Secondary analysis
| Per-protocol analysis | Allocated to BCG (n=2129). Number of hospitalisations (n) (mean*) | Allocated to control (n=2133). Number of hospitalisations (n) (mean*) | HR, crude | 95% CI | p Value of effect modification between the groups | HR, adjusted† | 95% CI | P Value of effect modification between the groups |
|---|---|---|---|---|---|---|---|---|
| Caesarean section n=892 | 239 (428) (0.56) | 281 (464) (0.61) | 0.91 | 0.72 to 1.16 | 0.19 | 0.98 | 0.77 to 1.26 | 0.53 |
| No n=3370 | 808 (1701) (0.48) | 722 (1669) (0.43) | 1.10 | 0.95 to 1.27 | 1.08 | 0.93 to 1.25 | ||
| Antibiotics during delivery n=712 | 233 (340) (0.69) | 213 (372) (0.57) | 1.22 | 0.92 to 1.61 | 0.24 | 1.23 | 0.92 to 1.65 | 0.25 |
| No n=3550 | 814 (1789) (0.46) | 790 (1761) (0.45) | 1.01 | 0.88 to 1.16 | 1.01 | 0.88 to 1.16 | ||
| Birth weight <2500 g n=123 | 46 (61) (0.75) | 53 (62) (0.86) | 0.91 | 0.51 to 1.62 | 0.62 | 1.05 | 0.59 to 1.88 | 0.99 |
| No n=4139 | 1001 (2068) (0.48) | 950 (2071) (0.46) | 1.05 | 0.93 to 1.19 | 1.05 | 0.93 to 1.20 | ||
| ≥1 older sibling n=1761 | 427 (905) (0.47) | 406 (856) (0.47) | 0.98 | 0.93 to 1.28 | 0.40 | 0.97 | 0.80 to 1.17 | 0.28 |
| No n=2498 | 619 (1223) (0.51) | 596 (1275) (0.47) | 1.09 | 0.81 to 1.19 | 1.11 | 0.94 to 1.32 | ||
| Disposition | ||||||||
| Parental atopic disease n=2558 | 664 (1286) (0.52) | 614 (1272) (0.48) | 1.07 | 0.91 to 1.24 | 0.26 | 1.08 | 0.92 to 1.27 | 0.36 |
| No n=1379 | 298 (675) (0.44) | 340 (704) (0.48) | 0.91 | 0.73 to 1.14 | 0.95 | 0.76 to 1.19 | ||
| Siblings with atopic disease n=532 | 149 (276) (0.54) | 123 (256) (0.48) | 1.11 | 0.79 to 1.58 | 0.68 | 1.16 | 0.81 to 1.66 | 0.57 |
| No n=3667 | 882 (1823) (0.48) | 873 (1854) (0.47) | 1.03 | 0.90 to 1.17 | 1.04 | 0.91 to 1.19 | ||
| Season‡ | ||||||||
| Winter n=1047 | 324 (522) (0.62) | 301 (525) (0.57) | 1.08 | 0.85 to 1.37 | 0.46 | 1.08 | 0.85 to 1.38 | 0.43 |
| Spring n=981 | 246 (488) (0.50) | 205 (493) (0.42) | 1.22 | 0.95 to 1.55 | 1.24 | 0.96 to 1.59 | ||
| Summer n=1057 | 192 (530) (0.36) | 199 (527) (0.38) | 0.96 | 0.74 to 1.25 | 0.97 | 0.74 to 1.28 | ||
| Autumn n=1177 | 285 (589) (0.48) | 298 (588) (0.51) | 0.96 | 0.76 to 1.20 | 0.95 | 0.75 to 1.20 | ||
| Mother BCG vaccinated n=740 | 168 (372) (0.45) | 206 (368) (0.56) | 0.81 | 0.60 to 1.09 | 0.05 | 0.83 | 0.60 to 1.13 | 0.09 |
| No n=3453 | 871 (1730) (0.50) | 775 (1723) (0.45) | 1.12 | 0.98 to 1.28 | 1.11 | 0.97 to 1.28 | ||
| Per-protocol analysis | BCG vaccinated (n=2118). Number of hospitalisations (n) (mean*) | Control group (n=2097). Number of hospitalisations (n) (mean*) | HR, crude | 95% CI | p Value of effect modification between the groups | HR, adjusted† | 95%-CI | p Value of effect modification between the groups |
| Caesarean section n=881 | 236 (424) (0.56) | 276 (457) (0.60) | 0.96 | 0.72 to 1.16 | 0.17 | 0.98 | 0.76 to 1.25 | 0.45 |
| No n=3334 | 808 (1694) (0.48) | 703 (1640) (0.43) | 1.12 | 0.97 to 1.29 | 1.09 | 0.94 to 1.26 | ||
| Antibiotics during delivery n=701 | 233 (339) (0.69) | 209 (362) (0.58) | 1.21 | 0.92 to 1.60 | 0.29 | 1.22 | 0.90 to 1.64 | 0.30 |
| No n=3514 | 811 (1779) (0.46) | 770 (1735) (0.44) | 1.02 | 0.89 to 1.17 | 1.02 | 0.89 to 1.18 | ||
| Birth weight <2500 g n=122 | 46 (61) (0.75) | 53 (61) (0.87) | 0.89 | 0.50 to 1.60 | 0.56 | 1.04 | 0.58 to 1.87 | 0.95 |
| No n=4093 | 998 (2057) (0.49) | 926 (2036) (0.46) | 1.07 | 0.94 to 1.21 | 1.06 | 0.93 to 1.21 | ||
| ≥1 older sibling n=1751 | 427 (901) (0.47) | 498 (850) (0.47) | 1.00 | 0.83 to 1.21 | 0.46 | 0.98 | 0.81 to 1.19 | 0.32 |
| No n=2461 | 616 (1216) (0.51) | 580 (1245) (0.47) | 1.10 | 0.93 to 1.29 | 1.12 | 0.94 to 1.32 | ||
| Atopic disposition | ||||||||
| Parental atopic disease n=2530 | 664 (1278) (0.52) | 599 (1252) (0.48) | 1.08 | 0.93 to 1.26 | 0.20 | 1.10 | 0.94 to 1.29 | 0.27 |
| No n=1361 | 295 (672) (0.44) | 332 (689) (0.48) | 0.89 | 0.73 to 1.13 | 0.69 | 0.94 | 0.75 to 1.18 | 0.59 |
| Siblings with atopic disease n=528 | 149 (274) (0.54) | 122 (254) (0.48) | 1.12 | 0.79 to 1.59 | 1.16 | 0.81 to 1.67 | ||
| No n=3634 | 879 (1814) (0.49) | 850 (1820) (0.47) | 1.04 | 0.91 to 1.19 | 1.05 | 0.91 to 1.20 | ||
| Season‡ | ||||||||
| Winter n=1035 | 321 (519) (0.62) | 299 (516) (0.58) | 1.07 | 0.84 to 1.36 | 0.48 | 1.06 | 0.83 to 1.35 | 0.44 |
| Spring n=970 | 246 (488) (0.50) | 196 (482) (0.41) | 1.24 | 0.97 to 1.59 | 1.26 | 0.98 to 1.63 | ||
| Summer n=1042 | 192 (525) (0.37) | 195 (517) (0.38) | 0.97 | 0.74 to 1.26 | 0.98 | 0.74 to 1.29 | ||
| Autumn n=1168 | 285 (586) (0.49) | 289 (582) (0.50) | 0.98 | 0.75 to 1.24 | 0.97 | 0.77 to 1.23 | ||
| Mother BCG vaccinated n=721 | 168 (371) (0.45) | 191 (350) (0.55) | 0.83 | 0.61 to 1.13 | 0.08 | 0.84 | 0.61 to 1.16 | 0.11 |
| No n=3427 | 868 (1722) (0.50) | 766 (1705) (0.45) | 1.08 | 0.98 to 1.28 | 1.11 | 0.97 to 1.28 | ||
| Child ≤2 days at vaccination‡ n=1775 | 863 (0.49) | 1.05 | 0.92 to 1.19 | 1.06 | 0.93 to 1.22 | |||
| >2 days§ n=343 | 181 (0.53) | 979 (2097) (0.47) | 1.11 | 0.89 to 1.39 | 0.60 (test of difference in the BCG effect) | 1.05 | 0.83 to 1.34 | 0.95 |
| Batch 111046B§¶ n=923 | 535 (0.58) | 979 (2097) (0.47) | 1.04 | 0.88 to 1.23 | 0.69 (test of difference in the BCG effect) | 1.06 | 0.88 to 1.27 | 0.70 |
| 112032A§¶ n=1195 | 509 (0.43) | 1.07 | 0.90 to 1.26 | 1.06 | 0.90 to 1.26 | |||
Test of effect modifications and differences in the BCG effect. HRs of hospitalisations among 4262 Danish children by allocation to BCG vaccination at birth or control group.
*Mean hospitalisation per child.
†Adjusted for baseline characteristics (sex, prematurity, study site, caesarean section, antibiotics during delivery, multiple birth, birth weight, child age at randomisation, maternal age, parental ethnicity (≥1 parent of ethnicity other than Danish), maternal education, parents living together, maternal BCG (by maternal recall), siblings, maternal atopy and maternal smoking during pregnancy).
‡Winter: December, January, February. Spring: March, April, May. Summer: June, July, August. Autumn: September, October, November.
§Among vaccinated children.
¶Adjusted for seasonality in months.