Table 3

Secondary outcomes

Placebo N=24*Caffeine citrate 5 mg/kg/day N=24Caffeine citrate 10 mg/kg/day N=27Caffeine citrate 15 mg/kg/day N=27Caffeine citrate 20 mg/kg/day N=27Any dose of caffeine N=105
Summary dataSummary dataMean difference (95% CI), p value vs placeboSummary dataMean difference (95% CI), p value vs placeboSummary dataMean difference (95% CI), p value vs placeboSummary dataMean difference (95% CI), p value vs placeboSummary dataMean difference (95% CI), p value vs placebo
Weight growth velocity (birth to term equivalent) (g/kg/day)*, ; mean (SD)8.8 (3.1)8.4 (3.4)−0.45 (−2.55 to 1.65);
0.67
7.5 (3.4)−1.51 (−3.59 to 0.56);
0.15
9.1 (3.4)0.02 (−2.10 to 2.15);
0.98
9.1 (3.5)−0.32 (−2.51 to 1.88); 0.788.5 (3.4)−0.62 (−2.27 to 1.04); 0.46
Length growth velocity (birth to term equivalent) (cm/week)*, †; mean (SD)0.7 (0.6)0.7 (0.4)−0.08 (−0.39 to 0.23); 0.610.7 (0.6)0.02 (−0.28 to 0.33); 0.891.0 (0.4)0.20 (−0.11 to 0.52); 0.200.6 (0.4)−0.08 (−0.41 to 0.25); 0.620.8 (0.5)0.02 (−0.23 to 0.26); 0.89
Head circumference growth velocity (birth to term equivalent) (cm/week)*, †; mean (SD)0.6 (0.3)0.4 (0.2)−0.23 (−0.40 to –0.07); 0.0060.5 (0.3)−0.12 (−0.28 to 0.04); 0.150.5 (0.2)−0.16 (−0.33 to 0.00); 0.050.5 (0.2)−0.16 (−0.34 to 0.01); 0.070.5 (0.2)−0.17 (−0.30 to –0.04); 0.010
Failure to regain birth weight by 2 weeks postnatal age; N (%)‡2 (8.3%)2 (8.3%)1.03 (0.13 to 8.21);
0.98
4 (14.8%)1.91 (0.28, 13.29);
0.51
7 (25.9%)4.33 (0.72 to 26.16);
0.11
6 (21.4%)3.50 (0.55 to 22.30); 0.1819 (17.9%)2.58 (0.51 to 13.11);
0.25
Sleep score; mean (SD)§,¶
Two weeks4.2 (0.6)4.3 (0.3)0.11 (−0.17 to 0.38); 0.454.3 (0.5)0.02 (−0.25 to 0.29); 0.874.2 (0.3)0.01 (−0.27 to 0.29); 0.944.1 (0.5)−0.09 (−0.38 to 0.20); 0.534.2 (0.4)0.02 (−0.20 to 0.23); 0.87
Term4.4 (0.5)4.4 (0.3)0.05 (−0.21 to 0.31); 0.704.5 (0.4)0.16 (−0.09 to 0.42); 0.214.3 (0.4)−0.03 (−0.30 to 0.23); 0.804.2 (0.4)−0.18 (−0.44 to 0.09); 0.194.4 (0.4)0.01 (−0.20 to 0.22); 0.94
Gastro-oesophageal symptoms; I-GERQ-R mean (SD)§
 Two weeks29.7 (4.3)27.6 (4.2)−2.35 (−5.56 to 0.85); 0.1525.3 (6.1)−3.80 (−6.96 to –0.64); 0.01926.1 (5.1)−3.27 (−6.46 to –0.08); 0.04527.5 (6.3)−2.75 (−6.13 to 0.63); 0.1126.6 (5.5)−3.07 (−5.54 to –0.60); 0.015
 Term27.5 (5.6)25.2 (4.7)−2.38 (−5.60 to 0.84); 0.1525.4 (4.9)−2.27 (−5.41 to 0.86);
0.15
25.8 (5.7)−2.16 (−5.36 to 1.05);
0.18
25.9 (4.1)−2.76 (−5.99 to 0.46); 0.0925.6 (4.8)−2.39 (−4.85 to 0.08); 0.06
 Duration of tube feeding (days); median (IQR) (geometric mean)7.0 (2.0, 13.0)
(2.6)
6.0 (3.5, 14.5)
(5.6)
1.67 (0.48 to 5.89);
0.42
13.0 (4.0, 15.0)
(6.2)
1.34 (0.39 to 4.68);
0.64
6.0 (1.0, 12.0)
(2.5)
0.77 (0.22 to 2.65); 0.6813.5 (1.5, 17.5)
(6.1)
0.79 (0.23 to 2.70); 0.719.0 (2.0, 15.0)
(3.4)
1.07 (0.40 to 2.87);
0.89
 Length of stay (number of days); median (IQR) (geometric mean)9.0 (5.0, 15.0)
(8.2)
7.5 (6.5, 20.0)
(8.6)
1.06 (0.76 to 1.48);
0.73
15.0 (8.0, 18.0)
(10.8)
1.31 (0.94 to 1.83);
0.11
11.0 (6.0, 16.0)
(10.5)
1.29 (0.95 to 1.75);
0.10
14.0 (6.0, 20.0)
(11.1)
1.36 (0.98 to 1.87); 0.0612.0 (6.0, 18.0)
(10.3)
1.26 (0.99 to 1.59);
0.06
  • *Number of infants with at least one anthropometric measurement at 2 weeks and term, respectively, are: 22 and 20 in placebo group; 21 and 19 in 5 mg/kg/day group; 26 and 21 in 10 mg/kg/day group; 21 and 19 in 15 mg/kg/day group and 22 and 18 in 20 mg/kg/day group.

  • †Growth velocity for weight was calculated using an exponential model43 for weight and linear models for length, and head circumference.

  • ‡Estimated group comparisons for failure to regain birth weight are ORs.

  • §Number of infants with feeding and sleeping data at 2 weeks and term, respectively, are: 22 and 20 in placebo group; 21 and 19 in 5 mg/kg/day group; 25 and 21 in 10 mg/kg/day group; 21 and 19 in 15 mg/kg/day group and 21 and 18 in 20 mg/kg/day group.

  • ¶Sleep score was calculated using subscale nine on the Infant Behaviour Questionnaire-Revised, modified for neonates.31