Figures
- FIGURE 1
Risk-of-bias assessment (Quality in Prognosis Studies) tool.
- FIGURE 2
Meta-analysis of association of age with obstructive sleep apnoea (OSA).
- FIGURE 3
Meta-analysis of association of sex with obstructive sleep apnoea (OSA).
Tables
- TABLE 1
Description of studies
First author, year [ref.] Design Subjects n SDB definition with respect to predictor SDB Indices of SDB severity Age years Objective Anand, 2021 [16] Prospective cross-sectional 53 OSA: AHI ≥1 events·h−1 96 Mean±sd AHI 8.96±1.8 events·h−1 Mean (range) 5.9 (3–11.8) 1) Assess the effect of quality of sleep on development and behaviour of children with trisomy 21
2) Assess the effect of sleep apnoea on development and behaviour of children with trisomy 21Austeng, 2014 [17] Cross-sectional 29 OSA: OAI/AHI >1.5 events·h−1 AHI >1.5 events·h−1 97%
OAI >1.5 events·h−1 69%Mean±sd AHI 10±8.8 events·h−1 Mean 8 1) Measure prevalence and medical follow-up of OSA in young children with Down syndrome
2) Identify the association between OSA and age, BMI and airway surgeryBanjar, 2013 [18] Prospective cohort 23 OSA: AHI >1 events·h−1 82.6% Mean AHI 12.3 events·h−1
Mean OAI 4.73 events·h−1Not reported Identify sleep abnormalities in children with Down syndrome Basil, 2016 [19] Retrospective cohort 303 OSAS: AHI ≥2 events·h−1 74% Mild OSAS: 38.9%
Moderate OSAS: 32.8%
Severe OSAS: 28.2%Mean±sd (range) 10.6±4.06 (2–18) 1) Investigate whether children with Down syndrome are at increased risk of obesity
2) Explore OSAS, which is associated with obesity in children with Down syndromeBreslin, 2014 [20] Prospective cohort 38 OSAS: AHI >1.5 events·h−1 61% Mean±sd AHI 5.79±9.86 events·h−1 Mean±sd (range) 9.6±.8 (7–12) 1) Investigate the association between OSAS and cognition in children with Down syndrome
2) Investigate the effect of OSAS on sleep physiology in children with Down syndromeBrooks, 2015 [21] Prospective cohort 25 OSA: AHI ≥5 events·h−1 40% Mean±sd AHI 13.42±15.89 events·h−1 Mean±sd (range) 10.14±3.39 (7.2–18.7) 1) Investigate the effect of sleep and SDB on neuropsychological functioning of children with Down syndrome
2) Determine whether treatment of SDB improves cognitive functioningChamseddin, 2019 [22] Qualitative study with retrospective data collection 106 OSA: AHI ≥1 events·h−1 90% Mean±sd AHI 16.7±6.25 events·h−1 Mean±sd 7.3±4 1) To evaluate demographic, clinical and polysomnographic features of children with Down syndrome with clinical suspicion of OSA
2) Identify factors that predict OSA in children with Down syndromeDurhan, 2019 [23] Cross-sectional 18 OSA: AHI ≥1 events·h−1 61.1% Mean AHI 3.23 events·h−1 Median (IQR) 6.6 (4.4–10.5) Determine the effect of OSA on periodontal and dental health in children with Down syndrome Dyken, 2003 [9] Prospective cohort 19 Sleep apnoea: apnoea index >1 event·h−1 and SaO2 low point <92% (with baseline SaO2 >92%) 79% Median (IQR) AHI 6.0 (3–8) events·h−1
Median (IQR) apnoea index 3.0 (2–5) events·h−1Mean±sd 9.1±4.7 1) Investigate OSA in young Down syndrome patients using PSG
2) Identify the effects of therapy on OSA in young Down syndrome patientsElsharkawi, 2017 [24] Cross-sectional 101 OSA: AHI ≥1 events·h−1 42.6% Mild OSA: 28%
Moderate OSA: 2%
Severe OSA: 13%Mean±sd 9.1±4.0 1) Compare urinary biomarkers of children with Down syndrome to neurotypically healthy controls
2) Determine whether urinary biomarkers could predict a diagnosis of OSAFriedman, 2018 [25] Cross-sectional 113 OSA: AHI ≥2 events·h−1 Not reported Mean AHI 13.76 events·h−1 Mean 5.89 1) Assess parents' accuracy in reporting their children's breathing patterns
2) Assess risk factors associated with abnormal sleep studyJayaratne, 2017 [26] Qualitative study with prospective data collection 63 OSA: AHI >1 events·h−1 44.2% Not reported Mean±sd (range) 7.49±4.86 (3.1–24.4) 1) Characterise the facial morphology of children with Down syndrome
2) Compare facial anthropometric characteristics of Down syndrome patients with published norms
3) Compare facial anthropometric characteristics of Down syndrome patients with and without OSA to predict OSA status in patients with Down syndromeLee, 2020 [27] Cross-sectional 30 OSA: AHI ≥1 events·h−1 80% Median (IQR) AHI 5.2 (1.7–15.7) events·h−1 Median (IQR) 11.3 (9.4–15.6) 1) Measure the prevalence of OSA in children with Down syndrome
2) Identify the role of OSA and sleep structure in affecting cognitive performanceMaris, 2016 [28] Cross-sectional 54 OSA: AHI 
2 events·h−157.1% Median (IQR) AHI 7.25 (5.7–9.8) events·h−1 Median (range) 7.5 (4–18) 1) Identify prevalence of sleep problems in children with Down syndrome as measured by Children's Sleep Habits Questionnaires
2) Compare prevalence of sleep problems in children with Down syndrome and controls
3) Investigate association between sleep problems and OSAMaris, 2016 [29] Cross-sectional 122 OSA: AHI 2 events·h−166.4% Median (IQR) AHI 8.2 (4.3–16.7) events·h−1 Median (IQR) 5.0 (2.8–10.5) 1) Measure prevalence of OSA in children with Down syndrome
2) Identify factors that are associated with disease severityde Miguel-Díez, 2003 [4] Prospective cohort 108 OSA: AHI 3 events·h−154.6% Mean±sd AHI 6.1±6.7 events·h−1 Mean±sd (range) 7.9±4.5 (1–18) 1) Measure the prevalence of SDB in children with Down syndrome
2) Identify factors that predispose children with Down syndrome to SDBNaime, 2021 [30] Retrospective cohort 158 CSA: CAI >2 events·h−1
OSAS: AHI >2 events·h−179.1% OSAS
12% CSAMedian (IQR) CAI 0.20 (0.0–0.83) events·h−1
Median (IQR) AHI 5.95 (2.40–16.52) events·h−1Median (IQR) 4.8 (0.04–18.3)
Median (IQR) 4.8 (2.31–9.02)1) Identify clinical predictors of central breathing problems in children with Down syndrome
2) The role of sex and OSA status on presence of central breathing problemsNehme, 2017 [8] Retrospective cohort 119 OSA: AHI >5 events·h−1
Hypoventilation: carbon dioxide 50 mmHg for ≥25% of total sleep time42.9% Median (IQR) AHI 3.6 (1.6–11.2) events·h−1 Median (IQR) (range) 6.6 (4.4–10.5) (0.05–16.8) Determine clinical predictors of SDB in children with Down syndrome Posada, 2019 [31] Qualitative study with retrospective data collection 53 OSA: AHI >2 events·h−1 50.9% Median (IQR) AHI:
0–23 months 7.0 (1.5–20.2) events·h−1
24–84 months 8.3 (1.9–30.0) events·h−1
85–156 months 8.4 (2.5–19.0) events·h−1
>156 months 13.0 (4.9–29.2) events·h−1Median (IQR) 3.4 (1.6–8.8) Measure the incidence of sleep-related breathing disorders in children with Down syndrome living at high altitude Richard, 2020 [32] Retrospective case–control study 56 Nocturnal hypoventilation: >25% of total sleep time spent with a PtcCO2 >50 mmHg OSA 85.7%
Nocturnal hypoventilation 17.9%Median (IQR) AHI 5 (3–10.2) events·h−1
Median (IQR) mean PtcCO2 44 (43–46.5) mmHgMedian (IQR) 4.9 (2.0–7.8) Compare PtcCO2 and pulse oximetry (SpO2) in children with Down syndrome and in control children with clinical signs of OSA Rosen, 2020 [33] Qualitative study with retrospective data collection 418 OSA: AHI >1 events·h−1 42.1% Mean AHI 3.6 events·h−1
Median AHI 0.6 events·h−1Mean (range) 7.27 (2–17)
Median 61) Identify the prevalence of increased periodic limb movements of sleep in children with Down syndrome
2) Determine the correlation of periodic limb movements of sleep with OSA and levels of ferritinShires, 2010 [34] Retrospective cohort 52 OSA: AHI >1.0 events·h−1 63.5% Mean AHI 18.7 events·h−1 Mean±sd 9.3±4.5 Identify the effect of body mass on the incidence of OSA in children with Down syndrome Skotko, 2017 [35] Prospective cohort 102 OSA: AHI >1 events·h−1 44.1% Not reported Median (range) 5.6 (3–24.4) To create a predictive model to help screen for OSA in children with Down syndrome Waters, 2020 [36] Qualitative study with retrospective data collection 152 OSA: AHI >2 events·h−1 85.5% Mean±sd AHI 13.1±22.4 events·h−1 First PSG: mean±sd 5.0±4.3
Last PSG: mean±sd 8.2±5.1Identify the spectrum of OSA in children with Down syndrome SDB: sleep disordered breathing; OSA: obstructive sleep apnoea; AHI: apnoea–hypopnoea index; OAI: obstructive apnoea index; BMI: body mass index; OSAS: OSA syndrome; IQR: interquartile range; SaO2: arterial oxygen saturation; PSG: polysomnography; CSA: central sleep apnoea; CAI: central apnoea index; PtcCO2: transcutaneous partial pressure of carbon dioxide; SpO2: oxygen saturation measured by pulse oximetry.
- TABLE 2
Summary of associations by study for selected predictors of sleep disordered breathing (SDB)
AHI oAHI CAI Nocturnal hypoventilation Positive association Negative association No association Positive association Negative association No association Positive association Negative association No association Positive association Negative association No association Age Shires [34], Lee [27] de Miguel-Díez [4] (r= −0.195; OR=2.9), Skotko [35]# Nehme [8], Breslin [20], Brooks [21], Durhan [23], Chamseddin [22], Skotko [35]# (d= −0.74) Rosen [33], Nehme [8] (OR=1.14) Maris [29] (r= −0.199), Waters [36] (Chi-squared=12.87) Nehme [8], Maris [29] Naime [30] Chamseddin [22] Richard [32] Male sex de Miguel-Díez [4] (OR=3.32) Brooks [21] Skotko [35], Shires [34], Austeng [17], Breslin [20] (OR=0.22), Lee [27] Maris [29], Rosen [33] Naime [30]# Naime [30]# Body mass index Shires [34]#, Dyken [9] (r=0.62), Basil [19] (risk ratios 2.4 and 1.4), Elsharkawi [24]# Brooks [21], Lee [27], Skotko [35], Breslin [20] (d= −0.15; OR=0.73), Austeng [17], Shires [34]# (R2=0.2), Elsharkawi [24]# (r=0.21), Durhan [23], de Miguel-Díez [4] (OR=0.7), Nehme [8] Basil [19] (Spearman ρ=0.16) Maris [29], Chamseddin [22], Nehme [8] (OR=0.71) Richard [32] Presence of GORD Nehme [8] (OR=0.70), Shires [34] Nehme [8] (OR=0.16) History of rhinitis/rhinorrhoea/sinusitis Nehme [8] (OR=2.13), Nehme [8] (adjustedOR=2.38) Nehme [8] (adjusted4.49) Nehme [8] (OR=2.22) Adenotonsillar hypertrophy Shires [34] (r2=0.75), de Miguel-Díez [4]# (OR=4.7) Nehme [8] (OR=1.16), de Miguel-Díez [4]# (OR=0.4) Maris [29], Nehme [8] (OR=1.26) Dental examinations Durhan [23]# Skotko [35], de Miguel-Díez [4], Durhan [23]# Parental questionnaires of sleep behaviours Breslin [20] (d=0.56, d=0.51), Brooks [21], Nehme [8] (OR=0.79–2.38), Friedman [25] Maris [28], Nehme [8] (OR=0.63–1.75), Brooks [21] Snoring Banjar [18] Posada [31] Parental questionnaires of neuropsychological or developmental function Anand [16] (ρ=0.42–0.83 Breslin [20] (d=0.91) Lee [27], Brooks [21], Breslin [20] (t: Mann–Whitney U=0.42–1.03, d=0.16–0.36) Cognitive function Anand [16]#, Breslin [20]# (t: Mann–Whitney U=55.50, d=1.06) Anand [16]# (ρ= −0.62), Breslin [20] (d=0.91), Lee [27]# (coefficientadjusted −9.773) Breslin [20]# (t: Mann–Whitney U=1.11–85.00, d= −0.54–0.58), Brooks [21], Lee [27]# (coefficientadjusted 6.515) Association estimates are listed where available. In cases where estimates were not available predictors were associated with SDB if the p-values did not cross the null hypothesis (p<0.05), or based on the author's reporting. AHI: apnoea–hypopnoea index; oAHI: obstructive AHI; CAI: central apnoea index; GORD: gastro-oesophageal reflux disease. #: in cases where authors are listed twice in different columns, different outcomes were assessed, details of which may be found in supplementary table A2.
Supplementary Material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Supplementary material ERR-0026-2022.SUPPLEMENT
Vol 31 Issue 164
Table of Contents
Predictors of sleep disordered breathing in children with Down syndrome: a systematic review and meta-analysis
