Introduction
Method
Study design and setting
Inclusion and exclusion criteria
Outcomes
The primary outcome
The secondary outcomes
Sample size
Procedure
Statistical analysis
Results
Baseline data
Variables | Surfactant group (n = 67) | Surfactant + budesonide group (n = 67) | |
---|---|---|---|
Gestational age (week) | Mean (SD) | 31 ± 2.96 | 31.66 ± 2.84 |
Birth weight (gr) | Mean (SD) | 1465.45 ± 520.88 | 1584.55 ± 505.02 |
Maternal age (year) | Mean (SD) | 29.97 ± 6.45 | 29.12 ± 4.86 |
Delivery mode | NVD (n %) | 19(28.4%) | 18(26.9%) |
CS (n %) | 48(71.6%) | 49(73.1%) | |
Sex | Male (n %) | 40(59.7%) | 29(43.3%) |
Female (n %) | 27(40.3%) | 38(56.7%) | |
Maternal medical problems | Yes | 22(32.8%) | 19(28.4%) |
No | 45(67.2%) | 48(71.6%) | |
Antenatal drug | No | 32(47.8%) | 33(49.3%) |
Betamethasone | 11(16.4%) | 17(25.4%) | |
Levothyroxine | 3(4.5%) | 5(7.5%) | |
Combination | 21(31.3%) | 12(17.9%) | |
Gestational age (week) | < 30 | 24(35.8%) | 16(23.9%) |
30–34 | 39(58.2%) | 32(47.8%) | |
> 34 | 12(17.9%) | 11(16.4%) | |
Birth weight (gr) | < 1500 | 30(44.8) | 40(59.7) |
1500–2000 | 22(32.8) | 13(19.4) | |
> 2000 | 15(22.4) | 14(20.9) |
The primary outcome results
Variables | Surfactant Group (n = 67) | Surfactant + Budesonide Group (n = 67) | P value* | Variables | Surfactant Group (n = 67) | Surfactant + Budesonide Group (n = 67) | P value** | |
---|---|---|---|---|---|---|---|---|
Mean (SD) | Mean (SD) | Frequency (%) | Frequency (%) | |||||
Ventilation use length (day) | 4.37 ± 2.81 | 2.85 ± 3.64 | 0.008 T value= -2.70 | Death † | Yes | 19(28.4) | 10(14.9) | 0.059 Chi-square values = 3.56 ***RR = 0.63, CI95% (0.37, 1.09) |
Mean diff = − 1.62, CI 95% (-2.63, − 0.41) | ||||||||
Hospital stay (day) | 16.21 ± 12.40 | 16.15 ± 15 | 0.679 T value= -0.02 | No | 48(71.6) | 57(85.1) | ||
Mean diff= -0.06, CI 95% (-4.76, 4.64) | ||||||||
First -day- MAP (mmHg) | 16.81 ± 1.64 | 15.48 ± 2.43 | 0.001 T value= -3.70 | BPD † | Yes | 10 (14.9) | 8 (11.9) | 0.612 Chi-square values = 0.257 RR = 0.87, CI95% (0.50, 1.50) |
Mean diff= -1.32, CI 95% (-2.03, -0.61) | ||||||||
Third -day – MAP (mmHg) | 11.05 ± 4.29 | 7.73 ± 2.86 | 0.001 T value= -5.22 | No | 57(85.1) | 59(88.1) | ||
Mean diff= -3.31, CI 95% (-4.57, -2.06) | ||||||||
First -day- oxygen index (%) | 15.09 ± 7.24 | 12.70 ± 7.01 | 0.055 T value= -1.94 | Pulmonary Hemorrhage | Yes | 21(31.3) | 8(11.9) | 0.006 Chi-square values = 7.43 RR = 0.49, CI95% (0.26, 0.90) |
Mean diff= -2.38, CI95% (-4.82, 0.04) | ||||||||
Third -day- oxygen index (%) | 4.87 ± 4.25 | 3.69 ± 4.13 | 0.111 T value=-1.60 | No | 46(68.7) | 59(88.1) | ||
Mean diff=-1.17, CI 95% (-2.62, 0.27) | ||||||||
First -day- Blood Sugar (mg/dL) | 86.93 ± 20.78 | 84.73 ± 21.25 | 0.547 T value=-0.60 | Pneumothorax | Yes | 6 [9] | 7(10.4) | 0.770 Chi-square values = 0.08 RR = 1.08, CI95% (0.63, 1.85) |
Mean diff=- 2.19, CI 95% (-9.37, 4.98) | ||||||||
Third -day- Blood Sugar (mg/dL) | 98.18 ± 21.46 | 95.27 ± 17.06 | 0.175 T value=-0.86 | No | 61(91) | 60(89.6) | ||
Mean diff=-2.91, CI 95% (-9.57, 3.74) | ||||||||
First -day- Mean Blood Pressure (mm Hg) | 36.04 ± 7.78 | 38.07 ± 4.95 | 0.010 T value = 2.41 | Intraventricular Hemorrhage | Yes | 16(23.9) | 9(13.4) | 0.121 Chi-square values = 2.41 RR = 0.67, CI95% (0.39, 1.17) |
Mean diff = 2.03, CI95% (0.36, 3.69) | ||||||||
Third -day- Mean Blood Pressure (mm Hg) | 38.17 ± 4.33 | 39.52 ± 4.04 | 0.064 T value = 1.86 | No | 51(76.1) | 58(86.6) | ||
Mean diff = 1.35, CI 95% (-0.08, 2.79) | ||||||||
* Independent t-test, **chi-square test, ***Risk Ratio (RR) † Primary Outcome | Second Dose Surfactant | Yes | 41(61.2) | 13(19.4) | 0.001 Chi-square values = 24.31 RR = 0.35, CI 95% (0.21, 0. 58) | |||
No | 26(38.8) | 54(80.6) |
The secondary outcomes result
Subgroup analysis result
Birth weight | Variables | Surfactant(n = 67) | Surfactant + Budesonide (n = 67) | P value | Gestational age | Surfactant(n = 67) | Surfactant + Budesonide (n = 67) | P value | |
---|---|---|---|---|---|---|---|---|---|
Frequency (%) | Frequency (%) | Frequency (%) | Frequency (%) | ||||||
< 1500 gr N G1= 30 people N G2=40 people | Death | Yes | 17(42.5) | 9(30) | 0.284 Chi-square values = 1.14 | < 30 weeks N G1= 24 people N G2=16 | 17(70.8) | 5(31.3) | 0.014 Chi-square values = 6.07 |
**RR = 0.72, CI 95% (0.39, 1.33) | RR = 0.37, CI 95% (0.15, 0.87) | ||||||||
BPD | Yes | 10(25) | 8(26.7) | 0.875 Chi-square values = 0.02 | 5(20.8) | 7(43.8) | 0.166 Chi-square values = 2.40 | ||
RR = 1.05, CI 95% (0.57, 1.92) | RR = 1.81, CI 95% (0.88, 3.72) | ||||||||
Pulmonary Hemorrhage | Yes | 18(45) | 7(23.3) | 0.061 Chi-square values = 3.50 | 16(66.7) | 3(18.8) | 0.003 Chi-square values = 8.83 | ||
RR = 0.54, CI 95% (0.27, 1.09) | |||||||||
RR = 0.25, CI 95% (0.08, 0.76) | |||||||||
Pneumothorax | Yes | 5(12.5) | 7(23.3) | 0.234 Chi-square values = 1.41 | 5(20.8) | 4(25) | 1 Chi-square values = 0.09 | ||
RR = 1.47, CI 95% (0.82, 2.61) | |||||||||
RR = 1.14, CI 95% (0.48, 2.69) | |||||||||
Intraventricular Hemorrhage | Yes | 14(35) | 8(26.7) | 0.457 Chi-square values = 0.55 | 10(41.7) | 7(43.8) | 0.896 Chi-square values = 0.01 | ||
RR = 0.79, CI 95% (0.42, 1.49) | |||||||||
RR = 1.05, CI 95% (0.49, 2.25) | |||||||||
Second Dose Surfactant | Yes | 35(87.5) | 9(30) | 0.001 Chi-square values = 24.27 | 23(95.8) | 5(31.3) | 0.001 Chi-square values = 19.06 | ||
RR = 0.25, CI 95% (0.13, 0.46) | |||||||||
RR = 0.19, CI 95% (0.08, 0.43) | |||||||||
1500–2000 gr N G1= 22 people N G2=13 people | Death | Yes | 2(15.4) | 1(4.5) | 0.541 Chi-square values = 1.22 | people30-34 weeks N G1= 39 people N G2=32 people | 2(6.3) | 4(10.3) | 0.683 Chi-square values = 0.36 |
RR = 0.50, CI 95% (0.10, 2.56) | |||||||||
RR = 1.23, CI 95% (0.67, 2.27) | |||||||||
BPD | Yes | 0 | 0 | - | 5(15.6) | 1(2.6) | 0.084 Chi-square values = 3.87 | ||
RR = 0.28, CI 95% (0.04, 1.72) | |||||||||
Pulmonary Hemorrhage | Yes | 3(23.1) | 1(4.5) | 0.134 Chi-square values = 2.77 | 5(15.6) | 4(10.3 | 0.722 Chi-square values = 0.45 | ||
RR = 0.36, CI 95% (0.06, 2.05) | |||||||||
RR = 0.78, CI 95% (0.36, 1.68) | |||||||||
Pneumothorax | Yes | 1(7.7) | 0 | 0.371 Chi-square values = 1.74 | 1(3.1) | 3(7.7) | 0.746 Chi-square values = 0.69 | ||
RR = 1.39, CI 95% (0.76, 2.56) | |||||||||
Intraventricular Hemorrhage | Yes | 2(15.4) | 1(4.5) | 0.541 Chi-square values = 1.22 | 10(41.7) | 7(43.8) | 0.196 Chi-square values = 3.26 | ||
RR = 0.50, CI 95% (0.50, 2.56) | RR = 0.42, CI 95% (0.12, 1.42) | ||||||||
Second Dose Surfactant | Yes | 5(38.5) | 2(9.1) | 0.075 Chi-square values = 4.40 | 23(95.8) | 5(31.3) | 0.001 Chi-square values = 11.43 | ||
RR = 0.40, CI 95% (0.12, 1.32) | RR = 0.37, CI 95% (0.18, 0.77) | ||||||||
2000–2500 gr N G1= 15 people N G2=14 people | Death | Yes | 0 | 0 | 0 | 34–37 weeks N G1= 12 people N G2=11 people | 0 | 1(8.3) | 1 Chi-square values = 0.95 |
BPD | Yes | 0 | 0 | 0 | 0 | 0 | - | ||
Pulmonary Hemorrhage | Yes | 0 | 0 | 0 | 0 | 1(8.3) | 1 Chi-square values = 0.95 | ||
Pneumothorax | Yes | 0 | 0 | 0 | 0 | 0 | - | ||
Intraventricular Hemorrhage | Yes | 0 | 0 | 0 | 0 | 0 | - | ||
Second Dose Surfactant | Yes | 1(7.1) | 2(13.3) | 1 Chi-square values = 0.29 | 1(19.1) | 2(16.7) | 1 Chi-square values = 0.29 | ||
RR = 1.33, CI 95% (0.54, 3.23) | |||||||||
RR = 1.33, CI 95% (0.53, 3.32) |
Birth weight subgroup | Variables | Surfactant Group (n = 67) | Surfactant + Budesonide Group (n = 67) | P value* | Gestational age subgroup | Surfactant Group (n = 67) | Surfactant + Budesonide Group (n = 67) | P value* |
---|---|---|---|---|---|---|---|---|
Mean (SD) | Mean (SD) | Mean (SD) | Mean (SD) | |||||
< 1500 gr N G1= 30 people N G2=40 people | First -day- MAP (mmHg) | 17.53 ± 1.30 | 16.57 ± 2.37 | 0.089 F = 4.66 | < 30 weeks N G1= 24 people N G2=16 people | 17.79 ± 0.93 | 16.88 ± 2.36 | 0.345 F = 2.95 |
Third -day – MAP (mmHg) | 13.67 ± 2.84 | 9.21 ± 3.45 | 0.001 F = 34.14 | 14.65 ± 2.19 | 9.80 ± 3.61 | 0.001 F = 26.75 | ||
First -day- oxygen index (%) | 18.60 ± 6.11 | 16.10 ± 0.8.39 | 0.090 F = 2.08 | 19.63 ± 5.32 | 18.06 ± 9.04 | 0.359 F = 0.47 | ||
Third -day- oxygen index (%) | 6.71 ± 4.39 | 5.26 ± 4.48 | 0.045 F = 1.64 | 8.45 ± 4.11 | 5.47 ± 4.65 | 0.010 F = 4.23 | ||
First -day- Blood Sugar (mg/dL) | 85.50 ± 22.24 | 78.53 ± 19.33 | 0.175 F = 1.87 | 87.54 ± 19.21 | 78.25 ± 18.51 | 0.137 F = 2.31 | ||
Third -day- Blood Sugar(mg/dL) | 97.46 ± 24.14 | 93.80 ± 18.23 | 0.491 F = 0.47 | 97.17 ± 17.77 | 96.31 ± 18.01 | 0.883 F = 0.02 | ||
First -day- Mean Blood Pressure (mmHg) | 33.45 ± 2.74 | 34.90 ± 4.54 | 0.058 F = 2.75 | 31.88 ± 1.60 | 33.13 ± 4.69 | 0.700 F = 1.46 | ||
Third -day- Mean Blood Pressure (mmHg) | 35.72 ± 2.61 | 36.70 ± 2.81 | 0.046 F = 2.25 | 34.91 ± 2.13 | 35.69 ± 2.85 | 0.263 F = 0.94 | ||
1500–2000 gr N G1= 22 people N G2=13 people | First -day- MAP (mmHg) | 16.16 ± 1.68 | 14.50 ± 2.26 | 0.062 F = 5.22 | 30–34 weeks N G1= 39 people N G2=32 people | 16.47 ± 1.80 | 14.95 ± 2.38 | 0.003 F = 8.87 |
Third -day – MAP (mmHg) | 8.38 ± 4.07 | 6.77 ± 1.95 | 0.853 F = 2.51 | 10.09 ± 4.05 | 7.18 ± 2.43 | 0.012 F = 14.06 | ||
First -day- oxygen index (%) | 12.15 ± 6.44 | 10.41 ± 4.44 | 0.647 F = 0.90 | 14.16 ± 7.14 | 11.38 ± 5.43 | 0.175 F = 3.44 | ||
Third -day- oxygen index (%) | 3 ± 3.10 | 2.90 ± 3.85 | 0.749 F = 0.01 | 3.44 ± 3.37 | 3.34 ± 4.16 | 0.691 F = 0.01 | ||
First -day- Blood Sugar (mg/dL) | 93.38 ± 18.62 | 88.0 ± 20.41 | 0.442 F = 0.60 | 90.22 ± 22.08 | 86 ± 21.24 | 0.416 F = 0.66 | ||
Third -day- Blood Sugar (mg/dL) | 99.0 ± 17.21 | 95.32 ± 17.75 | 0.553 F = 0.35 | 100.88 ± 24.86 | 94.10 ± 17.48 | 0.183 F = 1.80 | ||
First -day- Mean Blood Pressure (mmHg) | 37.31 ± 4.92 | 38.73 ± 2.66 | 0.578 F = 1.23 | 37.38 ± 4.12 | 38.44 ± 3.21 | 0.207 F = 1.48 | ||
Third -day- Mean Blood Pressure (mmHg) | 39.38 ± 3.97 | 40.18 ± 3 | 0.353 F = 0.45 | 38.75 ± 3.70 | 39.87 ± 3.92 | 0.122 F = 1.81 | ||
2000–2500 gr N G1= 15 people N G2=14 people | First -day- MAP (mmHg) | 15.36 ± 1.28 | 14.73 ± 1.98 | 0.451 F = 0.99 | 34–37 weeks N G1= 12 people N G2=11 people | 15.64 ± 1.21 | 15.33 ± 2.10 | 0.786 F = 0.17 |
Third -day – MAP (mmHg) | 6.21 ± 0.58 | 6.27 ± 0.59 | 0.621 F = 0.05 | 6.27 ± 0.65 | 6.92 ± 1.98 | 0.397 F = 1.06 | ||
First -day- oxygen index (%) | 7.79 ± 3.47 | 9.27 ± 3.24 | 0.186 F = 1.41 | 7.91 ± 3.70 | 9.83 ± 4.93 | 0.487 F = 1.10 | ||
Third -day- oxygen index (%) | 1.61 ± 0.59 | 1.83 ± 0.62 | 0.505 F = 1.01 | 1.86 ± 0.50 | 2.64 ± 2.72 | 0.976 F = 0.87 | ||
First -day- Blood Sugar | 85.0 ± 18.36 | 92.33 ± 23.84 | 0.364 F = 0.85 | 76 ± 17.97 | 89.25 ± 24.39 | 0.156 F = 2.16 | ||
Third -day- Blood Sugar (mg/dL) | 99.43 ± 17.93 | 98.13 ± 14.08 | 0.830 F = 0.04 | 92.45 ± 17.93 | 97.67 ± 15.39 | 0.462 F = 0.56 | ||
First -day- Mean Blood Pressure (mmHg) | 42.29 ± 2.61 | 43.47 ± 2.97 | 0.290 F = 1.28 | 41.27 ± 3.85 | 43.50 ± 3.66 | 0.235 F = 2.02 | ||
Third -day- Mean Blood Pressure (mmHg) | 43.86 ± 2.21 | 44.20 ± 2.46 | 0.561 F = 0.15 | 43.27 ± 3.90 | 43.50 ± 3.15 | 0.928 F = 0.02 |
Sum of Squares | df | Mean Square | F | P value* | Partial Eta Squared | |
---|---|---|---|---|---|---|
Third-Day MAP | 94.715 | 1 | 94.715 | 11.995 | 0.001 | 0.085 |
Third-Day OI | 0.188 | 1 | 0.188 | 0.027 | 0.870 | 0.000 |
Third-Day Blood Sugar | 130.376 | 1 | 130.376 | 0.442 | 0.507 | 0.003 |
Third-Day Mean Blood Pressure | 0.109 | 1 | 0.109 | 0.021 | 0.885 | 0.000 |