Background & Aims Screening for celiac disease (CD) is recommended in children with affected first-degree relatives (FDR). However, the frequency of screening and at what age remain unknown. The aims of this study were to detect variables influencing the risk of CD development and develop and validate clinical prediction models to provide individualized screening advice. Methods We analyzed prospective data from the 10 years of follow-up of the PreventCD-birth cohort involving 944 genetically predisposed children with CD-FDR. Variables significantly influencing the CD risk were combined to determine a risk score. Landmark analyses were performed at different ages. Prediction models were created using multivariable Cox proportional hazards regression analyses, backward elimination, and Harrell’s c-index for discrimination. Validation was done using data from the independent NeoCel cohort. Results In March 2019, the median follow-up was 8.3 years (22 days–12.0 years); 135/944 children developed CD (mean age, 4.3 years [range, 1.1–11.4]). CD developed significantly more often in girls (P = .005) and in Human Leukocyte Antigen (HLA)-DQ2 homozygous individuals (8-year cumulative incidence rate of 35.4% vs maximum of the other HLA-risk groups 18.2% [P < .001]). The effect of homozygosity DR3-DQ2/DR7-DQ2 on CD development was only present in girls (interaction P = .04). The prediction models showed good fit in the validation cohort (Cox regression 0.81 [0.54]). To calculate a personalized risk of CD development and provide screening advice, we designed the Prediction application https://hputter.shinyapps.io/preventcd/. Conclusion Children with CD-FDR develop CD early in life, and their risk depends on gender, age and HLA-DQ, which are all factors that are important for sound screening advice. These children should be screened early in life, including HLA-DQ2/8–typing, and if genetically predisposed to CD, they should get further personalized screening advice using our Prediction application. Trial Registration Number ISRCTN74582487 (https://www.isrctn.com/search?q=ISRCTN74582487).

Celiac disease (CD) is a common autoimmune disorder induced by ingestion of gluten in genetically susceptible individuals. Despite the prerequisite for a genetic predisposition, only a minority of the 40% of the Caucasian population that has this genetic predisposition develops the disease. Thus, environmental and/or lifestyle factors play a causal role in the development of CD. The incidence of CD has increased over the last half-century, resulting in rising interest in identifying risk factors for CD to enable primary prevention. Early infant feeding practices have been suggested as one of the factors influencing the risk of CD in genetically susceptible individuals. However, recent large prospective studies have shown that neither the timing of gluten introduction nor the duration or maintenance of breastfeeding influence the risk of CD. Also, other environmental influences have been investigated as potential risk factors, but have not led to primary prevention strategies. Secondary prevention is possible through early diagnosis and treatment. Since CD is significantly underdiagnosed and a large proportion of CD patients are asymptomatic at the time of diagnosis, secondary prevention will not identify all CD patients, as long as mass screening has not been introduced. As following a gluten-free diet is a major challenge, tertiary prevention strategies are discussed as well.

The aim of this study was (1) to prospectively evaluate the nationwide implementation of the ESPGHAN-guidelines for the diagnosis of celiac disease (CD), (2) to investigate the incidence and clinical presentation of diagnosed childhood CD (0–14 years) in the Netherlands, and (3) to compare the findings with national survey data from 1975 to 1990 and 1993 to 2000 using the same approach. From 2010 to 2013, all practicing paediatricians were invited to report new celiac diagnoses to the Dutch Pediatric Surveillance Unit. Data were collected via questionnaires. A total of 1107 children with newly diagnosed CD were reported (mean age, 5.8 years; range, 10 months–14.9 years; 60.5% female). After the introduction of the non-biopsy approach in 2012, 75% of the diagnoses were made according to the guideline with a significant decrease of 46.3% in biopsies. The use of EMA and HLA-typing significantly increased with 25.8% and 62.1%, respectively. The overall incidence rate of childhood CD was 8.8-fold higher than in 1975–1990 and 2.0-fold higher than in 1993–2000. During the study period, the prevalence of diagnosed CD was 0.14%, far below 0.7% of CD identified via screening in the general Dutch paediatric population. Clinical presentation has shifted towards less severe and extra-intestinal symptoms.Conclusion: ESPGHAN guidelines for CD diagnosis in children were effectively and rapidly implemented in the Netherlands. Incidence of diagnosed CD among children is still significantly rising with a continuous changing clinical presentation. Despite the increasing incidence of diagnoses, significant underdiagnosis still remains. What is Known:• Since 2000 the incidence of diagnosed childhood CD in the Netherlands has shown a steady rise.• The rise in incidence has been accompanied by a changing clinical presentation at diagnosis. What is New:• The ESPGHAN guidelines 2012 for CD diagnosis were effectively and rapidly implemented in the Netherlands.• The incidence of diagnosed childhood CD in the Netherlands has continued to rise significantly during the reported period.

Introduction Coeliac disease (CD) occurs in 1% of the population, develops early in life and is severely underdiagnosed. Undiagnosed and untreated disease is associated with short-term and long-term complications. The current healthcare approach is unable to solve the underdiagnosis of CD and timely diagnosis and treatment is only achieved by active case finding. Aim: to perform a case finding project to detect CD children who visit the Youth Health Care Centres (YHCCs) in a well-described region in the Netherlands to evaluate whether it is feasible, cost-effective and well accepted by the population. Methods/analysis Prospective intervention cohort study. Parents of all children aged 12 months and 4 years attending the YHCCs for a regular visit are asked whether their child has one or more CD-related symptoms from a standardised list. If so, they will be invited to participate in the case finding study. After informed consent, a point of care test (POCT) to assess CD-specific antibodies against tissue transglutaminase (TG2A) is performed onsite the YHCCs. If the POCT is positive, CD is highly suspected and the child will be referred to hospital for definitive diagnosis according to the Guideline Coeliac Disease of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guideline. Main outcomes Incidence rate of new CD diagnoses in the study region in comparison to the one in the same age diagnosed by standard of care in the rest of the Netherlands. Feasibility and cost-effectiveness of active CD case finding at the YHCCs. All costs of active case finding, diagnostics and treatment of CD and the potential short-term and long-term consequences of the disease will be calculated for the setting with and without case finding. Ethical acceptability: by questionnaires on parental and healthcare professionals’ satisfaction. Main outcomesA statistical analysis plan was prepared and is published on the GLUTENSCREEN website (Statistical-Analysis-Plan -11-5-2021_def.pdf (glutenscreen.nl) and added as annex 1). Ethics and dissemination The Medical Ethics Committee Leiden approved this study. If we prove that case finding at the YHCC is feasible, cost-effective and well accepted by the population, implementation is recommended. Trial registration number NL63291.058.17.