allergy ‐ childhood prevalence.

14.1 Term infants

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Open in table viewer
Comparison 7. Higher versus lower PUFA intake: sensitivity analysis

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Asthma Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 7.1

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 1 Asthma.

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 1 Asthma.

1.1 Infant incidence

1

489

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.66, 1.34]

2 Dermatitis/eczema Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 7.2

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 2 Dermatitis/eczema.

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 2 Dermatitis/eczema.

2.1 Infant incidence

1

484

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.71, 1.29]

3 Allergic rhinitis Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 7.3

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 3 Allergic rhinitis.

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 3 Allergic rhinitis.

3.1 Infant incidence

1

475

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.18, 0.89]

4 Food allergy Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 7.4

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 4 Food allergy.

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 4 Food allergy.

4.1 Infant incidence

1

473

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.67, 2.31]

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 1

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Higher versus lower PUFA intake, Outcome 1 All allergic disease.
Figuras y tablas -
Analysis 1.1

Comparison 1 Higher versus lower PUFA intake, Outcome 1 All allergic disease.

Comparison 1 Higher versus lower PUFA intake, Outcome 2 Asthma.
Figuras y tablas -
Analysis 1.2

Comparison 1 Higher versus lower PUFA intake, Outcome 2 Asthma.

Comparison 1 Higher versus lower PUFA intake, Outcome 3 Dermatitis/eczema.
Figuras y tablas -
Analysis 1.3

Comparison 1 Higher versus lower PUFA intake, Outcome 3 Dermatitis/eczema.

Comparison 1 Higher versus lower PUFA intake, Outcome 4 Allergic rhinitis.
Figuras y tablas -
Analysis 1.4

Comparison 1 Higher versus lower PUFA intake, Outcome 4 Allergic rhinitis.

Comparison 1 Higher versus lower PUFA intake, Outcome 5 Food allergy.
Figuras y tablas -
Analysis 1.5

Comparison 1 Higher versus lower PUFA intake, Outcome 5 Food allergy.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 1 All allergic disease ‐ infant incidence.
Figuras y tablas -
Analysis 2.1

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 1 All allergic disease ‐ infant incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 2 All allergic disease ‐ childhood incidence.
Figuras y tablas -
Analysis 2.2

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 2 All allergic disease ‐ childhood incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 3 All allergic disease ‐ childhood prevalence.
Figuras y tablas -
Analysis 2.3

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 3 All allergic disease ‐ childhood prevalence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 4 Asthma ‐ infant incidence.
Figuras y tablas -
Analysis 2.4

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 4 Asthma ‐ infant incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 5 Asthma ‐ childhood incidence.
Figuras y tablas -
Analysis 2.5

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 5 Asthma ‐ childhood incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 6 Asthma ‐ childhood prevalence.
Figuras y tablas -
Analysis 2.6

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 6 Asthma ‐ childhood prevalence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 7 Dermatitis/eczema ‐ infant incidence.
Figuras y tablas -
Analysis 2.7

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 7 Dermatitis/eczema ‐ infant incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 8 Dermatitis/eczema ‐ childhood incidence.
Figuras y tablas -
Analysis 2.8

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.
Figuras y tablas -
Analysis 2.9

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 10 Allergic rhinitis ‐ infant incidence.
Figuras y tablas -
Analysis 2.10

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 10 Allergic rhinitis ‐ infant incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 11 Allergic rhinitis ‐ childhood prevalence.
Figuras y tablas -
Analysis 2.11

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 12 Food allergy ‐ infant incidence.
Figuras y tablas -
Analysis 2.12

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 12 Food allergy ‐ infant incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 13 Food allergy ‐ childhood incidence.
Figuras y tablas -
Analysis 2.13

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 13 Food allergy ‐ childhood incidence.

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 14 Food allergy ‐ childhood prevalence.
Figuras y tablas -
Analysis 2.14

Comparison 2 Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother, Outcome 14 Food allergy ‐ childhood prevalence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 1 All allergic disease ‐ infant incidence.
Figuras y tablas -
Analysis 3.1

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 1 All allergic disease ‐ infant incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 2 All allergic disease ‐ childhood incidence.
Figuras y tablas -
Analysis 3.2

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 2 All allergic disease ‐ childhood incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 3 All allergic disease ‐ childhood prevalence.
Figuras y tablas -
Analysis 3.3

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 3 All allergic disease ‐ childhood prevalence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 4 Asthma ‐ infant incidence.
Figuras y tablas -
Analysis 3.4

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 4 Asthma ‐ infant incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 5 Asthma ‐ childhood incidence.
Figuras y tablas -
Analysis 3.5

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 5 Asthma ‐ childhood incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 6 Asthma ‐ childhood prevalence.
Figuras y tablas -
Analysis 3.6

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 6 Asthma ‐ childhood prevalence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 7 Dermatitis/eczema ‐ infant incidence.
Figuras y tablas -
Analysis 3.7

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 7 Dermatitis/eczema ‐ infant incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 8 Dermatitis/eczema ‐ childhood incidence.
Figuras y tablas -
Analysis 3.8

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.
Figuras y tablas -
Analysis 3.9

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 10 Allergic rhinitis ‐ infant incidence.
Figuras y tablas -
Analysis 3.10

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 10 Allergic rhinitis ‐ infant incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 11 Allergic rhinitis ‐ childhood prevalence.
Figuras y tablas -
Analysis 3.11

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 12 Food allergy ‐ infant incidence.
Figuras y tablas -
Analysis 3.12

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 12 Food allergy ‐ infant incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 13 Food allergy ‐ childhood incidence.
Figuras y tablas -
Analysis 3.13

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 13 Food allergy ‐ childhood incidence.

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 14 Food allergy ‐ childhood prevalence.
Figuras y tablas -
Analysis 3.14

Comparison 3 Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation, Outcome 14 Food allergy ‐ childhood prevalence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 1 All allergic disease ‐ infant incidence.
Figuras y tablas -
Analysis 4.1

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 1 All allergic disease ‐ infant incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 2 All allergic disease ‐ childhood incidence.
Figuras y tablas -
Analysis 4.2

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 2 All allergic disease ‐ childhood incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 3 All allergic disease ‐ childhood prevalence.
Figuras y tablas -
Analysis 4.3

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 3 All allergic disease ‐ childhood prevalence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 4 Asthma ‐ infant incidence.
Figuras y tablas -
Analysis 4.4

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 4 Asthma ‐ infant incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 5 Asthma ‐ childhood incidence.
Figuras y tablas -
Analysis 4.5

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 5 Asthma ‐ childhood incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 6 Asthma ‐ childhood prevalence.
Figuras y tablas -
Analysis 4.6

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 6 Asthma ‐ childhood prevalence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 7 Dermatitis/eczema ‐ infant incidence.
Figuras y tablas -
Analysis 4.7

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 7 Dermatitis/eczema ‐ infant incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 8 Dermatitis/eczema ‐ childhood incidence.
Figuras y tablas -
Analysis 4.8

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.
Figuras y tablas -
Analysis 4.9

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 10 Allergic rhinitis ‐ infant incidence.
Figuras y tablas -
Analysis 4.10

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 10 Allergic rhinitis ‐ infant incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 11 Allergic rhinitis ‐ childhood prevalence.
Figuras y tablas -
Analysis 4.11

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 12 Food allergy ‐ infant incidence.
Figuras y tablas -
Analysis 4.12

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 12 Food allergy ‐ infant incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 13 Food allergy ‐ childhood incidence.
Figuras y tablas -
Analysis 4.13

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 13 Food allergy ‐ childhood incidence.

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 14 Food allergy ‐ childhood prevalence.
Figuras y tablas -
Analysis 4.14

Comparison 4 Higher versus lower PUFA intake: subgrouped by method of infant feeding, Outcome 14 Food allergy ‐ childhood prevalence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 1 All allergic disease ‐ infant incidence.
Figuras y tablas -
Analysis 5.1

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 1 All allergic disease ‐ infant incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 2 All allergic disease ‐ childhood incidence.
Figuras y tablas -
Analysis 5.2

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 2 All allergic disease ‐ childhood incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 3 All allergic disease ‐ childhood prevalence.
Figuras y tablas -
Analysis 5.3

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 3 All allergic disease ‐ childhood prevalence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 4 Asthma ‐ infant incidence.
Figuras y tablas -
Analysis 5.4

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 4 Asthma ‐ infant incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 5 Asthma ‐ childhood incidence.
Figuras y tablas -
Analysis 5.5

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 5 Asthma ‐ childhood incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 6 Asthma ‐ childhood prevalence.
Figuras y tablas -
Analysis 5.6

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 6 Asthma ‐ childhood prevalence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 7 Dermatitis/eczema ‐ infant incidence.
Figuras y tablas -
Analysis 5.7

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 7 Dermatitis/eczema ‐ infant incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 8 Dermatitis/eczema ‐ childhood incidence.
Figuras y tablas -
Analysis 5.8

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.
Figuras y tablas -
Analysis 5.9

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 10 Allergic rhinitis ‐ infant incidence.
Figuras y tablas -
Analysis 5.10

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 10 Allergic rhinitis ‐ infant incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 11 Allergic rhinitis ‐ childhood prevalence.
Figuras y tablas -
Analysis 5.11

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 12 Food allergy ‐ infant incidence.
Figuras y tablas -
Analysis 5.12

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 12 Food allergy ‐ infant incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 13 Food allergy ‐ childhood incidence.
Figuras y tablas -
Analysis 5.13

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 13 Food allergy ‐ childhood incidence.

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 14 Food allergy ‐ childhood prevalence.
Figuras y tablas -
Analysis 5.14

Comparison 5 Higher versus lower PUFA intake: subgrouped by infant heredity for allergy, Outcome 14 Food allergy ‐ childhood prevalence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 1 All allergic disease ‐ infant incidence.
Figuras y tablas -
Analysis 6.1

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 1 All allergic disease ‐ infant incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 2 All allergic disease ‐ childhood incidence.
Figuras y tablas -
Analysis 6.2

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 2 All allergic disease ‐ childhood incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 3 All allergic disease ‐ childhood prevalence.
Figuras y tablas -
Analysis 6.3

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 3 All allergic disease ‐ childhood prevalence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 4 Asthma ‐ infant incidence.
Figuras y tablas -
Analysis 6.4

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 4 Asthma ‐ infant incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 5 Asthma ‐ childhood incidence.
Figuras y tablas -
Analysis 6.5

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 5 Asthma ‐ childhood incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 6 Asthma ‐ childhood prevalence.
Figuras y tablas -
Analysis 6.6

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 6 Asthma ‐ childhood prevalence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 7 Dermatitis/eczema ‐ infant incidence.
Figuras y tablas -
Analysis 6.7

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 7 Dermatitis/eczema ‐ infant incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 8 Dermatitis/eczema ‐ childhood incidence.
Figuras y tablas -
Analysis 6.8

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 8 Dermatitis/eczema ‐ childhood incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.
Figuras y tablas -
Analysis 6.9

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 9 Dermatitis/eczema ‐ childhood prevalence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 10 Allergic rhinitis ‐ infant incidence.
Figuras y tablas -
Analysis 6.10

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 10 Allergic rhinitis ‐ infant incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 11 Allergic rhinitis ‐ childhood prevalence.
Figuras y tablas -
Analysis 6.11

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 11 Allergic rhinitis ‐ childhood prevalence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 12 Food allergy ‐ infant incidence.
Figuras y tablas -
Analysis 6.12

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 12 Food allergy ‐ infant incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 13 Food allergy ‐ childhood incidence.
Figuras y tablas -
Analysis 6.13

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 13 Food allergy ‐ childhood incidence.

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 14 Food allergy ‐ childhood prevalence.
Figuras y tablas -
Analysis 6.14

Comparison 6 Higher versus lower PUFA intake: subgrouped by gestational age at birth, Outcome 14 Food allergy ‐ childhood prevalence.

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 1 Asthma.
Figuras y tablas -
Analysis 7.1

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 1 Asthma.

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 2 Dermatitis/eczema.
Figuras y tablas -
Analysis 7.2

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 2 Dermatitis/eczema.

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 3 Allergic rhinitis.
Figuras y tablas -
Analysis 7.3

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 3 Allergic rhinitis.

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 4 Food allergy.
Figuras y tablas -
Analysis 7.4

Comparison 7 Higher versus lower PUFA intake: sensitivity analysis, Outcome 4 Food allergy.

Summary of findings for the main comparison. Higher versus lower PUFA intake for the prevention of allergy ‐ infant incidence

Higher versus lower PUFA intake for the prevention of allergy ‐ infant incidence

Patient or population: infants
Settings: hospital or community
Intervention: higher versus lower PUFA intake

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Lower PUFA intake

Higher PUFA intake

All allergic disease ‐ infant incidence
Follow‐up: 1 years

Study population

RR 0.96
(0.73 to 1.26)

323
(1 study)

⊕⊝⊝⊝
very low1,2,3

395 per 1000

379 per 1000
(289 to 498)

Moderate

395 per 1000

379 per 1000
(288 to 498)

Asthma ‐ infant incidence
Follow‐up: 2 years

Study population

RR 1.04
(0.8 to 1.35)

1162
(3 studies)

⊕⊕⊝⊝
low4,5

160 per 1000

167 per 1000
(128 to 217)

Moderate

124 per 1000

129 per 1000
(99 to 167)

Dermatitis/eczema ‐ infant incidence
Follow‐up: 2 years

Study population

RR 0.93
(0.82 to 1.06)

1906
(7 studies)

⊕⊝⊝⊝
very low3,4,5

326 per 1000

303 per 1000
(267 to 346)

Moderate

323 per 1000

300 per 1000
(265 to 342)

Allergic rhinitis ‐ infant incidence
Follow‐up: 2 years

Study population

RR 0.47
(0.23 to 0.96)

594
(2 studies)

⊕⊝⊝⊝
very low3,4,5,6

74 per 1000

35 per 1000
(17 to 71)

Moderate

58 per 1000

27 per 1000
(13 to 56)

Food allergy ‐ infant incidence
Follow‐up: 2 years

Study population

RR 0.81
(0.56 to 1.19)

915
(3 studies)

⊕⊝⊝⊝
very low3,4,5,7

118 per 1000

95 per 1000
(66 to 140)

Moderate

150 per 1000

121 per 1000
(84 to 179)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; PUFA: polyunsaturated fatty acid; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Losses to follow‐up
2 Reported by single study only.
3 Wide confidence intervals.
4 Single high quality study.
5 Reported by a minority of studies.
6 Single study reported an effect.
7 Substantial heterogeneity.

Figuras y tablas -
Summary of findings for the main comparison. Higher versus lower PUFA intake for the prevention of allergy ‐ infant incidence
Summary of findings 2. Higher versus lower PUFA intake for the prevention of allergy ‐ childhood incidence

Higher versus lower PUFA intake for the prevention of allergy ‐ childhood incidence

Patient or population: infants
Settings: hospital or community
Intervention: higher versus lower PUFA intake

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Lower PUFA intake

Higher PUFA intake

All allergic disease ‐ childhood incidence
Follow‐up: 3 years

Study population

RR 0.69
(0.47 to 1.02)

154
(2 studies)

⊕⊝⊝⊝
very low1,2,3,4

519 per 1000

358 per 1000
(244 to 529)

Moderate

483 per 1000

333 per 1000
(227 to 493)

Asthma ‐ childhood incidence
Follow‐up: 3 years

Study population

RR 0.45
(0.2 to 1.02)

89
(1 study)

⊕⊝⊝⊝
very low1,3,5

353 per 1000

159 per 1000
(71 to 360)

Moderate

353 per 1000

159 per 1000
(71 to 360)

Dermatitis/eczema ‐ childhood incidence
Follow‐up: 3 years

Study population

RR 0.65
(0.34 to 1.24)

154
(2 studies)

⊕⊝⊝⊝
very low1,3,4

266 per 1000

173 per 1000
(90 to 330)

Moderate

238 per 1000

155 per 1000
(81 to 295)

Food allergy ‐ childhood incidence
Follow‐up: 3 years

Study population

RR 2.27
(0.25 to 20.68)

65
(1 study)

⊕⊝⊝⊝
very low1,3,5

36 per 1000

81 per 1000
(9 to 739)

Moderate

36 per 1000

82 per 1000
(9 to 744)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; PUFA: polyunsaturated fatty acid; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Very high losses to follow‐up.
2 Moderate heterogeneity.
3 Wide confidence intervals.
4 Minority of studies reported outcome.
5 Reported by single study.

Figuras y tablas -
Summary of findings 2. Higher versus lower PUFA intake for the prevention of allergy ‐ childhood incidence
Summary of findings 3. Higher versus lower PUFA intake for the prevention of allergy ‐ Childhood prevalence

Higher versus lower PUFA intake for the prevention of allergy ‐ childhood prevalence

Patient or population: infants
Settings: hospital or community
Intervention: higher versus lower PUFA intake

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Lower PUFA intake

Higher PUFA intake

All allergic disease ‐ childhood prevalence
Follow‐up: 3 years

Study population

RR 0.98
(0.81 to 1.19)

633
(2 studies)

⊕⊝⊝⊝
very low1,2,3

394 per 1000

386 per 1000
(319 to 469)

Moderate

372 per 1000

365 per 1000
(301 to 443)

Asthma ‐ childhood prevalence
Follow‐up: 3 years

Study population

RR 1.12
(0.82 to 1.53)

635
(2 studies)

⊕⊝⊝⊝
very low1,3,4,5

188 per 1000

210 per 1000
(154 to 287)

Moderate

164 per 1000

184 per 1000
(134 to 251)

Dermatitis/eczema ‐ childhood prevalence
Follow‐up: 3 years

Study population

RR 0.81
(0.59 to 1.09)

635
(2 studies)

⊕⊝⊝⊝
very low1,2,3

229 per 1000

186 per 1000
(135 to 250)

Moderate

219 per 1000

177 per 1000
(129 to 239)

Allergic rhinitis ‐ childhood prevalence
Follow‐up: 3 years

Study population

RR 1.02
(0.83 to 1.25)

635
(2 studies)

⊕⊝⊝⊝
very low1,2,3

331 per 1000

338 per 1000
(275 to 414)

Moderate

220 per 1000

224 per 1000
(183 to 275)

Food allergy ‐ childhood prevalence
Follow‐up: 3 years

Study population

RR 0.27
(0.06 to 1.19)

119
(1 study)

⊕⊝⊝⊝
very low2,4

138 per 1000

37 per 1000
(8 to 165)

Moderate

139 per 1000

38 per 1000
(8 to 165)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; PUFA: polyunsaturated fatty acid; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Losses to follow‐up > 10%.
2 Wide confidence intervals.
3 Reported by a minority of studies.
4 Reported by single study.
5 Very high losses to follow‐up.

Figuras y tablas -
Summary of findings 3. Higher versus lower PUFA intake for the prevention of allergy ‐ Childhood prevalence
Comparison 1. Higher versus lower PUFA intake

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Infant incidence

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

1.2 Childhood incidence

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.47, 1.02]

1.3 Childhood prevalence

2

633

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.81, 1.19]

2 Asthma Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Infant incidence

3

1162

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.80, 1.35]

2.2 Childhood incidence

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

2.3 Childhood prevalence

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.82, 1.53]

3 Dermatitis/eczema Show forest plot

9

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Infant incidence

7

1906

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.82, 1.06]

3.2 Childhood incidence

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.34, 1.24]

3.3 Childhood prevalence

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.59, 1.09]

4 Allergic rhinitis Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Infant incidence

2

594

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.23, 0.96]

4.2 Childhood prevalence

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.25]

5 Food allergy Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Infant incidence

3

915

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.56, 1.19]

5.2 Childhood incidence

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

5.3 Childhood prevalence

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Figuras y tablas -
Comparison 1. Higher versus lower PUFA intake
Comparison 2. Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease ‐ infant incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Infant supplementation

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

2 All allergic disease ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Infant supplementation

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.34, 0.92]

2.2 Maternal supplementation

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.51, 1.91]

3 All allergic disease ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Infant supplementation

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.83, 1.25]

3.2 Maternal supplementation

1

117

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.44, 1.38]

4 Asthma ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Infant supplementation

1

554

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.78, 1.81]

4.2 Maternal supplementation

2

608

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.69, 1.33]

5 Asthma ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Infant supplementation

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

6 Asthma ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Infant supplementation

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.82, 1.57]

6.2 Maternal supplementation

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.41, 2.72]

7 Dermatitis/eczema ‐ infant incidence Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Infant supplementation

5

1245

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.82, 1.11]

7.2 Maternal supplementation

3

661

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.68, 1.15]

8 Dermatitis/eczema ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 Infant supplementation

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.25, 1.20]

8.2 Maternal supplementation

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.28, 3.20]

9 Dermatitis/eczema ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 Infant supplementation

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.62, 1.18]

9.2 Maternal supplementation

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.23, 1.36]

10 Allergic rhinitis ‐ infant incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 Maternal supplementation

2

594

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.23, 0.96]

11 Allergic rhinitis ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

11.1 Infant supplementation

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.83, 1.25]

11.2 Maternal supplementation

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.18, 8.26]

12 Food allergy ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 Infant supplementation

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.47, 1.42]

12.2 Maternal supplementation

2

592

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.48, 1.37]

13 Food allergy ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 Maternal supplementation

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

14 Food allergy ‐ childhood prevalence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

14.1 Maternal supplementation

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Figuras y tablas -
Comparison 2. Higher versus lower PUFA intake: subgrouped by supplementation of infant versus supplementation of mother
Comparison 3. Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease ‐ infant incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 n‐3 supplementation

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

2 All allergic disease ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 n‐3 supplementation

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.47, 1.02]

3 All allergic disease ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 n‐3 supplementation

2

633

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.81, 1.19]

4 Asthma ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 n‐3 supplementation

3

1162

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.80, 1.35]

5 Asthma ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 n‐3 supplementation

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

6 Asthma ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 n‐3 supplementation

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.82, 1.53]

7 Dermatitis/eczema ‐ infant incidence Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 n‐3 supplementation

5

1657

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.82, 1.09]

7.2 n‐6 supplementation

2

249

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.59, 1.23]

8 Dermatitis/eczema ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 n‐3 supplementation

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.34, 1.24]

9 Dermatitis/eczema ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 n‐3 supplementation

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.59, 1.09]

10 Allergic rhinitis ‐ infant incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 n‐3 supplementation

2

594

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.23, 0.96]

11 Allergic rhinitis ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

11.1 n‐3 supplementation

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.25]

12 Food allergy ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 n‐3 supplementation

3

915

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.56, 1.19]

13 Food allergy ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 n‐3 supplementation

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

14 Food allergy ‐ childhood prevalence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

14.1 n‐3 supplementation

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Figuras y tablas -
Comparison 3. Higher versus lower PUFA intake: subgrouped by n‐3 versus n‐6 supplementation
Comparison 4. Higher versus lower PUFA intake: subgrouped by method of infant feeding

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease ‐ infant incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Human milk fed infants

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

2 All allergic disease ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Human milk fed infants

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.51, 1.91]

2.2 Formula fed infants

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.34, 0.92]

3 All allergic disease ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Human milk fed infants

2

633

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.81, 1.19]

4 Asthma ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5 Asthma ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Formula fed infants

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

6 Asthma ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Human milk fed infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.82, 1.53]

7 Dermatitis/eczema ‐ infant incidence Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Human milk fed infants

6

1715

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.82, 1.09]

7.2 Formula fed infants

2

191

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.57, 1.23]

8 Dermatitis/eczema ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 Human milk fed infants

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.28, 3.20]

8.2 Formula fed infants

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.25, 1.20]

9 Dermatitis/eczema ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 Human milk fed infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.59, 1.09]

10 Allergic rhinitis ‐ infant incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 Human milk fed infants

2

594

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.23, 0.96]

11 Allergic rhinitis ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

11.1 Human milk fed infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.25]

12 Food allergy ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 Human milk fed infants

3

915

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.56, 1.19]

13 Food allergy ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 Human milk fed infants

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

14 Food allergy ‐ childhood prevalence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

14.1 Human milk fed infants

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Figuras y tablas -
Comparison 4. Higher versus lower PUFA intake: subgrouped by method of infant feeding
Comparison 5. Higher versus lower PUFA intake: subgrouped by infant heredity for allergy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease ‐ infant incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 High risk for allergy

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

2 All allergic disease ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Risk for allergy not selected

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.47, 1.02]

3 All allergic disease ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 High risk for allergy

2

633

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.81, 1.19]

4 Asthma ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 High risk for allergy

2

673

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.79, 1.71]

4.2 Risk for allergy not selected

1

489

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.66, 1.34]

5 Asthma ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Risk for allergy not selected

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

6 Asthma ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 High risk for allergy

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.82, 1.53]

7 Dermatitis/eczema ‐ infant incidence Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 High risk for allergy

5

1245

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.81, 1.12]

7.2 Risk for allergy not selected

2

661

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.71, 1.12]

8 Dermatitis/eczema ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 Risk for allergy not selected

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.34, 1.24]

9 Dermatitis/eczema ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 High risk for allergy

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.59, 1.09]

10 Allergic rhinitis ‐ infant incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 High risk for allergy

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.18, 8.26]

10.2 Risk for allergy not selected

1

475

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.18, 0.89]

11 Allergic rhinitis ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

11.1 High risk for allergy

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.25]

12 Food allergy ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 High risk for allergy

2

442

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.38, 1.02]

12.2 Risk for allergy not selected

1

473

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.67, 2.31]

13 Food allergy ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 Risk for allergy not selected

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

14 Food allergy ‐ childhood prevalence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

14.1 High risk for allergy

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Figuras y tablas -
Comparison 5. Higher versus lower PUFA intake: subgrouped by infant heredity for allergy
Comparison 6. Higher versus lower PUFA intake: subgrouped by gestational age at birth

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All allergic disease ‐ infant incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Term infants

1

323

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.26]

2 All allergic disease ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Term infants

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.47, 1.02]

3 All allergic disease ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Term infants

2

633

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.81, 1.19]

4 Asthma ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Term infants

2

673

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.79, 1.71]

4.2 Preterm infants

1

489

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.66, 1.34]

5 Asthma ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Term infants

1

89

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.20, 1.02]

6 Asthma ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Term infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.82, 1.53]

7 Dermatitis/eczema ‐ infant incidence Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Term infants

6

1422

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.80, 1.07]

7.2 Preterm infants

1

484

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.71, 1.29]

8 Dermatitis/eczema ‐ childhood incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 Term infants

2

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.34, 1.24]

9 Dermatitis/eczema ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 Term infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.59, 1.09]

10 Allergic rhinitis ‐ infant incidence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 Term infants

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.18, 8.26]

10.2 Preterm infants

1

475

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.18, 0.89]

11 Allergic rhinitis ‐ childhood prevalence Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

11.1 Term infants

2

635

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.25]

12 Food allergy ‐ infant incidence Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 Term infants

2

442

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.38, 1.02]

12.2 Preterm infants

1

473

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.67, 2.31]

13 Food allergy ‐ childhood incidence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 Term infants

1

65

Risk Ratio (M‐H, Fixed, 95% CI)

2.27 [0.25, 20.68]

14 Food allergy ‐ childhood prevalence Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

14.1 Term infants

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.19]

Figuras y tablas -
Comparison 6. Higher versus lower PUFA intake: subgrouped by gestational age at birth
Comparison 7. Higher versus lower PUFA intake: sensitivity analysis

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Asthma Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Infant incidence

1

489

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.66, 1.34]

2 Dermatitis/eczema Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Infant incidence

1

484

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.71, 1.29]

3 Allergic rhinitis Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Infant incidence

1

475

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.18, 0.89]

4 Food allergy Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Infant incidence

1

473

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.67, 2.31]

Figuras y tablas -
Comparison 7. Higher versus lower PUFA intake: sensitivity analysis