S. Sicherer, R. Wood, D. Stablein, R. Lindblad, W. Burks, A. Liu, S. Jones, D. Fleischer, D. Leung, and H. Sampson. JACI 2010 in press

How does peanut sensitization occur? How can we prevent peanut sensitization? What are the risk factors associated with the development of peanut allergy?

There are  very few proven answers to these questions. The number of theories to explain this abound. Thankfully we are seeing more clinical research intent on finding answers to this common problem of peanut allergy (sensitization). Of note, many of our recommendations for preventing peanut allergy/sensitization have been challenged. This is in part due to the existence of a paucity of data to support current recommendations and conflicting results from newer studies. This article is the latest on the topic of risk factors for the development of peanut sensitization. The article will be published in the Journal of Allergy and Clinical Immunology 2010.

Current recommendations from the American Academy of Pediatrics (American Academy of Pediatrics, Committee on Nutrition. Hypoallergenic infant formulas. Pediatrics 2000;106:346-349.)are that peanuts should be avoided during pregnancy and lactation for an infant at risk for developing allergy. Two studies (published in 1996 and 2003) challenged that concept and concluded that peanut consumption during pregnancy/lactation was not a risk factor. We now have a much larger study performed with specific attention to mother’s dietary history that has concluded that peanut ingestion during pregnancy is indeed a risk factor.

The Purpose of the Study

The study came from the Consortium of Food Allergy Research. Five sites contributed to the work. This is a report on the clinical, demographic, and immunologic factors that were associated with an elevated specific IgE (value greater than 5 kU/L) to peanut (done by a blood test for peanut antibody) in a large group of children with known egg or milk allergy (without previously known peanut allergy). The specific interest was the discovery of a behavior that could be modified if relevant- mother’s ingestion of peanuts during pregnancy and the frequency of that ingestion.

Methods and Subjects in the Study

The cohort group was 512 infants and children, 3-15 months of age at enrollment (average age 9.4 months). To be in this group, the children had to have an allergic reaction and a positive allergy skin prick test to egg and/or milk. No child with a known peanut allergy or with a positive peanut specific IgE (blood test) done prior to the study was enrolled.

Questions were answered about the diet, the social situation, and the environment. There were five categories for maternal peanut ingestion; total avoidance, ingested <2 times/week, ingested more than 2 times/week, ingested daily, or unknown. The term ‘frequent’ meant that peanuts were eaten 2 or more times in a week.

Allergy testing included skin testing, blood tests for specific IgE, and tests for specific IgG to peanut.

What they found

A specific IgE of 5 kU/L or greater was selected as the cut-off point for evaluation. This was the level that was associated with more than a 70% chance of having a reaction to peanut (taken from other studies). There were 140 children (27.8%) who had a peanut specific IgE to peanut >5 kU/L.

The results were presented in a number of different ways; univariate analyses, multivariate analyses, and an analysis for receiver operator characteristics.

Looking at how a number of variables that could act alone as risk factors: there was no association between peanut IgE >5 kU/L and age at enrollment, age when formula was introduced, age when solid food was introduced, household income, parent education level, atopic disease in the parent, exposure to soy formula, breastfeeding, type of birth delivery, or use of antibiotics.

The variables that have a significant association included the following; male sex, race, atopic dermatitis severity, and peanut consumption during pregnancy >2 times/week. Peanut specific IgE was highly correlated to egg and milk specific IgE levels.

There was a dose-response associated with mother’s peanut consumption and peanut specific IgE >5 kU/L- the more peanuts consumed-the greater chance of having a child with a peanut specific IgE >5 kU/L. Further analyses showed peanut consumption during breast feeding to have no association with peanut IgE in one model of analysis.

Using a linear regression analysis and adjusting for egg IgE, milk IgE, severity of atopic dermatitis, sex, study site, and race, only peanut ingestion during pregnancy predicted peanut specific IgE.

The ratio of IgE to IgG for food has been noted to decrease for those who have achieved natural tolerance or in those who have undergone oral immunotherapy. A high IgE to IgG ratio may be related to a higher risk of demonstrating allergic reactions.

Conclusions

In a dose-dependent fashion (increase the amount eaten by the mother leads to an increase in sensitization of the child) mothers eating peanuts during pregnancy was associated with an increased chance of peanut allergy developing in the child known to have egg and/or milk allergy.

The factors that have been associated with this included; male sex, nonwhite race, and elevated milk/egg IgE levels.

Cautions and Concerns

The observation that boys tend to have more food allergy is well known. In regards to race, Asians tended to be at higher risk. The association with egg /milk allergy as a risk factor was not unexpected. Sensitization to these multiple foods is known from previous work.

Atopic disease was not a risk factor; however this group of children was selected for having atopic disease. There was no association with soy ingestion and peanut sensitization (both are legumes). There was also no association with the use of medications to suppress gastric acid. Having peanuts in the home was also not a risk factor in this group.

The authors point out that this was an observational study. They found associations or risk factors- not causative factors. To prove allergy, a peanut challenge would be required.

My comments

This report is to be published in an excellent peer-reviewed journal with authors who have national if not international reputations for excellent science in the world of peanut allergy.

The problems with other studies similar to this were identified in the discussion part of this study. One of the problems is the recall of peanut exposure during pregnancy by the mother. Here the enrollment and history was taken soon after birth. It was hoped that dietary exposure history would be less biased with this approach.

The study also points out that this was sensitization to peanut and not clinical peanut allergy: there was no history of a peanut reaction in these children. They worked with a laboratory value that was associated with a high risk of having an allergic reaction taken from a different group of children. So there was a very good chance that a reaction could occur.

The results also pertain to a specific population. The study was performed in a group of children who were selected due to known egg/milk allergy.

So the mothers of children who currently suffer with egg/milk allergy should not have eaten peanuts 2 or more times per week during pregnancy. This sounds like advice given too late to make a difference. The point however is the association of peanut ingestion in pregnancy with peanut sensitization in known egg/milk sensitive children.

The AAP recommendation is that mothers with infants at risk for atopy should not eat peanuts during pregnancy.  So that ‘at risk’ infant would be one with one parent and/or two parents, and/or a sibling with allergy.

Clearly more work is needed before declaring these associations as recommendations. This is the latest work on risk factors.  Mothers that eat peanuts less than twice a week may decrease the risk of peanut sensitization, if the child goes on to have egg/milk allergy. They may also not worry about eating peanuts during breast feeding of a child who has known egg/milk allergy.  

This also begs the question of how many peanuts were eaten. This is a frequency factor (>2 times per week). Perhaps there is a quantity factor as well. My guess is that a serving work be considered the standard exposure. One resource lists one ounce of peanuts or two tablespoons as a serving. The authors point out that this group needs to be followed with a peanut challenge in their future.

This was a fascinating study to read and review.

FEL

Up until a week ago, I had never heard of fenugreek.  On my first day back at Riley to start the 2009 new year, I had a young man, just under 2 years of age who presented with concerns about reactions to legumes. The list of suspects included peas, green beans, black beans, baked beans, and lentils. The mother also shared with me that during breast feeding she used ‘fenugreek’. This product is used to help nursing mothers. In our discussion, the mother brought up the concern that the fenugreek may have contributed to the legume reactions.

I had not heard of ‘fenugreek’ prior to this. I have been involved with allergy long enough to know that any food product ingested by mankind for as long as we have been on the planet has been implicated in an allergic response. I wanted to know more about this ‘fenugreek’.

I consulted my online food ‘Allergy Advisor’ regarding fenugreek and got a wealth of information to get me started. To my surprise later that week the Journal of Allergy and Clinical Immunology (JACI) had an article from a group in Norway regarding fenugreek.

Fenugreek (aka Greek hay, Greek fennel, Bird’s foot, Greek hay-seed) is a legume. It is used as a flavoring in many foods including curry, blends of spice, and even tea. As an herbal medication it has been touted as being helpful in initiating and maintaining milk production. There are references for its use in diabetes and hypertension. Importantly, it is a legume and many legumes share certain proteins and may be cross-reactive in some patients.

The purpose of the JACI article was to evaluate the allergenicity and antigenicity of the proteins in fenugreek. There were 29 patients in the study who had specific IgE antibodies to legumes, peanut, soy, pea, lupin, and fenugreek. These patients ranged from 1 to 53 years of age. High levels of antibody to both peanut and fenugreek were found in most patients and the sensitization to fenugreek was believed to be due to cross-reactivity in those patients with peanut allergy. In this study, the reactivity to the other legumes was weaker. Here the other legumes (specifically peanut) were implicated in causing sensitization to fenugreek. With the young lad that I saw I wondered if there is the possibility that the fenugreek may have worked in the opposite direction – fenugreek exposure causing sensitization to the other legumes.

I was not aware of this association: fenugreek and peanut. In my clinic notes I debated about doing the peanut test since he had no exposure, but since he reacted to a large number of the other legumes I had the skin test placed. His response was positive to peanut.

The world of IgE-mediated reactions to foods is growing significantly. Our diets are changing with significantly more opportunities for ingredients in foods from other lands becoming part of our lives. Herbal supplements may contain a variety of items that could lead to sensitization. It is important to inquire about the use of such products.