Correlation of Socioeconomic and Environmental Factors With Incidence of Crohn Disease in Children and Adolescents: Systematic Review and Meta-Regression
Authors: Weidner Jens , Glauche Ingmar , Manuwald Ulf , Kern Ivana , Reinecke Ines , Bathelt Franziska , Amin Makan , Dong Fan , Rothe Ulrike , Kugler Joachim 
Published: January 2024

Background
The worldwide incidence of Crohn disease (CD) in childhood and adolescence has an increasing trend, with significant differences between different geographic regions and individual countries. This includes an increase in the incidence of CD in countries and geographic regions where CD was not previously prevalent. In response to the increasing incidence, the pediatric care landscape is facing growing challenges.

Objective
This systematic review and meta-analysis were undertaken to comprehensively delineate the incidence rates of CD in pediatric populations across different countries and to explore potential influencing factors.

Methods
We performed a systematic review of PubMed and Embase (via Ovid) for studies from January 1, 1970, to December 31, 2019. In addition, a manual search was performed in relevant and previously published reviews. The results were evaluated quantitatively. For this purpose, random effects meta-analyses and meta-regressions were performed to investigate the overall incidence rate and possible factors influencing the incidence.

Results
A qualitative synthesis of 74 studies was performed, with 72 studies included in the meta-analyses and 52 in the meta-regressions. The results of our meta-analysis showed significant heterogeneity between the individual studies, which cannot be explained by a sample effect alone. Our findings showed geographical differences in incidence rates, which increased with increasing distance from the equator, although no global temporal trend was apparent. The meta-regression analysis also identified geographic location, UV index, and Human Development Index as significant moderators associated with CD incidence.

Conclusions
Our results suggest that pediatric CD incidence has increased in many countries since 1970 but varies widely with geographic location, which may pose challenges to the respective health care systems. We identified geographic, environmental, and socioeconomic factors that contribute to the observed heterogeneity in incidence rates. These results can serve as a basis for future research. To this end, implementations of internationally standardized and interoperable registries combined with the dissemination of health data through federated networks based on a common data model, such as the Observational Medical Outcomes Partnership, would be beneficial. This would deepen the understanding of CD and promote evidence-based approaches to preventive and interventional strategies as well as inform public health policies aimed at addressing the increasing burden of CD in children and adolescents.

Trial Registration
PROSPERO International prospective register of systematic reviews CRD42020168644; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=168644

International Registered Report Identifier (IRRID)
RR2-10.1136/bmjopen-2020-037669