Prediction models for celiac disease development in children from high-risk families: Data from the PreventCD cohort.

Fecha de publicación: 26/04/2022 Fecha Ahead of Print: 26/04/2022

Autores de IIS La Fe

Carmen Ribes Koninckx

Autor

Participantes ajenos a IIS La Fe

Meijer, Caroline R.
Auricchio, Renata
Putter, Hein
Castillejo, Gemma
Crespo, Paula
Gyimesi, Judit
Hartman, Corina
Kolacek, Sanja
Koletzko, Sibylle
Korponay-Szabo, Ilma
Ojinaga, Eva Martinez
Polanco, Isabel
Shamir, Raanan
Szajewska, Hania
Troncone, Riccardo
Villanacci, Vincenzo
Werkstetter, Katharina
Mearin, M. Luisa

Grupos

Enfermedad celíaca e Inmunopatología digestiva

Investigador Principal

Carmen Ribes Koninckx
Unidad Mixta De Investigación en Nutrición de Precisión para patologías digestivas (NUTRICURA PDig)

Investigador Principal

Carmen Ribes Koninckx

Abstract

BACKGROUND AND 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.

Datos de la publicación

ISSN/ISSNe:: 0016-5085, 1528-0012
Tipo:: Article
Páginas:: 426-436
DOI:: 10.1053/j.gastro.2022.04.030
Factor de Impacto:: 7,689 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

No hay documentos

Métricas

Filiaciones

Meijer, Caroline R.:: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
Auricchio, Renata:: Translational Medical Sciences and European Laboratory for the Investigation of Food-Induced Disease, University of Naples Federico II, Naples, Italy
Castillejo, Gemma:: Pediatric Gastroenterology Unit, Hospital Universitario Sant Joan de Reus, Reus, Spain
Crespo, Paula:: ADViSE, Department of Health Sciences, European University Miguel de Cervantes, Hospital Recoletas Campo Grande, Valladolid, Spain
Gyimesi, Judit:: Coeliac Disease Centre, Heim Pál National Paediatric Institute, Budapest, Hungary
Hartman, Corina:: Institute for Gastroenterology, Nutrition and Liver Disease, Schneider Children's Medical Center, Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel
Kolacek, Sanja:: Referral Center Pediatric Gastroenterology and Nutrition, Zagreb University, Medical School, Zagreb, Croatia
Koletzko, Sibylle:: Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany

Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland
Korponay-Szabo, Ilma:: Coeliac Disease Centre, Heim Pál National Paediatric Institute, Budapest, Hungary
Ojinaga, Eva Martinez:: Pediatric Gastroenterology and Nutrition, La Paz University Hospital, Madrid, Spain
Polanco, Isabel:: Pediatric Gastroenterology and Nutrition, La Paz University Hospital, Madrid, Spain
Ribes-Koninckx, Carmen:: Pediatric Gastroenterology Unit, La Fe Hospital, Valencia, Spain
Shamir, Raanan:: Institute for Gastroenterology, Nutrition and Liver Disease, Schneider Children's Medical Center, Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel
Szajewska, Hania:: Pediatrics, Warsaw, Medical University of Warsaw, Warsaw, Poland
Troncone, Riccardo:: Translational Medical Sciences and European Laboratory for the Investigation of Food-Induced Disease, University of Naples Federico II, Naples, Italy
Villanacci, Vincenzo:: Institute of Pathology, ASST-Spedali Civili Brescia, Brescia, Italy
Werkstetter, Katharina:: Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany
Mearin, M. Luisa:: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands