Does fish oil supplementation in pregnancy reduce the risk of allergic disease in infants?

Current Opinion in Allergy and Clinical Immunology

Volumn 5, Issue 3, 2005, Pages 215-221

  Dunstan, Janet A ^a,b   Prescott, Susan L ^a  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b PRINCESS MARGARET HOSPITAL FOR CHILDREN   (Australia)

Author keywords

Allergy; Asthma; Atopy; Cord blood; Cytokines; Fish oil; Neonate; Pregnancy; Primary prevention; PUFA

Indexed keywords

CYTOKINE; FISH OIL; GAMMA INTERFERON; OMEGA 3 FATTY ACID;

ALLERGIC DISEASE; ANTIINFLAMMATORY ACTIVITY; CARDIOVASCULAR DISEASE; DIABETES MELLITUS; DIET SUPPLEMENTATION; HUMAN; IMMUNOMODULATION; IMMUNOPATHOLOGY; INFANT; INFANT DISEASE; INFLAMMATION; MAJOR CLINICAL STUDY; MATERNAL NUTRITION; NON INVASIVE MEASUREMENT; PERINATAL PERIOD; PRENATAL EXPOSURE; PRIMARY PREVENTION; PRIORITY JOURNAL; REVIEW; RHEUMATOID ARTHRITIS; RISK REDUCTION; TH1 CELL;

EID: 18844400061     PISSN: 15284050     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.all.0000168784.74582.32     Document Type: Review

References (69)

1. Romagnani S. The Th2 hypothesis in allergy: 'Eppur si muove!'. Allergy Clin Immunol Intern 1998; 10:158-165.
2. Rottem M, Shoenfeld Y. Asthma as a paradigm for autoimmune disease. Int Arch Allergy Immunol 2003; 132:210-214.
3. Kimura M, Yamaide A, Tsuruta S, et al. Development of the capacity of peripheral blood mononuclear cells to produce IL-4, IL-5 and IFN-gamma upon stimulation with house dust mite in children with atopic dermatitis. Int Arch Allergy Immunol 2002; 127:191-197.
4. Ng TW, Holt PG, Prescott SL. Cellular immune responses to ovalbumin and house dust mite in egg-allergic children. Allergy 2002; 57:207-214.
5. Smart JM, Kemp AS. Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease. Clin Exp Allergy 2002; 32:796-802.
6. Grassegger A, Hopfl R. Significance of the cytokine interferon gamma in clinical dermatology. Clin Exp Dermatol 2004; 29:584-588.
7. Cho SH, Stanciu LA, Begishivili T, et al. Peripheral blood CD4+ and CD8+ T cell type 1 and type 2 cytokine production in atopic asthmatic and normal subjects. Clin Exp Allergy 2002; 32:427-433.
8. Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol 2001; 1:69-75.
9. Lange J, Ngoumou G, Berkenheide S, et al. High interleukin-13 production by phytohaemagglutinin- and Der p 1-stimulated cord blood mononuclear cells is associated with the subsequent development of atopic dermatitis at the age of 3 years. Clin Exp Allergy 2003; 33:1537-1543.
10. Neaville WA, Tisler C, Bhattacharya A, et al. Developmental cytokine response profiles and the clinical and immunologic expression of atopy during the first year of life. J Allergy Clin Immunol 2003; 112:740-746.
11. Upham JW, Holt PG, Taylor A, et al. HLA-DR expression on neonatal monocytes is associated with allergen-specific immune responses. J Allergy Clin Immunol 2004; 114:1202-1208.
12. Hagendorens MM, Ebo DG, Bridts CH, et al. Prenatal exposure to house dust mite allergen (Der p 1), cord blood T cell phenotype and cytokine production and atopic dermatitis during the first year of life. Pediatr Allergy Immunol 2004; 15:308-315.
13. Rowe J, Heaton T, Kusel M, et al. High IFN-gamma production by CD8+ T cells and early sensitization among infants at high risk of atopy. J Allergy Clin Immunol 2004; 113:710-716.
14. Macaubas C, de Klerk NH, Holt BJ, et al. Association between antenatal cytokine production and the development of atopy and asthma at age 6 years. Lancet 2003; 362:1192-1197.
15. Khair-el-Din TA, Sicher SC, Vazquez MA, et al. Docosahexaenoic acid, a major constituent of fetal serum and fish oil diets, inhibits IFN gamma-induced Ia-expression by murine macrophages in vitro. J Immunol 1995; 154:1296-1306.
16. Reece MS, McGregor JA, Allen KG, Harris MA. Maternal and perinatal long-chain fatty acids: possible roles in preterm birth. Am J Obstet Gynecol 1997; 176:907-914.
17. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? [see Comments]. Immunol Today 1993; 14:353-356.
18. Miles E, Aston L, Calder PC. In vitro effects of eicosanoids derived from different 20-carbon fatty acids on T helper type 1 and T helper type 2 cytokine production in human whole-blood cultures. Clin Exp Allergy 2003; 33:624-632.
19. Jones AC, Miles EA, Warner JO, et al. Fetal peripheral blood mononuclear cell proliferative responses to mitogenic and allergenic stimuli during gestation. Pediatr Allergy Immunol 1996; 7:109-116.
20. Hassan J, Reen DJ. Human recent thymic emigrants: identification, expansion, and survival characteristics. J Immunol 2001; 167:1970-1976.
21. Adkins B, Bu Y, Guevara P. The generation of Th memory in neonates versus adults: prolonged primary Th2 effector function and impaired development of Th1 memory effector function in murine neonates. J Immunol 2001; 166:918-925.
22. Thornton CA, Upham JW, Wikstrom ME, et al. Functional maturation of CD4+CD25+CTLA4+CD45RA+ T regulatory cells in human neonatal T cell responses to environmental antigens/allergens. J Immunol 2004; 173:3084-3092.
23. Galli E, Picardo M, Chini L, et al. Analysis of polyunsaturated fatty acids in newborn sera: a screening tool for atopic disease? Br J Dermatol 1994; 130:752-756.
24. Yu G, Kjellman NI, Bjorksten B. Phospholipid fatty acids in cord blood: family history and development of allergy. Acta Paediatr 1996; 85:679-683.
25. Beck M, Zelczak G, Lentze MJ. Abnormal fatty acid composition in umbilical cord blood of infants at high risk of atopic disease. Acta Paediatr 2000; 89:279-284.
26. Newson RB, Shaheen SO, Henderson AJ, et al. Umbilical cord and maternal blood red cell fatty acids and early childhood wheezing and eczema. J Allergy Clin Immunol 2004; 114:531-537. This paper reports positive associations (although not significant after taking into consideration multiple testing) between the ratio of n-6:n-3 PUFA in cord blood and outcomes of allergic disease in infants in the Avon Longitudinal Study of Parents and Children.
27. Duchen K, Yu G, Bjorksten B. Atopic sensitization during the first year of life in relation to long chain polyunsaturated fatty acid levels in human milk. Pediatr Res 1998; 44:478-484.
28. Stoney RM, Woods RK, Hosking CS, et al. Maternal breast milk long-chain n-3 fatty acids are associated with increased risk of atopy in breastfed infants. Clin Exp Allergy 2004; 34:194-200. The authors report that higher n-3 PUFA levels (DHA and DPA) in the colostrum were associated with sensitization in 29 infants at 6 months of age, adding to the controversy surrounding the role of breast-feeding in the prevention of allergic disease.
29. Kondo N, Kobayashi Y, Shinoda S, et al. Cord blood lymphocyte responses to food antigens for the prediction of allergic disorders. Arch Dis Child 1992; 67:1003-1007.
30. Warner JA, Miles EA, Jones AC, et al. Is deficiency of interferon gamma production by allergen triggered cord blood cells a predictor of atopic eczema? [see Comments]. Clin Exp Allergy 1994; 24:423-430.
31. Piccinni MP, Beloni L, Giannarini L, et al. Abnormal production of T helper 2 cytokines interleukin-4 and interleukin-5 by T cells from newborns with atopic parents. Eur J Immunol 1996; 26:2293-2298.
32. Ohshima Y, Yasutomi M, Omata N, et al. Dysregulation of IL-13 production by cord blood CD4+ T cells is associated with the subsequent development of atopic disease in infants. Pediatr Res 2002; 51:195-200.
33. Kondo N, Kobayashi Y, Shinoda S, et al. Reduced interferon gamma production by antigen-stimulated cord blood mononuclear cells is a risk factor of allergic disorders: 6-year follow-up study [see comments]. Clin Exp Allergy 1998; 28:1340-1344.
34. Matsuoka T, Matsubara T, Katayama K, et al. Increase of cord blood cytokine-producing T cells in intrauterine infection. Pediatr Int 2001; 43:453-457.
35. Dunstan J, Mori TA, Barden A, et al. Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomised controlled trial. J Allergy Clin Immunol 2003; 112:1178-1184.
36. Noakes PS, Holt PG, Prescott SL. Maternal smoking in pregnancy alters neonatal cytokine responses. Allergy 2003; 58:1053-1058.
37. Korotkova M, Telemo E, Hanson LA, Strandvik B. Modulation of neonatal immunological tolerance to ovalbumin by maternal essential fatty acid intake. Pediatr Allergy Immunol 2004; 15:112-122.
38. Korotkova M, Telemo E, Yamashiro Y, et al. The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin. Clin Exp Immunol 2004; 137:237-244. This paper by Korotkova and colleagues is the first to demonstrate (in a rat model) that failure to develop neonatal oral tolerance may be related to the ratio of n-6:n-3 PUFA in the diet.
39. Calder PC. N-3 polyunsaturated fatty acids and inflammation: from molecular biology to the clinic. Lipids 2003; 38:343-352.
40. Yaqoob P. Lipids and the immune response: from molecular mechanisms to clinical applications. Curr Opin Clin Nutr Metab Care 2003; 6:133-150.
41. Field CJ, Schley PD. Evidence for potential mechanisms for the effect of conjugated linoleic acid on tumor metabolism and immune function: lessons from n-3 fatty acids. Am J Clin Nutr 2004; 79(Suppl 6):1190S-1198S. This provides an excellent update and overview of the anti-inflammatory properties of n-3 PUFA, particularly in relation to the anti-cancer effects of n-3 PUFA.
42. Mori TA, Beilin LJ. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep 2004; 6:461-467. This provides an excellent update and overview of the anti-inflammatory properties of n-3 PUFA.
43. Spector SL, Surette ME. Diet and asthma: has the role of dietary lipids been overlooked in the management of asthma? Ann Allergy Asthma Immunol 2003; 90:371-377; quiz 377-378, 421.
44. Surette ME, Koumenis IL, Edens MB, et al. Inhibition of leukotriene biosynthesis by a novel dietary fatty acid formulation in patients with atopic asthma: a randomized, placebo-controlled, parallel-group, prospective trial. Clin Ther 2003; 25:972-979.
45. Serhan CN, Gotlinger K, Hong S, Arita M. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis. Prostaglandins Other Lipid Mediat 2004; 73:155-172. In this paper, Serhan and colleagues review novel anti-inflammatory lipid mediators, resolvins and docosatrienes which are derived from EPA and DHA and released from neutrophils.
46. Ma DW, Seo J, Switzer KC, et al. n-3 PUFA and membrane microdomains: a new frontier in bioactive lipid research. J Nutr Biochem 2004; 15:700-706. This excellent paper reviews the role of n-3 PUFA membrane composition in the modulation of functionality of lipid microdomains and the effects on cellular processes important in immune function.
47. Fan YY, McMurray DN, Ly LH, Chapkin RS. Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts. J Nutr 2003; 133:1913-1920.
48. Switzer KC, Fan YY, Wang N, et al. Dietary n-3 polyunsaturated fatty acids promote activation-induced cell death in Th1-polarized murine CD4+ T-cells. J Lipid Res 2004; 45:1482-1492.
49. Lee JY, Plakidas A, Lee WH, et al. Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res 2003; 44:479-486.
50. Lapillonne A, Clarke S, Heird W. Polyunsaturated fatty acids and gene expression. Curr Opin Clin Nutr Metab Care 2004; 7:151-156. This paper reviews data recently generated by cDNA microarray technology. The data confirm effects of n-3 polyunsaturated fatty acids on lipolytic and lipogenic gene expression and on a number of pathways important in immune response, including oxidative stress response and antioxidant capacity, cell proliferation, cell growth and apoptosis, cell signaling and cell transduction.
51. Sampath H, Ntambi JM. Polyunsaturated fatty acid regulation of gene expression. Nutr Rev 2004; 62:333-339. This paper also examines the important effects of n-3 PUFA expression on gene regulation. Specifically, the authors discuss effects of PUFA on transcription factors such as SREBP1c and nuclear receptors such as PPAR-alpha, HNF-4alpha and LXRalpha.
52. Woods RK, Thien FC, Abramson MJ. Dietary marine fatty acids (fish oil) for asthma in adults and children. Cochrane Database Syst Rev 2002: CD001283.
53. van Gool CJ, Zeegers MP, Thijs C. Oral essential fatty acid supplementation in atopic dermatitis: a meta-analysis of placebo-controlled trials. Br J Dermatol 2004; 150:728-740. This paper provides a summary of placebo-controlled trials with essential fatty acids for the treatment of atopic dermatitis. Only five trials with fish oil supplementation achieved the inclusion criteria for meta-analysis. The overall effect of fish oil on the severity of atopic dermatitis did not indicate any clinical benefit, although there were insufficient data to determine effectiveness in children.
54. Oddy WH, de Klerk NH, Kendall GE, et al. Ratio of omega-6 to omega-3 fatty acids and childhood asthma. J Asthma 2004; 41:319-326. Using a nested case-control cross-sectional study design within a prospective birth cohort (Western Australian Pregnancy Cohort Study), food-intake data were analysed from 166 children (6-8 years) and 169 controls. Following adjustment for covariates, the association between the ratio of n-6:n-3 fatty acids and risk for current asthma (P = 0.022). These data provide evidence that promotion of a diet with increased n-3 fatty acids and reduced n-6 fatty acids to protect children against symptoms of asthma is warranted.
55. Oddy WH, Sherriff JL, de Klerk NH, et al. The relation of breastfeeding and body mass index to asthma and atopy in children: a prospective cohort study to age 6 years. Am J Public Health 2004; 94:1531-1537.
56. Duchen K. Are human milk polyunsaturated fatty acids (PUFA) related to atopy in the mother and her child? Allergy 2001; 56:587-592.
57. Reichardt P, Muller D, Posselt U, et al. Fatty acids in colostrum from mothers of children at high risk of atopy in relation to clinical and laboratory signs of allergy in the first year of life. Allergy 2004; 59:394-400.
58. Laiho K, Lampi AM, Hamalainen M, et al. Breast milk fatty acids, eicosanoids, and cytokines in mothers with and without allergic disease. Pediatr Res 2003; 29:29.
59. Mihrshahi S, Peat JK, Marks GB, et al. Eighteen-month outcomes of house dust mite avoidance and dietary fatty acid modification in the Childhood Asthma Prevention Study (CAPS). J Allergy Clin Immunol 2003; 111:162-168.
60. Mihrshahi S, Peat JK, Webb K, et al. Effect of omega-3 fatty acid concentrations in plasma on symptoms of asthma at 18 months of age. Pediatr Allergy Immunol 2004; 15:517-522. This publication provides further data from the Childhood Allergy Prevention study (CAPS) [59], which examined the effect of reduced exposure to house dust mite and supplementation with fish oil on the reduction of allergic disease in infants at high risk of atopy (parents or siblings with atopy). At 18 months of age, there was a significant reduction in wheeze in children with high omega-3 fatty acid concentrations in plasma. HDM avoidance had no effect on serum IgE, atopy or asthma.
61. Peat JK, Mihrshahi S, Kemp AS, et al. Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study. J Allergy Clin Immunol 2004; 114:807-813. This is a follow-up publication from the CAPS study [59], examining the effects of the same intervention (above) at age 3 years. A significant 10% reduction (95% CI 3.7 to 16.4; P = 0.003) of cough in atopic but not non-atopic children was seen. This study indicates potential benefits of fish oil supplementation in early life to reduce some symptoms of allergic disease.
62. Dunstan JA, Mori TA, Barden A, et al. Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clin Exp Allergy 2003; 33:442-448.
63. Dunstan JA, Mori TA, Barden A, et al. Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition. Eur J Clin Nutr 2004; 58:429-437. This is one of a series of papers from our group which describe the key results from a randomized control trial using fish oil in pregnancy to assess the effects on PUFA status and immune function of infants at high risk of allergy (because of maternal allergic disease). This trial included 98 allergic women who were randomized to receive fish oil (3.7 g n-3 PUFA/day) or control (olive oil) capsules from 20 weeks' gestation until delivery. The results from the study confirm that maternal fish oil supplementation alters cellular n-3 and n-6 PUFA balance and has the capacity to influence neonatal immune function [62]. It provides important preliminary evidence that fish oil may have the potential to reduce the risk of allergic disease and provides a strong case for future larger studies.
64. ..] conducted by our group in which pregnant women received fish oil or placebo. Fish oil supplementation was associated with altered breast milk n-3 PUFA levels, which were positively associated with IgA, IL-6, IL-10 and sCD14. These data suggest potential immunoregulatory effects of n-3 supplementation in early life.
65. Stene LC, Ulriksen J, Magnus P, Joner G. Use of cod liver oil during pregnancy associated with lower risk of Type I diabetes in the offspring. Diabetologia 2000; 43:1093-1098.
66. Stene LC, Joner G. Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. Am J Clin Nutr 2003; 78:1128-1134.
67. Jacobs MN, Covaci A, Gheorghe A, Schepens P. Time trend investigation of PCBs, PBDEs, and organochlorine pesticides in selected n-3 polyunsaturated fatty acid rich dietary fish oil and vegetable oil supplements; nutritional relevance for human essential n-3 fatty acid requirements. J Agric Food Chem 2004; 52:1780-1788.
68. Napier JA, Beaudoin F, Michaelson LV, Sayanova O. The production of long chain polyunsaturated fatty acids in transgenic plants by reverse-engineering. Biochimie 2004; 86:785-792.
69. Costabile M, Hii CS, Melino M, et al. The immunomodulatory effects of novel beta-oxa, beta-thia, and gamma-thia polyunsaturated fatty acids on human T lymphocyte proliferation, cytokine production, and activation of protein kinase C and MAPKs. J Immunol 2005; 174:122-143. A report on the properties of novel synthetic long-chain PUFA which retain the immunosuppressive properties of the n-3 PUFAs (EPA and DHA) but not the neutrophil-stimulating properties indicating the potential to generate anti-inflammatory agents by chemically engineering PUFA.