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New Research on Gluten Introduction to Infants and Risk of Celiac Disease

If you’re worried about your child’s risk of celiac disease and wondering when to introduce gluten-containing foods, then you’ll want to know about two new studies published in the New England Journal of Medicine this week.

Gluten is delicious to most of us, but it can be devastating to those with celiac disease. Photo by Adrian van Leen

Gluten is delicious to most of us, but it can be devastating to those with celiac disease. Photo by Adrian van Leen

Celiac disease is an immune response to gluten, a protein found in wheat, barley, and rye. It causes inflammation and damage to the small intestine, and while it can be successfully managed with a gluten-free diet, it is a lifelong disease. (Celiac disease is distinct from non-celiac gluten sensitivity, which is a murky and controversial condition that may not be related to gluten at all.)

I reviewed the research on early infant feeding and risk of celiac disease on my blog about a year ago (Breastfeeding, Gluten Introduction, and Risk of Celiac Disease). I have since received lots of comments and messages from parents concerned about this, so I wanted to be sure to write about these important new studies.

These latest studies dramatically advance our understanding of this topic because they are randomized controlled trials. Both started with a group of babies already identified as being high-risk for celiac disease, randomly assigned them to different time of introduction of gluten, and then tracked their development of the disease. Previous studies were all observational, thus only able to identify associations between variables, and were limited by confounding factors and other sources of bias.

The first study was led by researchers in the Netherlands but included children born in 7 European countries and in Israel. 944 babies were identified as being high-risk for celiac based on a genetic predisposition (HLA genotype) and having a first-degree relative (parent or sibling) with celiac. The babies were randomized to two groups, and one group was given a small amount (100 mg) of gluten starting at 4 months of age, while the control group was given a placebo and instructed not to introduce gluten until 6 months, at which point parents in both groups were advised to gradually introduce gluten-containing foods. The incidence of celiac disease was tracked through 3 years of age, with all suspected cases confirmed with an intestinal biopsy. Overall, about 5% of the study participants developed celiac disease by age 3, and it made no difference whether gluten was introduced at 4 or 6 months. It also made no difference whether the babies were breastfed (exclusively or not) or currently breastfed at the time of gluten introduction.

The second study was conducted in Italy and had a similar design but instead compared gluten introduction at 6 vs. 12 months. This study found that delaying the introduction of gluten to 12 months did delay the diagnosis of celiac but didn’t prevent it. For example, at age 2, 12% of the 6-month gluten group had been diagnosed with celiac compared to only 5% of the 12-month gluten group. However, by 5 years of age, 16% of both groups had been diagnosed. As in the first study, duration of breastfeeding and breastfeeding at the time of gluten introduction did not impact risk for celiac. Neither did the type of relative with celiac (mother, father, sibling), gluten intake at 15 months, or the number of episodes of intestinal infections.

In a way, these findings are discouraging for parents concerned about their child’s risk of celiac. Previous research indicated that there might be a window of opportunity for gluten introduction between about 4 and 6 months, during which gradual introduction of gluten might “educate” the immune system about the gluten protein and prevent the development of celiac. The current studies indicate that this isn’t the case, and in fact, it may be worth waiting until 12 months to introduce gluten, if only to delay the development of celiac. Even if your child ends up with celiac, I can imagine that dealing with the symptoms, testing, and diagnosis of the disease with a barely verbal 2-year-old would be much harder than with a 4- or 5-year-old.

In an editorial accompanying the new studies, Jonas Ludvigsson and Peter Green write:

“We believe the studies in this issue of the Journal will change the conceptual landscape of celiac disease. From now on, it will be hard for anyone to continue to recommend the introduction of gluten specifically at the age of 4 to 6 months, since Vriezinga et al. did not find that exposure to gluten at this age decreased the risk of celiac disease, and Lionetti et al. in fact found a delay in the development of celiac disease in children who were first exposed to gluten at the age of 12 months.”

Previous research also suggested that breastfeeding at the time of gluten introduction might reduce the risk of celiac disease, and again, both of these current studies found this not to be the case. While there are some health benefits of breastfeeding, and you might choose to breastfeed for lots of good reasons, it probably won’t prevent the development of celiac disease.

It can be frustrating to see such big changes in official advice given to parents about introduction to solid foods, but this also demonstrates how quickly this field is evolving. And it shows the real value of investing in good randomized controlled trials, because the data gleaned from these studies are SO much more certain than the conclusions we try to draw from observational studies.

Of course, these findings still leave us with a big mystery. If how we feed children as babies has little impact on the development of celiac, then what does? The prevalence of celiac has increased 4-5-fold in the U.S., Finland, and the U.K. over the last 50 years. Meanwhile, the gluten content of flour and the presence of the HLA genotypes that predispose people to celiac haven’t changed. (About 25% in the Western world carry these gene variants, but most won’t actually develop the disease.) In their editorial, Ludvigsson and Green mention several other risk factors for celiac that have been identified in observational studies: elective cesarean sections, perinatal and childhood infections, and the use of antibiotics and proton-pump inhibitor drugs. Of course, these risk factors are darlings in both research and the media right now and seem to be blamed for an inordinate amount of modern ills. We need a lot more research before we can explain what’s going on with celiac.

In the meantime, parents of babies high-risk for celiac will have to keep feeding them as best as they can, accepting uncertainty and trying to minimize anxiety. We now know that waiting at least until baby’s first birthday to begin gradually introducing gluten may delay celiac in the short-term – but as far as we know, this only applies to high-risk babies (with a parent or sibling diagnosed with celiac and/or having the high-risk HLA variants).

28 Comments
  1. Thanks for this interesting post. From a whole lot of looking into gluten for myself and boys, I would say the best thing for everyone is to cut gluten out of the diet when pregnant, breast feeding and never introduce it to your little ones. Research is linking it to so many health issues that I am sure in the future it won’t be a matter of what age to introduce it.
    Gluten destroys the gut lining which allows undigested particles and other toxins straight through into the bloodstream. This wreaks havoc on the body in so many ways. Leaky gut syndrome. This then leads to issues such as ADHD, autism, headaches, fatigue, low immunity, other neurological issues, eczema, I won’t keep going on.
    I’m sure I sound crazy but it is so hard to watch people giving gluten to their kids, particularly at such early ages. It is only destroying their gut lining setting them up for a host of childhood issues. I gave it to my son and have paid the price… I haven’t needed any randomized control trials to see the effects of gluten on a sensitive child. And working with kids with disabilities, I see it even more.. 😦

    Like

    October 4, 2014
    • You’re proposing a very extreme path, and as far as I know, there is very little evidence to support it. I can tell that you believe it passionately, but on this blog, we focus on scientific evidence. Do you have any studies to support your statements?

      Humans have been eating gluten for a long time. Clearly, some don’t tolerate it well, but we’re talking about 1% of the population with celiac (many undiagnosed). What we’ve been calling “non-celiac gluten sensitivity” may not be linked to gluten at all but rather a type of carbohydrate. There’s a lot we don’t know, but we do know that gluten is part of staple foods consumed around the world, and most people tolerate it just fine. With food allergies, studies have shown that exposure to proteins during gestation might actually reduce risk of allergy in kids, so attempting to seal your children off from possibly offensive proteins for life could easily backfire. It’s also challenging to really eliminate gluten, and it’s likely that your kids will come into contact with it at some point in childhood – intentionally or not.

      Even if I had a baby high-risk for celiac, I think I’d probably introduce gluten within the first couple of years of life. In the Italian study described in this post, enrolled babies had both a first-degree relative with celiac and high-risk HLA variants. Even in these kids, only 1 in 5 had celiac autoimmunity at age 10. For the other 4 in 5, there were no signs of disease. I wouldn’t want to unnecessarily subject those kids to a restrictive diet all through childhood. The study from the Netherlands – conducted in a much broader population – found a much lower prevalence of celiac disease among high-risk kids.

      Like

      October 4, 2014
      • KJ #

        Thanks for bringing the focus back to the science. That’s what makes your blog excellent and, frankly, unique.

        Like

        October 6, 2014
      • SMH #

        This is a difficult one for me. I have biopsy confirmed celiac as well as my daughter. I wonder what would be the right decision for her regarding introducing gluten to her children when they come along. We have a completely gluten free household in order to protect ourselves from any cross contamination. It’s possible to set up a shared kitchen, but not easy…I tried that initially. I worry that my daughter would be putting herself at risk by feeding her child gluten. Since the current studies seem to indicate that it doesn’t protect a child from developing celiac disease by introducing it, I would argue that the best course of action would be to not introduce it at a young age. It’s possible to eat a healthy well balanced diet without gluten, so why not? The child can chose to eat gluten outside of the house when they are older and not at risk of getting mommy sick with gluten in the kitchen and goldfish cracker laced toddler kisses and cupcake crumb sticky fingers. Concern for the celiac parent’s health is also something that should be part of the conversation.

        Like

        November 4, 2014
        • Yes, I can see how this is a tough situation, and you need to consider the health of the whole family in this decision. If having gluten in the house will endanger mom’s health, then I wouldn’t want it either. You could be relaxed about gluten outside of the home (birthday parties, friends houses, etc), however, provided the child seems to tolerate it well.

          Like

          November 4, 2014
          • ElseB #

            I have Celiac Disease and am the mother of a 4.5 month old baby. I came across your site while researching when we should introduce gluten. Like many others, we have a gluten free home to protect me and my husband does all of his gluten eating elsewhere (he is a saint…..he has never once complained about this!). Introducing gluten to our baby makes me nervous because I’m worried about accidentally ingesting it myself. However, we want to know whether our child can tolerate gluten because it is a certainty that he will encounter it outside our house. Our house will always remain gluten free but if he can tolerate gluten then he can eat it elsewhere like his father. Our current thinking is that when it comes time to introducing gluten, my husband will do all of those feedings. Probably in the house, but in a contained area so we can easily clean up.

            Like

            December 1, 2014
  2. Tine Greve #

    Hi, very interesting. Could you please post the references to the two studies you’re talking about?

    Like

    October 5, 2014
    • Hi Tine – They’re linked in the text of the post (along with other studies throughout), but I think that the color of the hyperlinked text makes it harder to see. I should work on that. Do you prefer to see references listed at the bottom of a post? I go back and forth on that. Anyway, here are the two papers featured in this post:
      1.Lionetti, E. et al. Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children. New England Journal of Medicine 371, 1295–1303 (2014).

      2.Vriezinga, S. L. et al. Randomized Feeding Intervention in Infants at High Risk for Celiac Disease. N. Engl. J. Med. 371, 1304–1315 (2014).

      Like

      October 7, 2014
      • Even though the hyperlinks are good, it would be nice to have the studies referenced at the end as well in that format. Thanks for another great post!

        Like

        October 7, 2014
        • Good to know – maybe I’ll start doing both. Thanks for the feedback, Cigal!

          Like

          October 7, 2014
  3. maggie #

    Two questions:
    Did they separate the breastfeeding crowd into mothers with celiac and mothers without – in other words, if the mother didn’t have gluten in her system, why would we expect breastfeeding to have any impact…

    Also, my mother and her friends all stated that they started babies on cereal between 3 and 5 weeks old, long before the 4 months in this study. Certainly old paintings show babies of about that ages getting fed pap or pablum from a spoon. The transition away from that practice would have started about 50 years ago. If in-utero exposure is beneficial, could you make a case that 4 month is too old? Has anyone ever looked at introduction of gluten at a very young age?

    Like

    October 7, 2014
    • Great questions, Maggie. I also wondered about your breastfeeding question, and unfortunately, neither study analyzed the data based on what mom ate during pregnancy and breastfeeding. The Netherlands study (Vriezinga et al) reported that 455 moms in the study had celiac (of 944), and of these, 431 were on a gluten-free diet. They did not mention whether moms without celiac were following a gluten-free diet, but I wouldn’t be surprised if some were given that they knew their babies were high-risk for celiac. They also don’t mention giving participants any specific advice on this. All we know is that there was no effect of type of family member with celiac on the child’s risk of celiac (i.e. it didn’t matter whether mom, dad, or sibling had celiac). If BF was only protective when mom was consuming gluten, then we might expect to see lower risk in babies with father or sibling with celiac (and thus mom is more likely to be consuming gluten while breastfeeding). But that’s just my speculation. It’s too bad they didn’t look at this question!

      Second question – it’s true that babies used to get cereal products (presumably some wheat or barley in there) much earlier than is recommended today. Observational studies have found that introducing gluten too early (7 months) does as well. Here’s one: http://www.ncbi.nlm.nih.gov/pubmed/15900004

      These new studies call into question that too late finding, so maybe we should question the too early finding as well. However, other problems with early introduction of solids have been identified (Type 1 diabetes, obesity), so I think it is unlikely that this will be tested anytime soon. It’s a reasonable hypothesis though.

      Like

      October 7, 2014
      • maggie #

        Can you do some looking into the last point that you mention? Anecdotally, all the kids in my generation had cereal at about 3 to 5 weeks, and we “old farts” are statistically more healthy than the younger generation. Is it the type of solid, added sugar vs. pure grain, etc?

        Like

        October 7, 2014
  4. I believe that a lot of the gluten intolerances that we see today are caused more from our high technology, efficiently processed glutens that our culture depends on now. I gave my daughter gluten by 6 months, but glutens that came from natural sources that I prepared myself for her.. not the store bought cereals and baby foods that have so many other things in them that we should be more concerned about than gluten. She’s almost 2 now and has no signs of any intolerance. I’ve been doing a study course on ‘real foods’ and there is a book in that study that gives some really great insights into gluten and celiac, study based.. I would suggest anyone that has concerns to read it.. it definitely stirred some great insights into it all for me. The Vintage Remedies Guide To Bread by Jessie Hawkins http://www.vintageremedies.com/product-p/gb.htm
    Thanks Science of Mom for your blog and the way you stick to the evidence behind what you write.. As a mom of a toddler I greatly appreciate it!

    Like

    October 7, 2014
    • LDM #

      The article is less focused on gluten intolerance’s and more on celiac disease. Its important to differentiate the two. One is a life long disease and one is a lack of the bodies ability to break down gluten (that does not have many long term effects like untreated celiac does). Celiac is a genetic disease as well so if you dont have a family history, it is very unlikely that your children will develop the disease as well.

      Like

      December 4, 2015
  5. Another great blog. I’d just like to comment that although it’s true that the gluten in wheat has not changed since centuries past, our bread baking methods have in the way that there is more added gluten in commercial breads which to me is a good hypothesis for the rise in celiac disease and gluten sensitivity. Here’s a wonderful article in the New Yorker on this topic: http://www.newyorker.com/magazine/2014/11/03/grain

    Like

    October 31, 2014
    • Thanks, I’m reading this article now and finding it to be a great summary of the current state-of-the-science on gluten! Great resource.

      Like

      November 4, 2014
  6. Sara #

    How did they define their HLA risk categories? Is “high risk” two copies of DQ2 or DQ8 and “standard” is… just one? Because if standard is no copies of either DQ2 or DQ8, I’m confused as to how any of them could have developed celiac (I suppose it does happen, but once in a million).

    Like

    November 4, 2014
  7. Sara #

    Nevermind, I found my answer:

    “The detection of HLA alleles was performed with the use of the DQ-CD Typing Plus kit (BioDia-
    gene), and on the basis of this assessment, the children were classified as having no risk of ce-
    liac disease (the absence of HLA-DQ2 and HLA-DQ8), a standard risk of celiac disease (a single or double copy of the DQB1*02 allele associated with DQA1 alleles different from the DQA1*05,
    or a single DQ2 [DQA1*05-DQB1*02] either in cis or trans position, or DQ8 [DQA1*03-DQB1*0302/0305] haplotypes), or a high risk of celiac disease (homozygosity for DQA1*05-DQB1*02 or DQA1*05-DQB1*02-DQA1*0201-DQB1*02).”

    Like

    November 4, 2014
  8. Reblogged this on Goilala's District Development Forum Blog and commented:
    In the meantime, parents of babies high-risk for celiac will have to keep feeding them as best as they can, accepting uncertainty and trying to minimize anxiety. We now know that waiting at least until baby’s first birthday to begin gradually introducing gluten may delay celiac in the short-term – but as far as we know, this only applies to high-risk babies (with a parent or sibling diagnosed with celiac and/or having the high-risk HLA variants).

    Like

    December 4, 2014
  9. Thank you for this post. It strikes me, Babies don’t live in personal bubbles. Gluten is in the environment surrounding infants (spoon/sink/microwave) even when it’s not in baby food.

    Like

    March 2, 2015
    • Meagan #

      That is your preference. Our kitchen is gluten free so that is not the case. Babies dont live in bubbles but you are in control of what they are exposed to. Not to mention i always use clean utensils so I dont know why there would be gluten on his spoon.

      Like

      March 27, 2015
  10. Meagan #

    I don’t know if my son has an intolerance but I know there is no reason for us to introduce it to him. It is easy to provide a healthy well balanced meals without gluten. I don’t even understand the fuss of how difficult it is. It means very limited prepackaged items, which is healthier regardless of gluten allergies.
    Several of you mentioned that you didnt notice signs of intolerance in your little ones. Well both my brother and i had it for 15-20 years before we realized we had it. It affected us in ways we didnt know (and our Dr.s didnt know) it was the culprit. I had cholesterol of 300+ and was under weight for the majority of my childhood. I was put on sleeping pills to sleep at night and a cholesterol medication as a teenager, had intense itchy acne (that was actually Dermatitis Herpetiformis) all over my face and back, and frequent constipation. No one realized this was due to gluten allergy until i tried to get pregnant at 28 and stumbled across the genetics. If we hadn’t gotten lucky with by OBGYNs knowledge I wouldn’t have my son. I personally know several women that have experienced the same thing, and gluten intolerance is now showing links to PCOS which can frequently cause infertility.
    My brother suffered ADHD as a child, arthritis, and severe mood swings. He was also on medication until the age of 17 when he had an intestinal biopsy to show he had Celiac. Both of us live gluten free and all of our symptoms have vanished. Neither one of us had tummy troubles, and if we weren’t exposed to the life style by our celiac mother we might not have known. One of the Dr.s I see shared that he has read articles explaining that many don’t experience tummy troubles until they are older because as a child you are constantly creating new cells and able to repair the damage caused by gluten faster. I am a chemist so I obviously believe in using facts and data and research, but I do not believe that the full story is out there yet. I think its important that parents consider the concept of just because you cant see it doesn’t mean that no damage is occurring. What is your child really missing out on by not consuming gluten? In our book its better safe than sorry, and since there is no nutritional value in gluten that we cant get from somewhere else we dont see a reason to risk it.

    Like

    March 27, 2015
  11. I know this was written a few years back, but I just wanted to thank you for it. I have been diagnosed with both Celiac Disease and a gluten allergy (not intolerance or sensitivity, think like bees or peanuts) and wasn’t diagnosed until I was in my 20s. I now have an 8 month old and so I have been worried about when/if I will feed her gluten. Thank you for summarizing two important studies in an easy and quick way. I feel a little better that it is out of my hands and it will happen if it is going to happen.

    Like

    March 14, 2016

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