Introducing gluten to babies

We are often asked when and if babies should be introduced to gluten. One of the first foods parents are told to give their babies is gluten-rich grains and cereals. Many parents are worried about their child’s risk of coeliac disease, especially if the disease runs in the family.

The current advice from governments around the world is to introduce gluten somewhere between 4 and 7 months of age and preferably whilst still breastfeeding, in order to lower the risk of coeliac disease. This advice is based on the results of observational studies, many of which were retrospective surveys based on parental recall. Observational studies are prone to confounding variables and bias and unlike randomized controlled trials, cannot determine cause and effect.

In October, two new randomized controlled trials were published in the New England Journal of Medicine. Both studied babies at high-risk of coeliac disease. Both used randomization to assign them to groups and then followed their development until the age of 3.

Study one, undertaken in the Netherlands, looked at 944 high-risk children (an HLA genotype and a parent or sibling with coeliac disease) from 7 European countries and Israel. The experimental group introduced gluten at 4 months of age and the control group introduced gluten at 6 months of age, when both groups added gluten to the diet. When the children were 3 years old, those suspected of having coeliac disease were given an intestinal biopsy to confirm the diagnosis. 5.9% of those given gluten at 4 months developed coeliac disease, compared with 4.5% of those who were given gluten at 6 months. The difference was not statistically significant, but it nevertheless shows a slightly increased risk of coeliac disease in high-risk children introduced to gluten at 4 months. Breastfeeding did not make any difference, even if the babies were exclusively breastfed. However, 431 of the mothers with coeliac were on a gluten-free diet and the researchers did not evaluate the impact of a mothers’ diet on the results. Since IgG antibodies are actively transported across the placenta, it is possible that the consumption of gluten during pregnancy could also affect the results.

Study two looked at 832 children with family history of coeliac disease. The children were randomly assigned as newborns to receive gluten-containing foods at 6 (group A) or 12 (group B) months of age. The researchers then followed the children until the age of 5, when suspected coeliac cases were confirmed with intestinal biopsies. By age 2, significantly more children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01).

By age 5, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or obvious disease (16% and 16%, P=0.78 by the log-rank test). By the age of 10, the risk of celiac disease autoimmunity was significantly higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables accounted for, including breast-feeding, were not associated with coeliac disease.

Therefore, although postponing gluten introduction did not seem to effect a child’s long-term risk of developing coeliac disease, it did delay onset, which could mean that waiting to introduce gluten could protect a child’s health in other ways according to the study’s authors. The immune response associated with coeliac disease could have other detrimental effects, so according to Dr. Alessio Fasano, co-author of one of the studies and director of the Center for Celiac Research and Treatment at MassGeneral Hospital for Children: “A delay of 8 to 10 months can be important.” “This time is crucial for the development of many organs, including the brain.”

“This research is likely to change medical advice”, says a commentary in the journal by Dr Jonas Ludvigsson of the Karolinska Institute in Stockholm and Dr Peter H.R. Green of Columbia University in New York.

“From now on, it will be hard for anyone to continue to recommend the introduction of gluten specifically at the age of four to six months” as many doctors have been doing.

Because the prevalence of the genes related to risk have not changed, nor the gluten content of wheat flour, “other environmental factors must be contributing” to the rise in coeliac disease” he said.

Overall, these studies suggest that genetic factors are more important in the long-term than timing of introduction to gluten, however delaying gluten introduction could be protective in the short-term. The failure to evaluate the impact of maternal diet during pregnancy and, in the second study, the fact that those diagnosed with coeliac disease at the age of 2 were less likely to consume it at the age of 10 raises some questions that will need to be addressed in the future.