Asthma and allergic disease: influence of early nutrition
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1 Asthma and allergic disease: influence of early nutrition Graham Devereux University of Aberdeen. Aberdeen Royal Infirmary.
2 Importance of asthma and allergic disease Importance of antenatal influences Maternal diet during pregnancy Breast feeding
3 Asthma & allergic disease Asthma Eczema (atopic dermatitis) Hayfever (allergic rhinoconjunctivitis) Food allergy Characterised by: Tissue inflammation Th2 biased immune responses (IL-4, IL-5, IL-13) IgE, allergen specific IgE eosinophils, allergen skin prick tests
4 Importance of asthma & allergic disease Common: 39% children, 30% adults 1 conditions Asthma; 1.1 million children 4.1 million adults Eczema; 30% pre-school children 15-20% school children 7% adults Hayfever; 20% of UK population (10 million) Food allergy; 5% children, 3-4% adults
5 Importance of asthma & allergic disease Expensive: 6% GP consultations, 0.8% of hospital admissions 10% of NHS primary care prescribing costs Asthma; NHS Indirect 1 billion 1.4 billion Eczema; similar to asthma Food allergy; $500 million direct & indirect costs
6 Importance of asthma & allergic disease prevalence Aberdeen school children 9-12 yrs % 20 Lifetime prevalence 15 Asthma Eczema Hayfever % increase in childhood food allergy from
7 Importance of antenatal influences 1). Associations between birth measurements & asthma/allergy Godfrey et al (1994) Children born in Preston detailed birth measurements 50 Birth head circumference 0.30 inches (p=0.004) Birth weight 5.6oz (p=0.04)? Nutritional compromise: sustaining fetal head growth at expense of trunk & limbs, effects on thymus, immune development
8 Importance of antenatal influences 1). Associations between birth measurements & asthma/allergy Numerous studies birth weight asthma birth weight, head circumference hayfever eczema IgE Mechanism unclear, not thymus development
9 Importance of antenatal influences Fetal measurements at 10 weeks gestation and 5 year wheeze/asthma Adjusted OR (95% CI) 10 CRL quartiles 1 Q1 Q2 Q3 Q4 0.1 Wheeze p=0.034 Asthma p= Thorax 2010; 65: 391.
10 t PTEF /t E at birth 0.34 Importance of antenatal influences 2). Associations between lung function at birth & asthma/wheeze Never History Asthma asthma of asthma at 10 yrs NEJM 2006; 355:1682
11 Importance of antenatal influences 3). Associations between cord blood immune responses & allergy (asthma) Stimulus: PHA Stimulus: House dust mite
12 Maternal dietary intake of food allergens 1990s Concerns that fetal exposure to allergens childhood asthma/allergy Reports of allergic reactions to peanuts on first exposure Allergens identified in: amniotic fluid cord blood Cord blood mononuclear cell responses to allergens CBMC proliferate after stimulation with allergen. CBMC responses associated with childhood allergic disease
13 Maternal dietary intake of food allergens Cord blood mononuclear cell responses to allergens HR1 allergic parents, allergic children HR2 allergic parents, non-allergic children LR non allergic parents and children
14 Maternal dietary intake of food allergens Cord blood mononuclear cell responses to allergens Interpretation: Exposure & sensitisation to maternally derived food allergens risk allergy Department of Health advice, June 1998 Pregnant women who are allergic should not consume peanuts during pregnancy in order to reduce the risk of peanut allergy in their children
15 Cord blood mononuclear cell responses to allergens BUT: Perennial allergens No association: CBMC responses & exposure to dust mite Seasonal allergens CBMC non-responders : exposed CBMC responders : not exposed
16 Seasonal allergens Responders not exposed Responders not exposed Non-responders but exposed J Allergy Clin Immunol 2000; 106:530
17 The systematic review: no clear evidence to suggest that either maternal exposure, or early or delayed introduction of peanut in the diets of children, impacts upon subsequent development of sensitisation or allergy to peanut. Br J Nutrition 2010; 103: : COT & DoH Advice: pregnant women can eat peanuts
18 Allergen avoidance Trials of allergen avoidance during pregnancy & infancy (dietary & aero allergens) Mono allergen avoidance meta-analysis 5 OR 1.22 (95% CI )? flawed concept: early life allergen exposure promotes tolerance trials of allergen exposure underway J Allergy Clin Immunol 2007;119:1323
19 Maternal diet during pregnancy: nutrients Maternal diet during pregnancy Changing diet contributing to the increase in asthma and allergy? Hypotheses 1. Antioxidant hypothesis: antioxidants (Thorax 1994;49:171) 2. Lipid hypothesis: n-6 PUFA, n-3 PUFA (Eur Respir J 1997;10:6) 3. Vitamin D hypotheses: vitamin D supplements (Allergy 1999;54:757) vitamin D deficiency (JACI 2007;120:1031) 4. Mediterranean diet hypothesis: Mediterranean diet (Thorax 2007;62:677)
20 Maternal diet during pregnancy: nutrients Maternal diet during pregnancy: Vitamin D Maternal vitamin D intake & recurrent childhood wheeze 2-6 years Maternal vitamin D intake & childhood asthma 5-6 years Clinical trials underway, USA, NZ, Europe J Allergy Clin Immunol 2011; 127: 724
21 Maternal vitamin D status during pregnancy BUT 25(OH) D (>75 vs <30nmol/l) 32 wks gestation associated with: eczema at 9 months: OR 3.26 ( ) asthma at 9 years: OR 5.40 ( ) 7648 adults age 31 Use of high dose (>2000 IU/d) vitamin D supplements during infancy Regular vs non/irregular use of vitamin D supplements as infant Atopy OR 1.46 ( ) Allergic rhinitis OR 1.66 ( ) Asthma OR 1.35 ( ) Eur J Clin Nutr 2008; 62:68 Ann N York Acad Sciences 2004;1037:84
22 Cord blood 25(OH)D and allergen specific IgE 1-5 years Tuscon birth cohort n= p=0.02 p= Adjusted OR (95% CI) < Cord blood 25(OH)D (nmol/l)? U shaped association, low and high deleterious < < J Allergy Clin Immunol 2011;128:1093
23 Maternal diet during pregnancy: nutrients Maternal diet during pregnancy: Vitamin E Maternal vitamin E intake & childhood wheeze 2-3 years Maternal vitamin E : lung function, wheeze & 5 yrs Pilot trial of vitamin E intervention underway J Allergy Clin Immunol 2011; 127: 724
24 Maternal diet during pregnancy: nutrients Maternal diet during pregnancy: lipids Observational studies of maternal dietary lipids during pregnancy & childhood allergy/asthma Inconsistent, suggestive Interventional studies
25 Maternal diet during pregnancy: lipids Pregnant mothers given placebo or fish oil capsules (n-3 PUFA) from 20 weeks gestation J Allergy Clin Immunol 2003; 112: 1178
26 Maternal diet during pregnancy: lipids 145 pregnant women, high allergy risk pregnancies Randomised to: 1.6g EPA + 1.1g DHA (9 caps)/d from 25 wks gestation Placebo control 12 month follow up. n-3 PUFA supplementation Positive SPT OR 0.36 ( ) Positive SPT egg OR 0.31 ( ) IgE associated eczema OR 0.22 ( ) Food allergy OR 0.09 ( )?long term benefits Acta Pædiatrica 2009; 98: 1461
27 Maternal diet during pregnancy: lipids 706 pregnant women, high allergy risk pregnancies Randomised to: 3 fish oil caps/d 100mg EPA + 800mg DHA from 21 wks gestation Placebo control 12 month follow up. n-3 PUFA supplementation allergic disease OR 0.70 ( ) Positive SPT egg OR 0.62 ( ) IgE associated eczema OR 0.64 ( ) Food allergy OR 0.96 ( )?long term benefits BMJ 2012;344:e184
28 Maternal diet during pregnancy: Mediterranean diet Birth cohort, 482 children in Menorca, 96% follow up at 6.5 yrs A high Mediterranean Diet Score during pregnancy: persistent wheeze OR 0.22 ( ) allergic wheeze OR 0.30 ( ) allergic sensitisation OR 0.55 ( ) High level of adherence to a Mediterranean diet during pregnancy protective against asthma-like symptoms and allergy in childhood Pilot trial of Mediterranean Diet during pregnancy recently completed Thorax 2008;63:507
29 Breastfeeding and asthma/allergy in children Huge number of studies Virtually no interventional studies (ethics) Systematic reviews, systematic reviews of systematic reviews American Academy of Pediatrics Consensus statement Breastfeeding of high allergic risk infants 3-4 mo risk of atopic eczema risk asthma 2-5yrs Breastfeeding: viral associated wheeze up to 4 years Breastfeeding beyond 3-4 months: no additional benefit.? Long term benefits Pediatrics 2008; 121:183
30 Breastfeeding and asthma/allergy in children A systematic review long term effects of breastfeeding (>5 years) 31 publications: breast feeding 3months wheezing & asthma >5 yr OR 0.97 ( ) wheeze > 5 yr OR 0.92 ( ) asthma OR 1.10 ( ) Paed Perinatal Epidemiol 2011; 25:507
31 Take home messages Asthma and allergic disease are common, important & expensive Antenatal and early life influences appear to play key roles in aetiology Maternal allergen avoidance appears not to prevent allergic disease Maternal nutrient intake during pregnancy may influence asthma/allergy Trials underway/imminent of maternal diet during pregnancy Breast feeding, effects on asthma/allergy, especially long term, not clear
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