PreventCD: a European scientific research project to prevent coeliac disease.
The project studies the influence of the dietary history in the prevention of coeliac disease: possibilities of induction of tolerance for gluten in genetic predisposed children for coeliac disease.
 
Meeting 2023

In PreventCD, 944 children from 8 different countries (Croatia, Germany, Hungary, Italy, Israel, the Netherlands, Poland and Spain, in cooperation with the AOECS (Association of European Coeliac Societies) participated since birth in a research project that started in 2007. All of the children have a genetic predisposition for celiac disease. The study was initially supported by a grant from the European Commission (FP6-2005-FOOD-4B-36383–PREVENTCD). In addition, the research project has also been supported by grants from the Azrieli Foundation, Deutsche Zőeliakie Gesellschaft, Eurospital, Fondazione Celiachia, Fria Brőd Sweden, Instituto de Salud Carlos III, Spanish Society for Pediatric Gastroenterolgy, Hepatology, and Nutrition, Komitet Badań Naukowych (1715/B/P01/2008/34), Fundacja Nutricia (1W44/FNUT3/2013), Hungarian Scientific Research Funds (OTKA101788 and TAMOP 2.2.11/1/KONV-2012-0023), Stichting Coeliakie Onderzoek Nederland, Thermo Fisher Scientific, and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).

Based on previous research it was thought that ingesting small amounts of gluten at a young age would prevent celiac disease, especially if this was done during the period of breastfeeding. This was thought to allow the immune system to get used to gluten, therefore not reacting with a harmful immune response. However, this hypothesis had not been thoroughly studied.

To investigate this initially, the children were included in a randomized gluten intervention study. During the ages of 4 to 6 months, half of the children were allocated by lottery to receive 100 milligrams of gluten daily. At the age of 3 years 5.9 percent of these children were diagnosed with celiac disease. The other half received placebo during this period and only received gluten for the first time at the age of 6 months. In this last group 4.5 percent developed celiac disease. "Not a statistically significant difference", according to the researchers, coordinated by the project leader Prof. Dr. M. Luisa Mearin, paediatric gastroenterologist at the Leiden University Medical Center, the Netherlands. Moreover, it was shown that breastfeeding did not protect against the development of celiac disease.

Before the results of PreventCD, (paediatric) gastroenterologists around the world advised parents to introduce small quantities of gluten to their babies between the age of 4 to 6 months during the period of breastfeeding. This was also recommended by the guidelines. The results of the PreventCD study changed the way we think about celiac disease. "Of course breastfeeding is the best food for babies. However, on the basis of our study, we now know that it will not influence the risk of developing celiac disease" Mearin says.

The PreventCD researchers have continued studying the  development of celiac disease in the participating children. This includes analysis of their blood samples and duodenal biopsies. In this way we have learned a lot about the natural history of celiac disease. We have learnt that celiac disease develops at a very young age and that girls have a higher risk of developing CD compared to boys.  In fact, girls with two doses of HLA-DQ2 genes (homozygous) have the highest risk of developing celiac disease at a young age. Predictive factors of celiac disease development  are the HLA-genes (one or two doses of HLA-DQ2 and/or DQ8), gender, age, as well as the amount of gluten intake in the first few years of life. However, which amount of gluten intake would be “safe” is unknown. We can now predict the development of celiac disease in children from celiac families using the “Prediction App” designed by the Prevent CD project: https://hputter.shinyapps.io/preventcd/. By using this App parents can get personal advise about at what age and how frequently their children should be tested for celiac disease.

A lot is still unknown about celiac disease. In the future, and thanks to the generous collaboration of the participating children, we hope to discover what exactly happens within the immune system that leads to the disease. 


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