Cardiovascular Complications in Children with Down Syndrome and Sleep Disordered Breathing

Abstract

Study Objectives:

Children with Down syndrome (DS) often present with craniofacial and neuromuscular features that increase the risk of sleep-disordered breathing (SDB), which may lead to cardiovascular morbidity. We conducted a scoping review to profile the current evidence base describing cardiovascular complications in children with DS and SDB. Findings from this work are expected to identify knowledge gaps that could inform future research and clinical care.

Methods:

We performed a systematic scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Comprehensive searches of Embase, Scopus, and MEDLINE were conducted, and eligible studies included children aged 1–18 with DS and SDB reporting cardiovascular outcomes.

Results:

Seven studies involving 1,437 participants were included. Across various study designs, children with DS and SDB showed blunted autonomic responses to apneic events, impaired nocturnal dipping of heart rate and blood pressure, increased hypoxic burden even with mild OSA severity, and early signs of left ventricular diastolic dysfunction and bi-ventricular remodeling.

Conclusions:

SDB and DS are linked to a constellation of clinical signs consistent with cardiopulmonary end-organ dysfunction and elevated clinical risk. Ongoing cardiac monitoring and use of physiologic measures beyond the apnea-hypopnea index are necessary. Addressing persistent upper airway obstruction with multimodal treatments, including surgery, positive airway pressure, and new therapies like hypoglossal nerve stimulation, may be crucial to lowering long-term cardiovascular risk in this vulnerable group.

Introduction

Down syndrome (DS) is the most common inherited chromosomal disorder [1,2] characterized by a distinctive set of craniofacial and neuromuscular features that narrow the upper airway and decrease pharyngeal tone during sleep [3,4]. Sleep-disordered breathing (SDB), including primary snoring, upper airway resistance syndrome, obstructive hypoventilation, and obstructive sleep apnea (OSA), involves recurrent upper-airway collapsibility leading to sleep disruption and subsequent cardiopulmonary stress [5–7]. Obstructive sleep apnea, the most severe form of SDB, affects children with DS disproportionately, with an estimated prevalence of up to 70% [8,9] compared to 5% in typically developing (TD) children [10]. The distinctive anatomical and physiological traits of DS, such as adenotonsillar hypertrophy [4], midface and mandibular hypoplasia [11,12], hypotonia [13], and obesity [14] contribute to increased OSA burden.

OSA is characterized by cyclical upper airway obstruction resulting in intermittent hypoxemia, hypercapnia, and sleep fragmentation [10]. In non-DS adults, untreated OSA is linked to systemic hypertension [15], autonomic imbalance [16], endothelial dysfunction [17], right ventricular remodeling [18], pulmonary vascular disease [19], and a greater risk of cardiovascular morbidity [20]. In TD children, OSA has been shown to increase the risk of autonomic dysfunction [21], endothelial dysfunction [22], and left ventricular remodeling [23]. However, relationship between OSA and cardiovascular disease in children with DS remains incompletely understood [24]. This knowledge gap is critical as children with DS experience a markedly higher prevalence and severity of SDB than TD peers. At the same time, DS is associated independently with baseline risk of cardiovascular complications, irrespective of congenital (structural) heart disease per se [25]. These factors likely act synergistically, meaning SDB in children with DS may have disproportionately severe cardiovascular effects compared to the general pediatric population, and often amplified by sociodemographic factors [26]. Therefore, it is plausible that SDB plays a significant and potentially modifiable role in driving cardiovascular morbidity in children with DS, highlighting the importance of reviewing available evidence. Consequently, this scoping review aims to explore the cardiovascular complications linked to SDB in children with DS.

Methods

We conducted this scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines [27], and the protocol was registered with PROSPERO (ID: 1106369). In consultation with a medical librarian, we searched Embase, Scopus, and MEDLINE (PubMed) using keywords related to Down syndrome, pediatric populations, sleep-disordered breathing, obstructive sleep apnea, and cardiovascular outcomes (Supplement 1). No date or language restrictions were applied. Eligible studies included children under 18 years old with Down syndrome who had SDB or OSA and reported at least one cardiovascular outcome. OSA was defined as AHI ≥ 1, while SDB included snoring, upper airway resistance syndrome and central sleep apnea. We excluded review articles, abstracts, editorials, clinical trial protocols, hypoventilation syndrome only studies, and studies published before 1976, the year pediatric OSA was first described [28].

All references were imported into Covidence (Veritas Health Innovation, Melbourne, Australia) for de-duplication and screening. Two reviewers (W.G. and K.Z.) independently screened titles and abstracts, and studies that appeared potentially eligible underwent full-text review. Discrepancies were resolved through discussion until consensus was achieved. Data were extracted into a standardized spreadsheet. Extracted variables included study design, country of origin, and sample size, as well as participant demographics such as age, sex, body mass index, and blood pressure (BP). Sleep study measures included the apnea-hypopnea index (AHI), arousal index, oxygen saturation (SpO₂) nadir, and hypoxic burden. Cardiovascular outcomes included autonomic indices like heart rate (HR) variability, percent change in HR, and pulse transit time (PTT); echocardiographic measures such as tricuspid annular plane systolic excursion (TAPSE), left ventricular mass, and mitral lateral E/e′; congenital cardiac findings, including the presence of congenital heart disease (CHD); and circulating biomarkers like B-type natriuretic peptide (BNP) and urinary catecholamines. Due to heterogeneity in study designs, patient cohorts, and reported outcomes, the findings were synthesized narratively rather than through meta-analysis. Additional references identified through peer review were included in the narrative synthesis.

Results

Study Characteristics

The database search retrieved 390 records, of which 107 duplicates were removed, leaving 283 unique references for screening. After reviewing titles and abstracts, 29 studies were selected for full-text assessment. We identified a total of 22 publications not included in our analysis due the following reasons: 11 were abstracts only, 6 described incorrect patient populations, 2 reported interventions and three others provided insufficient information (Figure 1). Ultimately, seven studies met the inclusion criteria. These studies collectively cover 13 years of patient data (2005–2018) (Table 1). The most common study design was matched cohort (n=3) [29,30], followed by n=1 case-control [31], n=1 retrospective cohort [32], n=1 cross-sectional survey [33], and n=1 randomized double-blind controlled trial [34]. Of the 7 studies, a majority were conducted in Australia (n=4), with the remaining in the United States (n=2) and Japan (n=1).

Figure 1. PRISMA-ScR flow diagram showing study identification, screening, eligibility assessment, and inclusion.

The initial search yielded 390 records. After removal of 107 duplicates, 283 records were screened by title and abstract, and 29 full-text articles were assessed for eligibility. Of these, 22 were excluded (11 abstracts, 6 with incorrect patient populations, 2 reporting interventions, 1 correspondence, 1 with incorrect outcomes, and 1 with no full text available). A total of 7 studies met inclusion criteria and were included in the final synthesis.

Table 1.

Summary of included studies examining cardiovascular outcomes of sleep-disordered breathing in children with Down syndrome.

Study	Year	Title	Design	Aim
O’Driscoll et al.	2012	Cardiac and sympathetic activation are reduced in children with Down Syndrome and sleep disordered breathing	Case-control	Test hypotheses that (1) the cardiovascular response at obstructive event termination in children with DS is reduced compared with control children; (2) that this is reflected in more prolonged oxygen desaturation following obstructive events; and (3) that overnight sympathetic activity is lower in children with DS compared with control children.
Goffinski et al.	2014	Obstructive sleep apnea in young infants with Down Syndrome evaluated in a Down Syndrome specialty clinic	Retrospective cohort	To explore OSA among a sample of young infants with DS at a specialty clinic.
Konstantinopoulou et al.	2015	Relationship between obstructive sleep apnea, cardiac complications, and sleepiness in children with Down Syndrome	Randomized, double-blind, controlled trial	To determine if presence/severity of OSAS was associated with cardiovascular dysfunction in children with DS, and to assess response to continuous positive airway pressure treatment.
Sawatari et al.	2015	A nationwide cross-sectional study on congenital heart diseases and symptoms of sleep-disordered breathing among Japanese Down’s Syndrome people	Cross-sectional survey	To investigate the prevalence of SDB symptoms and congenital heart disease and to establish the relationship between SDB and congenital heart disease in Japanese DS individuals using data from a nationwide survey.
Bassam et al.	2021	Nocturnal dipping of heart rate is impaired in children with Down Syndrome and sleep disordered breathing	Matched cohort	To compare nocturnal dipping of HR and pulse transit time (PTT, surrogate inverse measure of BP change) in children with DS and SDB to those of typically developing children with and without SDB.
Walter et al.	2024	The surge in heart rate and blood pressure at respiratory event termination is dampened in children with Down Syndrome	Matched cohort	To compare cardiovascular autonomic function in children with DS and TD children matched for SDB severity, age and sex by analyzing the changes in HR and pulse transit time (PTT; a surrogate inverse measure of BP changes) associated with obstructive and central respiratory events during sleep stages.
Walter et al.	2025	Sleep apnea–specific hypoxic burden in children with Down Syndrome and typically developing children.	Matched cohort	Assess whether hypoxic burden (a metric integrating the frequency, depth, and duration of desaturations) is elevated in children with DS compared to typically developing children, and examine its relationship to heart rate variability (as an indicator of autonomic cardiovascular function).

Study details include author, year, title, study design, and primary objectives.

Patient Demographics

Participant ages were generally within the school-age range, although reporting methods varied: two studies reported mean age [32,33], while the others reported median age [29–31,34,35]. Across all studies (Table 2), ages ranged from infancy to 18 years. Most cohorts were male-predominant, though one sample included 57.9% females [35] and another 56.8% females [29]. Racial and ethnic data were infrequently reported.

Table 2.

Participant characteristics across included studies.

Study	Number of participants	Males (%)	Age Mean (SD) OR Median (IQR)	AHI	SpO2 nadir
O’Driscoll et al. (2012)	32	18 (56.3)	5.5 (3.5–8.2) years	2.9 (0.5–8.1)	NA
Goffinski et al. (2014)	56	32 (57.1)	44 ± 48 days	19 ± 14	NA
Konstantinopoulou et al. (2015)	20	13 (65)	10 (9–13.4) years	13.9 (6.8–21.5)	87 (85.5–88)
Sawatari et al. (2015)	1222	678 (55.5)	14.5 ± 9.9 years	NA	NA
Bassam et al. (2021)	19	8 (42.1)	9.1 (6.3–15) years	5 (1.6–22.9)	87 (86–90)
Walter et el. (2024)	44	19 (43.2)	8.4 (5.3–12.8) years	4.2 (1.0–12.7)	88 (88.5–90.3)
Walter et al. (2025)	44	22 (50)	10.5 (6.3–15.7) years	13.9 (7.8–28)	86 (81.5–88)

Data presented include sample size, sex distribution, age (mean or median with range or interquartile range, as reported), apnea-hypopnea index (AHI), and oxygen saturation (SpO₂) nadir. These details provide context for interpreting variability in study findings

Blunted Autonomic Responses to Respiratory Events

As shown in Table 3, two independent studies demonstrated children with DS have a blunted attenuation in HR and BP responses to apnea/hypopnea events compared to controls [29,31]. Normally, obstructive apnea causes characteristic cardiovascular changes: initially HR and BP decrease, then as hypoxia worsens, both increase, and upon arousal from sleep, there is a surge in sympathetic activity with a spike in HR and BP [36]. O’Driscoll and colleagues [31] analyzed beat-by-beat HR throughout the apnea cycle - pre-event, early-event, late-event, and post-event – between children with DS and TD children. They examined ~200 events in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and found no difference in pre-event baseline HR between groups. However, children with DS showed a significantly smaller post-event increase in HR (percent change from baseline) compared to controls. The change in HR during events was also smaller in children with DS during NREM sleep, with a similar but not statistically significant trend in REM sleep. While both groups had similar baseline oxyhemoglobin saturation (SpO₂), event durations, and mean desaturation levels, children with DS experienced a significantly longer time to reoxygenation after events in NREM and REM sleep. Overnight creatinine-normalized urinary catecholamine levels (noradrenaline, adrenaline, and dopamine) were also markedly lower in children with DS, reinforcing the evidence of blunted sympathetic activation.

Table 3.

Key findings of included studies examining cardiovascular outcomes of sleep-disordered breathing (SDB) in children with Down syndrome (DS).

Study	OSA metrics	CV Outcomes	Main Result	Notable Statistics
O’Driscoll et al. (2012)	Polysomnography with event-level analysis (NREM/REM).	ΔHR at event termination, oxygen resaturaion time, and urinary catecholamines	In children with DS (vs. controls): (1) HR surge at the end of obstructive events was significantly smaller (blunted) during NREM sleep; (2) reoxygenation after obstructive events was delayed; (3) overnight sympathetic activation was lower.	Post-event HR increase was lower in DS (NREM: +21.4% vs +26.6% in controls). Urinary catecholamines were significantly reduced in DS (noradrenaline P<0.01; adrenaline P<0.05; dopamine P<0.01).
Goffinski et al. (2014)	PSG in symptomatic infants	OSA prevalence/severity; co-morbid predictors (including congenital heart disease).	OSA was extremely common in infants with DS (minimum prevalence 31% overall; of those tested, 95% had OSA, 71% with severe OSA). Dysphagia and congenital heart disease were strong co-predictors of OSA in these infants.	The combination of dysphagia + congenital heart disease predicted 36% of OSA cases (overall predictive accuracy 71%).
Konstantinopoulou et al. (2015)	PSG parameters (AHI; arousal index; SpO2 nadir)	Echocardiography (lateral E/e′, LV mass z-score, TAPSE); BNP; daytime sleepiness scores.	Worse LV diastolic function (higher E/e′) was associated with more severe OSA (higher AHI, higher arousal index) and with deeper desaturations (lower SpO2 nadir)	E/e′ vs. AHI r = 0.61 (P = 0.002); vs. arousal r = 0.42 (P = 0.043); vs. SpO2 nadir r = −0.61 (P = 0.002); CPAP hours vs. E/e′ r = −0.48 (P = 0.044)
Sawatari et al. (2015)	Caregiver-reported SDB symptoms (apnea pauses, snoring, arousals, nocturia, daytime naps).	Presence and type of congenital heart disease.	Certain CHD subtypes were associated with higher likelihood of reported apnea. Children with tetralogy of Fallot had significantly higher odds of observed apneas. Conversely, snoring was reported less frequently in children with congenital heart disease.	DS children with TOF had higher odds of apnea than those without congenital heart disease (OR ~3.1, 95% CI 1.36–7.05, P<0.01).
Bassam et al. (2021)	Full PSG; OSA group (DS) matched to a control OSA group by AHI, and a control group without OSA.	Nocturnal HR dipping; nocturnal BP dipping (via PTT).	Children with DS + OSA showed attenuated nocturnal HR dipping across all sleep stages and reduced BP dipping (significantly in N2 stage) compared to both TD children with OSA and those without OSA.	A smaller proportion of DS children exhibited >10% decline in HR from wake to N2 or REM (vs. control with OSA). In DS, PTT was higher (indicating less BP drop) in N2 compared to control.
Walter et al. (2024)	PSG with analysis of obstructive & central events in NREM and REM.	ΔHR and ΔPTT from pre-event to post-event (magnitude of HR and BP surges).	Children with DS had significantly smaller HR and BP surges at respiratory event termination across event types and sleep stages, compared to TD controls.	For obstructive events, the percentage increase in HR from late-event to post-event was significantly lower in DS (in both NREM and REM, P<0.05). For central apneas, the HR surge was lower in DS during REM (P<0.01). The increase in PTT (reflecting BP rise) was smaller in DS for both NREM and REM.
Walter et al. (2025)	PSG; calculation of Sleep Apnea-Specific Hypoxic Burden	Heart rate variability (HRV) as an autonomic function measure; morning ΔHR (change in HR upon awakening).	Hypoxic burden was higher in children with DS (especially in primary snoring and mild OSA) than in severity-matched TD children. In DS children, a higher hypoxic burden was associated with dampened autonomic activity (lower HRV), whereas in TD children hypoxic burden was not as strongly related to HRV.	In the DS group, hypoxic burden accounted for a significant proportion of variance in heart rate variability (R2 = 0.12, β = –10.6 ± 4.6, P = 0.03), indicating that greater oxygen desaturation load predicted reduced autonomic responsiveness.

Data include study-level sleep metrics [apnea-hypopnea index (AHI), polysomnography (PSG) features, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep], cardiovascular outcomes [heart rate (HR), change in heart rate (ΔHR), heart rate variability (HRV), blood pressure (BP), pulse transit time (PTT), tricuspid annular plane systolic excursion (TAPSE), left ventricular (LV) mass, mitral lateral E/e′ ratio], and biomarkers [B-type natriuretic peptide (BNP), urinary catecholamines]. The table summarizes main results and notable statistics across studies, highlighting consistent evidence of autonomic blunting, impaired nocturnal dipping, elevated hypoxic burden, and early cardiac structural changes in this population.

Walter and colleagues [29] likewise reported reduced surges in HR and BP at respiratory-event termination in DS. In 44 children with DS (779 total events), the percent change in pulse transit time (PTT) from pre- to late- to post-event was significantly smaller in children with DS than in matched controls during NREM and REM sleep, indicating a diminished BP response. Similarly, the post-event HR surge was significantly less pronounced in children with DS. Collectively, these findings from two separate cohorts demonstrate that children with DS have a weakened autonomic response to obstructive events, along with slower oxygen saturation recovery and lower overnight catecholamine excretion despite similar AHI. This suggests that respiratory events in DS cause more prolonged hypoxemia and a reduced sympathetic response.

Changes in Nocturnal Heart Rate and Blood Pressure “Dipping”

Under normal conditions, HR and BP decrease at night during sleep (nocturnal dipping) from higher daytime levels. This nocturnal decline is believed to be restorative for the cardiovascular system [37]. Bassam et al [35]. examined nocturnal dipping in 19 children with DS and SDB by measuring the percentage change in HR and pulse transit time (PTT) from wakefulness to each sleep stage. While TD children showed the expected pattern of higher awake HR with a drop during sleep, the DS group showed no significant HR differences between wakefulness and any sleep stage. Blood pressure, reflected by PTT, was lower (meaning PTT was higher) in children with DS compared to TD children during N2 sleep stage only. Notably, significantly fewer children with DS achieved a greater than 10% reduction in HR during N2 or REM sleep. In summary, children with DS showed markedly reduced nocturnal HR and BP dipping, leading to less cardiovascular “recovery” time during sleep.

Hypoxic Burden as a Risk Marker

Beyond conventional metrics like AHI, Walter et al. [30] assessed the OSA-specific hypoxic burden in children with DS, a measure capturing total area of oxygen desaturation below a baseline, summed across all respiratory events. In adults, a higher hypoxic burden has been linked to adverse health outcomes [38] which include cardiovascular mortality [39], incident heart failure [40,41], stroke [41], acute myocardial infarction and all-cause mortality [42]. Walter et al. [30] retrospectively analyzed the Bassam et al. cohort [35], calculating hypoxic burden by multiplying the average desaturation area per event by the AHI and examining the total time with SpO₂ <90%. They found children with DS had significantly lower SpO₂ nadirs than TD children at each level of OSA severity (primary snoring, mild OSA, and moderate-severe OSA). Although hypoxic burden in children with DS with moderate to severe OSA was also higher than in their TD peers, this difference did not reach statistical significance. The study noted that hypoxic burden in children with DS did not correlate with overall quality-of-life scores. Still, there was a weak link between higher hypoxic burden and specific physical symptoms (e.g., mouth breathing, frequent colds, nasal discharge, difficulty swallowing). These findings suggest that children with DS endure greater cumulative hypoxic stress from OSA, which may help explain their heightened susceptibility to cardiovascular consequences of OSA. Importantly, hypoxic burden also appeared to be a better indicator of autonomic dysfunction than AHI: when DS and control groups were matched for hypoxic burden, differences in autonomic responses were reduced, indicating that intermittent hypoxemia is a key factor driving the autonomic impairments observed in DS with OSA.

Cardiac Structure and Function

Obstructive sleep apnea may also adversely affect cardiac structure and function in children with DS. Konstantinopoulou et al. [34] studied 20 children with DS and OSA in a randomized trial comparing continuous positive airway pressure (CPAP) to sham CPAP over four months. Nineteen subjects had already undergone adenotonsillectomy; their data were included for baseline cardiovascular insights. Initially, no child exhibited signs of pulmonary hypertension, and all had B-type natriuretic peptide levels <10 pg/mL. Several links between sleep study parameters and echocardiographic measures were identified. Specifically, the early diastolic mitral annular velocity ratio (lateral E/e′), indicating left ventricular (LV) diastolic function [43], was positively associated with AHI and arousal index, and negatively associated with SpO₂ nadir. AHI was inversely correlated with diastolic BP. Surprisingly, AHI was positively correlated with the TAPSE z-score, implying greater OSA severity was associated with better right ventricular systolic function in this group. TAPSE, defined as tricuspid annular plane systolic excursion, is a non-invasive echo scoring system that evaluates the lateral tricuspid annulus displacement toward the apex and is thus used to assess right ventricular function [44]. This positive correlation was particularly unexpected as the opposite relationship has been robustly established in non-DS adult populations [43]. After four months of treatment, no significant differences in echocardiographic outcomes between the CPAP and sham groups were identified. However, better adherence to CPAP showed a trend toward improved LV diastolic function, indicated by a lower E/e′. While the cardiac changes at baseline were subtle and no immediate CPAP effects were observed, these correlations suggest potential pathways by which OSA could lead to cardiac remodeling over time. Notably, the partial improvements in LV metrics with CPAP suggest that some OSA-related cardiac issues may be reversible with treatment.

Association of OSA with Congenital Heart Disease

Two studies explored the relationship between OSA and congenital heart disease (CHD). In a retrospective review of 59 infants with DS (average age 44 ± 48 days), Goffinski et al. [32] reported 95% of DS infants had OSA. The combination of dysphagia and CHD was the strongest predictor of OSA, resulting in a model accuracy of 71%. Although authors did not evaluate cardiovascular outcomes, findings indicated DS infants with CHD and feeding difficulties are at particularly high risk for early-onset OSA, which may further increase their cardiopulmonary burden.

A nationwide survey by Sawatari et al. [33] investigated CHD and SDB in a Japanese DS group (n=1,222). Among respondents, ventricular septal defect was the most common condition (53.2%), followed by atrial septal defect (33.8%) and patent ductus arteriosus among others. Notably, caregivers of children with CHD reported habitual snoring significantly less often than those without. Children with CHD also showed a higher frequency of observed apneic events at night, although this did not reach statistical significance. While this survey did not measure OSA severity or fully assess CHD severity, it highlights the SDB and CHD link in children with DS. The presence of structural heart defects may alter the clinical presentation of OSA (e.g., less snoring) and could indicate additional cardiovascular risks over time.

Discussion

Children with DS have distinctive upper airway features that predispose them to OSA and often make the condition resistant to standard treatments [46,47]. Their unique craniofacial features, combined with adenotonsillar hypertrophy and relative macroglossia, decrease airway size [48]. Generalized pharyngeal muscle hypotonia contributes to dynamic airway collapse during sleep, and adenoids can encroach on the nasopharyngeal space even in infancy, with many children with DS by preschool age developing enlarged tonsils that further restrict the oropharynx [49]. Furthermore, children with DS tend to gain excess weight in later childhood, worsening airway narrowing due to adiposity in the neck and tongue [14]. The development of OSA in DS is therefore multifactorial and changes with age: craniofacial restriction and hypotonia are dominant in early years, while by adolescence, obesity and sometimes lingual tonsil or adenoid regrowth add extra airflow resistance [50]. This unique combination of risk factors explains both the high prevalence of OSA in DS [51] and its persistent nature throughout the lifespan. The consistent airway obstruction means airflow resistance seldom normalizes in this population, despite interventions such as adenotonsillectomy, as observed in studies that show persistent residual postoperative OSA in children with DS [46,52–55]. This chronic increase in upper airway resistance leads to sustained rises in intrathoracic pressure, which in turn raise pulmonary vascular resistance and right heart strain. Over time, this cycle of increased airway resistance and elevated pulmonary vascular load may accelerate the development of pulmonary hypertension [56]. OSA in DS is not just a temporary, early childhood issue; rather, it is a chronic condition that causes ongoing obstruction and contributes to cardiovascular morbidity, often requiring ongoing, multimodal management.

This scoping review synthesizes emerging evidence that SDB has measurable cardiovascular effects in children with DS, affecting autonomic regulation, hypoxemic load, and cardiac structure and function. Across the seven included studies, a common theme is blunted autonomic responses to obstructive respiratory events in DS. Compared to TD peers, children with DS show reduced HR and BP surges at apnea termination [29,31], prolonged post-event reoxygenation [31], lower sympathetic activation [31], impaired nocturnal HR dipping [35], and a higher hypoxic burden [30].

First, two independent cohorts showed significantly reduced HR and BP responses to apnea-induced arousals in children with DS. Walter et al. [29] found that the increase in HR and BP during arousals from respiratory events was diminished in children with DS during both NREM and REM sleep. This is supported by earlier work by O’Driscoll et al. showing smaller HR increase in response to spontaneous arousals from sleep in a separate DS group, indicating a reduced chronotropic response [57]. Recently, Walter et al. also demonstrated OSA reduction may mitigate worsening of these dampened HR responses to respiratory events, thus emphasizing the importance of early identification and treatment of sleep apnea [58]. Collectively, these findings suggest DS involves a unique and reversible autonomic dysregulation during sleep aligning with broader reports of baseline autonomic dysfunction in individuals with DS [59,60].

One consequence of this autonomic profile is impaired nocturnal dipping of HR and BP. Children with DS had a significantly smaller decline in HR during sleep, with a reduced cardiovascular system “resting” state overnight [35]. In otherwise healthy individuals, a blunted nocturnal decline in heart rate has been linked to a 2.4-fold increased risk of future cardiovascular events [61]. Therefore, the markedly reduced nocturnal HR/BP dipping seen in children with DS and OSA may lead to greater long-term cardiovascular strain.

Another key finding is the disproportionately high hypoxic burden in children with DS and OSA [30]. As observed in comparisons of polysomnographic parameters in children with DS and TD peers, children with DS appear to experience more obstructive burden, hypoxia and hypercapnia [62]. Since hypoxia-driven pulmonary vasoconstriction triggers pulmonary hypertension and other cardiovascular issues, this increased hypoxic stress could be a crucial factor in cardiovascular risk for DS [63,64]. In fact, hypoxic burden appeared to be a better predictor of autonomic impairment than AHI in children with DS [30]. When children were matched for hypoxic burden, the differences in HR/BP surges disappeared, indicating that intermittent hypoxemia, rather than the number of apneas itself, is the main cause of autonomic dysfunction.

There is also evidence that OSA affects the cardiac structure and function in children with DS. The link between OSA severity (higher AHI and arousal index, lower SpO₂ nadir) with increased LV diastolic filling pressure (higher E/e′) and greater LV mass suggests untreated OSA may lead to early cardiac remodeling. Mechanistically, repeated cycles of hypoxemia, hypercapnia, negative intrathoracic pressure swings, and sympathetic surges are known to put pressure and volume stress on the heart, with time potentially causing ventricular hypertrophy and diastolic dysfunction [65,66]. Additionally, electrophysiological evaluations of heart rate variability during sleep show children with DS and SDB to have an autonomic control imbalance with reduced parasympathetic activity [67] and increased sympathetic function [60]. This autonomic dysfunction seems to worsen when SDB persists, and remains stable when SDB improves [68]. Encouragingly, the CPAP therapy improvements in E/e′ and LV mass [34] imply that some cardiac changes are also partly reversible with treatment, similar to the cardiac remodeling reversal seen with CPAP use in adults [69]. This aligns with the findings on autonomic function and oxygenation: by preventing desaturations and reducing sympathetic overactivity, OSA therapy may help the cardiovascular system in children with DS to recover and remodel positively.

In summary, our review of the literature emphasizes that children with Down syndrome have a unique OSA phenotype linked to a significant risk of cardiovascular morbidity. With routine screening by age 4 already recommended [70], clinicians should remain highly alert for OSA in this group as our findings support asymptomatic children should be evaluated. Managing OSA in DS involves multiple approaches, including surgery, CPAP, medication, orthodontic or surgical adjuncts, and close collaboration among specialists and with families [52,54,55,71]. As evidence develops, new therapies like hypoglossal nerve stimulation are providing hope for those unable to use CPAP or with persistent OSA [72]. Ultimately, addressing SDB in DS is crucial for reducing increased cardiovascular risk.

Future Research Directions

Future research should focus on large, multicenter longitudinal studies to define the natural history of cardiovascular changes in children with Down syndrome and SDB, and to determine whether earlier treatment can influence long-term outcomes. Besides relying on the AHI, adding physiologic markers such as hypoxic burden, autonomic indices, and nocturnal blood pressure dipping could improve risk assessment. Mechanistic studies that incorporate imaging, biomarkers, and omics approaches are needed to clarify how genetic, anatomical, and neuromuscular traits unique to Down syndrome interact with SDB to contribute to cardiovascular morbidity. Finally, trials of multimodal therapies, including orthodontic approaches, weight management, and emerging techniques such as hypoglossal nerve stimulation, are essential in this high-risk group.

Limitations

This scoping review has some limitations. First, the variation in the included studies - regarding design, sample characteristics, and outcome measures - prevented meta-analytic pooling of results. The evidence is based on small groups and differing methods, which restricts how broadly conclusions can be applied. Furthermore, several studies come from the same research group, which may bias the range of outcomes and interventions examined. Polysomnographic reference values have evolved over time, and some reports lack objective measures such as AHI. Despite best efforts using a systematic search, additional relevant studies were identified through peer review, which were incorporated into the discussion to provide a broader context. There is still a need for larger, multi-center studies on cardiovascular outcomes in children with DS and SDB to confirm and expand these initial findings.

Conclusion

Children with DS and SDB exhibit unique vulnerabilities in cardiovascular health, with current evidence indicating greater hypoxic stress, reduced autonomic responses, and decreased nocturnal cardiovascular recovery during obstructive respiratory events. These physiological features emphasize vigilant OSA screening and early intervention within the DS population. Continued long-term cardiac and broadened monitoring beyond AHI may be crucial for comprehensive risk assessment, treatment guidance and mitigating long-term cardiovascular complications.

Educational Aims.

1. To summarize current evidence linking sleep-disordered breathing with cardiovascular risk in children with Down syndrome

2. To highlight physiologic mechanisms including hypoxic burden, autonomic dysfunction, and early structural cardiac changes

3. To evaluate polysomnographic measures (e.g., apnea hypopnea index) for risk stratification

4. To outline implications for clinical screening, management, and future research priorities