Tag Archives: introducing gluten to infant

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Introducing Gluten to the Baby At-Risk for Celiac Disease (2014 update)

My youngest daughter, Claire, who I had in 2012, was my first baby born after my celiac diagnosis. I really struggled during her infancy to figure out if/when I should ever feed her gluten, as I wanted to do everything possible to prevent her from developing this disease. Based on all of the available research at the time, I made the decision to introduce her to small amounts of gluten when she was about 5 months old, and I breastfed her as long as I could (see my previous post for more details). I also freaked out a bit, as I was pretty sure that I had introduced gluten at the “wrong” times for my 3 oldest kids, beyond the 4-6 month “window” that had been supported by the literature, and I had not even been breastfeeding when my 2nd child was given gluten for the first time.

Fortunately, thanks to two recent studies published in the October 2nd New England Journal of Medicine, moms of infants at-risk of celiac disease will no longer need to struggle with their decision making the way that I did. Both of these beautifully designed, randomized, placebo-controlled European studies, including large numbers of subjects, demonstrate that neither the timing of gluten introduction, nor breastfeeding during gluten introduction, make any difference in the eventual development of celiac disease in at-risk babies. I wish that these results had been available in 2012 when I was struggling with my decision-making for baby Claire!

The first paper, entitled “Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children,” discusses results from the Italian Risk of Celiac Disease and Age at Gluten Introduction (CELIPREV) trial. In this study, 707 infants who were at risk of celiac disease (having either a parent and/or sibling with celiac) were randomized to be introduced to gluten at either 6 months of age (Group A) or 12 months of age (Group B). Infants in the study who carried the celiac genes (HLA-DQ2 and/or DQ8, n=553) were then followed for the development of celiac disease via repeated celiac antibody testing at age 15 months, 24 months, and 3, 5, 8, and 10 years of age. Celiac disease autoimmunity was defined as having positive results for celiac antibodies. In total, 117 of the 553 subjects met the criteria for celiac disease autoimmunity during the study, and 91 of the 117 with celiac disease autoimmunity were diagnosed with celiac disease.

In the CELIPREV trial, earlier introduction of gluten was associated with earlier development of both celiac disease and celiac autoimmunity, but by age 5 there was no difference in the rates of celiac disease or celiac disease autoimmunity between the groups. At age 2, there were significantly more children with celiac disease from study Group A (early introduction) than study group B (late introduction), 12% v. 5%, but by age 5, the percentages of children with celiac disease in both the early and late groups were the same (16%). Likewise, although there was a significantly higher risk of celiac disease autoimmunity in the early group v. the late group at age 2 (16% v. 7%), the difference resolved by age 5 years (21% v. 20%). In addition, breastfeeding duration was not associated with the development of celiac disease. The authors conclude that postponing the introduction of gluten until 12 months of age had no effect on the eventual development of celiac disease in at-risk children.

The second paper, “Randomized Feeding Intervention in Infants at High Risk of Celiac Disease,” discusses results from ongoing the Prevent CD trial. In this study, infants at-risk for celiac disease (defined as having both a first degree relative with celiac disease and the presence of one of the 2 main celiac genes) were randomized to be given either gluten (n=475) or placebo (n=469) between 16 and 24 weeks of age. All of the infants were then followed closely for the development of celiac disease until they were 3 years old. Overall, 80 of the subjects developed celiac disease by age 3. Rates of celiac disease in the gluten v. placebo groups were similar at age 3 (5.9% in the gluten group v. 4.5% in the placebo group) and breastfeeding duration was not found to have an influence on the development of celiac. When evaluated by gender, however, there was a small increase in celiac disease at age 3 in girls who were exposed to gluten v. placebo (8.9% v. 5.5% in boys), which the authors speculate may be due to the fact that there were more girls who were double DQ2 positive, or homozygous (this is the highest risk gene combination for celiac disease). The authors conclude that giving small amounts of gluten between 4 and 6 months of age makes no difference in the eventual development of celiac in genetically predisposed infants.

In conclusion, we now know that there is nothing that we can do, feeding-wise, to prevent the development of celiac disease in our at-risk babies. While these results are sobering, as I know that many of us wish that we could do something to prevent out babies from developing celiac, I hope that future moms will be able to be a little easier on themselves than I was regarding the timing of gluten introduction. As a mom and neonatologist (pediatrician) I am a huge advocate of breastfeeding, and despite the aforementioned research showing that it does not seem to effect celiac disease development, it has numerous other health benefits for babies. I encourage moms to provide breast milk, in at least some capacity, during infancy (realizing that exclusive breastfeeding is sometimes not possible). Lastly, I feel much less guilty for exposing my 4 kids to gluten as babies, as I now know that if they do develop celiac, that it is not because of how I fed them!

Thank you for reading! As always, comments, questions, stories, etc. are appreciated!

References

Lionetti, E., Castellaneta, S., Francavilla, R., et al. Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children. New England Journal of Medicine. 2014. 371: 1295-1303.

Vriezinga, S., Auricchio, R., Bravi, E., et al. Randomized Feeding Intervention in Infants at High Risk of Celiac Disease. New England Journal of Medicine. 2014. 371: 1304-1315.

InfantRisk Center

Early Feeding and Risk of Celiac Disease in a Prospective Birth Cohort

**This is the first guest post on my page by Cristen Pantano, an incredibly talented scientist and mother of two children. Her youngest child was diagnosed with Celiac disease earlier this year. Many thanks to Cristen for tackling this challenging topic! 

Celiac is known to have a large genetic component and people with Celiac disease carry the HLA-DQ2 or HLA-DQ8 genes. However, only around 4% of people that carry these genes develop Celiac. The big question then is, what else is contributing to the development of Celiac?

Scientists are currently looking at other candidate genes, and so far, seven additional genes that make individuals more susceptible to developing Celiac have been identified. Genes are a great place to start, but as we all know, gluten is the big culprit in Celiac. It is the known environmental “trigger” for Celiac. Why is it that some people that carry the “Celiac genes” develop the disease after gluten exposure while others don’t?

Scientists and doctors are asking this question a lot these day. One area that is being investigated is infant feeding. Studies looking back on the Swedish Celiac epidemic of the 1980-1990s have shown that more than half of the epidemic could be explained by infant feeding practices (see link). During the time of the epidemic, Swedish infants were being introduced to gluten, on average, at around five months of age. Breastfeeding ended around this time and was replaced with formula thickened with wheat flour. When breastfeeding averages extended toward seven months and the popularity of wheat-laden formulas decreased, so did the rates of Celiac.

The Swedish epidemic got researchers thinking about infant feeding and many studies have since been published showing an effect of the age of gluten introduction, the amount of gluten introduced, and breast feeding on Celiac development.

A new study looking at the effect of these factors on the development of Celiac was recently published in the journal Pediatrics. This study, out of Norway, looked at the early feeding practices in 324 children that developed Celiac disease compared to a cohort with 81,843 children that did not develop the disease. The strength of the study is that it was prospective. Unlike most population studies where parents have to look back in time and remember details of early milestones, in a prospective study, parents fill out surveys to provide information in real time.

So what did this most recent study find? The authors found that 3.68/1000 children developed Celiac when introduced to gluten at six months compared to 4.24/1000 when introduced at four months and 4.15/1000 after six months. The increased risk for Celiac disease when gluten is introduced before four months, or after six, has been previously observed.

In this new study, the average length of breastfeeding in children that developed Celiac was 10.4 months compared to 9.9 months in the control population. The researchers found a positive association of prolonged (greater than 12 months) breastfeeding and  the development of Celiac disease. When all their breastfeeding data was adjusted for confounding factors such as maternal Celiac disease, this increased risk was borderline significant. That means that statistically speaking, the data set is on the weaker side and needs to be interpreted with caution. However, it does still demonstrate that in this data set, children that were nursed for twelve months or more had a greater risk for developing Celiac.

These findings have been met with frustration by many mothers of children with Celiac. Are women responsible for the development of their child’s Celiac disease because they chose to hold off solid foods and nurse up to, or past, one year? Of course they aren’t, and the authors of this study are not saying that they are. In their discussion, the authors caution that while their data on age of gluten introduction closely matches data from earlier studies, their data on breastfeeding does not.

Many, if not all, previous studies looking at breastfeeding and Celiac disease have found a protective effect from nursing. A 2006 review of the literature found that breastfeeding at the time of gluten introduction provided a 52% reduction in the development of Celiac disease. In 2005, two Swedish studies found a significant reduction in the onset of Celiac in babies that were nursed at the time of gluten introduction and continued to be nursed after that first introduction.

This latest study found that breastfeeding did not protect against Celiac and that nursing past twelve months increased the risk. Sounds strange right? In their discussion, the authors hypothesize that the greater risk in those breastfed past 12 months may have more to do with gluten than with breast milk. When a child is breastfed longer, the introduction of gluten may be later, after six months of age. Furthermore, since the child is older at gluten introduction, he may be exposed to larger amounts. The authors also mention that some mothers may have nursed longer due to perceived food sensitivities.

In the end, what is the take away from this study, and others, looking at infant feeding and the development of Celiac? It seems that there may be a window for gluten introduction between 5-6 months. Introduction before and after this time seem to increase the risk of Celiac. As far as breastfeeding, most studies point toward a large protective effect.

The development of Celiac Disease seems to be a perfect storm of genetic and environmental factors. Factors that may be out of any one person’s control. Studies should continue to look at early infant feeding and disease development, but all data should also be interpreted knowing that as hard as we try, some times, some things just can’t be prevented.