Table 3. Stratification of estimated effect size for cognitive function.
| Variable | # Studies | # Comparisons | SMD (95% CI) |
% Weight | I2 | p* | p** |
|---|---|---|---|---|---|---|---|
| Animal model | |||||||
| Species | |||||||
| Rat | 9 | 40 | 2.53 (2.33–2.73) | 82.89 | 84.0% | 0.000 | 0.637 |
| Mouse | 2 | 6 | 3.19 (2.74–3.63) | 17.11 | 91.6% | 0.000 | |
| Strain | |||||||
| Sprague-Dawley | 7 | 35 | 2.34 (2.12–2.56) | 69.84 | 83.3% | 0.000 | 0.253 |
| C57/Bl6 | 2 | 6 | 3.12 (2.74–3.63) | 17.11 | 91.6% | 0.000 | |
| Wistar | 2 | 5 | 3.57 (3.06–4.08) | 13.05 | 81.5% | 0.000 | |
| Gender | |||||||
| Male | 7 | 35 | 2.34 (2.12–2.60) | 69.84 | 83.3% | 0.000 | 0.000 |
| Mixed | 2 | 6 | 3.19 (2.74–3.63) | 17.11 | 91.6% | 0.000 | |
| Not reported | 2 | 5 | 3.57 (3.06–4.08) | 13.05 | 81.5% | 0.000 | |
| Age (at HIE) | |||||||
| < 7 days | 1 | 1 | 4.17 (2.63–5.71) | 1.44 | 0.0% | 0.000 | 0.396 |
| 7 days | 6 | 34 | 2.50 (2.29–2.72) | 72.24 | 86.1% | 0.000 | |
| > 7 days | 2 | 6 | 3.19 (2.74–3.63) | 17.11 | 91.6% | 0.000 | |
| Not reported | 2 | 5 | 2.50 (1.89–3.11) | 9.21 | 0.0% | 0.682 | |
| Study Design | |||||||
| HIE model | |||||||
| CAO + hypoxia | 9 | 41 | 2.66 (2.46–2.85) | 90.79 | 87.0% | 0.000 | 0.264 |
| Not reported | 2 | 5 | 2.50 (1.89–3.11) | 9.21 | 0.0% | 0.682 | |
| Anesthetic | |||||||
| Isoflurane | 2 | 6 | 3.19 (2.74–3.63) | 17.11 | 91.6% | 0.000 | 0.658 |
| Halothane | 3 | 6 | 1.64 (1.15–2.13) | 14.30 | 79.1% | 0.000 | |
| Ether | 2 | 19 | 2.94 (2.62–3.26) | 33.47 | 85.5% | 0.000 | |
| Chloral | 1 | 1 | 6.76 (3.22–10.29) | 0.27 | 0.0% | 0.000 | |
| Not reported | 3 | 9 | 2.47 (1.26–2.78) | 34.85 | 83.7% | 0.000 | |
| Intervention | |||||||
| Source | |||||||
| Bone marrow | 2 | 6 | 2.70 (2.30–3.09) | 21.42 | 88.4% | 0.000 | 0.961 |
| Umbilical cord | 5 | 30 | 2.55 (2.29–2.82) | 47.76 | 84.7% | 0.000 | |
| Placenta | 1 | 1 | 6.76 (3.22–10.29) | 0.27 | 0.0% | 0.000 | |
| Not reported | 3 | 9 | 2.71 (2.38–3.05) | 30.55 | 88.9% | 0.000 | |
| Origin | |||||||
| Allogeneic | 6 | 16 | 2.73 (2.47–2.98) | 52.24 | 87.5% | 0.000 | 0.670 |
| Xenogeneic | 5 | 30 | 2.55 (2.29–2.82) | 47.76 | 84.7% | 0.000 | |
| Dose | |||||||
| ≤250,000 | 5 | 11 | 1.78 (1.48–2.90) | 36.38 | 0.0% | 0.001 | 0.054 |
| >250,000 - ≤500,000 | 3 | 25 | 2.92 (2.64–3.20) | 42.54 | 88.1% | 0.000 | |
| >500,000 - ≤1 million | 1 | 1 | 4.17 (2.63–5.71) | 1.44 | 0.0% | 0.003 | |
| >1 million | 2 | 9 | 3.53 (3.11–3.95) | 19.64 | 67.8% | 0.000 | |
| Delivery | |||||||
| Intracerebral | 6 | 16 | 2.54 (1.99–2.52) | 49.42 | 82.8% | 0.000 | 0.047 |
| Intranasal | 2 | 6 | 3.19 (2.74–3.63) | 17.11 | 91.6% | 0.000 | |
| Intraperitoneal | 2 | 6 | 3.69 (3.05–4.33) | 8.31 | 7.9% | 0.366 | |
| IV | 1 | 18 | 2.69 (2.33–3.06) | 25.16 | 87.3% | 0.000 | |
| Timing | |||||||
| < 72 hrs | 3 | 28 | 3.08 (2.81–3.36) | 45.07 | 84.2% | 0.000 | 0.158 |
| > 72 hrs | 6 | 15 | 2.05 (1.78–2.31) | 49.36 | 84.6% | 0.000 | |
| Multiple doses | 2 | 3 | 4.39 (3.61–5.18) | 5.57 | 0.0% | 0.877 | |
| Expansion media | |||||||
| DMEM | 5 | 11 | 2.60 (2.26–2.95) | 28.51 | 86.1% | 0.000 | 0.716 |
| Commercial | 1 | 18 | 2.89 (2.56–3.21) | 32.03 | 84.7% | 0.000 | |
| Alpha | 1 | 1 | 6.76 (3.22–10.29) | 0.27 | 0.0% | 0.000 | |
| Not reported | 4 | 11 | 2.45 (2.15–2.74) | 39.19 | 88.2% | 0.000 |
Note
*p value for subgroup differences.
**p value for heterogeneity between subgroups with meta-regression analysis.