Screening of coeliac disease in the Preventive Youth Health Care Centres in the Netherlands

Coeliac disease (CD) is an immune-mediated systemic disorder elicited by gluten
and related proteins from the normal diet in genetically susceptible
individuals. CD is treated with a gluten-free diet (GFD). In the Netherlands
for every child diagnosed with CD, there are seven who have unrecognized, and
therefore, untreated disease. This is partially due to the variable clinical
presentation and symptoms. In addition, CD may be asymptomatic. Untreated
disease is associated with long-term complications, such as delayed puberty,
neuropsychiatric disturbances, associated autoimmune disease, miscarriages,
small-for-date-births, osteoporosis, and, rarely, malignancy. CD increases the
overall mortality risk, reduces the quality of life and yields extensive
negative economic consequences, thereby presenting a resource challenge for
current and future health systems. The current standard health care is unable
to solve the problem, and early diagnosis and treatment may only be achieved on
a large scale by mass screening in the general population. Recent prospective
studies show that CD develops very early in life and that treatment of CD
patients detected by mass screening results in health improvement.
In the Netherlands, more than 95% of all children aged 12 months-4 years visit
the Young Health Care Centres (YHCC) whose goal is to promote and secure the
health and safety of all children, among others by prevention of diseases.
Secondary prevention of CD fits within these goals.

The aim of our project is to perform a novel mass screening to detect CD in 12
months-4 years old children who visit the YHCCs in a well-described region in
the Netherlands, to show that it is feasible, efficient, cost-effective and
well accepted by the population.

Prospective intervention cohort study. Cluster randomisation of 12000 children
aged 12 months-4 years, attending the YHCCs in the region Kennemerland to: 1.
mass screening for CD (6000 children) or; 2. current standard health-care (6000
children). Sample size calculation is based on the overall crude incidence rate
of clinically diagnosed childhood CD of 1.56/1000 live births, and in an
estimated incidence rate of 0.62/1000 child years in children aged 12 months-4
years (40% of all CD cases with the most severe clinical presentation). Per
1000 children followed for an average of 2,5 years, we expect 1.24 cases of
clinically diagnosed CD. We assume that in the control population the
proportion of children with a diagnosis of CD equals 1.24/1000 and that in the
screening population the proportion of children with a diagnosis of CD equals
7.5/1000. To be able to detect a difference in proportions of CD between the
screening and the control populations with 80% power, using an alpha level of
0.05, ten clusters of an (average) size of 1200 children are needed: Five
randomised to control and five randomised to screening. We expect 50%
participation in both populations, making a total of 6000 children (control
group 3000 children, screening group 3000 children). CD will be diagnosed after
positive screening following accepted guidelines.

The novel, validated, rapid point of contact (POC) tests to determine CD
specific blood antibodies against the enzyme tissue transglutaminase2 (TG2A) in
children aged 12 months-4 years visiting the YHCCs.

The overall burden and risk for participation in this study is low. A
finger-prick will be done at the YHC; limited pain form prick, risk of skin
infection and hematoma is negligible. Biopsies will only be performed when
medically indicated for the child and not just for purpose of the study. If
endoscopy is indicated: low risk from anaesthesia and endoscopy (bleeding,
perforation, risk estimated approximately 1:10000).