Multiple morbidity across the lifespan in people with Down syndrome or intellectual disabilities: a population-based cohort study using electronic health records

The Down syndrome phenotype is well established, but our understanding of its morbidity patterns is limited. We comprehensively estimated the risk of multiple morbidity across the lifespan in people with Down syndrome compared with the general population and controls with other forms of intellectual disability. In this matched population-based cohort-study design, we used electronic health-record data from the UK Clinical Practice Research Datalink (CRPD) from Jan 1, 1990, to June 29, 2020. We aimed to explore the pattern of morbidities throughout the lifespan of people with Down syndrome compared with people with other intellectual disabilities and the general population, to identify syndrome-specific health conditions and their age-related incidence. We estimated incidence rates per 1000 person-years and incidence rate ratios (IRRs) for 32 common morbidities. Hierarchical clustering was used to identify groups of associated conditions using prevalence data. Between Jan 1, 1990, and June 29, 2020, a total of 10 204 people with Down syndrome, 39 814 controls, and 69 150 people with intellectual disabilities were included. Compared with controls, people with Down syndrome had increased risk of dementia (IRR 94·7, 95% CI 69·9–128·4), hypothyroidism (IRR 10·6, 9·6–11·8), epilepsy (IRR 9·7, 8·5–10·9), and haematological malignancy (IRR 4·7, 3·4–6·3), whereas asthma (IRR 0·88, 0·79–0·98), cancer (solid tumour IRR 0·75, 0·62–0·89), ischaemic heart disease (IRR 0·65, 0·51–0·85), and particularly hypertension (IRR 0·26, 0·22–0·32) were less frequent in people with Down syndrome than in controls. Compared to people with intellectual disabilities, risk of dementia (IRR 16·60, 14·23–19·37), hypothyroidism (IRR 7·22, 6·62–7·88), obstructive sleep apnoea (IRR 4·45, 3·72–5·31), and haematological malignancy (IRR 3·44, 2·58–4·59) were higher in people with Down syndrome, with reduced rates for a third of conditions, including new onset of dental inflammation (IRR 0·88, 0·78–0·99), asthma (IRR 0·82, 0·73–0·91), cancer (solid tumour IRR 0·78, 0·65–0·93), sleep disorder (IRR 0·74, 0·68–0·80), hypercholesterolaemia (IRR 0·69, 0·60–0·80), diabetes (IRR 0·59, 0·52–0·66), mood disorder (IRR 0·55, 0·50–0·60), glaucoma (IRR 0·47, 0·29–0·78), and anxiety disorder (IRR 0·43, 0·38–0·48). Morbidities in Down syndrome could be categorised on age-related incidence trajectories, and their prevalence clustered into typical syndromic conditions, cardiovascular diseases, autoimmune disorde