This is the first known study to engage adults with DS and their caregivers to assess productive functional status, neuropsychiatric conditions, and QOL, with specific isolation of comorbid CHD and its impact on these meaningful outcomes. This is a topic of increasing relevance given improving lifespan among individuals born with DS, with a parallel trend in pediatric cardiology with more adults than children living with CHD in the U.S. today [37]. Health and functional outcomes in this aging group with both DS and CHD has been highlighted more broadly in a recent Scientific Statement from the American Heart Association, underscoring the priority to better understand which comorbidities could merit greater resources for outcomes optimization [10]. Results from our cross-sectional survey assessment directly comparing two cohorts—DS only and CHD + DS—did not show that having CHD significantly impacts employment rates among adults with DS, nor did it have an association with worse QOL or depression (regardless of prior cardiac surgeries and greater rates of neurologic comorbidities). This novel information may convey optimism to families of individuals both with both DS and CHD, and it could serve to uncover existing interventions and systems that may be preventing worse outcomes to then apply more broadly.

Employment and other components of community participation are demonstrated to be vital to QOL and psychological well-being in adulthood, including individuals with disabilities and their families [29]. However, individuals with disabilities have significantly lower employment rates than those without (24.2% compared to 65.8% according to the most recent Bureau of Labor Statistics) [38]. When more specifically examining employment outcomes among adults with DS, as Kumin et al. initially surveyed in 2015 with input in questionnaire design directly from adults with DS and their families, this group reported a more favorable “current paid employment rate” of 57% in comparison to broader groups with disabilities [35]. The similar employment rate of 54% among adults with both DS and CHD in this study cohort has not previously been reported and is largely encouraging, suggesting that cardiac history seems to not add detriment.

Volunteer work also should not be overlooked as a potentially meaningful way that individuals with DS contribute to their communities. Adults with DS have reported significantly higher rates of volunteerism than the population of typical adults (42% in the Kumin et al. cohort, 23% in our overall study group). The higher volunteer participation rates among study respondents with CHD plus DS compared to DS alone could reflect more motivated caregivers to identify opportunities or earlier involvement in volunteer organizations in childhood and adolescence. However, an alternate argument is that this may reflect the difficulty in finding enough hours of paid employment or adequate daytime care for these adults. This topic could be further explored in future studies. Regardless, these reported rates of community participation not only have meaning to patients and their families but also for health care providers who engage with these individuals often throughout the entirety of their childhood and can influence future transition planning and goals. This data could impart similar meaning to educators, policymakers, rehabilitation counselors, and employers to broaden the trajectory for community engagement opportunities for adults with DS beyond education attainment.

Children born with CHD are at increased risk for neurocognitive and psychologic problems at all stages of early development, with increased vulnerability demonstrated among those with genetic abnormalities [39,40,41]. Cognitive challenges may include difficulties in memory, attention, executive functions (planning, problem solving, flexibility), processing speed, language, and visuospatial skills. Many tertiary children’s heart centers have incorporated neurodevelopmental assessments and therapies among infants and children with complex CHD seemingly at highest risk [42]. Additional threats to neurocognitive abilities in children with CHD (with or without genetic syndromes) include higher rates of neurologic conditions, including perioperative stroke and seizures, which are risks that interestingly persist throughout the lifespan. Seizures occur with increased frequency in adult CHD patients, particularly those with more complex CHD, and stroke incidence in young adults is nearly eleven times that of the general population [22, 23, 43, 44]. In general, both stroke and seizure have been associated with lower executive functioning, employment challenges, and worse QOL [12, 45, 46] With mutually well-described patterns of neurocognitive pathology and learning impairments among individuals with DS, regular developmental assessments throughout childhood and educational assistance is recommended. Individuals with DS also exhibit more frequent rates of stroke and seizures, the former less well understood with most reports in case series; presumably having certain types of CHD or prior cardiac surgery may heighten one’s risk for either issue [47]. This investigation is the first to confirm this prediction among adults with both DS and CHD. The more intriguing finding in this work is that these higher rates of stroke and seizure were not associated with reduced community engagement or lower QOL compared to adults with without these prior neurologic comorbidities. Interestingly, there was a significant difference in the reported QOL domain of “environment” with lower perceived QOL among adults with both CHD + DS compared to those without CHD. This raises additional questions regarding differences in the surroundings, resources and access to services or activities, and functional abilities translating to a satisfactory daily environment in the CHD + DS group. Some adults with CHD have physical activity restrictions, or there is a fear among caregivers that activity should be restricted, and perhaps this contributes. Additional study is needed to better understand relevant factors.

Increased caregiver burden scores among respondents of subjects with CHD + DS compared to DS alone may reflect both the medical complexity of CHD and the additional support needs for community engagement. However, it should be noted that both groups reported only “mild” degree of burden on the instrument score, which ranges 1–48 and each group’s mean score of < 13. The study questionnaire did not further characterize the caregiver’s actual role in the subject’s daily life, and there may be substantial variability in responsibility among caregiver respondents.

Adults with DS reported a high prevalence of mental health problems, regardless of CHD status. This is consistent with existing evidence describing conditions specifically associated with DS, including Alzheimer’s disease, attention deficit disorder, autism, anxiety, and depression [3, 48,49,50]. Higher risks for cognitive and neurodevelopmental deficiencies exist among adults with CHD as well, postulated for years and recently formally evaluated and demonstrated among those with more complex CHD types [13]. This study originally aimed to perform a similar pilot assessment of cognitive ability and adaptive behaviors in adults with DS compared to those with complex CHD to evaluate CHD-mediated differences in this special young adult cohort. However, sample size was unable to be achieved largely related to COVID-19 pandemic-related testing space and safety concerns impacting enrollment. The aim may be more feasible in a post-pandemic period given that half of the entire cohort (50.2%, n = 143) self-reported willingness to complete neuropsychological testing.

Limitations to the study include the validity of self-reported data and mixed response groups, including exclusive self-report, exclusive proxy-report by caregiver, and collaborative report. A variety of questionnaire response options were permitted to account for the wide range of functional ability among adult subjects with DS; however, mixing reporting modes can introduce measurement inconsistency, response bias, and comparability problems. Additional study limitations included hacking of web-based questionnaires resulting in subsequent restriction of study advertisement, consent in vulnerable populations, and selection bias in more motivated subjects and families with greater willingness to participate. There may be outcomes differences among the age ranges of adult subjects with DS included (18–45 years), and future studies could stratify into more specific categories. Study enrollment began immediately prior to the COVID-19 pandemic, and while survey instrument questions were re-phrased to query subjects’ community engagement status “pre-pandemic,” this still may have impacted subject recruitment and/or responses given lower rates of employment and volunteer participation nationally at this time. Similarly, the COVID-19 pandemic was associated with an increased prevalence of mental health problems and potentially greater caregiver burden with closures of adult day programs and other occupational facilities and resources, and this may have confounded survey responses.