Sun exposure and risk of paediatric inflammatory bowel disease
Creators: name: Holmes, Elizabeth
Publisher: name: The Australian National University
Year: 2021

description: Background: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing, incurable diseases of the large and small bowel. Although relatively uncommon in children, the incidence of paediatric IBD (PIBD) is increasing rapidly. Both genetic and environmental factors likely contribute to the pathogenesis of PIBD; identifying modifiable risk factors for PIBD may facilitate disease prevention. This thesis focuses on one potential modifiable environmental risk factor for PIBD, low sun exposure. The thesis presents three published papers, and one submitted for publication. Methods: The first published paper presents a narrative review of the evidence for the plausibility of low sun exposure, through both vitamin D-dependent and independent pathways, as a risk factor for IBD, with a focus on PIBD. This is followed by a systematic review of the literature and meta-regression of the global incidence of CD in relation to latitude and levels of ambient ultraviolet radiation. This ecological analysis used negative binomial regression to summarize data from individual studies across both hemispheres on PIBD incidence in relation to latitude and ambient ultraviolet radiation (UVR). Following from these reviews, I used pre-existing data to conduct a matched case-control study testing the association between past/recent sun exposure and the risk of PIBD in children &lt;18 years of age. Finally, I undertook a qualitative study with a group of Australian adolescents who had been diagnosed with IBD in order to better understand the difficulties they faced and the strategies they used in coping with their disease. Results and Discussion: In the narrative review, I found indirect, but not direct, support for an association between low sun exposure and increased risk of PIBD. Laboratory studies showed that exposure to UVR led to changes in the microbiome and modulation of immune function that would plausibly reduce the risk of IBD. Human ecological studies suggested a gradient of increasing incidence of PIBD with increasing latitude in the northern hemisphere, but this was not consistently found. The systematic review focused on CD, with insufficient evidence to include UC. In the meta-regression, for a 10-degree increase in latitude the annual incidence of paediatric CD increased by 0.23 (95%CI, 0.02 to 0.44) cases per 100,000 population. CD incidence was higher by 0.08 (95%CI. 0.01 to 0.15) cases per 100,000 for every additional month where the daily ambient UVR was lower than a previously defined threshold of 1.488 kJ/m2. These findings are consistent with the hypothesis that higher sun exposure protects against the development of paediatric CD, possibly with a threshold of effect. In the matched case-control study, for each 10 min increment in leisure-time sun exposure in the summer or winter prior to diagnosis there was a linear 6% reduction in the odds of being a PIBD case (adjusted OR=0.94, 95%CI 0.91-0.98 for both summer and winter). Sensitivity analyses to minimise the risk of reverse causality returned similar results. Adolescents in the qualitative study reported negative emotions related to several unpleasant experiences, but also strategies, adjustments and resilience in their approach to this life-long disease. This contextual information confirmed the importance of identifying modifiable risk factors to reduce the risk of PIBD. Conclusion: This thesis found a consistent line of evidence from laboratory/animal studies, through human ecological and individual-level observational studies suggesting that low sun exposure was associated with increased risk of developing PIBD, a disease demonstrated to test the emotional as well as physical well-being of affected children and adolescents. Our findings need to be replicated in additional studies, with the case-control design likely to be the only feasible study design to further define risk factors.