Differences in morbidity and mortality in Down syndrome are related to the type of congenital heart defect

Abstract

Morbidity and mortality in Down syndrome (DS) are mainly related to congenital heart defects (CHDs). While CHDs with high prevalence in DS (typical CHDs), such as endocardial cushion defects, have been extensively described, little is known about the impact of less common CHDs (atypical CHDs), such as aortic coarctation and univentricular hearts. In our single-center study, we analyzed, in observational, retrospective manner, data regarding cardiac features, surgical management, and outcomes of a cohort of DS patients. Literature review was performed to investigate previously reported studies on atypical CHDs in DS. Patients with CHDs were subclassified as having typical or atypical CHDs. Statistical analysis was performed for comparison between the groups. The study population encompassed 859 DS patients, 72.2% with CHDs, of which 4.7% were atypical. Statistical analysis showed a significant excess in multiple surgeries, all-cause mortality and cardiac mortality in patients with atypical CHDs (p = .0067, p = .0038, p = .0001, respectively). According to the Kaplan-Meier method, survival at 10 and 40 years was significantly higher in typical CHDs (99 and 98% vs. 91 and 84%, log rank <0.05). Among atypical CHDs, it seems that particularly multiple complex defects in univentricular physiology associate with a worse outcome. This may be due to the surgical difficulty in managing univentricular hearts with multiple defects concurring to the clinical picture or to the severity of associated defects themselves. Further studies need to address this specific issue, also considering the higher pulmonary pressures, infective complications, and potential comorbidities in DS patients. K E Y W O R D S atrioventricular septal defects, congenital heart defects, Down syndrome, left-sided congenital heart defects, univentricular physiology

Medical conditions of children and young people with Down syndrome

“…2008), the prevalence in patients with DS is very high ranging from 40% to 50% (Baban et al . 2020). Our results showed that the CHDs were the most common among the congenital diseases, followed by cryptorchidism and gastrointestinal malformations.…”

Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome Children

“…Life expectancy in children with DS has increased significantly over the past decade, but children with DS remain at higher risk of neonatal and infant mortality than children without DS, respectively (1.65% vs. 0.36 and 4% vs. 0.48%) [2]. Some of the most prominent features of the DS phenotype include mental retardation as well as an increased incidence of congenital heart disease, hypothyroidism, diabetes, leukemia and by the age of 40 they reported an increased risk of developing Alzheimer like dementia [3][4][5][6][7][8][9]. Furthermore, patients with DS show multiple defects in both numbers and function of innate and adaptive immunity [10,11].…”

Cardiac Defects and Genetic Syndromes: Old Uncertainties and New Insights

“…Atypical CHDs in DS patients can be found in a minority of patients, including left-sided lesions, structural myocardial changes and univentricular physiology [ 41 ]. In this subgroup of patients, a significant excess of multiple surgeries is documented, in consideration of the multiple and complex anatomical defects.…”