Introducing Allergens

Emily Oster:

My standard school lunch as a kid sent by my mother was whole wheat bread with natural peanut butter on it, no jam. I swore when I was a parent that I would give my kid Jif because the natural peanut butter that I was served came in chunks. When I became an adult, two things happened. First, I immediately started using natural peanut butter because in fact, of course, my mother was right. And second, I actually couldn’t use peanut butter for my kids’ school lunches. That was true for two reasons. One is an appropriately heightened sense of caution and respect for kids with allergies, but the other is a substantial increase in allergies among kids over time. Somewhere along the way, along with these school restrictions, we also introduced cautions about when kids could first have allergens. When my daughter was born, I was told no peanut products until one, and it turns out that this was precisely wrong. It wasn’t just not necessary, it was actually really harmful.

Dr. Gideon Lack:

My name is Gideon Lack. It’s a pleasure to be on this program. I’m a Professor of Pediatric Allergy and Immunology. My main area of interest is food allergies. I work at King’s College London. I happen to be on vacation in the mountains.

Emily Oster:

You have a nice backdrop for this podcast.

Dr. Gideon Lack:

Thank you.

Emily Oster:

So my first introduction to you is through the LEAP study, which is a study about peanut allergies in particular. And just to set the stage for people who are not pediatric allergy experts, peanuts are a very common allergen and for many years, and I will say I have a 12-year-old and an eight-year-old. So with my first child born in 2011, I got the advice that I should avoid giving my kid peanuts until she was at least one, possibly even two. What you show in the LEAP study is that this is literally the opposite of the correct advice. And in this paper there’s a large randomized trial with kids who are relatively high risk of allergies and shows that exposing them to peanuts at four months actually made them much, much less likely to develop a peanut allergy.

Dr. Gideon Lack:

Absolutely, Emily. So as you say, for many decades and for long periods of time while food allergies became prevalent, we mistakenly believed that eating peanuts was the cause of developing peanut allergy. And that was a sort of intuitive belief in terms of cause and effect. You give a baby peanuts, the baby has peanut allergy, they develop hives. Therefore, by virtue of giving the baby the peanut, you must have caused the problem. That’s a bit though, as simplistic as saying that exercise causes angina or heart pain and coronary artery disease, therefore exercise causes heart disease, therefore we shouldn’t exercise. And there was that sort of paradox that was going on. And while I trained in the ‘90s in Denver at National Jewish in pediatric allergy, I was working on mouse models. And it was very apparent that in mice, in order to provoke allergic responses to foods, they had to be exposed through a braided skin or inflamed skin.

Emily Oster:

It’s interesting because so much in science, so often I see people say, “We have some result in mice, it must also be true in people.” But it sounds like here it was, “We have some result in mice, but we think the opposite is true in people.”

Dr. Gideon Lack:

Exactly. But of course, these animal models were not developed with a view to testing food allergy, there were observations that were made. It actually applies in a number of diseases. But yes, I mean not all that happens in mice happens in humans, but here is a good example. You are absolutely right. But even in mice, the critical thing is that it had to be early.

Emily Oster:

That seems likely to me. So before you even got to the randomized trial where you tested this in kids, you actually have an earlier 2008 paper which just compares peanut allergy rates for kids in Israel and the UK. It shows that allergen rates are lower in Israel and then you talk about peanut snacks. I’m right that that’s your paper, right?

Dr. Gideon Lack:

That is right, yes. That’s the Israel-UK paper. And that all came as a result of a lecture I gave in Tel Aviv to a group of pediatricians and allergists, probably it must have been in the late 1990s. And they asked me to come and talk about peanut allergy because with a lot more literature coming out in peanut allergy in the UK specialist journals, particularly in the US specialist journals, and they weren’t seeing much in Israel, but they wanted to be informed about it. So when I gave this actually, there were about 200 pediatricians, I asked, “How many of you have seen a case of peanut allergy in the last year?” And only two or three in the audience put up their hand. Whereas in the UK or US, my guess, it would’ve been 100% virtually or close to that number. And actually many of the specialists there had been trained in the US, so I didn’t think this was an under-diagnosis or lack of recognition. And not wishing to belittle my specialty, diagnosing peanut allergy isn’t that difficult.

Emily Oster:

It’s not that hard.

Dr. Gideon Lack:

It’s pretty obvious to the parent the first time it happens. So I wondered, what’s going on here? And then I spoke to the pediatricians and to some friends who had babies and they all told me they were giving this snack called Bamba, which contains peanut protein. And it’s a puff that babies start very early at about four months of age, it dissolves on the tongue and in fact the whole population eats it. And I wondered, A, whether, first of all, there really is a lower rate of peanut allergy in Israel compared to the UK and whether they really were eating peanuts to that extent. We did a survey looking at 5,000 babies in Israel who were largely Jewish and chose 5,000 children from Jewish day schools in the UK comparing them so that they would have similar ancestral origin and any differences would be due to environment and behavior rather than genetics.

Emily Oster:

No. But I mean, I will say what I absolutely love, and I use this all the time as an example, is that’s observational data and you could easily say Israel, UK differences in diagnoses. I mean, what makes this so powerful obviously and such a great example of how science evolves is that you then did a trial, that you did a randomized trial where you could be more confident about the causality.

Dr. Gideon Lack:

Exactly. And I’m delighted and very grateful that we were funded by the NIH and other bodies for that. I would say that we had been trying to get funding for a study like this for a while. We were lucky to be able to do it because it was such a strongly entrenched belief that exposing babies to peanuts would be dangerous, that it was an obstacle. And we went through a lot of ethical discussions and review committees as was to whether this was the right thing to do. But anyway, that study took off.

Emily Oster:

The study took off and the effects are very large. But actually, I think in some ways the study is very easy to describe and the reductions are very big, but it has not had, I think, as much effect as it should have on behavior. So I’m going to read you a question, which is emblematic of some of the questions that I get from people. So this person asks, “Is there any flexibility regarding the recommendation to introduce allergens at six months? I’ve been dragging my feet on this because I’m worried my son will have a reaction, I’m also worried that the dragging of the feet will end up being the thing that causes the allergy. Is there any wiggle room? Is there a specific reason why the recommendation is to do it when they’re young?”

Dr. Gideon Lack:

Absolutely. I mean, although I like to think of this not so much as a treatment, but a behavior.

Emily Oster:

A lifestyle choice.

Dr. Gideon Lack:

Exactly, it’s a lifestyle because one wants to demedicalize this. It’s about basically eating the foods that are eaten in your environment. Essentially what we did in this study was we took a high risk population. By high risk, we mean children with eczema or egg allergy, between four to 11 months of age. We selected 640 such children who had severe eczema and egg allergy. Why? Because such children, we estimated would have about a 15% risk of developing peanut allergy, whereas the background risk of general population is 2%. So we took a population where the disease was very likely to develop and we randomized 640 babies at that age into either consumption of peanuts or avoidance of peanuts, all the way through five years of age. So as you point out, Emily, it was not just one peanut, it was recurrent, consistent consumption of peanuts, right from the word go.

Emily Oster:

So what’s the age you guys started at?

Dr. Gideon Lack:

So we started between four and 11 months of age.

Emily Oster:

Okay.

Dr. Gideon Lack:

That is a really critical thing. Whoever asked that question gets right to really the essence of the problem here, is there wiggle room? And disappointingly, there isn’t a lot of wiggle room, especially in the high risk babies who have eczema. But what we showed in the LEAP study was that those babies who continually ate peanut, the majority till five years, and the protocol definition, what we were meant to do was eat regularly until two years of age, had a marked reduction in peanut allergy. And these babies were eating six grams of peanut protein per week, which is the equivalent of about 20 to 25 grams of peanut butter, one to two tablespoons or about six teaspoons of peanut butter a week. And at the end of this five-year study, we compared the avoidant group with the consuming group, and we found that the rate of peanut allergy in the children who were avoiding was 13.7%, very close to the 15% we’d projected. And in the consuming group it was 1.9%. Which represents about an 86% reduction in peanut allergy. But, there’s a but here, is that there is-

Emily Oster:

All good so far. Okay.

Dr. Gideon Lack:

All good so far. But 76 babies out of the 800 or so babies we evaluated, we enrolled 640, 76 were excluded because already at baseline, between four and 11 months of age, they had peanut allergy. And we found that the majority of these children had peanut allergy between the age of seven and 11 months is when they developed it, if you looked on a month by month basis.

Emily Oster:

So I think then the question people have when you say, not only did you intervene early, but also that, I mean, two tablespoons of peanut butter a week is not, I certainly eat far more than two tablespoons of peanut butter a week, but it’s not remembering to do it once, it’s just a food you should have in the rotation for your kids starting in a young age. And this is where I think we get into the second piece that holds some people back beyond the information issues, the I’m afraid issue. Then there’s, “Well, what do I give them?” And so one answer may be Bamba, we should all be importing these Israeli peanut snacks. But this is something you have thought about and you have thought about the questions of access. And I think it’s an interesting one because I’m an economist, I think a lot about the market and the ways in which sometimes the market is under providing what we need.

Dr. Gideon Lack:

Yeah, absolutely. And behind this picture too lie the World Health Organization recommendations that babies should be exclusively breastfed for the first six months of life. So with all of this together, there’s been a belief that babies shouldn’t have any solids before six months of age. So not surprisingly, there are not many natural home recipes and there are not many products on shelves that are geared towards giving babies peanuts and indeed other allergens.

Emily Oster:

Just to be clear, you cannot give a baby just a peanut, obviously they will choke. And giving them peanut butter alone is actually not a super baby friendly food.

Dr. Gideon Lack:

It can be mixed and diluted with pureed fruit, but that’s a bit of work. Whole peanuts is an absolute no-no because that’s a major cause of choking and aspiration, like with any sort of small piece of solid food at that age. And the remarkable success story of the Israel puff was that it’s a puff that is readily… Apart from being nutritious and tasty, it dissolves and is very easy for the baby as early as four months to have it, especially if mixed with a bit of water or milk. And in fact, it’s really interesting because you talk about what’s happened to the industry since, and there have been moves in the industry. So one which I was asked to be involved in, I personally don’t like that direction, was to medicalize this and create formulae or powders rather containing X amounts of peanut other food allergens. The problem with that, as I said, is it’s medicalizing this. And again, babies aren’t going to drink milk with powder for the first few years of life, they’ll do it for a few months in transition.

Emily Oster:

You don’t like a mix-in.

Dr. Gideon Lack:

Well, the problem with the mix-ins is there’s a few problems with that, Emily. One very real and the other theoretical. So the real problem with a mix-in and a powder is getting enough of the food proteins in. And there have been products out there that contain milligram quantities of peanut, whereas we know that you need gram quantities and we’ve done modeling showing the minimum you really require is two grams of peanut protein, two grams of egg white protein. So the powders usually, not all, but usually contain lower amounts. My other concern about the powder is that it comes in mixed with formula. And I’m afraid you didn’t want to get to the dual allergen exposure hypothesis.

Emily Oster:

I do. Yeah.

Dr. Gideon Lack:

That sort of ties in because we have belief and there’s strong evidence for that, that babies develop peanut and other food allergies through their skin. Why through their skins? Well, in general, babies have a thinner skin, a less effective skin barrier, and that is particularly the case in babies who have eczema or dry skin.

Emily Oster:

So I want to turn a little bit to something else that we’ve talked about a bit, which for me was some of the most surprising things I heard from you and we touched on a little bit early on when we were talking about your work in mice. But one of the things that parents hear quite a lot and has come up in this conversation is that allergies and eczema are linked. If your child has eczema, they’re at a higher risk of allergies. And that fact is just true in the data, there’s a strong correlation there. And I had always interpreted this as reflecting some underlying shared cause. That basically some people’s immune system reacts differently to things and so it is that underlying cause that is both the eczema and the allergies. But my sense from you is that there’s another school of thought that you think is correct is effectively that the eczema is causing the allergies or is contributing to the allergies. Is that the right way to say that or am I getting that wrong?

Dr. Gideon Lack:

Well, you’re saying it absolutely where… I mean, logically there’re three possibilities if two things are strongly associated. One is there’s an underlying shared cause. And I think to some extent that is true for peanut allergy and eczema or food allergies and eczema. The other is that food allergies cause eczema. And the third is that eczema causes food allergies. And this is a perfect example where correlation does not prove causality. We saw this very high correlation in pediatrics amongst babies with eczema and saw they had food allergies and we said, “Well, it must be the food allergies that’s causing their eczema. Remove the milk, remove the eggs, remove the peanuts.” And that’s the worst thing you can do. Why? Because it’s the eczema that leads to the food allergies.

Emily Oster:

That’s worms. Just so people… That’s worms. Yeah.

Dr. Gideon Lack:

And that’s a worm. Absolutely. And the body to reject it would mount IgE allergic antibodies. So really what this is a rejection response. So we believe that we misinterpreted this association to mean food allergies calls eczema, whereas I believe it’s more, and a lot of colleagues believe now that eczema leads to food allergies. But as you say, there may way be an underlying shared genetic or other factors involved.

Emily Oster:

But I mean it’s an extremely interesting idea. And just to recap in slightly more lay terms, effectively the idea is that the allergens are going through the window and they should have gone through the door and when they come in through the window, there’s a response mounted and your body says, “Hey, this is something we don’t like. This is a problematic entrant of some type.” And then when you see it again, even coming in the right way, your body is already sensitized to this.

Dr. Gideon Lack:

Absolutely. And I like your window, door analogy, only I would flip it the other way around. If you take a day-to-day scenario, someone knocks at your front door and politely asks you directions or something, you’ll be civil to that person. But if that person knocks through your bedroom window and tries to break into your house that way, you won’t be quite as friendly in your greetings. And the body is like that, it depends on the route of entry. If it comes in through the mouth very early on, well that must be a food, it must be a good protein antigen and we mount what’s called a tolerogenic response where the immune system goes in a direction that will prevent the development of food allergies. If you are exposed very early on through a broken down skin, the immune system and the cell sitting in that skin issue out an alarm, “Hey, there’s an invader coming in, let’s mount an allergic response to repel it.”

Emily Oster:

Taking the logical step I think for parents, and I understand this is still not something where we have large randomized trial evidence and I want to talk about how we’d get that. But if this is true, and one thing I might conclude as a parent is that if I have a baby with eczema, and I did have two of those, that the best way to prevent allergies is initially when they are infants, before they’re having solid food, for me to avoid allergens in my household and then to introduce allergens to them more or less as soon as they’re having solid food, so I avoid this kind of other alternative exposure approach.

Dr. Gideon Lack:

Yes, and logically that makes sense. In countries where peanuts are not consumed, you don’t see peanut allergy. So you could argue in households where peanuts and other allergens are not consumed, you won’t see those food allergies. But bear in mind there’s not just peanuts, there’s eggs, milk, tree nut, sesame, wheat, fish, et cetera. And that would mean you’d need to avoid all these foods in your household. And even so it wouldn’t be a guarantee, first of all because peanut is a very tenacious, persistent protein that hangs around for long periods of time. Secondly, there’s going to be so-called contamination from people who are eating peanut, entering your home environment, friends, relatives. So although it may be a strategy that is-

Emily Oster:

It’s a lot of work.

Dr. Gideon Lack:

… very difficult to put to the test, as you say, it’s a lot of work. It’s a lot of work and may not work. And our view now, mine and that of many of my colleagues is introduce babies to those foods much earlier on orally. And we do believe that the oral route trumps the skin route. So if a baby’s exposed both through the skin, and it takes tiny doses, this is the interesting thing, it only takes tiny doses, less than microgram doses to cause the development of food allergy through the skin. Whereas to protect orally, you need gram doses. So get the baby onto good amounts of these foods, the same way the rest of the family is eating them, and that ought to protect against peanuts and we believe other food allergies as well.

Emily Oster:

Are there efforts to test these dual allergen eczema hypotheses in randomized trials?

Dr. Gideon Lack:

So there’s observational data. For example, we did a case-control study where Adam Fox, a colleague of mine, when he did his PhD thesis equivalent in the UK, looked at environmental peanut consumption in the home and found there was a strong association between that and the risk of developing peanut allergy. It was almost like a dose-response curve. The more peanut there was around in these babies [inaudible 00:31:37], the higher the chance of developing peanut allergy. But when, and although this wasn’t a randomized controlled study, when you looked at the babies who’d eaten significant quantities of peanut early on in the first year of life, that relationship was destroyed. The line was flat. So you saw both oral versus skin interacting.

Emily Oster:

It’s fascinating.

Dr. Gideon Lack:

But there’ve been studies that have been a bit disappointing using emollients. So those are moisturizers essentially to try and protect the skin barrier in babies with dry skin and eczema. Regrettably, so far we’ve not seen a reduction in peanut allergy. It may take more than that, but also the use of topical steroids, try to reduce the inflammation that is already present. So there is definitely, and in fact I’m involved in a multicenter study with my colleagues in the UK and in the US called the SEAL study where we are taking very young babies in the first weeks, couple of months of life, at high risk who have already very early onset eczema or dry skin. And we are regularly moisturizing them and as soon as they develop any hint of redness of the skin, the beginnings of inflammatory eczema, we treat proactively with topical steroids. So that may be an approach that is promising.

Emily Oster:

Also very unpleasant to begin with. Yes.

Dr. Gideon Lack:

Not a pleasant… Yeah, sleepless nights and everything. So that based on the dual allergen exposure hypothesis, you can make a number of predictions. One is that oral consumption will prevent food allergies.

Emily Oster:

That’s the actionable… I mean I think if we had to say, what’s the actionable takeaway? I think that that is for parents the actionable takeaway. It’s really that oral exposure in a consistent manner to these allergens, starting as soon as you introduce foods is the best way we know to prevent allergens at the moment.

Dr. Gideon Lack:

Yeah. And early on you’d ask me about my concerns about putting powder in formula. I mentioned two concerns. One is that there’s not enough of the allergen getting into the baby because it’s difficult to put this in powder form already mixed with milk. But the other is that eczema and dry skin occurs primarily initially on the cheeks of babies. And if they are being exposed to low dose, microgram or milligram exposure through their inflamed skin and are not having sufficient quantities going down the gastrointestinal route because one, let’s face it, milk does tend to spill as do all foods, but particularly milk and liquid on the baby’s cheek. There’s a theoretical concern by giving low dose allergen or foreign proteins that cause allergies through the skin and not sufficient through the gut as this is a potential setup for paradoxically increasing food allergies. Of course, that-

Emily Oster:

It’s a theory.

Dr. Gideon Lack:

… remains to be proven and very difficult to prove, that is theory. But what we do know is that low dose exposure through the skin does lead to food, especially peanut allergies.

Emily Oster:

Okay, so here are a couple lightning round questions about allergies that I’ve gotten from readers over the years. Allergens and the exposure to allergens through breast milk and through pregnancy. So I think a question we get a lot from people is, if I consume a lot of some allergens, peanuts, eggs, et cetera, while I’m pregnant or while I’m breastfeeding, is that going to make my kid less likely to be allergic, more likely to be allergic, does it not matter?

Dr. Gideon Lack:

So people have looked at this, obviously not in a randomized controlled trial, but observational studies go both ways. So there’re some studies showing that mothers who eat more peanuts while breastfeeding, the babies are protected, others that show the exact opposite. This study that I mentioned to you where we showed the dose-response curve between environmental exposure, which basically was based on total family consumption. Each family unit member, we calculated the amount of peanut they were eating and came up with a total family consumption and that was the environmental exposure that young babies had. And we did find that maternal consumption of peanut during both pregnancy and the breastfeeding period was slightly correlated with developing peanut allergy.

Emily Oster:

Okay, second question. Let’s imagine that my kid does develop an allergy. Is that necessarily an allergy forever or do allergies pass? And does that differ across different allergens?

Dr. Gideon Lack:

So egg and milk allergy go away in the majority of babies, usually between one and three years of life. But a not insignificant minority, about 10% to 20% will have persistent egg and milk allergy. With peanuts, nuts, seeds, we see the reverse. These food allergies develop very early on, but tend to persist later into adolescence and young adulthood. No one has actually followed up people with peanut allergy for 50 years, but we know that bar the 20% to 25% of children with peanut allergy who outgrow it, because about a fifth to a quarter will outgrow it, the vast majority will have lifelong peanut allergy. Same seems to apply to tree nuts and seeds. But that’s one of the reasons too, by the way, that peanut and nuts are such an important group because you don’t want something…. Okay, if it’s a problem that’s there for year or two, you can live with it, adapt to it, but if it’s going to be there for the duration of that person’s life, it becomes a huge burden and affects all sorts of things, quality of life, et cetera.

Emily Oster:

This has been amazing. I feel like for me this is such a treat because I really am an enormous fan of your work and I think it is such a great example of how science evolves.

Dr. Gideon Lack:

Well, it’s been a pleasure talking to you, Emily. I’m a big fan of your work and you’re good at debunking a lot of science myths, so it was good to talk to you.

Emily Oster:

It was great to talk to you. Thank you so much.

Dr. Gideon Lack:

Bye-bye.

Emily Oster:

Thank you again to Dr. Gideon Lack for joining me and for his tremendous work in this field. You can read his paper on the LEAP study as well as The American Academy of Pediatrics response to its recommendations on our episode website and in the show notes. More ParentData, including your own stories about introducing allergens after the break.

Voice 1:

Hi, Emily. I wanted to share an introducing allergen story.

Voice 2:

Hi, my name is Hailey Goodwin.

Voice 3:

Hello, my name is Amy Timpe, and this is a story about allergen introduction. My story regarding allergens pertains to how different the recommendations can be depending on where you bring your child for a pediatric visit.

Voice 4:

When our first daughter turned six months old, I made her a peanut butter, egg and banana pancake just like everyone else on Instagram. And of course she developed a red rash around her face and my husband was like, “Darn, I guess she has an egg allergy. Continue on with the peanut butter.”

Voice 2:

When my firstborn was an infant, we lived in a University City. The pediatrician educated us on the risk for allergies and at six months told us that my daughter was moderate risk and that she should begin introducing peanut products.

Voice 4:

Little did we know, she also had peanut, walnut and pecan allergies. And so as we continued to introduce these nuts, she continued to get this red rash. And so we saw the allergist who was fairly out of date and said, “No nuts of any type until she’s five.”

Voice 2:

Flash forward a few years and we moved to a different city and my second born at her nine-month visit was told not to introduce peanuts, eggs or other allergens. And when I told her, “Well, we’ve actually already introduced them because she’s moderate risk.” She looked at me like I was crazy. I then ended up informing the pediatrician and she said that yes, it should have been corrected and that their binders the nurses were educating parents on were outdated.

Voice 4:

Thankfully, we chose not to follow that advice and sought the advice of a different allergist who introduced us to oral immunotherapy or OIT. We started OIT for our daughter at two and a half and did weekly visits to the allergist who lived about three hours away, and now she is in first grade with no Benadryl, no EpiPen. She regularly eats peanuts freely and enjoys them. She still doesn’t like eggs, but she no longer is allergic to them.

Voice 2:

So with my first, super anxious about introducing allergens, and I was told, “With eggs, mix it with breast milk. Boom, you’re good.” So I hard-boiled the egg, took the yolk, mashed it up, mixed it with breast milk, baby loved it. Great. Then a month later, I have scrambled eggs again, and this time we’re at a park and his ears start swelling up. And I stopped feeding him the egg right away, realized it was an allergic reaction. But book an allergist appointment and find out that the actual allergen for egg is usually in the whites, not the yolk. So by introducing him to this yolk and breast milk, which is what everyone says to do, I actually wasn’t exposing him to the allergen and didn’t catch it. But anyways, I always share that anecdote with people because I think it’s important to know where the allergen lies in eggs.

Voice 4:

And that’s our story of having an allergic reaction at six months old.

Voice 2:

Thanks for listening.

Emily Oster:

Thank you so much for sharing your stories with me. Please keep an eye out for our calls for more stories like these. ParentData is produced by Tamar Avishai, with support from the ParentData team and PRX. Also, special thanks to our house violinist, my daughter Penelope.

Penelope:

No problem, mom.

Emily Oster:

If you have thoughts on this episode, please join the conversation on my Instagram @Profemilyoster. And if you want to support the show, become a subscriber to the ParentData Newsletter at Parentdata.org where I write weekly posts on everything to do with parents and data to help you make better, more informed parenting decisions. You can subscribe for free or sign up for a paid subscription, which comes with great benefits, including an ad-free version of this podcast and full access to literally hundreds of my posts at Parentdata.org. If you like what you hear, please leave the show a positive review on Apple Podcasts, it really helps people find out about us. Right, Penelope?

Penelope:

Right, mom.

Emily Oster:

We’ll see you next time.