Cheng Yin, Chuanjie Deng, Catherine M. Crespi, Sari Bar, Chandra D. Carey, M. Elizabeth Brickner, Eugenia Chock, Erin C. Schafer, Igor Barjaktarevic, Kosuke Inoue, Johnni Hansen, Julia E. Heck
University of North Texas. University of California, Los Angeles. University of Texas Southwestern Medical Center. University of Pittsburgh. Yale School of Medicine. Graduate School of Medicine of Kyoto University. Danish Cancer Society.
Research in Developmental Disabilities
Res Dev Disabil 2025;
DOI: 10.1016/j.ridd.2025.105167
Abstract
Background and objective: Recognizing the common co-occurring conditions among individuals with Down syndrome (DS) is essential for maintaining appropriate screening and optimizing healthcare resources. However, many previous studies relied on hospital- or community-based convenience samples with small sample sizes, limiting their generalizability. This study aimed to investigate the association between DS and co-occurring conditions in a large cohort of children and young adults.
Methods: We conducted a population-based retrospective cohort study using Danish national registers. The cohort had 1779912 participants born from 1977 to 2013 including 1385 with DS. For congenital conditions, we estimated inverse-probability-weighted (IPTW) absolute prevalence and prevalence difference. Time to event analyses (proportional hazard regression and IPTW cumulative incidence function estimation) were utilized to estimate the association between DS and risk for non-congenital co-occurring conditions. Sub-analyses examined risks among individuals with leukemia and sex-specific differences.
Results: Analyses showed very large prevalence ratios for many congenital conditions, including atrioventricular septal defects (PD=0.181, 95 % CI: 0.162, 0.203; PR=489, 95 % CI: 425-562), atrial septal defects (PD=0.215, 95 % CI: 0.194, 0.238; PR=94, 95 % CI: 84-105), and tetralogy of Fallot (PD=0.020, 95 % CI: 0.014, 0.029; PR=67, 95 % CI: 45-99). Individuals with DS had higher risks for cardiovascular disorders: pulmonary hypertension (HR=103.44, 95 % CI: 71.26-150.15), and stroke (HR=6.50, 95 % CI: 3.09-13.65). Additionally, the diagnosis was associated with increased risks of autoimmune diseases including celiac disease (HR=14.03, 95 % CI: 10.65-18.49) and type 1 diabetes (HR=3.40, 95 % CI: 2.08-5.54). Positive associations were also found for cerebral palsy (HR=9.77, 95 % CI: 7.32-13.06), and respiratory failure (HR=12.97, 95 % CI: 9.30-18.10). At 30 years of follow-up, IPTW absolute risks illustrated the clinical burden: e.g., pulmonary hypertension (AR1=0.028 vs AR0=0.0002, RD=0.026, RR=138.50), keratoconus (AR1=0.025 vs AR0=0.006, RD=0.025, RR=43.19), and respiratory failure (AR1=0.034 vs AR0=0.002, RD=0.031, RR=13.98).
Discussion and conclusion: Individuals with DS have notably higher risks of many co-occurring conditions. Our findings suggest that attention should be given to the management of autoimmune and ophthalmologic conditions, particularly regarding their incidence patterns over time and by gender.
Category
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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