1. PreventCD Zrinjka Mišak Referral Centre for Paediatric Gastroenteorology and Nutrition Children’s Hospital Zagreb, Croatia

2. PreventCD – ‘to prevent coeliac disease’ multicenter European project sponsored by the 6th frame program of the EU performed by 16 centers in 10 European countries + AOECS Project leader: Luisa Mearin Leiden, The Netherlands

3. Israel PREVENT CD PARTNERS PREVENT CD TASK FORCE

4. PreventCD – ‘to prevent coeliac disease’ Start 2007 the project studied the influence of the dietary history in the prevention of CD the idea was - if gradually small amounts of food substances were administered – the immune system would ‘learn’ not to respond to this substance

5. PreventCD Hypothesis: The introduction of small amounts of gluten at the 5 th and 6 th months of age while still breast feeding will reduce the number of CD by 50%.

6. PreventCD – inclusion criteria a total of 1000 newborns with higher risk of CD included and followed up to 3 years of age Randomized double blind intervention study

7. PreventCD – inclusion criteria Children at risk for CD: CD diagnosed by intestinal biopsy in mother and/or father and/or sibling (1° relatives)

8. PreventCD – aims of the project 1. to enrolle a cohort at risk of developing CD and to follow it prospectively up to 3 years of age 2. to study the natural history of the disease 3. to prevent CD by giving small amount of gluten (100 mg) from the 4th to the 6th month of life during breast feeding according to a randomised double blind protocol

9. PreventCD – objective is to significantly reduce the number of people suffering from CD in Europe, by developing primary prevention strategies for CD if the proposed early dietary intervention results in effective prevention of CD => new European guidelines for early nutrition

10. PreventCD – project protocol ENROLLMENT Families with a CD patient BIRTH HLA analysis (cord blood) HLA DQ2 and/orDQ8 positive HLA DQ2 and DQ8 negative Encouragement of breast feeding Intervention 4-6 mo (100 mg gliadin/day or placebo) Gradual introduction of gluten at 6 months Clinical and serological (AGAA-TGA) examination every 3-6 months Clinical and serological (AGAA-TGA) examination at 3 y

11. The Frequency of Coeliac Disease (CD) in High Risk Young Children from Families with CD: The PreventCD Cohort R. Auricchio 1, C. E. Hogen Esch 2, G. Castillejo 3, E. Mummert 4, E. Bravi 5, I. Korponay-Szabo 6, S. Koletzko 7, L. Greco 1, R. Troncone 1, M. L. Mearin 2 on behalf of Prevent CD Study Group 1 Department of Pediatrics, University Federico II, Naples, Italy, 2 Department of Pediatric Gastroenterology, University Medical Center, Leiden, Netherlands, 3 Pediatrics Department, Hospital Universitari de Sant Joan de Reus, Reus, Spain, 4 Phadia, Friburg, Germany, 5 Eurospital, Trieste, Italy, 6 Department of Paediatrics, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary, 7 Kinderspital,, Ludwig Maximilians University, Munich, Germany

12. PreventCD - HLA status of the cohort 1345 total number of children recruited 986 (73%) HLA DQ positive: HLA DQ2 positive802 HLA DQ2/DQ8 positive 81 HLA DQ8 positive103

13. PreventCD – progression of the PreventCD cohort More than half of children older than 2 years

14. PreventCD - breastfeeding > 60% of children are still BF at 6 months of age Cumulative percentage of children who stopped breastfeeding

15. PreventCD – criteria for biopsy Symptoms ± 2 consecutive positive a-tTG tests or 3 times AGA-A positive Biopsy

16. PreventCD – performed biopsies and confirmed diagnosis CenterEnrolledBiopsiesCasestTGAGAtTG+AGASymptomsAtrophy 101-Netherlands13410400434 102-Italy1429400424 103-Poland531100101 104-Madrid785300323 105-Valencia803300333 106-Israel986200222 107-Croatia80000000 108-Hungary1368720517 109-Catalonia937700767 110-Germany1140000000 TOTAL936493120291931

17. PreventCD CD group (31)No CD group (18) Median age (months)26.121.4 Symptoms present1913 tTG22 AGA-A + tTG291 AGA-A04 tTG median titre883.3 AGA-A median titre57.618.4 Villous Atrophy312 CLINICAL, SEROLOGICAL AND HISTOLOGICAL FEATURES OF BIOPSIED PATIENTS WITH CONFIRMED CD AND NON-CD PATIENTS

18. PreventCD – cumulative incidence of CD in the PreventCD cohort The cumulative incidence of CD in this high risk cohort is about 6.6% at 3 years of age 31/936 => 3.3% Codes are still not unblided.

19. PreventCD – cumulative incidence by HLA Exceptional risk: 0% Very low/low risk: 1.6% (1.6%) Medium risk (blue narrow): 4.3% (SE=1.3%) High risk (red narrow): 25.6% (SE=6.7%) % Incidence HLA DQ2 homozygous will have an incidence of 25% of cases versus the 1-5% in the lower risk class.

20. PreventCD 1. 6.6% cumulative incidence at 3 years 2. Symptoms are not predictive 3. Anti-tTG antibodies, but not AGA, are very predictive The Frequency Of Coeliac Disease (CD) In High Risk Young Children From Families With CD: The PreventCD Cohort Auricchio R, et al, 2011

21. Acknowledgements