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How early-life adversity affects the risk of pediatric-onset immune-mediated inflammatory disease
Mikkel Malham1, Christoffer Sejling2, Megan Davies3
1Copenhagen Health Complexity Center, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, 1353, Copenhagen, Denmark; Department of Pediatric- and Adolescent Medicine, Copenhagen University Hospital - Amager & Hvidovre, Kettegaard alle 36, 2650, Hvidovre, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Copenhagen University Hospital - Hvidovre, Kettegaard alle 36, 2650, Hvidovre, Denmark; Departments of Epidemiology and Global Health, Boston University School of Public Health, 715 Albany Street, Boston, MA, 02118, United States of America.
Insights
Early-life biological adversities significantly increase the risk of pediatric-onset immune-mediated inflammatory diseases (pIMID). Familial adversities showed a protective effect, warranting further investigation into healthcare disparities.
Area of Science:
- Pediatric immunology and epidemiology
- Life-course research
- Environmental influences on health
Background:
- The origins of pediatric-onset immune-mediated inflammatory diseases (pIMID) are not well understood, especially the role of early-life adversities.
- This study investigates the impact of interrelated early-life adversities on pIMID risk within a birth cohort.
Purpose of the Study:
- To examine the association between cumulative early-life adversities and the risk of developing pIMID.
- To identify specific patterns of adversities linked to increased pIMID risk using machine learning.
Main Methods:
- Utilized Danish registry data for children born between 1981-2015.
- Categorized early-life adversities (first 1000 days) into biological, material, and familial dimensions.
- Employed Cox proportional hazards models and a machine learning approach to analyze pIMID development (ages 2-18).
Main Results:
- A cumulative burden of biological adversities was linked to increased pIMID risk (aHR ≥4 adversities: 1.8).
- Conversely, multiple familial adversities were associated with a reduced risk (aHR >2: 0.66).
- Machine learning identified a specific adversity pattern associated with a five-fold higher pIMID risk in a subgroup.
Conclusions:
- Early-life biological adversities are significant risk factors for pIMID.
- The unexpected protective association of familial adversities may indicate delayed diagnoses in vulnerable populations.
- Potential healthcare inequalities require further investigation.
Background:
The etiology of pediatric-onset immune-mediated inflammatory disease (pIMID) is poorly understood, particularly the interplay of early-life adversities. We explored how interrelated early-life adversities affect the pIMID risk in a life-course birth cohort.
Methods:
We included all children born in Denmark between 1981 and 2015. Adversities encountered during the first 1000 days of life were obtained from the Danish registries and categorized into three dimensions: biological, material, and familial. The outcome was developing pIMID (autoimmune liver disease, inflammatory bowel disease, juvenile idiopathic arthritis, vasculitis, and systemic lupus erythematosus) between ages 2 and 18. Cox proportional hazards and additive hazard model assessed the effect of the cumulative adversity load on developing pIMID. A machine learning model identified exposure patterns associated with increased absolute risk estimates.
Results:
Of 2,123,827 children, 9070 developed pIMID. The cumulative burden of biological adversities was associated with higher risks of developing pIMID; aHR of two adversities was 1.23 (95 %CI: 1.07 to 1.41), aHR of ≥4 adversities was 1.8 (95 %CI: 1.4 to 2.2). Conversely, >2 familial adversities were associated with a reduced risk (0.66 [95 %CI: 0.41 to 1.1]). No associations were found in the material dimension. The machine learning model identified a pattern of adversities associated with a five-fold higher pIMID risk in a population subgroup.
Conclusion:
Early-life biological adversities are important risk factors for developing pIMID. The lower risk observed in the familial dimension was unexpected but may reflect delayed diagnosis in socially vulnerable families. This potential inequality in healthcare needs further exploration.
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