NIHR Signal Early exposure to peanut snacks can lead to sustained protection in high-risk children

Published on 10 May 2016

Early exposure, up to age five, to peanut products in children with severe eczema or egg allergy appears to induce tolerance that is sustained when peanut products are later avoided, suggesting it is not necessary to keep eating peanuts long term.

This trial and its follow up study examined the effect of giving peanut products to very young children (aged four to 11 months) who were at high risk of peanut allergy. Children given regular peanut butter snacks until five years of age were much less likely to have a peanut allergy than those avoiding peanuts. There was a benefit even if they had an initial positive skin prick test suggesting allergy at the start. The protective effect of eating peanut products appeared to be sustained after avoidance of peanuts for a year in the follow-up study.

The trial findings provide some evidence that early exposure may be protective. At present, there is no national guidance on the topic, but this research is likely to influence future advice to clinical staff including how best to deliver peanuts to children.

Early exposure to peanut snacks can lead to sustained protection in high-risk children

Why was this study needed?

Peanut allergy is estimated to affect 1 in 50 young infants and it is becoming increasingly common. Most reactions are mild, though some are severe and cause difficulty in breathing or a drop in blood pressure. There is no recommended treatment to eliminate the condition once it is diagnosed, although there are treatments available for serious reactions. Trials of oral peanut immunotherapy have proved successful in desensitising people to peanuts.

The prevalence of peanut allergy varies globally. In earlier research, the current study’s authors found UK prevalence among Jewish children was 1.85% while in Israel this was just 0.17%, for children with similar ancestry. In Israel, peanut products are introduced earlier and eaten more frequently than in the UK which may be responsible for the difference.

Current practice for children who are not in high risk groups is to not introduce foods containing peanuts before six months of age. After this it is suggested food containing nuts, which could trigger allergy, should be introduced one at a time to spot any reaction.

After the first study it remained unknown whether continued consumption of peanuts throughout life is required in order to be able to safely eat peanuts without reacting. The follow on study was designed to address this question.

Previous findings from reliable reviews on the effects of early exposure to peanuts have been mixed, and found very limited evidence.

What did this study do?

This NIHR funded UK trial (called LEAP) and its 12 month follow-up (called LEAP-On) tracked peanut allergy prevalence in children who were at high risk of peanut allergy, defined as having severe eczema, egg allergy or both.

Children aged four to 11 months were given a skin-prick test of peanut extract and those with a reaction greater than 4mm were excluded from the study. The children were then randomly assigned to peanut avoidance or consumption in the form of peanut containing snacks (equivalent to 6 grams or more of peanut protein distributed over three or more meals each week) until five years of age, at which time they were tested for peanut allergy. All children in the follow up study were then asked to avoid peanuts for 12 months. Children who had not shown signs of peanut allergy during this period were then tested by giving them a small amount of peanut protein and observing to see if they showed any signs of an allergic reaction to it.

The trial was well designed and results can be interpreted with some certainty.

What did it find?

At the start of the LEAP trial, skin tests showed 530 infants did not have peanut allergy while 98 infants had a positive skin prick test. By the end of this large trial, there were complete results on 550 six-year old children.

  • At age five, of the 530 infants who initially had a negative skin test, more in the avoidance group had acquired peanut allergy (13.7%) than in the consumption group (1.9%). The absolute difference in risk of 11.8% (95% confidence interval [CI], 3.4 to 20.3) represents an 86.1% relative reduction in the prevalence of peanut allergy.
  • Among the 98 infants who initially had a positive peanut skin test, the prevalence of peanut allergy was higher in the avoidance group (35.3%) than in the consumption group (10.6%).
  • In the follow up study, LEAP-On, after the year of peanut product avoidance the proportion of children with peanut allergy at six years of age was still significantly higher in the initial avoidance group (18.6%) than the initial consumption group (4.8%). P<0.001, meaning that the difference was very unlikely to be a chance finding.
  • The proportion of children in the trial’s peanut consuming group who had peanut allergy had only increased slightly between the end of the original trial (when 3.6% had peanut allergy), and the end of the year of follow up (when 4.8% had peanut allergy), this difference was not statistically significant.

This means that the early exposure to peanuts still appears to protect children from developing an allergy at six years of age despite having not eaten peanuts for a year. The benefits are likely to come from exposure before age five.

What does current guidance say on this issue?

NICE guidance from 2011 on allergy in young people does not include recommendations for preventing peanut allergy by giving peanut products from a young age. Guidance from the US (published in 2010) suggests that peanut products may be given to children around four to six months of age.

What are the implications?

This study has shown that protection built up from initial early exposure to peanut products can continue even after avoiding peanut products for a year. However, if an effect persists for even longer is not known. Overall, the findings show promise for children at high risk of peanut allergy. The practical considerations of how this intervention might be delivered in the NHS will need careful thought. It is important to note that the products tested in this trial were not whole peanuts, as there is a risk of choking if whole peanuts are given to small children. At present, there is a lack of UK guidance on preventing peanut allergy in this way.

Citation and Funding

Du Toit G, Sayre PH, Roberts G, et al. Effect of avoidance on peanut allergy after early peanut consumption. New Engl J Med. 2016;374(15):1435-43.

Supported by grants (NO1-AI-15416, UM1AI109565, HHSN272200800029C, and UM2AI117870) from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and by Food Allergy Research and Education, the Medical Research Council and Asthma U.K. Centre, and the U.K. Department of Health through a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy’s and St. Thomas’ NHS Foundation Trust, in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. The clinical trials unit was supported by the National Peanut Board, Atlanta. The U.K. Food Standards Agency provided additional support for the costs of phlebotomy.

Bibliography

Allergy UK. Peanut and tree nut allergy [internet]. Sidcup: Allergy UK; 2012.

Boyce JA, Assa’ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010;126: Suppl:S1-S58.

Du Toit G, Katz Y, Sasieni P, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 2008;122:984-91.

Du Toit G, Roberts G, Sayre P, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. New Engl J Med. 2015;372(9):803-13.

Immune Tolerance Network. Learning Early About Peanut allergy (LEAP study website). Seattle (WA): National Institute of Allergy and Infectious Diseases: Immune Tolerance Network; 2016.

NHS Choices. Food allergies in babies [internet]. Leeds: NHS Choices, 2015.

NICE. Food allergy in under 19’s: assessment and diagnosis. CG116. London: National Institute for Health and Care Excellence; 2011.

Nicolaou N, Poorafshar M, Murray C et al. Allergy or tolerance in children sensitized to peanut: prevalence and differentiation using component-resolved diagnostics. J Allergy Clin Immunol. 2010;125:191-7.

Nurmatov U, Venderbosch I, Devereux G, et al. Allergen-specific oral immunotherapy for peanut allergy. Cochrane Database of Syst Revs. 2012;(9):CD009014.

Thompson RL, Miles LM, Lunn J, et al. Peanut sensitisation and allergy: influence of early life exposure to peanuts. Br J  Nutr. 2010;103(09):1278-86.

Why was this study needed?

Peanut allergy is estimated to affect 1 in 50 young infants and it is becoming increasingly common. Most reactions are mild, though some are severe and cause difficulty in breathing or a drop in blood pressure. There is no recommended treatment to eliminate the condition once it is diagnosed, although there are treatments available for serious reactions. Trials of oral peanut immunotherapy have proved successful in desensitising people to peanuts.

The prevalence of peanut allergy varies globally. In earlier research, the current study’s authors found UK prevalence among Jewish children was 1.85% while in Israel this was just 0.17%, for children with similar ancestry. In Israel, peanut products are introduced earlier and eaten more frequently than in the UK which may be responsible for the difference.

Current practice for children who are not in high risk groups is to not introduce foods containing peanuts before six months of age. After this it is suggested food containing nuts, which could trigger allergy, should be introduced one at a time to spot any reaction.

After the first study it remained unknown whether continued consumption of peanuts throughout life is required in order to be able to safely eat peanuts without reacting. The follow on study was designed to address this question.

Previous findings from reliable reviews on the effects of early exposure to peanuts have been mixed, and found very limited evidence.

What did this study do?

This NIHR funded UK trial (called LEAP) and its 12 month follow-up (called LEAP-On) tracked peanut allergy prevalence in children who were at high risk of peanut allergy, defined as having severe eczema, egg allergy or both.

Children aged four to 11 months were given a skin-prick test of peanut extract and those with a reaction greater than 4mm were excluded from the study. The children were then randomly assigned to peanut avoidance or consumption in the form of peanut containing snacks (equivalent to 6 grams or more of peanut protein distributed over three or more meals each week) until five years of age, at which time they were tested for peanut allergy. All children in the follow up study were then asked to avoid peanuts for 12 months. Children who had not shown signs of peanut allergy during this period were then tested by giving them a small amount of peanut protein and observing to see if they showed any signs of an allergic reaction to it.

The trial was well designed and results can be interpreted with some certainty.

What did it find?

At the start of the LEAP trial, skin tests showed 530 infants did not have peanut allergy while 98 infants had a positive skin prick test. By the end of this large trial, there were complete results on 550 six-year old children.

  • At age five, of the 530 infants who initially had a negative skin test, more in the avoidance group had acquired peanut allergy (13.7%) than in the consumption group (1.9%). The absolute difference in risk of 11.8% (95% confidence interval [CI], 3.4 to 20.3) represents an 86.1% relative reduction in the prevalence of peanut allergy.
  • Among the 98 infants who initially had a positive peanut skin test, the prevalence of peanut allergy was higher in the avoidance group (35.3%) than in the consumption group (10.6%).
  • In the follow up study, LEAP-On, after the year of peanut product avoidance the proportion of children with peanut allergy at six years of age was still significantly higher in the initial avoidance group (18.6%) than the initial consumption group (4.8%). P<0.001, meaning that the difference was very unlikely to be a chance finding.
  • The proportion of children in the trial’s peanut consuming group who had peanut allergy had only increased slightly between the end of the original trial (when 3.6% had peanut allergy), and the end of the year of follow up (when 4.8% had peanut allergy), this difference was not statistically significant.

This means that the early exposure to peanuts still appears to protect children from developing an allergy at six years of age despite having not eaten peanuts for a year. The benefits are likely to come from exposure before age five.

What does current guidance say on this issue?

NICE guidance from 2011 on allergy in young people does not include recommendations for preventing peanut allergy by giving peanut products from a young age. Guidance from the US (published in 2010) suggests that peanut products may be given to children around four to six months of age.

What are the implications?

This study has shown that protection built up from initial early exposure to peanut products can continue even after avoiding peanut products for a year. However, if an effect persists for even longer is not known. Overall, the findings show promise for children at high risk of peanut allergy. The practical considerations of how this intervention might be delivered in the NHS will need careful thought. It is important to note that the products tested in this trial were not whole peanuts, as there is a risk of choking if whole peanuts are given to small children. At present, there is a lack of UK guidance on preventing peanut allergy in this way.

Citation and Funding

Du Toit G, Sayre PH, Roberts G, et al. Effect of avoidance on peanut allergy after early peanut consumption. New Engl J Med. 2016;374(15):1435-43.

Supported by grants (NO1-AI-15416, UM1AI109565, HHSN272200800029C, and UM2AI117870) from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and by Food Allergy Research and Education, the Medical Research Council and Asthma U.K. Centre, and the U.K. Department of Health through a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy’s and St. Thomas’ NHS Foundation Trust, in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. The clinical trials unit was supported by the National Peanut Board, Atlanta. The U.K. Food Standards Agency provided additional support for the costs of phlebotomy.

Bibliography

Allergy UK. Peanut and tree nut allergy [internet]. Sidcup: Allergy UK; 2012.

Boyce JA, Assa’ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010;126: Suppl:S1-S58.

Du Toit G, Katz Y, Sasieni P, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 2008;122:984-91.

Du Toit G, Roberts G, Sayre P, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. New Engl J Med. 2015;372(9):803-13.

Immune Tolerance Network. Learning Early About Peanut allergy (LEAP study website). Seattle (WA): National Institute of Allergy and Infectious Diseases: Immune Tolerance Network; 2016.

NHS Choices. Food allergies in babies [internet]. Leeds: NHS Choices, 2015.

NICE. Food allergy in under 19’s: assessment and diagnosis. CG116. London: National Institute for Health and Care Excellence; 2011.

Nicolaou N, Poorafshar M, Murray C et al. Allergy or tolerance in children sensitized to peanut: prevalence and differentiation using component-resolved diagnostics. J Allergy Clin Immunol. 2010;125:191-7.

Nurmatov U, Venderbosch I, Devereux G, et al. Allergen-specific oral immunotherapy for peanut allergy. Cochrane Database of Syst Revs. 2012;(9):CD009014.

Thompson RL, Miles LM, Lunn J, et al. Peanut sensitisation and allergy: influence of early life exposure to peanuts. Br J  Nutr. 2010;103(09):1278-86.

Effect of Avoidance on Peanut Allergy after Early Peanut Consumption

Published on 26 February 2016

G Du Toit, G Roberts, P Sayre, M L Sever, K Lawson, H T Bahnson, H A Brough, A F Santos, K M Harris, S Radulovic, M Basting, V Turcanu, M Plaut, G Lack, for the Immune Tolerance Network LEAP-On Study Team.

New England Journal of Medicine , 2016

BACKGROUND In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group). METHODS At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age. RESULTS We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P<0.001). Three new cases of allergy developed in each group, but after 12 months of avoidance there was no significant increase in the prevalence of allergy among participants in the consumption group (3.6% [10 of 274 participants] at 60 months and 4.8% [13 of 270] at 72 months, P=0.25). Fewer participants in the peanut-consumption group than in the peanut-avoidance group had high levels of Ara h2 (a component of peanut protein)–specific IgE and peanut-specific IgE; in addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4:IgE ratio. CONCLUSIONS Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846.)

Interpretation of skin prick tests for peanut allergy can be challenging. According to low quality evidence, the likelihood of a positive skin prick test correctly identifying peanut allergy ranges from 55% to 94% (positive predictive value). The likelihood of a negative test correctly ruling out peanut allergy ranges from 50% to 100% (negative predictive value). Diagnosis relies on an allergy-focussed clinical history and skin prick test or blood test, with only a minority of children requiring an oral food challenge.

Expert commentary

This study confirms that regularly eating peanut from an early age can prevent peanut allergy, in high-risk infants who don't already have peanut allergy. Historical recommendations to delay the introduction of peanut and other allergenic foods to the infant diet may have been mistaken. Two changes to current practice should be considered. First peanut should be given to infants sooner rather than later, in families that eat peanut as part of their diet. Second, in infants who show early signs of allergy i.e. troublesome eczema or food allergy, an allergy skin prick test, in a specialist centre, could be undertaken to determine the extent of any reaction and whether peanut can be safely introduced into their diet.

Dr Robert Boyle, Clinical Senior Lecturer in Paediatric Allergy, Imperial College London

Expert commentary

This study provides clear evidence that the impact of early peanut introduction into the diet of high risk (eczema and/or egg allergy) children is to induce tolerance. A sustained tolerance rather than just a temporary state of desensitisation that no longer provides protection once regular peanut ingestion is stopped. This increases the value of this strategy for peanut allergy prevention and is already impacting on guidelines around the world.

Dr Adam T Fox, Clinical Director, GRIDA (Genetics, Rheumatology & Lupus, Infection & HIV, Sexual & Reproductive Health, Dermatology and Allergy), Guy's & St Thomas' Hospitals NHS Foundation Trust

Expert commentary

This study offers convincing evidence that peanut allergy can be significantly reduced in selected high risk infants through early and regular consumption of peanuts for five years and that this effect is sustained for 12 months post withdrawal of peanuts from the child’s diet. The study excluded low risk populations and high-risk infants with a skin prick test more than 4mm to peanuts.

Safe implementation of this recommendation in the UK would require a significant shift in clinical practice, necessitating rapid access to skin prick testing for high risk infants and the provision of safe facilities for challenge testing to peanut. The findings are specific for peanut and cannot be extrapolated to other tree-nuts or foods.

Dr Helen Cox, Consultant in Paediatric Allergy & Immunology, Imperial College London

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