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Published on: July 5, 2022
Prediction Models for Celiac Disease Development in Children From High-Risk Families: Data From the PreventCD Cohort
Caroline R Meijer1, Renata Auricchio2, Hein Putter3
1Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.
Insights
Children with celiac disease (CD) risk factors should be screened early. A new prediction tool uses gender, age, and HLA-DQ to personalize screening advice for children with a family history of CD.
Area of Science:
- Pediatric Gastroenterology
- Genetics
- Immunology
Background:
- Celiac disease (CD) screening is recommended for children with affected first-degree relatives (FDR).
- Optimal screening frequency and age remain undetermined.
- This study aimed to identify CD risk factors and develop predictive models for personalized screening strategies.
Purpose of the Study:
- To identify variables influencing celiac disease (CD) risk in genetically predisposed children.
- To develop and validate clinical prediction models for individualized CD screening advice.
- To create a risk score and prediction tool for personalized CD risk assessment.
Main Methods:
- Prospective analysis of the PreventCD-birth cohort (944 children) over 10 years.
- Development of prediction models using multivariable Cox regression and backward elimination.
- Validation of models using the independent NeoCel cohort, assessing discrimination with Harrell's c-index.
Main Results:
- 135/944 children developed CD, with a mean age of 4.3 years.
- CD risk was significantly higher in girls and Human Leukocyte Antigen (HLA)-DQ2 homozygous individuals.
- Prediction models demonstrated good fit in the validation cohort (Cox regression 0.81).
Conclusions:
- Celiac disease (CD) develops early in genetically predisposed children.
- Risk is influenced by gender, age, and HLA-DQ type, crucial for screening advice.
- An online tool, Prediction, is available for personalized screening recommendations.
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).
