PreventCD

Zrinjka MišakReferral Centre for Paediatric Gastroenteorology

and NutritionChildren’s Hospital Zagreb, Croatia

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

Israel

PREVENT CD PARTNERS

PREVENT CD TASK FORCE

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

PreventCD

Hypothesis:

The introduction of small amounts of gluten

at the 5th and 6th months of age while still breast feeding

will reduce the number of CD

by 50%.

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

PreventCD – inclusion criteria

Children at risk for CD:

CD diagnosed by intestinal biopsy in

mother and/or

fatherand/or

sibling

(1° relatives)

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 disease3. 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

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

PreventCD – project protocolENROLLMENT

Families with a CD patient

BIRTHHLA 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

The Frequency of Coeliac Disease (CD) in High Risk Young Children from Families with CD: The

PreventCD Cohort

R. Auricchio1, C. E. Hogen Esch2, G. Castillejo3, E. Mummert 4, E. Bravi 5, I. Korponay-Szabo6, S. Koletzko 7, L. Greco 1, R. Troncone 1, M. L. Mearin2 on behalf of Prevent CD Study Group

1Department of Pediatrics, University Federico II, Naples, Italy, 2Department of Pediatric Gastroenterology, University Medical Center, Leiden, Netherlands, 3Pediatrics Department, Hospital Universitari de Sant Joan de Reus , Reus, Spain, 4Phadia, Friburg, Germany, 5Eurospital, Trieste, Italy, 6Department of Paediatrics, Medical and Health Science Centre , University of Debrecen, Debrecen, Hungary, 7 Kinderspital, , Ludwig Maximilians University, Munich, Germany

PreventCD - HLA status of the cohort

1345 total number of children recruited

986 (73%) HLA DQ positive:

HLA DQ2 positive 802HLA DQ2/DQ8 positive 81HLA DQ8 positive 103

PreventCD – progression of the PreventCD cohort

More than half of children older than 2 years

PreventCD - breastfeeding

> 60% of children are still BF at 6 months of

age

Cumulative percentage of children who stopped breastfeeding

PreventCD – criteria for biopsy

Symptoms ± 2 consecutive positive

a-tTG tests or 3 times AGA-A positive

Biopsy

PreventCD – performed biopsies and confirmed diagnosis

Center Enrolled Biopsies Cases tTG AGA tTG+AGA Symptoms Atrophy

101-Netherlands 134 10 4 0 0 4 3 4

102-Italy 142 9 4 0 0 4 2 4

103-Poland 53 1 1 0 0 1 0 1

104-Madrid 78 5 3 0 0 3 2 3

105-Valencia 80 3 3 0 0 3 3 3

106-Israel 98 6 2 0 0 2 2 2

107-Croatia 8 0 0 0 0 0 0 0

108-Hungary 136 8 7 2 0 5 1 7

109-Catalonia 93 7 7 0 0 7 6 7

110-Germany 114 0 0 0 0 0 0 0

TOTAL 936 49 31 2 0 29 19 31

PreventCD

CD group (31) No CD group (18)

Median age (months) 26.1 21.4

Symptoms present 19 13

tTG 2 2

AGA-A + tTG 29 1

AGA-A 0 4

tTG median titre 88 3.3

AGA-A median titre 57.6 18.4

Villous Atrophy 31 2

CLINICAL, SEROLOGICAL AND HISTOLOGICAL FEATURES OF BIOPSIED PATIENTS WITH CONFIRMED CD AND NON-CD PATIENTS

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.

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%)

% I

nci

den

ce HLA DQ2 homozygous will have an

incidence of 25% of cases versus the 1-5% in the lower

risk class.

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

Acknowledgements