| 1.1 All‐cause mortality prior to hospital discharge |
5 |
723 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.86 [0.53, 1.38] |
| 1.1.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
4 |
559 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.92 [0.52, 1.63] |
| 1.1.2 Standard‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
164 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.73 [0.31, 1.71] |
| 1.2 Major neurodevelopmental disability in children aged three to five years |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Totals not selected |
| 1.2.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Totals not selected |
| 1.3 Failure to extubate within one week of commencing treatment |
4 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.3.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
4 |
521 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.54 [0.40, 0.73] |
| 1.4 Reintubation within one week of commencing treatment |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.4.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
238 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.36 [0.19, 0.71] |
| 1.5 Apnea: number of infants with at least one episode (defined as interruption of breathing for more than 20 seconds) after 24 hours from commencing treatment, in a 24‐hour period and over one week |
1 |
78 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.01 [0.59, 1.75] |
| 1.5.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
78 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.01 [0.59, 1.75] |
| 1.6 Side effects (tachycardia, agitation, or feed intolerance) leading to a reduction in dose or withholding of caffeine |
5 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.6.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
5 |
593 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.66 [0.86, 3.23] |
| 1.7 Bronchopulmonary dysplasia/chronic lung disease: 28 days of oxygen exposure |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.8 Bronchopulmonary dysplasia/chronic lung disease at 36 weeks' postmenstrual age |
5 |
723 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.75 [0.60, 0.94] |
| 1.8.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
4 |
559 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.76 [0.60, 0.97] |
| 1.8.2 Standard‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
164 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.68 [0.36, 1.29] |
| 1.9 Number of days using mechanical ventilation |
2 |
|
Mean Difference (IV, Fixed, 95% CI) |
Subtotals only |
| 1.9.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
2 |
201 |
Mean Difference (IV, Fixed, 95% CI) |
0.01 [‐0.85, 0.87] |
| 1.10 Intraventricular hemorrhage, any grade |
2 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.10.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
2 |
361 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.90 [0.63, 1.27] |
| 1.11 Intraventricular hemorrhage, grade 3 to 4 |
5 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.11.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
5 |
686 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.26 [0.67, 2.36] |
| 1.12 Cerebellar hemorrhage at brain ultrasound (yes/no) |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.12.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
74 |
Risk Ratio (M‐H, Fixed, 95% CI) |
3.33 [1.00, 11.15] |
| 1.13 Magnetic resonance imaging (MRI) abnormalities at term equivalent age (yes/no), defined as white matter lesions (i.e. cavitations [Rutherford 2010]) and punctate lesions (Cornette 2002); germinal matrix‐intraventricular hemorrhage (Parodi 2015); or cerebellar hemorrhage (Limperopoulos 2007) |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.13.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
74 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.50 [0.10, 2.56] |
| 1.14 Periventricular leukomalacia |
3 |
272 |
Risk Difference (M‐H, Fixed, 95% CI) |
0.02 [‐0.04, 0.08] |
| 1.14.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
3 |
272 |
Risk Difference (M‐H, Fixed, 95% CI) |
0.02 [‐0.04, 0.08] |
| 1.15 Necrotizing enterocolitis (proven = Bell stage of 2 or greater) (Bell 1978) |
5 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.15.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
5 |
637 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.80 [0.43, 1.51] |
| 1.16 Patent ductus arteriosus (PDA) requiring treatment (cyclo‐oxygenase inhibitors or surgical ligation) |
2 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.16.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
2 |
201 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.87 [0.59, 1.27] |
| 1.17 Retinopathy of prematurity (ROP) (any ROP) (International Committee 2005) |
2 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.17.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
2 |
365 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.85 [0.56, 1.29] |
| 1.18 Retinopathy of prematurity (ROP) (severe ROP [stage 3 or greater]) (International Committee 2005) |
3 |
|
Risk Difference (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.18.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
3 |
481 |
Risk Difference (M‐H, Fixed, 95% CI) |
‐0.03 [‐0.07, 0.01] |
| 1.19 Seizures (clinically diagnosed; diagnosed by electroencephalography) |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 1.19.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
74 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.42 [0.79, 2.53] |
| 1.20 Developmental delay (Bayley Mental Developmental Index or Griffiths Mental Development Scale in children aged 18 to 24 months |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Totals not selected |
| 1.20.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Totals not selected |
| 1.21 Bayley‐III cognitive score in children at 18 to 24 months CA |
1 |
42 |
Mean Difference (IV, Fixed, 95% CI) |
‐1.90 [‐8.60, 4.80] |
| 1.22 Cerebral palsy in children aged 18 to 24 months |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Totals not selected |
| 1.22.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Totals not selected |
| 1.23 Blindness in children aged 18 to 24 months |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Totals not selected |
| 1.23.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Totals not selected |
| 1.24 Deafness in children aged 18 to 24 months |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Totals not selected |
| 1.24.1 High‐loading and high‐maintenance dose versus standard‐loading and standard‐maintenance dose |
1 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Totals not selected |
