There’s no doubting that allergies are on the rise. We know it because when we were in school it was pretty rare, but for kids in school nowadays its all too common. The United States, who have been collecting data on the rates of peanut allergy over time, found that in 1997, 0.4% of people reported peanut allergy, and this had tripled by 2008 to 1.4%. Currently, it’s around 2%. Medicine has done a complete 360 in the way that it thinks about allergies and it’s all thanks to the LEAP trial. (…or is it a 180?)
Could it be that expert guidelines have contributed to this massive rise in allergies?
Almost all guidelines, up until recently, have been recommending that we avoid giving babies any sort of allergic foods. The theory was that if babies don’t come into contact with their allergen early in life, they will be less likely to develop an allergy. The United Kingdom Department of Health commissioned a working group on allergies who issued the following recommendations in 1998: If the mother or father or any siblings of the baby have any sort of atopic disease (hay fever, asthma, eczema or allergies), they should avoid eating peanuts during pregnancy, avoid eating peanuts while breastfeeding and avoid giving any peanut products to the child until they are at least 3 years old!
Meanwhile, in the US, the American Academy of Paediatrics, in the year 2000, issued the same recommendations. Here’s a quote from the guidelines: “Mothers should eliminate peanuts and tree nuts (eg, almonds, walnuts, etc) and consider eliminating eggs, cow’s milk, fish, and perhaps other foods from their diets while nursing. Solid foods should not be introduced into the diet of high-risk infants until 6 months of age, with dairy products delayed until 1 year, eggs until 2 years, and peanuts, nuts, and fish until 3 years of age”
Amazing that there was universal agreement on this despite no evidence to back up these recommendations.
Unfortunately, making recommendations without any scientific evidence to back them up is all too common for guidelines. A group of researchers showed that only 6% of recommendations made by endocrinology guidelines were based on randomised controlled trial evidence. And Pierluigi Tricoci and colleagues (JAMA 2009) showed that for cardiology guidelines, this was 11%. Now that’s not the issue, there are a lot of things in our practice that don’t have randomised controlled trial data to guide our decisions. Fine. But here’s the problem: This study also found that 50% of the recommendations were based on opinion only. So no evidence to back it up WHATSOEVER! Again, this is not necessarily a bad thing. But what is completely unacceptable, is that these recommendations are written with the exact same authority as the ones based on high-quality evidence. The same tone, the same language, the same style. And then these become absolute truths. It’s even more frightening when you consider that 50-80% of members in guideline committees have financial conflicts of interest (Neuman 2011). Guidelines need to be more humble when they are making recommendations that are based purely on expert opinion – they should change their wording to something like: “there is no evidence for this recommendation but the committee felt that this was the best approach to manage this situation”. Therefore, patients and doctors can exercise their judgment when applying these recommendations to the very nuanced clinical scenario they are facing.
Back to peanuts. What if the recommendations to exclude dietary allergens early in life was actually harmful? What if it contributed to the huge rise in allergies we’ve been facing?
In 2008, a team of researchers, led by George Du Toit, published an interesting observational study that got everyone thinking.
They surveyed 5,600 parents of Jewish kids in Israel to determine their rates of peanut allergy, and they also surveyed 5,100 parents of Jewish kids in the UK so that they could compare the difference in peanut allergies rates. The thinking was that as they share a common heritage, any difference in peanut allergy rates, would likely be due to environmental influences rather than genetic factors. They also did surveys on both of these populations on how they weaned, when they introduce peanuts and when they introduced other solids to their child’s diet. They found that peanut allergies were more than 10 times higher in Jewish kids in the UK compared to Jewish kids in Israel. The prevalence was 1.85% in the UK compared to only 0.17% in Israel. So whats the difference between these two populations that led to such a massive discrepancy in the rates of peanut allergy?
Well interestingly, while in the UK parents were not giving their children any peanut products, presumably to comply with the guidelines, in Israel, they were giving their babies heaps of peanuts products. Most babies had been introduced to peanuts by 7 months of age. It turns out that Israel has a peanut snack called Bamba – it’s like a dissolving cheese puff- similar to Cheeze Doodles, but it’s made from peanuts and is marketed in Israel for babies as well as adults.
Interestingly, the rates of egg and milk allergy where pretty similar between the two groups which reflects the fact that they both populations introduced them to the diet at similar times.
The researchers who did this study got thinking: perhaps we got it wrong – perhaps the early introduction of allergenic foods protects kids from developing allergies to those foods?
This led those same researchers to conduct the LEAP study (Learning Early About Peanut Allergy).
This was a very well designed, randomised controlled trial. It was “open-label”, which means it was not blinded, which is reasonable given that it would be very difficult to blind parents who are giving their children regular peanut products. The peanut product they used was this Bamba snack, but if they couldn’t tolerate that they could use smooth peanut butter. The study did not receive any money form the manufacturers of any of these products. They recruited 640 babies between the ages of 4 and 11 months and then randomised them to either receive regular peanuts (Bamba) – 6 grams of peanut protein every week (divided into 3 meals) until the age of 5. Or to avoid peanut products entirely until the age of 5. Now the authors didn’t call it five years old….they called it 60 months old. I just translated it for you. I’m good at that because I’m always translating my wife: “how old’s your boy?” “29 months” my wife would say. And as I stand there, watching them looking like they’re trying to solve a calculus equation, I swoop in with: “2 and a half” and watch the sigh of relief come over their face. These babies were all at very high risk of developing an allergy – they had to have either an already established egg allergy or severe eczema.
When it comes to allergy prevention there’s “primary prevention” and “secondary prevention”. Primary prevention is when the child has no evidence of an IgE mediated reaction to the allergen. In other words, they have a completely negative skin prick test or RAST test. Secondary prevention is when a child does have an IgE related reaction to the allergen – so they do have a positive reaction to skin prick testing or RAST testing but you want to prevent them getting a clinical allergy (i.e a rash, tissue swelling, angioedema or anaphylaxis when actually eating the allergen).
The researchers were keen to find out if the early introduction of peanuts could prevent the development of an allergy in both primary and secondary prevention. So for each of the 640 babies in the study, they first did a peanut allergy skin prick test. They then divided the babies into two groups: those that had absolutely no reaction to the skin prick test and those that did have a reaction. The reaction had to be wheal greater than 1mm in diameter but less than 4mm. They excluded anyone who had a wheal greater than 4mm in diameter.
Anyone who was randomised to the peanut group had to have a peanut challenge – This is where they gave the babies peanut products (under strict clinical monitoring and with resuscitation equipment on standby). If they had an allergic reaction to the peanut challenge then they were told to avoid peanuts. But if they didn’t have an allergic reaction they could continue with the study. Interestingly, 87% of those who had a positive skin prick test did not have a reaction to the peanuts when given the food challenge.
At the end of the study, all 640 babies got a peanut challenge after they turned 5. The researchers were keen to find out how many babies in each group developed a proper peanut allergy.
The average age of the baby was just over 7 and a half months. 98 of the 640 kids did have a positive skin prick test and the rest did not. The families in the peanut group were very good at giving their babies peanut products – with an average of 7.7 grams of peanut protein per week across the group.
So what did they find?
Of those who were told to avoid peanuts: 17.2% had a confirmed peanut allergy by 5 years of age. Of those who were given peanuts form an early age, only 3.2% developed a peanut allergy. So there was a 5 fold increase in peanut allergies in those who avoided them. Or to put it another way, an 82% relative reduction in peanut allergies with early and regular exposure to peanuts.
These were the results of the intention to treat analysis. They also did a per-protocol analysis where they excluded people who didn’t follow the protocol either because they had an allergic reaction to the initial food challenge and so couldn’t get peanuts even though they were randomised to the peanut group, or for whatever reason. And as expected with sort of analysis the results were even more impressive – a similar amount of those who avoided peanuts got allergies – 17.3% but much less in the peanut exposure group – 0.3% making it a 57 fold decrease in the rate of peanut allergy with early exposure, or a relative risk reduction of 98%.
They also separated the results based on whether there was a positive skin prick test initially or not. And the results were very similar.
The authors of the LEAP study did a follow on study after this, which they called the LEAP-on study. They followed these children up for another 12 months (or 1 year for all those engaging in calculus) to see whether the benefits persisted and they did.
There’s been other studies as well. Most of them for peanut and egg allergy – all showing early exposure to be beneficial. One particular study, also published in 2016 in the NEJM, randomised 1,300 to either start giving their kids allergenic foods at 3 months, or to start giving them at 6 months. The foods included milk, peanuts, eggs, fish and wheat. And here they found that starting at 3 months was better than at 6 months 2.4% had any allergy in the 3 month exposure group versus 7.3% in the 6 months exposure group.
Among kids with a high risk of atopic disease, introducing peanuts into their diet before 11 months and giving it to them regularly results in an 86% reduction in the development of peanut allergies compared to when they avoid peanut altogether. The benefits hold true even in children who have a positive reaction to peanut on skin prick testing. Guidelines should be more upfront when making recommendations that do not have a basis in the evidence. This may have prevented some of the massive increase in peanut allergies that we have witnessed.