Table 3.
Pooled mean of sleep macrostructure in RTT subjects and the comparison with literature normative values for typically developing population (49) (Part 1).
| RTT stratification | Statistical analysis | TST | SOL | WASO | SEI | Stage N1 | Stage N2 | Stage N3 | REM | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TD population | Total group | Normative values | Mean ± SD (n) | 490.94 ± 26.56 (209) |
25.81 ± 5.73 (209) | 32.06 ± 14.27 (209) |
89.53 ± 2.59 (209) | 7.15 ± 0.52 (209) |
39.69 ± 6.56 (209) | 30.40 ± 4.84 (209) |
21.32 ± 2.10 (209) | |||||||||||
| < 5 years old | Mean ± SD (n) | 507.96 ± 30.81 (70) |
29.97 ± 4.65 (70) | 42.80 ± 22.13 (70) |
87.50 ± 3.30 (70) | 6.88 ± 0.47 (70) |
32.54 ± 3.69 (70) | 35.34 ± 2.81 (70) |
23.74 ± 1.57 (70) | |||||||||||||
| > 5 years old | Mean ± SD (n) | 482.37 ± 22.08 (139) |
23.71 ± 5.34 (139) | 26.65 ± 4.50 (139) |
90.56 ± 1.61 (139) | 7.28 ± 0.54 (139) |
43.30 ± 4.08 (139) | 27.92 ± 3.49 (139) |
20.11 ± 0.84 (139) | |||||||||||||
| RTT - Total group | Pooled mean | n | 76 (19, 20, 23, 27, 53, 54, 56) |
75 (19, 20, 23, 51, 53, 56) |
64 (19, 20, 23, 53, 54, 56) |
99 (19, 20, 23, 27, 51–54, 56) |
92 (19, 20, 23, 27, 51, 53, 56, 57) |
92 (19, 20, 23, 27, 51, 52, 55–57) |
114 (19, 20, 23, 27, 51–53, 55–57) |
104 (19, 20, 23, 27, 51, 52, 55–57) |
||||||||||||
| ES ± SD (95% CI) |
441.02 ±184.91 (399.45, 482.59) |
19.34 ± 34.39 (11.56, 27.13) |
66.06 ± 102.28 (41.00, 91.12) |
74.22 ± 70.58 (60.31, 88.12) |
8.11 ± 13.40 (5.37, 10.85) |
40.16 ± 36.40 (32.72, 47.60) |
35.47 ± 32.35 (29.53, 41.41) |
16.38 ± 22.15 (12.12, 20.64) |
||||||||||||||
| Heterogeneity | Q (6) = 42.13, p <0.01; 85.76% | Q (5) = 13.41, p = 0.02; 62.73% | Q (5) = 35.20, p <0.01; 85.79% | Q (8) = 782.91, p <0.01; 98.98% | Q (7) = 211.67, p <0.01; 96.69% | Q (7) = 115.84, p <0.01; 93.96% | Q (9) = 156.99, p <0.01; 94.27% | Q (8) = 769.71, p <0.01; 98.96% | ||||||||||||||
| τ2 | 2097.67% | 45.25% | 604.40% | 397.84% | 11.84% | 89.92% | 71.00% | 33.47% | ||||||||||||||
| Test of overall effect | 20.79, p < 0.01 | 4.87, p < 0.01 | 5.17, p < 0.01 | 10.46, p < 0.01 | 5.81, p < 0.01 | 10.58, p < 0.01 | 11.71, p < 0.01 | 7.54, p < 0.01 | ||||||||||||||
| Compared to TD | SMDTD, p | 0.51, p < 0.01 | 0.35, p = 0.01 | −0.67, p < 0.01 | 0.38, p < 0.01 | −0.13, p = 0.30 | −0.02, p = 0.86 | −0.26, p = 0.03 | 0.38, p < 0.01 | |||||||||||||
| RTT - Gene | MECP2 | Pooled mean | n | 11 (27) |
– | – | 21 (27, 52) |
11 (27) |
11 (27) |
21 (27, 52) |
11 (27) |
|||||||||||
| ES ± SD (95% CI) |
364.91 ± 105.17 | – | – | 54.08 ± 17.56 (46.56, 61.59) |
1.64 ± 1.63 | 27.73 ± 15.82 | 53.06 ± 12.29 (47.80, 58.31) |
12.64 ± 10.77 | ||||||||||||||
| Heterogeneity | – | – | – | Q (2) = 3.45, p = 0.18; 41.96% |
– | – | Q (1) = 0.62, p = 0.43; 0% |
- | ||||||||||||||
| τ2 | – | – | – | 19.37% | – | – | 0% | – | ||||||||||||||
| Test of overall effect | – | – | – | 14.11, p < 0.01 | – | – | 19.78, p < 0.01 | – | ||||||||||||||
| Compared to TD | SMDTD, p | – | – | – | 6.15, p < 0.01 | – | – | −3.85, p < 0.01 | – | |||||||||||||
| RTT - Age |
<
5 years (2 – 5 years) |
Pooled mean | n | 5 (53, 56) |
5 (53, 56) |
5 (53, 56) |
9 (52, 53, 56) |
8 (53, 56, 57) |
8 (53, 56, 57) |
14 (53, 55–57) |
14 (53, 55–57) |
|||||||||||
| ES ± SD (95% CI) |
524.13 ±214.61 (336.02, 712.24) |
19.64 ± 31.79 (0, 47.50) |
146.98 ± 262.07 (0, 376.70) |
68.19 ± 35.52 (44.98, 91.40) |
17.87 ± 15.95 (6.81, 28.92) |
30.15 ± 7.52 (24.94, 35.37) |
29.81 ± 21.14 (18.74, 40.88) |
19.24 ±10.50 (13.74, 24.73) |
||||||||||||||
| Heterogeneity | Q (1) = 10.71, p <0.01; 90.66% | Q (1) = 0.44, p = 0.51; 0% | Q (1) = 17.04, p <0.01; 94.13% | Q (2) = 34.60, p <0.01; 94.22% | Q (2) = 40.79, p <0.01; 95.10 % | Q (2) = 2.39, p = 0.30; 16.37% | Q (3) = 27.88, p <0.01; 89.24% | Q (3) = 14.69, p <0.01; 79.58% | ||||||||||||||
| τ2 | 16785.24% | 0% | 25922.69% | 393.72% | 80.48% | 4.77% | 102.91% | 23.31% | ||||||||||||||
| Test of overall effect | 5.46, p < 0.01 | 1.38, p = 0.17 | 1.25, p = 0.21 | 5.76, p < 0.01 | 3.17, p < 0.01 | 11.34, p < 0.01 | 5.28, p < 0.01 | 6.86, p < 0.01 | ||||||||||||||
| Compared to TD | SMDTD, p | −0.28, p = 0.55 | 1.19, p = 0.01 | −1.60, p < 0.01 | 1.63, p < 0.01 | −2.26, p < 0.01 | 0.57, p = 0.13 | 0.63, p = 0.03 | 1.02, p < 0.01 | |||||||||||||
|
>
5 years (6 – 17 years) |
Pooled mean | n | 16 (27, 54, 56) |
2 (56) |
4 (54, 56) |
22 (27, 52, 54, 56) |
16 (27, 56, 57) |
16 (27, 56, 57) |
22 (27, 55–57) |
22 (27, 55–57) |
||||||||||||
| ES ± SD (95% CI) |
403.61 ± 220.46 (295.59, 511.64) |
0.30 ± 0.28 | 18.51 ± 24.48 (0, 42.50) |
70.17 ± 66.72 (42.29, 98.05) |
11.52 ± 26.86 (0, 24.68) |
35.43 ± 19.03 (26.10, 44.75) |
36.04 ± 21.18 (27.19, 44.89) |
18.52 ± 18.45 (10.81, 26.23) |
||||||||||||||
| Heterogeneity | Q (2) = 9.35, p = 0.01; 78.62% | – | Q (1) = 1.00, p = 0.32; 0% | Q (3) = 57.70, p <0.01; 94.80% | Q (2) = 9.18, p = 0.01; 78.21% | Q (2) = 5.04, p = 0.08; 60.35% | Q (3) = 29.40, p <0.01; 89.80% | Q (3) = 19.17, p <0.01; 84.35% | ||||||||||||||
| τ2 | 5714.03% | - | 0% | 641.02% | 102.99% | 41.32% | 66.42% | 51.50% | ||||||||||||||
| Test of overall effect | 7.32, p < 0.01 | - | 1.51, p = 0.13 | 4.93, p < 0.01 | 1.72, p = 0.09 | 7.45, p < 0.01 | 7.98, p < 0.01 | 4.71, p < 0.01 | ||||||||||||||
| Compared to TD | SMDTD, p | 1.09, p < 0.01 | - | 1.43, p = 0.01 | 0.84, p < 0.01 | −0.50, p = 0.06 | 1.11, p < 0.01 | −0.97, p < 0.01 | 0.23, p = 0.31 | |||||||||||||
| RTT- Clinical features | Epilepsy-present | Pooled mean | n | 19 (27, 53, 56) |
8 (53, 56) |
8 (53, 56) |
19 (27, 53, 56) |
19 (27, 53, 56) |
19 (27, 53, 56) |
19 (27, 53, 56) |
19 (27, 53, 56) |
|||||||||||
| ES ± SD (95% CI) |
477.98 ± 293.86 (345.85, 610.11) |
10.04 ± 21.15 (0, 24.69) |
127.24 ± 300.03 (0, 335.14) |
75.16 ± 46.01 (54.48, 95.85) |
15.43 ± 38.00 (0, 32.52) |
36.48 ± 12.34 (30.93, 42.03) |
27.33 ± 10.73 (22.50, 32.15) |
11.86 ± 9.90 (7.41, 16.31) |
||||||||||||||
| Heterogeneity | Q (2) = 25.37, p <0.01; 92.12% | Q (1) = 0.88, p = 0.35; 0% | Q (1) = 17.73, p <0.01; 94.36% | Q (2) = 25.47, p <0.01; 92.15% | Q (2) = 93.20, p <0.01; 97.85% | Q (2) = 1.28, p = 0.53; 0% | Q (2) = 0.95, p = 0.62; 0% | Q (2) = 2.79, | τ2 | 12233.32% | 0% | 21292.38% | 305.86% | 218.61% | 0% | 0% | 4.41% | |||||
| Test of overall effect | 7.09, p < 0.01 | 1.34, p = 0.18 | 1.20, p = 0.23 | 7.12, p < 0.01 | 1.77, p = 0.08 | 12.89, p < 0.01 | 11.10, p < 0.01 | 5.22, p < 0.01 | ||||||||||||||
| Compared to TD | SMDTD, p | 0.15, p = 0.53 | 2.32, p < 0.01 | −1.70, p < 0.01 | 1.09, p < 0.01 | −0.77, p < 0.01 | 0.45, p = 0.06 | 0.55, p = 0.02 | 2.75, p < 0.01 | |||||||||||||
Meta-analysis is not applicable if there is only one study included for the parameter. 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. The bold numbers are statistically significant. ES, effect size; MECP2, methyl-CpG-binding protein-2; REM, rapid eye movement sleep (%); RTT, Rett Syndrome; SD, standard deviation; SEI, sleep efficiency (%); 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; SOL, sleep onset latency (min); stage N1, non-rapid eye movement sleep stage 1 (%); stage N2, non-rapid eye movement sleep stage 2 (%); stage N3, non-rapid eye movement sleep stage 3 (%); TD, typically developing; TST, total sleep time (min); WASO, wake after sleep onset (min); 95%CI, 95% confidence interval.