HEALTH CARE PROBLEM:
Coeliac disease (CD) is an immune-mediated systemic disorder elicited by the ingestion of gluten containing cereals (among others wheat, rye and barley) 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, including 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. Recent prospective studies show that CD develops very early in life and that treatment of CD patients detected by early diagnosis results in health improvement. The current standard health care is unable to solve the problem of underdiagnose of CD and early diagnosis and treatment may only be achieved on a large scale by mass screening or by early and active case-finding.
In the Netherlands, more than 95% of all children aged 12 months-4 years visit the YHCC whose goal is to promote and secure the health and safety of all children, among others by early detection or prevention of diseases. Secondary prevention of CD by active case-finding fits within these goals.
To perform a novel case-finding project to detect CD in 12 months-4 years old symptomatic 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. All children aged 12 months-4 years attending scheduled visits to the YHCCs in the Kennemerland region. At the YHCC a questionnaire on CD-related symptoms will be checked. If one or more CD-associated symptoms are present the child is eligible for the study. Sample size calculation is based on the overall crude incidence rate of clinically diagnosed 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. Per 1000 children followed for an average of 2,5 years, we expect 1.56 cases of clinically diagnosed CD. We assume that in the Dutch population outside the case-finding project, the incidence of children with a diagnosis of CD equals 0.62/1000 children years and that in the case-finding population the incidence of children that will be detected (incidence rate) will be at least 8 times as high. With 2.5 years follow-up, 5434 subjects followed for case-finding are sufficient to detect an incidence rate ratio of 8, with 80% power, using an alpha level of 0.05. We expect 60% of the children to be symptomatic, and 60% participation of those symptomatic children in the case-finding population, so 15,100 children need to be requested for participation, in order to obtain 5434 children available for case-finding using a rapid point of contact test (POC). Since the population in the YHCCs in the Kennemerland region is approximately 12,000 children/year with additional 4,000 added per year and 2.5 years of follow-up will be sufficient to achieve the sample size. CD will be diagnosed after positive POC test following accepted guidelines.
After informed consent the novel, validated, POC tests to determine CD specific blood antibodies against the enzyme tissue transglutaminase2 (TG2A) will be performed. If the POC test is positive, the child will be referred to the paediatrician-gastroenterologist for further investigation for CD.
1.Number of children with a positive POC test in which the diagnosis of CD is confirmed.
2. Feasibility and cost-effectiveness of active case-finding for CD in the YHCCs. All costs of active case-finding, diagnostics and treatment of CD and the potential short and long term consequences of the disease will be calculated for the settings with and without active case-finding. Healthcare use will be valued according to the Dutch guideline for costing research using patient's questionnaires and data from the literature.
3. Ethical acceptability: by questionnaires on parental satisfaction and focus groups.