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.

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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).

Image may be NSFW.
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Image may be NSFW.
Clik here to view.