Narrator:

Introducing Dr Patrick Tounian a distinguished figure in pediatric healthcare, serving as a Professor of Pediatrics at Sorbonne University and heading the pediatric nutrition and gastroenterology department at Trousseau Hospital in Paris. With a vast background in clinical research, Dr Tounian focuses on childhood obesity, pediatric dyslipidemia, iron deficiency and food allergy. His extensive contributions to the field include 130 publications in peer reviewed journals, primarily addressing these critical pediatric health topics. Dr Tounian is passionate and dedicated to advancing pediatric healthcare and has significant influence within the medical community, which underscore his commitment to improving the wellbeing of children in France and beyond. In addition to his clinical roles, Dr Tounian holds prominent positions, including President of the French speaking Pediatric Association and Vice President of the French Pediatric Society. Please welcome Dr Tounian.

Dr Patrick Tounian:

I really enjoyed to be presented as a rock star. Really. Good morning. Buenos Dias, Los Americano and thank you to Mead Johnson team, because I'm very happy to be here in Thailand the first time, but I hope it's not the last. So my topic today is on cow’s milk protein allergy, of course, from allergy prevention to tolerance development. But first you are going to answer two questions. Please. May I have the two questions? They are easy.

The first one giving complimentary bottles containing whole cow’s milk protein to newborns were intended to be exclusively breast fed at maternity ward, of course, in the first days of life on maternity ward for you is that:

Decreases the later risk of cow’s milk protein allergy.

Increases the later risk.

Or it has not effect; Or has not any effect.

Answer, just one or two bottles, no more at maternity ward, neonates, who are intended to be exclusively with breastfed. Ok, the first one is leading, OK? The answer please.

So you have to listen to me, because you don't know.

The second you have a second chance, in infants with cow’s milk protein allergy treated with an amino acid formula. We have just talked it before. Switch to an extensively hydrolyzed formula with casein with LGG, will

Promote faster tolerance acquisition

Will delay, faster tolerance acquisition,

Or as no effect.

Second chance.

But the last I have no more questions. Okay, congrats. Thank you. Good so at the end of my presentation, so you have to listen to the beginning. So cow’s milk protein allergy has an impact on nutrition and growth, and in order to reduce this impact, we have to improve prevention. It was not the first, oh, sorry. It's not really the first. Oh, sorry, okay.

Cow’s milk protein allergy has also an impact on quality of life and cost incurred by the families and the insurances. And in order to reduce this second impact, we have to accelerate tolerance acquisition. So first, we are going to see how to reduce the impact on nutrition and growth, and what is really this impact on nutrition and growth when complementary feeding begins. I've just talked about with Rosan, then the. Infants could reduce their hydrolysate intake, and if they excessively reduce their hydrolysate intake, since they cannot compensate with eating dairy products because they are allergic to dairy products, and since hydrolysate represents, for these infants, the main source of calcium, they become at risk of calcium deficiency.

So we should, you should choose the formulas with the highest content of calcium, if the child, the child is excessively reducing is intake of hydrolysate. In France, for example, the highest content is Mead Johnson products. I don't know if it is the case in your countries, and if the recommended intake of calcium are not covered, then you should give a supplementation of calcium to these infants.

Now, the impact of CMPA on quality of life in this study, a questionnaire was given to parents of infants with cow’s milk protein allergy. They showed that the longer CMPA lasts, the worse quality of life becomes. It's really clear in this picture.

And finally, the cost, the cost of cow's milk protein allergy for families, for incidences. We performed this study last year, and we used the study from Canani et al. Rosan talked it, Benjamin, talk about it. And we showed that the cost, the global cost, of cow’s milk protein allergy, is around 2000 euros, $2,000 if you want, so it's very expensive. And if we use amino acid formula, it's more and more expensive. So we should reduce this cost. So we are going to see now how to reduce both impacts on nutrition and growth first, and to reduce this impact, we have to improve prevention. First, there is really insufficient evidence to recommend the use of probiotics, prebiotics, symbiotic for CMPA preventions, many studies showed it.

Dietary restriction and particularly diary restriction during pregnancy and lactation are not indicated. Here, I asked, asked yesterday, because you in Thailand, you are eating a lot of peanut and Panote said me that peanut allergy is very rare here, probably because pregnant women, perhaps lactating women are eating a lot of peanut. This is the same in many other countries where eating peanut is very frequent. So it's important to encourage your pregnant women to eat a lot of allergenic foods, particularly peanut and here, now dairy products, of course. Moreover, in a study we performed comparing 554 CMPA infants and 211 controls, we demonstrated that avoiding eating dairy products could during pregnancy and lactating, pregnancy or breastfeeding, yes, could even increase the risk of cow’s milk protein allergy. So it's very important to continue to eat these products.

Now let's move to the first concept, the dangerous bottle. What does it mean this? This woman has just given birth to her baby, and she wants to exclusively breast feed her baby. She was probably tired, and the night after the delivery, the nurse gave the baby a bottle containing whole cow’s milk protein. It was well intentioned, but it is dangerous. I remember you this mother wants to exclusively breastfeed her baby.

Why is it dangerous? We know from the last century that giving a bottle at maternity ward, one or two bottles to infants, to neonates who are exclusively breast feed, fed, could increase the risk of cow’s milk protein allergy. Yeah, more than 5000 breast fed neonates required a complimentary bottle because of risk of hyperglycemia, for example, and they were not only assigned to the three groups. The first one received a cow’s milk formula with whole cow’s milk proteins, the second one pasteurized human milk and the third one, a whey hydrolysate formula, 18 to 34 months later, the risk of cow’s milk protein allergy was 1.5 fold higher in the group who received the first formula with whole cause milk protein, indicating that it increased the risk of cow’s milk protein allergy.

This was last century, but more recent studies confirmed this data here, 211 children with CMPA compared with controls, and this famous dangerous bottle in maternity ward increased five-fold the risk of cow’s milk protein allergy, and when the children. The child was born from C section, C section plus dangerous bottle increased 12-fold the risk of cow’s milk protein allergy.

Another study, again, randomized study, more than 300 newborns. They were randomly assigned to receive a complimentary bottle, one bottle, a complimentary bottle with whole cow’s milk proteins, and another group who did not receive any complimentary bottle, so exclusively breastfed, all of them are exclusively breastfed. You understand that, so one with one bottle of cow’s milk protein, with cow’s milk protein, and other one exclusively breastfed or receiving an amino acid formula. Then they compared the two groups, and they showed that sensitization, higher CMPA specific, IG level and cow’s milk protein allergy were higher in the group who received the cow’s milk protein,

We also in the study I talked before, we also confirmed that showed the same thing, but we asked another question. Here at maternity ward, the neonate is exclusively breastfed, okay, but after discharge from the maternity ward, after three days, he's going home, and it could receive also one or two bottles, not continuously. You understand that it's only one bottle two bottle, because the mother is not available one evening, and then the father gave him a bottle with cow’s milk protein. And our question was, is it only at maternity ward, or is it also the same in the first month of life after discharge from maternity and our answer was no, it could be exclusively in maternity ward. This was our result, but another study didn't find the same result.

It was a better study, sure nearly almost 2000 infants with cow’s milk protein allergy, and they tried to see that fitting patterns could influence the risk of later cow’s milk protein allergy. And when they compare, when they compared the, it was in red. It is in red here. So they are breastfed. I want to be clear this. The children are breastfed, exclusively breastfed, and during the first two months of life, they are at home. They received no more than five bottles. So in two months, they receive, perhaps at day 10, at day 20, less than five bottles during the first two months of life. You understand it so exclusively breastfed and 1, 2, 3, bottles during the these two months, and when compared with those who receive continuously cow’s milk protein because they are not breastfed or because they are mixed they have mixed feeding, breastfeeding and bottle feeding, then you see that the risk with these dangerous bottles of later cow’s milk protein energy is really increased.

So my first conclusion is at maternity ward first when the mother decided to exclusively breastfeed her infant, we should avoid a complimentary bottle, but some and probably during the first two months of life, but sometimes some neonates need a complimentary bottle because they are at risk of hypoglycemia, then we should use an extensively hydrolyzed formula or an amino acid formula, but never a bottle containing whole cow’s milk protein.

Second concept difficult to understand. This is the first study. It's a randomized control trial. They took infants exclusively breastfed, and at one point of life, they separated them into two groups, randomly outside. The first group in blue received 10 milliliters per day, two teaspoons of milk. They are exclusively breastfed, and they receive every day, two teaspoons, 10 milliliters per day. The other group in red, here was remain on exclusive breastfeeding. So two groups, one, all of them are exclusively breastfed. One, receive every day. It's not the same that dangerous bottles. Dangerous bottles was one, two or three bottles. Now every day, they receive 10 minutes per day of cow’s milk, and the other group is exclusively breakfast, and this between one and three months of life. At six months, the risk of CMPA was eight-fold lower in infants who received these 10 milliliters per day of cow’s milk protein. You understand the difference one or two bottle at maternity ward or during the first two months of life for the dangers. But here every day, they received 10 milliliters per day.

And these results were confirmed with other papers. This one, I already showed it, it was the risk of CMPA according to feeding patterns. And as you can see here in dark blue, the IGE mediated CMPA, the most civil form of cow’s protein allergy, was exclusively seen in infants, exclusively breastfed. The other forms were seen in whatever the feeding pattern, but the most civil form was in exclusively breastfed infants.

And finally, this, later, this late last study showed that the earlier the discontinuation of CMPA ingestion, you see 41% of cow's milk protein energy, and the higher the risk of cow's milk protein allergy. And you see at the right part of the slide that those who received continuously everyday cow’s milk protein because they are not breastfed, or because they are mixed breastfed, or because they are receiving 10 millimeters per day of cow’s milk, only 0.6% of cow’s milk protein allergy. So the second conclusion is that after discharge of the maternity giving 10 millimeters per day to teaspoons of cow's milk to infants who are exclusively breastfed. You understand this is continuously, not occasionally, like dangerous bottles infants at risk of allergy, then it could reduce the risk of later, cow’s milk protein allergy. But of course, further study are necessary to. Confirm, to confirm this recommendation, to better define the beginning time at birth, at one month. We don't know exactly the volume and the frequency of this milk supplementation, of course, the result of components, because they are saying that you are going to give cow’s milk to breastfed infants, though, so the duration of breastfeeding could be reduced, perhaps.

But the study, the space study, is the study I talked about just before. You know, 10 millimeters per day versus exclusive breastfeeding. Blue and Red showed that 70% of the infants were still breastfed after six months, so it didn't modify the duration of breastfeeding.

So this was the first part, second part shorter, reducing the impact on quality of life and cost by accelerating the tolerance acquisition. We already you already heard that, but you know, teaching is the repetition, so it's very good. First Choice in cosmic protein allergy, hydro extensive hydrolyzed formula from whey or casein or rice, hydrolysate, but ESPGHAN recommended in simple form of cow’s milk protein allergy to use as a first choice an amino acid formula. We're going to see if it is really justified and we already, you already heard that. So infant formula should be a second choice, but in some countries, it could be difficult. This is ESPGHAN recommendations, but DRACMA recommendations, Rosan had just showed it before they consider that amino acid formula should be always a second choice, the first choice an extensively hydrolyzed formula or a rice formula. And Rosan said it, but I repeat it, they recommend also to choose an extensively hydrolyzed casin formula with LGG. Why? Because, more than 10 years ago, Bernie Cannania, its team, showed that comparing EHCF with LGG with the same formula without LGG, accelerate tolerance acquisition in IGE and non-IgE forms of cow’s milk protein allergy. This was a randomized control, control type trial, trial, in an open trial. They also showed that EHCF with LGG accelerates tolerance acquisition, when compared with all other for all of the hydrolysate, EHCF without LGG, rise formula, sorry, formula, amino acid formula, it was an upper trial and some other studies when comparing EHCF without LGG or extensive hydrolyze Whey formula without LGG and rice formula didn't find difference in tolerance acquisition, but it was not with LGG.

Final study, but very important. This was a very beautiful study. They took infants with cow’s milk protein allergy, where the physician decided to give them amino acid formula, probably because it was a simple form of cow’s milk protein allergy. So you understand there are, they have cow’s milk protein allergy, and the physician decided to give them an amino acid formula. First, they performed an oral food challenge to see if they are allergic or not to EHCF, with LGG, all of them tolerated. Except one, there were 60 minus 1, 59, 59 infants were then randomized, randomized in two groups. The first group remained on amino acid formula. The second group was changed to extensively hydrolyzed casein formula with LGG. And then at 12 months, they tried to see the tolerance accusation.

The figure is very clear. The infants who remained on amino acid formula delayed tolerance acquisition when compared with infants who will switch up to extensively hydrolyzed formula, casein formula with LGG. So it's very important to rapidly switch the infants on amino acid formula to an extensively hydrolyzed formula method with LGG, but perhaps also without LGG. This is why I told you just before, is it really justified to keep to give amino acid formula in several forms of cow’s milk protein allergy?

So and I will be on time, the take home messages, first, complimentary bottles containing whole cow’s milk protein should be avoided in the day, in the first day of life, of life at maternity ward, in newborns who were who are intended to be exclusively breast fed. I'm not speaking about mixed feeding; I'm speaking only exclusively breastfed. They should not have a complementary bottle with cow’s milk protein, whole cow’s milk protein at maternity ward.

Secondly, the early introduction of CMPA, 10 milliliters per day in exclusively breastfed infant at risk of allergy, may prevent later CMPA, but further study, further studies are necessary to confirm it.

Three, use of an extensive hydrolase casein formula with LGG accelerates the rate of tolerance acquisition when compared with other hydrolysates.

Four, in efforts with a severe CMPA treated by amino acid formula, I remember, I remember you ESPGHAN consider that in the several form, you should give an amino acid formula, then step down in an extensively hydrolyzed formula, better with LGG, could accelerate tolerance. In my department, even in the severe form, we give first a hydrolysate, and then, if they don't tolerate hydrolysate as a second choice, we give an amino acid formula.

And finally, acceleration of CMP tolerance is an, really an important issue. This was my introduction, to avoid nutrition deficiencies, on growth, perhaps, but also on calcium deficiency. Reduce the cost of CMPA, you remember 2000 euros, $2,000 and finally, finally, and we talked about that in the previous presentation, improve the quality of life. Thank you very much.