Narrator:

Andrea Moreno is the dietetic lead for allergy in the northwest area of England, a role that involves a main caseload of complex, multi allergenic children age within the tertiary Allergy Service in Alder Hey Children's Hospital. She also has close links to the community dietitians and infant feeding teams of the area, providing them with support and supervision. Andrea is very experienced in dealing with infants suffering a variety of allergies, specifically cow's milk protein allergy, and is passionate about shortening their clinical journey by acquisition of early tolerance, and understands the different approaches followed in different countries. She also runs her own private practice in Spain. Please welcome Andrea Moreno.

Andrea Moreno:

Thank you. Good afternoon, everyone. Buenas tardes. Muchas gracias por venir a escucharme hoy. [Good evening. Thank you very much for coming to listen to me today] Thank you very much for such a warm welcome. Today my talk is going to be focusing about what we see in clinic. It's going to be a very practical talk, and I do hope that I can be lots of bridges and connections from some of the talks you have already seen, and some of the talks and speakers that are going to be coming after me.

So these are just quickly my disclosures, just in case. These are the objectives of today's talks. So I'm going to give you an overview of milk allergy, and then we're going to move on to when to suspect actually a cow’s milk protein allergy. I'm going to go through the different differential diagnosis and management of a suspected milk allergy. And then I'm going to focus about what else can we do. But the first thing I will need to do today to see if the coffee has worked is to please pick your phones up. And I'm going to ask you all a very quick question. So let me see if that question is popping up. And it is: what is the worldwide prevalence of cow’s milk protein allergy (in the pediatric population only)? And I'm giving you 4 different options. Is it 0.5%. Is it 2%. Is it 5% or is it 10%? Let's see what your thoughts are about this. I can see everyone inputting some answers. And let's see. Great. Oh, that's a very mixed bag. That's very interesting, actually. Because this was a trick question. So, I don't have a very straight answer about what is the prevalence worldwide. It really depends on where you are based. So, this links in really well onto my next slide, which suggests that prevalence worldwide of milk allergy can be anything from 1.9%, let's round it up to 2-5%. It is the allergy that affects most children worldwide. And actually, in the UK where I work, we have the highest prevalence of milk allergy in the whole of Europe. But it's quite interesting. There has been a recent study that we've done in the UK, really close to us, and it actually suggests that IgE mediated milk allergy, is more common in the pediatric population rather than non-IgE mediated milk allergy, which I was very shocked to see. Cow’s milk protein allergy in formula-fed babies is around 3% and in breastfed babies is somewhere around 0.5 to 2%. So, it affects a little bit less breastfed babies, but it does still affect them. 86%, so most of them, are diagnosed normally in primary care. Some more stats just to let you know: the cost of food allergies estimated to be around €1,500 to €2,000, so more or less that's your basic salary for a whole month that the families are having to spend on the cost of food allergies.

It took an average of 2 to 6 visits to a GP, to a general practitioner, and around 2 months from initial presentation with symptoms until milk allergy was even considered. We are not talking diagnosing, we're saying considered. And there is another real-world study that was done in 4 different European countries that it found the mean duration of symptoms varied quite a lot. So in countries like Belgium, it was around 7 weeks. But in countries like the United Kingdom, it can take up to 24 weeks for a baby to be diagnosed with a milk allergy. And I think that's a very, very delayed diagnosis.

Some differential diagnoses that you will need to think about when you are seeing a baby in clinic are things like colic, and I'm going to take you quickly through all of these, colic, reflux, is it [Gastro-oesophageal] reflux disease (GORD) – it’s highly unlikely to be lactose intolerance, and I'm also going to be touching about this, but we also need to consider things like eczema or atopic dermatitis. What I always advise, is don't delay treating milk allergy if you suspect it, but please try not to start 2 treatments at once, because then we don't know what's actually working.

So, in terms of colic, colic is very, very difficult to actually understand, but it's defined as general irritability, fussing, crying, that starts and ends with clearly no apparent reason, and it lasts for at least 3 hours a day for at least 3 days a week. And it has to last a time of at least 1 week. And it can only happen on infants up to 4 months of age, and there should be no evidence of any other symptoms whatsoever. So, no faltering growth. Colic is very frequent in the first 6 weeks of life, up to 25%. So, 1 out of 4 of our babies will likely present with colic. It decreases to around 10% by the age of 8 to 9 weeks, and it reduces further to around 0.6% by 12 weeks of age, so by 3 months.

Again, the worldwide prevalence is estimated to be around 20%. And as I said it gets resolved. There is no evidence, no strong evidence, to use colic remedies, so things like Simeticone or adding lactase drops, changing maternal diet — there is a degree of using probiotics to help with some of the symptoms, but there is no strong recommendations about using them yet. I think this is going to change in the next 5 years.

Again, no evidence whatsoever about herbal supplements or using manipulative strategies for babies and they actually are quite unsafe, so we always advise against them. Reflux is very, very common in babies. It's not GORD, not the disease. So, reflux, it’s only a baby that possets or vomits with no effort, will just bring up their meal quite easily. They may have a little bit of back arching, dystonic neck position, they can be quite hard to settle, and they don't want to lay down or go to sleep flat. They may cough, gag, refuse the odd bottle, but there should be no faltering growth. There should be no diarrhea. There should be no other symptom.

All of the symptoms are gut-up. It improves with age, we normally say at around 12 weeks it starts to improve because we have the sphincter at the top of the stomach that starts to close and that stops the vomiting and normally resolves, in 90% of the cases, by 1 year of age. It's normal. It affects 40% of the babies. So, it's really important that you reassure parents, yes, it's messy. Yes, we have to do a lot of clean up, but actually probably we don't need to do anything. It will just get better by itself. And this is just a quick number that I like to put across, but babies should drink around 150mls per kilo, of formula at the age of about 1 or 2 months. If I, as an adult, say 65 kilos, have to drink that, I will need to drink 10 liters of fluid a day. I can tell you I will be vomiting. So, just bear that in mind, because it's very, very important to think of it that way.

In terms of lactose intolerance, we can have a primary lactose intolerance or a secondary lactose intolerance. Primary lactose intolerance, it's extremely rare. Babies are created and designed to tolerate lactose because breast milk is really rich in lactose. Some groups are at a higher risk, so if you have people that have an Asian or African heritage, they have a higher risk of having a primary lactose intolerance. But if that is the case, they will not outgrow it.

Secondary lactose intolerance is extremely common, normally linked to things like antibiotic use, diarrhea, any type of infection that has happened in the gut. It normally self resolves within 2 weeks, but if it's very persistent or if the baby is really struggling with it, you could always try something like a lactose free formula over the counter or lactase drops, if this is a mom that is breastfeeding. The symptoms, so reflux is gut-up, in your lactose intolerance, it’s gut-down, so you will only see diarrhea. You will only see bloating, abdominal distention, flatulence, pain, but you should never see any vomiting, blood in the stool, you shouldn't see any rashes. So, it's kind of your other things to be thinking about.

So, moving on to cow’s milk protein allergy. We have mainly 3 types. People tend to think we have 2, but I actually normally see patients with 3 types of allergies. So, you have your non IgE mediated your IgE mediated and also mixed type, which is a mixed bag. So non-IgE mediated you will have normal GI symptoms, so it can be loose stools, diarrhea, blood in the stool and the more severe of the cases of a non-IgE milk allergy will be your FPIES. So, those are your babies that vomit a lot, projectile vomit, they go cold, they go pale, they go floppy, because they have lost so much fluid. They can have eczema and that can be concomitant. And normally a non-IgE delayed milk allergy will happen 2 to 48 hours after exposure so, a very long window. Normally we also see it link in with poor weight gain, but it doesn't always have to happen.

Your IgE mediated, your clear allergy, so it can be urticaria, they can break out in hives, they can have lip swelling, and it normally happens really, really quick, maximum 1 or 2 hours after exposure. There is a risk of severe reactions. So, there is a risk of children developing anaphylaxis. Although very reassuringly, anaphylaxis to milk in under-ones is very, very rarely seen. If that is the case you will obviously need to use an adrenaline auto injector, and it's important to mention that it can also cause GI symptoms, it can cause vomiting, it can cause diarrhea, but it will never be a standalone symptom. And then your mixed type milk allergy, that will be a little bit of a mixed bag. So, it can be someone that a baby that, say, drinks a bottle and they develop lip swelling, but then they have diarrhea 24 to 48 hours later. And interestingly enough, they can outgrow one side of the allergy before the other.

Diagnosis of milk allergy, there are lots of different tools and algorithms, and I've mentioned some guidelines there. But what you always need to do is take a very good allergy focused history. If you are suspecting a delayed milk allergy, you will then need to confirm this, and I'll take you through how to do this. So, in terms of management of non-IgE mediated milk allergy, if it's a breastfed baby and only if they are reacting through maternal breast milk, mum will need to exclude cow's milk from their diet. There can be a clear-out period of up to 2 weeks. And a tip I normally give in-practice is to, if you have that mum, ask them to express breast milk before they go dairy-free. They can freeze that milk and then 2 to 4 weeks later, once symptom resolution has occurred, you can use that milk to challenge the baby without having to, let's say, spoil mum's milk, because then that baby will keep on reacting for a while.

If they are bottle fed, you will need to try a suitable formula based on symptoms and diagnosis for 4 weeks and then challenge. And if it's a mixed-fed baby, only ask mum to avoid milk in the diet if the baby's reacting to her breast milk. Just remember, breast milk is our liquid gold. It's life. It changes every day based on what mum eats. And this is a very good visual slide that I like, just telling you everything that can be included in your breast milk. So, this is some advice that we normally use for how to confirm or how to perform a challenge for a suspected delayed milk allergy. So, we normally advise children or mums or parents to start with a very small amount around 30mls of a normal cow's milk formula, or the express breast milk, and offer that on the first feed of the day. If they don't see any reactions, they keep on doubling that amount, so they go up to 60, 90, 120mls every day until they can tolerate either a whole bottle of formula or a whole bottle of express breast milk. If symptoms reoccur, then we are confirming a delayed milk allergy and mum needs to continue avoiding milk. If there is no symptoms, milk allergy is ruled out. If you have a baby that you suspect an IgE mediated milk allergy, mixed type, or if you also suspect FPIES, the management is the same in terms of exclusion, but you do not challenge them. So for that, you will need to refer them on to the specialist service, and then that service will decide on how to manage that baby.

Broadly speaking, the types of formulas that we have available, and I know we have people from so many countries here today, I know that all of the countries will have EHF and amino acid formulas available, but you may not have either rice or soya in your country, so it's important to bear that in mind. Your extensively hydrolyzed formulas are broken down into peptides. They should be tolerated by around 90% of children with a milk allergy, and there are different options available, some with probiotics, some with prebiotics. It's meant to be more palatable. I always feel very queasy saying this, I think that all formula stinks, so I don't think that these formulas are much better, but just to put it out there, it's meant to be more palatable. And they can be either whey or casein based. Both are proteins of cow’s milk. Your amino acid formulas are completely broken down on to the building blocks. Rarely used first line, they are more expensive and even less palatable. And then rice and soya, very similar, so not available in all countries. Some are very rarely used first line, mostly second line. They are meant to be both a little bit more palatable and they both have an in between price point on in, between EHF and amino acid formula. So, what we do know is that exposure to EHF, either if it's whey based or casein based, helps to drive tolerance in comparison to just using amino acid formulas. Some have added benefits, some formulas have added probiotics, for example, that are proven to help tolerance acquisition. We normally use EHF as first line, amino acid on the second line. And normally we will only need to use amino acid formula first line for things like faltering growth or severe allergies, but in practice it happens quite often. More children should be able to tolerate EGF, but from what I see in my clinic, it's at around 75% of the children tolerated and 25% of them need to go up to an amino acid formula. There is a significant price difference over the formulas. And it is also important to mention that if symptoms don't improve on an amino acid formula, you are not dealing with a cow’s milk protein allergy, and you need to explore another diagnosis. Some practicalities if you are thinking of using a formula with probiotics. So, they need to be made up to different standards to the W.H.O., because you need to make them with water under 65-70 degrees, because if not, you kill the probiotic you deactivate it. There is no harm of doing that, but you don't get the added benefit. Just to put that into context, it's the same risk of using things like a perfect prep machine. It's important to discuss it with a family because you prescribe it, because if you are considering prescription of these formulas, and they are going to be deactivating the probiotic, there is probably no point.

What else can we do to prevent allergy? So, we currently know that there is research going on about very early milk introduction. So those first couple of weeks after birth, we do know that if a child gets exposed to cow's milk and then we remove it, so what we normally call a top up, that actually increases the risk of developing an IgE mediated milk allergy later in life. So, it's better to continue using very small amounts of milk around 10mLs daily to help these children not develop a milk allergy later in life. We do know that maternal diet, even throughout pregnancy, has an impact on the future development of allergies, and there is not a specific food or nutrient that is linked. It's all about dietary variety. We also know that aggressive eczema management early on can help against developing allergies later in life, and there is also dietary modifications that we can do. So, early introduction of other allergens, things like egg or peanut, can also help to reduce the incidence of egg and peanut allergy later in life.

What else can we do for a child that already has a milk allergy? We normally move towards proactive reintroduction of milk, both for IgE and non-IgE mediated milk allergies. In countries like Ireland, they have started doing this from 6 months of age, so very early on. In my practice I tend to do it from 9 months of age, as long as the child has a good diet, in terms of weaning variety. You need to use the right formula, so escalate to amino acid only if needed, and then try to step down as soon as possible. The fact that you have a baby that's a 2-month-old that needs amino acid formula doesn't mean that they are going to need amino acid formula at 9 months, too. Limit avoidance as much as possible for both mum and the baby. The dietary variety significantly impacts on a healthy microbiome long-term. And I think you've heard these so many times already today, and you're going to keep on hearing this, and try and optimize eczema control as early as possible for the better outcome. So, some tips. Just try and be reassuring to parents, listen to them. They come to you, and they are normally at the end of their tether. The baby doesn't stop crying. They don't know what else to do. You are going to be that rock for them that can tell them, look, this is how we are going to improve things.

Try to avoid changing formulas too rapidly unless there is a very clear reason for it. And don't advise mum to avoid more than one allergen at a time, because then we don't know what's made the difference. Vomiting. It's normal. It's very messy. But if a child is growing, feeding well, there is no need to do anything, just leave it there. It will get better naturally. Try and set realistic goals for the family. You are trying to improve the symptoms. You may not be aiming for complete resolution. Just an improvement. And what is the time frame? We are achieving x, y and z in 2 or 3 weeks. And also for some babies try to aim not for perfect skin. They are human and a little bit of redness here and there can be very, very normal.

So, as a summary: early diagnosis of milk allergy is key, long-term outcomes of milk allergy can be influenced by the use of probiotic, but if you're choosing that strategy, please make sure not to use them. Promote breastfeeding as much as possible. It should be our gold standard, and it is liquid gold. Use express breast milk if you can for a challenge. Try to pick the right formula for the right patient and diet and early introduction of allergens can decrease the risk of developing allergies, maybe because we are also influencing the microbiome.

I think we're going to hear a lot more about this from one of our next speakers, so thank you very much.