Prevention of allergy through dietary interventions: What is the evidence? Hania Szajewska The Medical University of Warsaw Department of Paediatrics Dietary interventions to prevent allergy • Maternal pregnancy/lactation diet • Exclusive breastfeeding • Use se of dietary products with reduced allergenicity • Timing of introduction of complementary foods ESPGHAN Committee on Nutrition AAP Committee on Nutrition and Section of Allergy and Immunology Replaces the AAP 2000 policy statement on hypoallergenic formulas EAACI, Section of Pediatrics Maternal pregnancy and/or lactation diet Is it effective? Maternal pregnancy diet Outcome measure RR (95% CI) Atopic eczema in first 12-18 months (2 RCTs, n=334) 1.01 (0.6-1.8) Asthma in first 18 months (2 RCTs, n=334) 2.2 (0.4-13) Allergic urticaria in first 18 months (1 RCT, n=163) 1.01 (0.20-5.15) Any atopic condition in first 18 months (1 RCT, n=163) 0.71 (0.34-1.49) Favours elimination diet 1 Favours regular diet Kramer, Kakuma. Cochrane Review 2006 Maternal pregnancy diet • Unlikely to reduce substantially her child’s risk of atopic diseases • Such diet may have an adverse effect on maternal and/or fetal nutrition – Lower mean gestational weight gain – Higher risk of preterm birth – Reduction in mean birthweight Kramer, Kakuma. Cochrane Review 2006 Maternal lactation diet Outcome measure RR (95% CI) Atopic eczema in first 18 mo (1 RCT, n=26) 0.7 (0.3-1.7) 1 Outcome measure WMD (95% CI) Eczema area score (1 RCT, n=34) -0.8 (-4.4 to 2.8) Eczema activity score (1 RCT, n=34) -1.4 (-7 to 4.4) Favours elimination diet 0 Favours regular diet Maternal pregnancy/lactation diet Recommendations • AAP 2008 – Not recommended • EAACI 2008 – No conclusive evidence for protective effect • ESPGHAN – Not recommended Studies with methodological shortcomings, shortcomings many non-RCTs Breastfeeding • What is already known on this topic? – Reduction in the risk of atopic dermatitis in children with a family history of atopy and exclusivey breast fed for at least 3 months AHRQ April 2007 Breastfeeding • What is already known on this topic? – Evidence is conflicting as to whether prolonged and exclusive BF increases, decreases, or has no effect on the risks of athma and allergy – Virtually all evidence is based on observational studies • What is new on this topic? Kramer et al. BMJ 2007;335:815 Breastfeeding PROBIT Study • Setting – Belarussian maternity hospitals & polyclinics • Participants – 17 046 mother-infant infant pairs – 13 889 (81.5%) followed up at age 6.5 years • Intervention – BF promotion intervention modeled on the WHO/UNICEF baby-friendly friendly hospital initiative Kramer et al. BMJ 2007;335:815 PROBIT Study • Main outcome measures – Asthma and allergies in childhood questionnaire – Skin prick tests of five inhalant antigens Kramer et al. BMJ 2007;335:815 What the study adds? • Prolonged and exclusive BF had no protective effect on allergic symptoms and diagnoses or on positive skin prick tests Kramer et al. BMJ 2007;335:815 Limitations • Cluster randomised trials have not always been well designed and analysed • Lack of blinding in the identification and randomisation of individual participants can be a problem Eldridge S et al. BMJ 2008;336:876-80 Limitations • Highly selected sample – those intending to breast-feed feed • True prevalence of asthma/allergy – may not have been measured by either history of asthma symptoms or positive SPT for airborne allergens • Reported asthma prevalence low compared to many countries • Low positive predictive value of SPT • Still, the best evidence to date Recommendations • AAP 2008 – For infants at high risk of atopy, exclusive BF for at least 4 mo vs intact CMP formula decreases AD and CMA in the first 2 years of life – Exclusive xclusive BF for at least 3 months protects against wheezing in early life – No conclusive effect beyond 6 yrs y of age Recommendations • EAACI 2008 – BF for at least 4-6 6 months all infants irrespective of atopic heredity • ESPGHAN 2008 – Exclusive or full BF [in all infants] for about 6 months is a desirable goal. Hydrolysed formulas • Partially hydrolysed (PH) formula – Contains reduced oligopeptides that have a molecular weight of generally less than 5000 d • Extensively hydrolysed (EH) formula – Contains only peptides that have a molecular weight of less than 3000 d Greer et al. Pediatrics 2008;121:183-191 Cochrane Review 2006 Formulas containing hydrolysed protein • Objective – To determine whether use of HF prevents allergy and food intolerance. – If HF are effective, to determine what type of HF is most effective HF, hydrolysed formula Osborn DA, Sinn J. Cochrane Review 2006 Cochrane Review 2006 Formulas containing hydrolysed protein • Search Strategy – Cochrane Library, MEDLINE, EMBASE, CINAHL – All up to March 2006 – RCTs, with ≥80% follow-up up • Updates a previous version (2003) • Major differences – Inclusion of GINI Study (1 y) – Exclusion of RCTs, if original data unable to be verified Osborn DA, Sinn J. Cochrane Review 2006 Comparisons to be discussed • • • • • HF vs PHF vs EHF (whey) vs EHF (casein) vs EHF vs CMF CMF CMF CMF PHF HF, hydrolysed formula; PHF, partially hydrolysed; EHF, extensively hydrolysed; CMF, cow’s milk formula Hydrolysed formula vs cow’s milk formula Outcome RR (95% CI) Any allergy 7 RCTs (n=2514) Cow’s milk allergy 1 RCT (n=67) 0.8 (0.7 to 0.9) Favours hydrolysed formula 0.4 (0.2 to 0.9) 1 Favours cow’s milk formula Osborn DA, Sinn J. Cochrane Review 2006 Hydrolysed formula vs cow’s milk formula Any allergy NNT 12 (95% CI 9 to 20) Osborn DA, Sinn J. Cochrane Review 2006 Hydrolysed formula vs cow’s milk formula • No significant difference – Incidence of childhood allergy – Infant eczema – Childhood eczema incidence – Childhood eczema prevalence – Infant asthma – Childhood asthma – Rhinitis – Food allergy Osborn DA, Sinn J. Cochrane Review 2006 Partially hydrolysed whey formula vs cow’s milk formula Outcome RR (95% CI) Any allergy 7 RCTs (n=1482) Cow’s milk allergy 1 RCT (n=67) 0.8 (0.7 to 0.97) Favours hydrolysed formula 0.4 (0.2 to 0.9) 1 Favours cow’s milk formula Osborn DA, Sinn J. Cochrane Review 2006 Partially hydrolysed whey formula vs cow’s milk formula Any allergy NNT 19 (95% CI 11 to 71) Osborn DA, Sinn J. Cochrane Review 2006 Partially hydrolysed whey formula vs cow’s milk formula • No significant difference – Childhood allergy – Infant or childhood asthma – Eczema – Rhinitis – Food allergy Osborn DA, Sinn J. Cochrane Review 2006 Extensively hydrolysed whey formula vs cow’s milk formula • No significant difference – Any allergy infancy & childhood – Asthma childhood – Eczema infancy & childhood Osborn DA, Sinn J. Cochrane Review 2006 Extensively hydrolysed casein formula vs cow’s milk formula Outcome RR (95% CI) Any allergy childhood 1 RCT (n=431) Eczema infancy 3 RCTs (n=1237) 0.7 (0.5 to 0.97) Favours hydrolysed formula 0.7 (0.5 to 0.97) 1 Favours cow’s milk formula Osborn DA, Sinn J. Cochrane Review 2006 Extensively hydrolysed casein formula vs cow’s milk formula Any allergy childhood NNT 11 (95% CI 6 to 103 Osborn DA, Sinn J. Cochrane Review 2006 Extensively hydrolysed casein formula vs cow’s milk formula Eczema in infancy NNT 27 (95% CI 14 to 322) Osborn DA, Sinn J. Cochrane Review 2006 Extensively hydrolysed casein formula vs cow’s milk formula • No significant difference – Any allergy infancy – Eczema childhood – Asthma infancy – Asthma childhood Osborn DA, Sinn J. Cochrane Review 2006 Extensively hydrolysed formula vs partially hydrolysed formula • ↓ Food allergy • No significant difference – All allergy – Any other specific allergy (e.g. eczema, asthma) Osborn DA, Sinn J. Cochrane Review 2006 Cochrane Review 2006 Summary (positive results) Comparison Outcome HF vs CMF PH vs CMF EH casein vs CMF EH vs PH NNT 95% CI Any allergy 12 9 to 20 Cow’s milk allergy 4 3 to 19 Any allergy 19 11 to 71 Cow’s milk allergy 4 3 to 19 Any allergy 11 6 to 103 Eczema 27 14 to 322 Food allergy 15 8 to 64 CMF, cow’s milk formula; EH, extensively hydrolysed; HF, hydrolysed formula; PH, partially hydrolysed Methodological problems Would you recommend HF to prevent allergy? If yes, what type of HF? Protein hydrolysates Recommendations • AAP 2008 – Not ot all HF provide the same degree of benefit – eHF HF may be more effective than pHF p • EAACI 2008 – Formula rmula with documented reduced allergenicity for at least 4 months • ESPGHAN/ESPACI (1999) – Formula with confirmed reduced allergenicty Complementary feeding • What is already known on this topic? – Systematic review: search date March 2005 – Early feeding may increase the risk of eczema – Little data supporting an association between early solid feeding and other allergic conditions • What is new on this topic? Tarinii BA et al. Arch Pediatr Adolesc Med 2006;160:502-7 Allergic diseases & Potentially allergenic foods • What is already known on this topic? – Only little information about timing of complementary food introduction and its association with the development of allergic diseases in available Potentially allergenic foods Previous recommendations AAP 2000 ASCIA 2006 ACAAI 2006 Solid foods Cow’s milk Eggs Peanuts Fish >4 mo >12 mo >24 mo >36 mo >36 mo Option Option >36 mo >36 mo >4-6 mo >12 mo >24 mo Potentially allergenic foods • What is new on this topic? GINI Study Prospective birth cohort study • Aim – To assess the association between the introdution of solids in the first 12 m and the occurence of eczema during the first 4 y of life • Prospective birth cohort study • N=4753 – Intervention group (family history of atopy) – Non-intervention intervention group (no history of atopy) Filipiak et al. J Pediatr 2007;151:352-8 GINI Study Prospective birth cohort study • Outcomes – Doctor-diagnosed diagnosed and symptomatic eczema • Results – No association between the time of introduction of solids or the diversity of solids and eczema – Non-intervention intervention group – risk for doctor diagnosed eczema • ↓ avoidance of soybean/nuts • ↑ avoidance of egg in the first year Filipiak et al. J Pediatr 2007;151:352-8 GINI Study What the study adds? • No evidence supporting a delayed introduction of solids >4 m or a delayed introduction of most potentially allergenic solids >6 m for the prevention of eczema Filipiak et al. J Pediatr 2007;151:352-8 LISA Study Prospective birth cohort study • Aim – To investigate whether a delayed introduction of solids (past 4 or 6 m) is protective against the development of eczema, asthma, allergic rhinitis, and food or inhalant sensitisation at the age of 6 y • Prospective birth cohort study • N=2073 Zutavern et al. Pediatrics 2008;121:e44-e52 LISA Study Eczema • A - In relation to first introduction of solids • B - In relation to first introduction of any solids in children without early symptoms Zutavern et al. Pediatrics 2008;121:e44-e52 LISA Study Eczema Eczema more frequent in children who received a more diverse diet within the first 4 months • A - In relation to first introduction of solids • B - In relation to first introduction of any solids in children without early symptoms Zutavern et al. Pediatrics 2008;121:e44-e52 LISA Study Asthma • C - In relation to first introduction of solids • D - In relation to first introduction of any solids in children without early symptoms Zutavern et al. Pediatrics 2008;121:e44-e52 LISA Study Allergic rhinitis • E - In relation to first introduction of solids • F - In relation to first introduction of any solids in children without early symptoms Zutavern et al. Pediatrics 2008;121:e44-e52 LISA Study What the study adds? • No evidence supporting a delayed introduction of solids beyond 4 or 6 months for the prevention of asthma, allergic rhinitis, and food or inhalant sensitisation at the age of 6 y • For eczema, conflicting results Zutavern et al. Pediatrics 2008;121:e44-e52 KOALA Birth Cohort Study • Aim – To evalaute any associations between the introduction of cow milk products/other solid food products and infant atopic manifestations in the second year of life • Birth cohort study, n=2558, The Netherlands Snijders et al. Pediatrics 2008;122:e115-122 KOALA Birth Cohort Study Delayed introduction of both cow milk products and other food products was associated with a higher risk for eczema Snijders et al. Pediatrics 2008;122:e115-122 KOALA Birth Cohort Study • Conclusion – Delaying the introduction of cow milk or other products may not be favourable in preventing the development of atopy Snijders et al. Pediatrics 2008;122:e115-122 What would be your recommendations for complementary foods for the prevention of allergic diseases? Potentially allergenic foods Recommendations • ESPGHAN 2008 – Avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, has not been convincingly shown to reduce allergies ESPGHAN Committee on Nutrition. JPGN 2008; 46: 99–110 99 Potentially allergenic foods Recommendations • AAP 2008 – Solid foods not before 4 to 6 mo – Delayed introduction • No evidence that prevents atopy • Also lso applies to foods thought to be highly allergic, such as fish, eggs, and foods containing peanut protein • EAACI 2008 – Avoidance voidance of solid food and cow’s milk for at least 4 mo Potentially allergenic foods • In summary, what’s new – New guidelines downplay role of diet in preventing pediatric allergies Dietary interventions to prevent allergy • Maternal pregnancy/lactation diet • Exclusive breastfeeding • Use se of dietary products with reduced allergenicity • Delayed introduction of solid foods Thank you for your attention