Table 4.
Pooled mean of sleep respiratory indexes in RTT subjects and the comparison with literature normative values for typically developing population (50) (Part 1).
| RTT stratification | Statistical analysis | AHI | OAHI | ODI | SpO2 mean | SpO2 nadir | ||
|---|---|---|---|---|---|---|---|---|
| TD population | Total group | Normative values | Mean ± SD (n) |
0.89 ± 0.84 (209) |
0.00 ± 0.00 (209) |
0.05 ± 0.05 (209) |
97.00 ± 0.94 (209) |
94.00 ± 1.05 (209) |
| < 5 years old | Mean ± SD (n) |
1.77 ± 0.88 (70) |
0.00 ± 0.00 (70) |
0.10 ± 0.00 (70) |
98.00 ± 0.00 (70) |
92.71 ± 1.17 (70) |
||
| > 5 years old | Mean ± SD (n) |
0.45 ± 0.32 (139) |
0.00 ± 0.00 (139) |
0.02 ± 0.05 (139) |
97.65 ± 0.32 (139) |
93.71 ± 0.24 (139) |
||
| RTT - Total group | Pooled mean | n | 64 (21–23, 27, 51, 53) |
35 (22, 27, 51) |
35 (22, 23, 27) |
42 (22, 23, 27, 53, 56) |
53 (21, 22, 27, 51, 53, 56) |
|
| ES ± SD (95% CI) |
9.24 ± 29.60 (1.99, 16.48) |
5.60 ± 11.83 (1.68, 9.52) |
12.53 ± 11.42 (8.75, 16.32) |
95.80 ± 2.83 (94.94, 96.65) |
87.79 ± 13.72 (84.10, 91.49) |
|||
| Heterogeneity | Q (5) = 117.34, p <0.01; 95.74% |
Q (2) = 5.24, p = 0.07; 61.80% |
Q (2) = 2.50, p = 0.29; 19.90% |
Q (4) = 21.50, p <0.01; 81.39% |
Q (5) = 31.17, p <0.01; 83.96% |
|||
| τ2 | 66.36% | 7.12% | 3.22% | 0.70% | 15.68% | |||
| Test of overall effect | 2.50, p = 0.01 | 2.80, p = 0.01 | 6.49, p < 0.01 | 219.68, p < 0.01 | 46.60, p < 0.01 | |||
| Compared to TD | SMDTD, p | −0.58, p < 0.01 | NA | −2.92, p < 0.01 | 0.84, p < 0.01 | 1.00, p < 0.01 | ||
| RTT - Gene | MECP2 | Pooled mean | n | 31 (22, 27, 51) |
31 (22, 27, 51) |
20 (22, 27) |
20 (22, 27) |
31 (22, 27, 51) |
| ES ± SD (95% CI) |
6.14 ± 12.36 (1.79, 10.49) |
5.02 ± 9.76 (1.58, 8.45) |
13.85 ± 32.60 (0, 28.15) |
95.90 ± 2.84 (94.66, 97.15) |
83.64 ± 13.01 (79.06, 88.22) |
|||
| Heterogeneity | Q (2) = 3.37, p = 0.19; 40.71% | Q (2) = 3.73, p = 0.15; 46.45% | Q (1) = 1.54 p = 0.21; 35.25% | Q (1) = 1.47, p = 0.23; 32.07% | Q (2) = 3.00, p = 0.22; 33.42% | |||
| τ2 | 5.92% | 4.22% | 53.91% | 0.26% | 5.80% | |||
| Test of overall effect | 2.76, p = 0.01 | 2.86, p < 0.01 | 1.90, p = 0.06 | 150.86, p < 0.01 | 35.78, p < 0.01 | |||
| Compared to TD | SMDTD, p | −1.18, p < 0.01 | NA | −1.79, p < 0.01 | 0.90, p < 0.01 | 2.19, p < 0.01 | ||
| RTT - Age |
<
5 years (1.9–5 years) |
Pooled mean | n | 16 (21, 22, 51, 53) |
6 (27, 51) |
4 (22) |
6 (22, 27) |
16 (21, 22, 51, 53, 56) |
| ES ± SD (95% CI) |
1.89 ± 4.48 (0, 4.09) |
0.81 ± 2.28 (0, 2.63) |
6.65 ± 9.77 | 96.22 ± 2.84 (95.74, 96.70) |
90.15 ± 6.68 (86.87, 93.42) |
|||
| Heterogeneity | Q (3) = 5.16, p = 0.16; 41.82% | Q (1) = 1.26, p = 0.26; 20.39% | – | Q (1) = 0.39, p = 0.53; 0% | Q (4) = 7.93, p = 0.09; 49.53% | |||
| τ2 | 2.01% | 0.79% | – | 0% | 6.30% | |||
| Test of overall effect | 1.68, p = 0.09 | 0.87, p = 0.39 | – | 393.40, p < 0.01 | 53.97, p < 0.01 | |||
| Compared to TD | SMDTD, p | −0.06, p = 0.83 | NA | − | NA | 0.85, p < 0.01 | ||
|
>
5 years (5 – 33 years) |
Pooled mean | n | 34 (21, 22, 27, 51) |
29 (22, 27, 51) |
18 (22, 27) |
20 (22, 27, 56) |
34 (21, 22, 27, 51) |
|
| ES ± SD (95% CI) |
5.75 ± 15.39 (0.58, 10.92) |
6.18 ± 12.60 (1.59, 10.76) |
15.64 ± 31.33 (1.16, 30.11) |
96.67 ± 1.02 (96.22, 97.11) |
85.76 ± 21.12 (78.66, 92.86) |
|||
| Heterogeneity | Q (3) = 15.40, p <0.01; 80.52% | Q (2) = 5.54, p = 0.06; 63.87% | Q (1) = 1.56, p = 0.21; 35.70% | Q (2) = 1.53, p = 0.47; 0% | Q (3) = 25.89, p <0.01; 88.41% | |||
| τ2 | 18.21% | 10.19% | 49.44% | 0% | 41.47% | |||
| Test of overall effect | 2.18, p = 0.03 | 2.64, p = 0.01 | 2.12, p = 0.03 | 425.78, p < 0.01 | 23.67, p < 0.01 | |||
| Compared to TD | SMDTD, p | −0.78, p < 0.01 | NA | −1.50, p < 0.01 | 2.11, p < 0.01 | 0.86, p < 0.01 | ||
| RTT – Clinical features | Epilepsy-present | Pooled mean | n | 22 (27, 51, 53) |
19 (27, 51) |
11 (27) |
18 (27, 51, 56) |
26 (27, 51, 53, 56) |
| ES ± SD (95% CI) |
6.29 ± 20.29 (0, 14.77) |
7.53 ± 12.93 (1.72, 13.35) |
30.14 ± 44.10 | 96.44 ± 0.70 (96.12, 96.76) |
89.15 ± 10.55 (85.10, 93.21) |
|||
| Heterogeneity | Q (2) = 6.11, p = 0.05; 67.28% | Q (1) = 1.79, p = 0.18; 44.00% | – | Q (2) = 0.30, p = 0.86; 0% | Q (3) = 14.96, p <0.01; 79.95% | |||
| τ2 | 33.50% | 8.37% | – | 0% | 11.96% | |||
| Test of overall effect | 1.45, p = 0.15 | 2.54, p = 0.01 | – | 587.90, p < 0.01 | 43.09, p < 0.01 | |||
| Compared to TD | SMDTD, p | −0.87, p < 0.01 | NA | – | 0.61, p = 0.01 | 1.35, p < 0.01 | ||
| Scoliosis-present | Pooled mean | n | 23 (27, 51) |
23 (27, 51) |
12 (27) |
12 (27) |
23 (27, 51) |
|
| ES ± SD (95% CI) |
12.36 ± 28.05 (0.90, 23.83) |
7.96 ± 9.14 (4.23, 11.70) |
27.79 ± 42.83 | 96.58 ± 2.15 | 85.27 ± 8.38 (81.84, 88.69) |
|||
| Heterogeneity | Q (1) = 1.42, p = 0.23; 29.59% | Q (1) = 0.62, p = 0.43; 0% | – | – | Q (1) = 0.12, p = 0.73; 0% | |||
| τ2 | 33.96% | 0% | – | – | 0% | |||
| Test of overall effect | 2.11, p = 0.03 | 4.18, p < 0.01 | – | – | 48.80, p < 0.01 | |||
| Compared to TD | SMDTD, p | −1.32, p < 0.01 | NA | – | – | 3.15, p < 0.01 | ||
Meta-analysis is not applicable if there is only one study included for the parameter, and SMDTD test is not applicable if SD is 0 or the value not available. Heterogeneity is presented as Q (df) = value, p-value; I2. whereas τ2 stands for Between-study variance. The test of overall effect is printed as Z-value, p-value. Numbers in bold are statistically significant. AHI, apnea/hypopnea index per hour of TST (/h TST), normal value ≤ 1/h; ES, effect size; MECP2, methyl-CpG-binding protein-2; NA, not applicable; OAHI, obstructive apnea hypopnea index per hour of TST (/h TST); ODI, oxygen desaturation index per hour of TST (/h TST); RTT, Rett Syndrome; SD, standard deviation; SMDTD, standardized mean difference test with literature normative values from a TD sample, a negative SMDTD indicates that the pooled mean in RTT > TD population, while a positive SMDTD indicates that the pooled mean in RTT < TD population; SpO2 mean, Mean oxygen saturation (%); SpO2% nadir, Minimal oxygen saturation (%), normal range > 90%; TD, typically developing; TST, total sleep time; 95%CI, 95% confidence interval.