How can parents with the autoimmune disorder celiac disease prevent or delay the condition’s development in their children? An international study led by investigators associated with the Center for Celiac Research and Treatment at MassGeneral Hospital for Children challenges some of the current thinking on possible measures to take.
Loss of tolerance to gluten—a protein composite found in wheat, rye and barley—is a dynamic process and neither breastfeeding nor delaying the introduction of gluten-containing foods provides significant protection against the disorder, they report in the New England Journal of Medicine.
“One of our most important findings was that the timing of gluten introduction—whether early or late in the first year of life—made no difference to the subsequent development of celiac disease,” said Carlo Catassi, co-director of the Center for Celiac Research and Treatment at MassGeneral Hospital for Children and a member of the pediatrics faculty at Università Politecnica delle Marche in Acona, Italy. He is the principal investigator of the study. “While earlier studies led to the hypothesis that there was a time window, between four and seven months of age, during which gluten could safely be introduced to at-risk children, our results indicate we can tell mothers not to worry so much about when they introduce gluten into their children’s diet.”
Alessio Fasano, Harvard Medical School visiting professor of pediatrics at Massachusetts General Hospital and a co-author of the NEJM report, said, “Of the several factors we studied, it’s very clear that genetic background is by far the most important in determining which infants will develop this autoimmune condition. We were particularly surprised that breastfeeding at any age provided no protective effect.”
Between 2003 and 2008 the Italian Baby Study on Weaning and CD Risk enrolled more than 700 infants considered to be at risk of celiac disease because a parent or sibling had the condition. Participants at 20 centers in Italy were randomly assigned to two groups; the first was introduced to gluten-containing foods at six months of age and the second at 12 months of age. The children’s mothers provided information on their child’s diet—including amount of gluten ingested—intestinal infections, breastfeeding and other factors thought to have an effect on celiac risk.
The children were followed for at least five years, during which they were periodically tested for the presence of immune-system factors indicating gluten-associated autoimmune reactions. If signs of autoimmunity were detected, intestinal biopsies were conducted to determine whether celiac disease had developed.
While a greater percentage of infants who had been introduced to gluten at six months had evidence of possible celiac disease at the two-year follow up, there was little difference between the two groups by five years. Overall, 64 children in the early-introduction group developed celiac disease, while 53 in the late-introduction group did so—a difference not considered statistically significant.
The only factor that increased risk was inheriting versions of the immune system’s HLA molecules. These molecules flag antigens for immune system attack and are known to be associated with celiac disease and other autoimmune disorders.
Catassi noted that a simple blood test of HLA genotype could quickly determine which infants are at high risk of celiac disease, possibly a first step toward primary prevention efforts. In addition, delaying the development of celiac disease by later introduction to gluten could prove to be beneficial by reducing the impact of the condition on developing organs, such as the brain. The fact that 80 percent of the children who did develop celiac disease did so within the first three years of life points to the importance of screening children when they reach school age, he said.
The results of this investigation will “pave the way for breakthrough studies that will capitalize on these findings and lead to preventive interventions,” Fasano said. There have been many developments in the treatment and study of celiac disease since this study began more than 10 years ago, he added, particularly the increased recognition of the importance of the gut microbiome—the microbial population of the gastrointestinal system—in the development of autoimmune and other disorders.
After completing a small 2011 pilot study finding that increases in particular bacterial species precede the development of celiac disease and Type 1 diabetes in infants, Fasano and Catassi have embarked on a larger study that will enroll approximately 500 infants to learn more about how a wide variety of factors may contribute the development of celiac disease.
The study was funded by the Celiac Foundation of the Italian Celiac Society.
Adapted from a Mass General news release.
