Asthma and pregnancy: Emerging evidence of epigenetic interactions in utero

Current Opinion in Allergy and Clinical Immunology

Volumn 9, Issue 5, 2009, Pages 417-426

  Prescott, Susan L ^a   Clifton, Vicki ^b  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

Allergic disease; Asthma; Cord blood; Cytokines; Epigenetics; Fetus; Folate; Maternal diet; Pregnancy

Indexed keywords

ALLERGEN; ANTIBIOTIC AGENT; BUDESONIDE; FOLIC ACID; PARACETAMOL; STEROID;

ACETYLATION; ASTHMA; CHROMATIN STRUCTURE; DELIVERY; DISEASE PREDISPOSITION; DNA METHYLATION; ENVIRONMENTAL EXPOSURE; EPIGENETICS; FETUS DEVELOPMENT; GENE ACTIVATION; GENE CONTROL; GENE EXPRESSION; GENE INTERACTION; GENE SILENCING; HUMAN; LYMPHOCYTE FUNCTION; MATERNAL NUTRITION; MATERNAL SMOKING; MATERNAL STRESS; METHYLATION; NONHUMAN; POLLUTANT; PREGNANCY; PREMATURITY; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; TH1 CELL; TH17 CELL; TH2 CELL;

ANIMALS; ASTHMA; DISEASE SUSCEPTIBILITY; EPIGENESIS, GENETIC; FEMALE; FETAL DEVELOPMENT; FOLIC ACID; HUMANS; IMMUNE SYSTEM; IMMUNITY, MATERNALLY-ACQUIRED; INFANT, NEWBORN; PREGNANCY; PREGNANCY COMPLICATIONS;

EID: 69749111973     PISSN: 15284050     EISSN: 14736322     Source Type: Journal    
DOI: 10.1097/ACI.0b013e328330634f     Document Type: Review

References (97)

1. Murphy VE, Gibson P, Talbot PI, Clifton VL. Severe asthma exacerbations during pregnancy. Obstet Gynecol 2005; 106:1046-1054.
2. Bakhireva LN, Schatz M, Jones KL, Chambers CD. Asthma control during pregnancy and the risk of preterm delivery or impaired fetal growth. Ann Allergy Asthma Immunol 2008; 101:137-143.
3. Tata LJ, Lewis SA, McKeever TM, et al. Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study. Thorax 2008; 63:981-987.
4. Breton MC, Beauchesne MF, Lemiere C, et al. Risk of perinatal mortality associated with asthma during pregnancy. Thorax 2009; 64:101-106.
5. Breckler L, Hale J, Jung W, et al. Modulation of in vivo and in vitro cytokine production over the course of pregnancy in allergic and nonallergic mothers. Pediatr Allergy Immunol 2009 [Epub ahead of print].
6. Breckler LA, Hale J, Taylor A, et al. Pregnancy IFN-gamma responses to foetal alloantigens are altered by maternal allergy and gravidity status. Allergy 2008; 63:1473-1480.
7. + cells, involved in immunosuppression and tolerance, proliferate in the mouse uterus in response to paternal antigens derived from seminal fluid, suggesting that maternal tolerance of paternal antigens that ultimately contribute to the formation of a fetus may commence prior to fertilization and pregnancy.
8. Bernsen RM, Nagelkerke NJ. Impairment of regulatory T cells in cord blood of atopic mothers. J Allergy Clin Immunol 2008; 122:841; author reply 841.
9. Osei-Kumah A, Ammit AJ, Smith R, et al. Inflammatory mediator release in normal bronchial smooth muscle cells is altered by pregnant maternal and fetal plasma independent of asthma. Placenta 2006; 27:847-852. (Pubitemid 43905920)
10. Murphy VE, Johnson RF, Wang YC, et al. Proteomic study of plasma proteins in pregnant women with asthma. Respirology 2006; 11:41-48.
11. Murphy VE, Clifton VL. Alterations in human placental 11beta-hydroxysteroid dehydrogenase type 1 and 2 with gestational age and labour. Placenta 2003; 24:739-744.
12. Scott NM, Hodyl NA, Murphy VE, et al. Placental cytokine expression covaries with maternal asthma severity and fetal sex. J Immunol 2009; 182:1411-1420. Placental expressions of TNFα, IL-1β, , IL-8, and IL-5 mRNA were all increased significantly in placentae of female fetuses whose mothers had mild asthma, but no changes were observed in placentae of male fetuses. The pro-inflammatory cytokines TNFα, IL-1β and IL-6 were negatively correlated with female cord blood cortisol, but there were no such correlations in placentae from male fetuses. Multivariate analysis indicated the strongest predictor of cytokine mRNA expression in the placenta was fetal cortisol, but only in female fetuses. Placental cytokine mRNA levels were not significantly altered by inhaled glucocorticoid use, placental macrophage numbers, cigarette use, moderate-severe asthma, or male sex. These data suggest that placental basal cytokine mRNA expression is sex specifically regulated by cortisol in pregnancies complicated by asthma.
13. Clifton VL. Sexually dimorphic effects of maternal asthma during pregnancy on placental glucocorticoid metabolism and fetal growth. Cell Tissue Res 2005; 322:63-71.
14. Williamson AC. Pregnancy concomitant with asthma or hayfever. Am J Obstet Gynecol 1930; 20:192-197.
15. Bakhireva LN, Schatz M, Jones KL, et al. Fetal sex and maternal asthma control in pregnancy. J Asthma 2008; 45:403-407. (Pubitemid 351882723)
16. Simpson JL, Brooks C, Douwes J. Innate immunity in asthma. Paediatr Respir Rev 2008; 9:263-270.
17. Cazzola M, Matera MG. Treatment of asthma during pregnancy: more solid evidence needed. Thorax 2008; 63:944-945.
18. Christensson C, Thoren A, Lindberg B. Safety of inhaled budesonide: clinical manifestations of systemic corticosteroid-related adverse effects. Drug Saf 2008; 31:965-988.
19. Mayhew TM, Jenkins H, Todd B, Clifton VL. Maternal asthma and placental morphometry: effects of severity, treatment and fetal sex. Placenta 2008; 29:366-373.
20. Clifton VL, Murphy VE. Maternal asthma as a model for examining fetal sex-specific effects on maternal physiology and placental mechanisms that regulate human fetal growth. Placenta 2004; 25 (Suppl A):S45-S52.
21. Murphy VE, Clifton VL, Gibson PG. Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes. Thorax 2006; 61:169-176.
22. Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr 2007; 27:363-388.
23. Hollingsworth JW, Maruoka S, Boon K, et al. In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Invest 2008; 118:3462-3469. In this murine model, maternal supplementation with folate (a dietary methyl donor) lead to hypermethylation and gene silencing of the Runx3 gene in the offspring. The suppression of this gene, which is normally important for inhibiting airways inflammation, resulted in an increased allergic airways disease, with associated increased production of IgE, chemokines, and inflammatory cytokines. Moreover, this effect was transmitted to subsequent generations.
24. Miller RL, Ho SM. Environmental epigenetics and asthma: current concepts and call for studies. Am J Respir Crit Care Med 2008; 177:567-573. This is a cutting edge review on the emerging field of epigenetics in the field of asthma and allergic disease.
25. ••] in the context of the emerging data on epigenetics in asthma and allergic disease.
26. Janson PC, Winerdal ME, Winqvist O. At the crossroads of T helper lineage commitment: epigenetics points the way. Biochim Biophys Acta 2008. [Epub ahead of print]
27. White GP, Watt PM, Holt BJ, Holt PG. Differential patterns of methylation of the IFN-gamma promoter at CpG and non-CpG sites underlie differences in IFN-gamma gene expression between human neonatal and adult CD45RO-T cells. J Immunol 2002; 168:2820-2827.
28. Fujimaki W, Takahashi N, Ohnuma K, et al. Comparative study of regulatory T cell function of human CD25CD4 T cells from thymocytes, cord blood, and adult peripheral blood. Clin Dev Immunol 2008; 2008:305859.
29. Schaub B, Liu J, Schleich I, et al. Impairment of T helper and T regulatory cell responses at birth. Allergy 2008; 63:1438-1447.
30. Janson PC, Winerdal ME, Marits P, et al. FOXP3 promoter demethylation reveals the committed Treg population in humans. PLoS ONE 2008; 3:e1612. (Pubitemid 351850770)
31. Polansky JK, Kretschmer K, Freyer J, et al. DNA methylation controls Foxp3 gene expression. Eur J Immunol 2008; 38:1654-1663.
32. Bousquet J, Jacot W, Yssel H, et al. Epigenetic inheritance of fetal genes in allergic asthma. Allergy 2004; 59:138-147. (Pubitemid 38250767)
33. Ito K, Hanazawa T, Tomita K, et al. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun 2004; 315:240-245. (Pubitemid 38175212)
34. Su R, Becker A, Kozyrskyj A, Hayglass K. Epigenetic regulation of established human type 1 versus type 2 cytokine responses. J Allergy Clin Immunol 2008; 121:57-63.
35. Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases. J Allergy Clin Immunol 2008; 121:580-584.
36. Koenen HJ, Smeets RL, Vink PM, et al. Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 2008; 112:2340-2352.
37. Schaub B, Liu J, Hoppler S, et al. Impairment of T-regulatory cells in cord blood of atopic mothers. J Allergy Clin Immunol 2008; 121:1491-1499; 1499.e1-1499.e13. In this study, Schaub et al. report that high-risk infants have reduced numbers, markers, and function of Treg compared with low-risk infants, based on maternal atopy.
38. Polte T, Hennig C, Hansen G. Allergy prevention starts before conception: maternofetal transfer of tolerance protects against the development of asthma. J Allergy Clin Immunol 2008; 122:1022.e5-1030.e5.
39. Polte T, Hansen G. Maternal tolerance achieved during pregnancy is transferred to the offspring via breast milk and persistently protects the offspring from allergic asthma. Clin Exp Allergy 2008; 38:1950-1958.
40. Mold JE, Michaelsson J, Burt TD, et al. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 2008; 322:1562-1565.
41. Prescott SL. Early origins of allergic disease: a review of processes and influences during early immune development. Curr Opin Allergy Clin Immunol 2003; 3:125-132.
42. Smith M, Tourigny MR, Noakes P, et al. Children with egg allergy have evidence of reduced neonatal CD4(+)CD25(+)CD127(lo/-) regulatory T cell function. J Allergy Clin Immunol 2008; 121:1460-1466; 1466.e1-1466.e7. This study provides preliminary evidence of altered Treg function in infants who subsequently develop allergic disease (symptomatic IgE-mediated food allergy in the first year of life).
43. Prescott SL, Noakes P, Chow BW, et al. Presymptomatic differences in Toll-like receptor function in infants who have allergy. J Allergy Clin Immunol 2008; 122:391-399; 399.e1-399.e5. This study used a wide range of TLR ligands to assess neonatal innate responses, and demonstrated significantly higher TLR responses in relation to both maternal atopy and subsequent infant allergic outcomes, an observation we have now replicated in another population (awaiting publication). Further studies are underway to determine the role and significance of possible differences in neonatal innate immune function in the development of subsequent allergic disease.
44. Osei-Kumah A, Smith R, Clifton VL. Maternal and cord plasma cytokine and chemokine profile in pregnancies complicated by asthma. Cytokine 2008; 43:187-193.
45. Stencel-Gabriel K, Gabriel I, Czuba Z, et al. CD30 on stimulated CD4+ T lymphocytes in newborns regarding atopic heredity. Pediatr Allergy Immunol 2007; 18:659-664. (Pubitemid 350231114)
46. Sandberg M, Frykman A, Ernerudh J, et al. Cord blood cytokines and chemokines and development of allergic disease. Pediatr Allergy Immunol 2008 [Epub ahead of print].
47. Prescott SL, Irvine J, Dunstan JA, et al. Protein kinase-C zeta: a novel 'protective' neonatal T cell marker that can be up-regulated by allergy prevention strategies. J Allergy Clin Immunol 2007; 120:200-206.
48. Sanders VM. Epigenetic regulation of Th1 and Th2 cell development. Brain Behav Immun 2006; 20:317-324. (Pubitemid 43775788)
49. Shaheen SO. Prenatal nutrition and asthma: hope or hype? Thorax 2008; 63:483-485.
50. Castro-Rodriguez JA, Garcia-Marcos L, Alfonseda Rojas JD, et al. Mediterranean diet as a protective factor for wheezing in preschool children. J Pediatr 2008; 152:823-828; 828.e1-828.e2.
51. Chatzi L, Torrent M, Romieu I, et al. Mediterranean diet in pregnancy is protective for wheeze and atopy in childhood. Thorax 2008; 63:507-513. (Pubitemid 351831159)
52. Shaheen SO, Northstone K, Newson RB, et al. Dietary patterns in pregnancy and respiratory and atopic outcomes in childhood. Thorax 2009; 64:411-417. In a large population-based UK birth cohort, some dietary patterns were associated with eczema, IgE, lung function, and asthma; however, none had any effect after allowing for other environmental confounders.
53. Haberg SE, London SJD, Stigum H, et al. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child 2009; 94:180-184.
54. Sala-Vila A, Miles EA, Calder PC. Fatty acid composition abnormalities in atopic disease: evidence explored and role in the disease process examined. Clin Exp Allergy 2008; 38:1432-1450.
55. Olsen SF, Osterdal ML, Salvig JD, et al. Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 y of registry-based follow-up froma randomized controlled trial.AmJ Clin Nutr 2008; 88:167-175. A long-term (16-year) follow-up of a pregnancy fish oil supplementation study (providing 2.7 g n-3 PUFA in the active group) suggested that the risk of asthma was subsequently reduced compared with the placebo group (receiving olive oil), although these outcomes were based on reports to a mandatory registry reported from hospital visits rather than clinical follow-up and allergy testing.
56. Krauss-Etschmann S, Hartl D, Rzehak P, et al. Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-beta levels after fish oil supplementation of pregnant women. J Allergy Clin Immunol 2008; 121:464.e6-470.e6. Fish oil supplementation in pregnancy was associated with increase maternal and cord blood TGFβ mRNA expression. Cord blood mRNA levels of Th2-related molecules (IL-4, IL-13, and CCR4) were also reduced in the fish oil group. (Pubitemid 351215168)
57. Blumer N, Herz U, Wegmann M, Renz H. Prenatal lipopolysaccharide-exposure prevents allergic sensitisation and airway inflammation, but not airway responsiveness in a murine model of experimental asthma. Clin Exp Allergy 2005; 35:397-402. (Pubitemid 40516669)
58. Blumer N, Sel S, Virna S, et al. Perinatal maternal application of Lactobacillus rhamnosus GG suppresses allergic airway inflammation in mouse offspring. Clin Exp Allergy 2007; 37:348-357. (Pubitemid 46393247)
59. Douwes J, Cheng S, Travier N, et al. Farm exposure in utero may protect against asthma, hay fever and eczema. Eur Respir J 2008; 32:603-611.
60. Ege MJ, Bieli C, Frei R, et al. Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. J Allergy Clin Immunol 2006; 117:817-823.
61. Ege MJ, Herzum I, Buchele G, et al. Specific IgE to allergens in cord blood is associated with maternal immunity to Toxoplasma gondii and rubella virus. Allergy 2008; 63:1505-1511.
62. Osborn D, Sinn J. Probiotics in infants for prevention of allergic disease and food hypersensitivity. Cochrane Database Syst Rev 2007; CD006475. (Pubitemid 351805343)
63. Wickens K, Black PN, Stanley TV, et al. A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 2008; 122:788-794.
64. Prescott SL, Wickens K, Westcott L, et al. Supplementation with Lactobacillus rhamnosus or Bifidobacterium lactis probiotics in pregnancy increases cord blood interferon-gamma and breast milk transforming growth factor-beta and immunoglobin A detection. Clin Exp Allergy 2008; 38:1606-1614.
65. Boyle RJ, Mah LJ, Chen A, et al. Effects of Lactobacillus GG treatment during pregnancy on the development of fetal antigen-specific immune responses. Clin Exp Allergy 2008; 38:1882-1890.
66. Han YY, Lee YL, Guo YL. Indoor environmental risk factors and seasonal variation of childhood asthma. Pediatr Allergy Immunol 2009 [Epub ahead of print].
67. Karmaus W, Dobai AL, Ogbuanu I, et al. Long-term effects of breastfeeding, maternal smoking during pregnancy, and recurrent lower respiratory tract infections on asthma in children. J Asthma 2008; 45:688-695.
68. Tanaka K, Miyake Y, Sasaki S, et al. Maternal smoking and environmental tobacco smoke exposure and the risk of allergic diseases in Japanese infants: the Osaka Maternal and Child Health Study. J Asthma 2008; 45:833-838.
69. Gilliland FD, Berhane K, McConnell R, et al. Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function. Thorax 2000; 55:271-276. (Pubitemid 30248795)
70. Keil T, Lau S, Roll S, et al. Maternal smoking increases risk of allergic sensitization and wheezing only in children with allergic predisposition: longitudinal analysis from birth to 10 years. Allergy 2009; 64:445-451.
71. Noakes PS, Taylor P, Wilkinson S, Prescott SL. The relationship between persistent organic pollutants in maternal and neonatal tissues and immune responses to allergens: a novel exploratory study. Chemosphere 2006; 63:1304-1311.
72. Hertz-Picciotto I, Park HY, Dostal M, et al. Prenatal exposures to persistent and nonpersistent organic compounds and effects on immune system development. Basic Clin Pharmacol Toxicol 2008; 102:146-154. (Pubitemid 351143438)
73. Dehlink E, Yen E, Leichtner AM, et al. First evidence of a possible association between gastric acid suppression during pregnancy and childhood asthma: a population-based register study. Clin Exp Allergy 2009; 39:246-253. This is the first study in humans to show that exposure to acid-suppressive medications in pregnancy was associated with an increased odds ratio (OR) of developing childhood allergy [OR 1.43, 95% confidence interval (CI) 1.29-1.59] and asthma (OR 1.51, 95% CI 1.35-1.69).
74. Rebordosa C, Kogevinas M, Sorensen HT, Olsen J. Prenatal exposure to paracetamol and risk of wheezing and asthma in children: a birth cohort study. Int J Epidemiol 2008; 37:583-590. In this large study involving 66 445 women from the Danish National Birth Cohort, paracetamol use during any time of pregnancy was associated with a significantly increased risk of physician-diagnosed asthma at 18 months and 7 years and increased hospitalizations due to asthma. The effects were greatest for paracetamol use during the first trimester of pregnancy. (Pubitemid 351804012)
75. Bisgaard H, Loland L, Holst KK, Pipper CB. Prenatal determinants of neonatal lung function in high-risk newborns. J Allergy Clin Immunol 2009; 123:651-657; 657.e1-657.e4.
76. Garcia-Marcos L, Sanchez-Solis M, Perez-Fernandez V, et al. Is the effect of prenatal paracetamol exposure on wheezing in preschool children modified by asthma in the mother? Int Arch Allergy Immunol 2008; 149:33-37.
77. Persky V, Piorkowski J, Hernandez E, et al. Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life. Ann Allergy Asthma Immunol 2008; 101:271-278.
78. Shaheen SO, Newson RB, Sherriff A, et al. Paracetamol use in pregnancy and wheezing in early childhood. Thorax 2002; 57:958-963. (Pubitemid 35316274)
79. Kenyon S, Brocklehurst P, Jones D, et al., MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes. BMC Preg Childbirth 2008; 8:14.
80. Thavagnanam S, Fleming J, Bromley A, et al. A meta-analysis of the association between caesarean section and childhood asthma. Clin Exp Allergy 2008; 38:629-633.
81. Bager P, Wohlfahrt J, Westergaard T. Caesarean delivery and risk of atopy and allergic disease: meta-analyses. Clin Exp Allergy 2008; 38:634-642.
82. Tollanes MC, Moster D, Daltveit AK, Irgens LM. Caesarean section and risk of severe childhood asthma: a population-based cohort study. J Pediatr 2008; 153:112-116. This Norwegian population-based cohort study of 1 756 700 singletons was followed to age 18 years (or the year 2002) and reported that delivered by caesarean section had a 52% increased risk of asthma compared with spontaneously vaginal delivery (adjusted hazard ratio = 1.52; 95% CI = 1.42-1.62) with a stronger association with emergency compared with elective sections.
83. Metsala J, Kilkkinen A, Kaila M, et al. Perinatal factors and the risk of asthma in childhood: a population-based register study in Finland. Am J Epidemiol 2008; 168:170-178. (Pubitemid 351951594)
84. Pistiner M, Gold DR, Abdulkerim H, et al. Birth by cesarean section, allergic rhinitis, and allergic sensitization among children with a parental history of atopy. J Allergy Clin Immunol 2008; 122:274-279.
85. Joffe TH, Simpson NA. Cesarean section and risk of asthma: the role of intrapartum antibiotics: a missing piece? J Pediatr 2009; 154:154.
86. Pfefferle PI, Sel S, Ege MJ, et al. Cord blood allergen-specific IgE is associated with reduced IFN-gamma production by cord blood cells: the Protection against Allergy-Study in Rural Environments (PASTURE) Study. J Allergy Clin Immunol 2008; 122:711-716. Pfefferle et al. detected allergen-specific IgE in cord blood of almost 25% of newborns, noting that levels were inversely correlated with Th1 IFNγ production. However, correlation between fetal and maternal levels of specific IgE (particularly to foods) has led to speculation that this IgE may be of maternal origin [88], although this is not clear.
87. Bonnelykke K, Pipper CB, Bisgaard H. Sensitization does not develop in utero. J Allergy Clin Immunol 2008; 121:646-651. These authors also found that 14% of neonates had detected specific IgE to inhalant allergens in patterns corresponding to maternal sensitisation, but not to subsequent infant levels, further challenging notions that CB-IgE is produced by the fetus in response to environmental allergen exposure in utero. (Pubitemid 351323858)
88. Holt PG. Prenatal versus postnatal priming of allergen specific immunologic memory: the debate continues. J Allergy Clin Immunol 2008; 122:717-718.
89. Greer FR, Sicherer SH, Burks AW. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 2008; 121:183-191.
90. Prescott SL, Smith P, Tang MLK, et al. The importance of early complementary feeding in the development of oral tolerance: concerns and controversies. Pediatr Allergy Immunol 2008; 19:375-380. (Pubitemid 351989325)
91. Agostoni C, Decsi T, Fewtrell M, et al. Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 2008; 46:99-110.
92. Snijders BE, Thijs C, van Ree R, van den Brandt PA. Age at first introduction of cow milk products and other food products in relation to infant atopic manifestations in the first 2 years of life: the KOALA Birth Cohort Study. Pediatrics 2008; 122:e115-e122.
93. Fox AT, Sasieni P, du Toit G, et al. Household peanut consumption as a risk factor for the development of peanut allergy. J Allergy Clin Immunol 2009; 123:417-423.
94. Venter C, Pereira B, Voigt K, et al. Factors associated with maternal dietary intake, feeding and weaning practices, and the development of food hypersensitivity in the infant. Pediatr Allergy Immunol 2009.
95. Willers SM, Wijga AH, Brunekreef B, et al. Maternal food consumption during pregnancy and the longitudinal development of childhood asthma. Am J Respir Crit Care Med 2008; 178:124-131. In this recent large birth cohort (n = 4146), there were no consistent relationships between consumption of potential allergenic foods in pregnancy and the risk of asthma during the first 8 years of life. Curiously, although there was a higher risk of asthma in relationship to maternal consumption of 'nut products' but not 'nuts' per se. Furthermore, although this study did not focus on food allergy, nut products in pregnancy were not associated with and increased risk of peanut allergy.
96. Shanks N, Windle RJ, Perks PA, et al. Early-life exposure to endotoxin alters hypothalamic-pituitary-adrenal function and predisposition to inflammation. Proc Natl Acad Sci U S A 2000; 97:5645-5650. (Pubitemid 30313772)
97. Mattes E, McCarthy S,Gong G, et al. Maternal mood scores in mid-pregnancy are related to aspects of neonatal immune function. Brain Behav Immun 2009; 23:380-388.