Background: Inflammatory bowel disease (IBD) is a chronic lifelong condition which comprises Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBDU). Around 8% of IBD cases diagnosed each year present in childhood (under 18 years) and can cause impairment of linear growth and pubertal development, affecting education and future employment. The incidence of paediatric IBD (PIBD) is increasing both within Scotland, as evidenced by previous publications, but also worldwide as demonstrated in a recent systematic review. As the number of cases are increasing, it has become critical that effective treatments are available to manage symptoms in this patient cohort. Anti-TNF alpha antagonists have been used to treat PIBD and shown in large single centre studies to be effective at the induction and maintenance of remission. However, these studies may not reflect the general PIBD patients’ clinicians treat daily so “real life” experience are needed to inform clinical practice. Aims: The aims of my thesis were 1) to determine if the incidence and prevalence of PIBD continue to increase worldwide and to examine the durability of any incidence rise seen in Scotland; 2) to investigate in a nationwide population-based study the incidence and natural history of IBDU; 3) to examine the efficacy, safety and long-term effects of anti-TNF alpha drugs; and lastly, 4) to assess the long-term risk of PIBD on cancer and mortality rates in a nationwide population-based study. Methods: Data was collected from all 4 PIBD centers across Scotland (Glasgow, Edinburgh, Aberdeen and Dundee) from 2009-2014 on new cases of IBD as well as those diagnosed with IBDU from 2003-2013, those treated with anti-TNF drugs from 2000-2012 and cases of cancer/deaths within the PIBD population from 2003-2013. Results: Thirty-six studies from 18 countries were included in the incidence systematic review, most from North America and Western Europe. The highest incidence was 15.2 per 100,000 in Nova Scotia, Canada with the lowest 0.47 per 100,000 in Saudi Arabia, for CD the highest incidence was 9.2 per 100,000 in Nova Scotia and lowest in Saudi Arabia at 0.27 per 100,000 whilst for UC rates were highest in Finland at 8 per 100,000 and lowest in Saudi Arabia at 0.2 per 100,000. In the prevalence systematic review, 27 studies were included from 12 countries with the highest prevalence of 301 per 100,000 in Israel and lowest in Libya at 3.6 per 100,000. CD was highest in Sweden at 41 per 100,000 and lowest in Libya at 2.0 per 100,000 which was similar for UC with a high of 30.7 per 100,000 in Sweden and lowest at 1.36 in Libya. Most studies that reported on temporal trends saw an increase in PIBD, CD and UC. Significant heterogeneity existed in studies in both incidence and prevalence due to varying methodological approaches, age cut offs and diagnostic algorithms so meta-analysis was not performed. The incidence of PIBD in Scotland demonstrated a significant and sustained rise from 430 cases in 2003-2008 with an incidence rate of 7.6 per 100,000 (95%CI 7.1-8.6) to 582 cases in 2009-2014 and incidence of 10.6 per 100,000 (95%CI 9.8-11.5) (p < 0.001); primarily due to an increase in paediatric Crohn’s disease. When compared with historical data there was a sustained and durable increase over the last 40 years, again mostly driven by increasing CD. The incidence of IBDU also increased from 2003-2013, accounting for around 20% of new PIBD cases in Scotland. Most children with this subtype had a relatively mild disease course, however 43% required immunosuppression and a small number escalated to anti-TNF therapy. 23% of IBDU patients had their diagnosis changed after endoscopic re evaluation, most 62%, to CD. A Scottish nationwide registry of all children treated with anti TNF drugs (infliximab (IFX) and adalimumab (ADA) was created from 2000-2012. 87% had improvement of their symptoms within 3 months post induction to IFX and 86% achieved remission with ADA. Growth was improved after one year of treatment with IFX but only in those children who responded after induction, had been diagnosed for over 2 years with IBD and were in the early stages of puberty (Tanner stage 1 and 2). Anti-TNF agents were generally safe and well tolerated with only 13% having an acute adverse reaction to IFX, ADA was also well tolerated with 16/57 having an adverse event. Death in children with PIBD was a rare occurrence with only 3 cases over 10 years, 2 cases were PIBD related with 2 cases of malignancy were observed, both had been treated with azathioprine with one subsequent death. Conclusions: The incidence and prevalence of PIBD is increasing worldwide with the highest incidence rates from Nova Scotia, Canada and highest prevalence rates from Israel, although there is a propensity of data from North America and Western Europe. In these population-based studies of paediatric-onset inflammatory bowel disease in Scotland, the number of new cases continue to rise with IBDU, as a subtype of IBD, more commonly diagnosed compared to other countries. Most children with IBDU had a mild disease course with 23% changing diagnosis following endoscopic reassessment most, 62% to CD. In Scotland, anti-TNF drugs are effective at managing symptoms of IBD with relatively few serious side effects with other benefits including improving linear growth in those treated with infliximab. Finally, cancer and death are a rare outcome in children with IBD in Scotland. The continued increase in incidence of PIBD with higher rates of IBDU observed in Scotland may suggest environmental factors, such as urbanization or latitude, influencing the onset of PIBD. Prospective case control studies can further explore these environmental risk factors taking advantage of the nationwide collaborative approach to care and research within Scotland.