Overview of the RCTs included in the present study
| RCT (#) | Time period | Study design | Place of inclusion (%) | Eligibility criteria | Strain(s) of BCG given | Infants enrolled | Infants that received BCG within 1 week of Birth | Found at home at the 2 month visit* | BCG reaction evaluated at the home visit | All-cause mortality between 2 and 12 months of age |
| LBW I (I)†17 | 2002–2004 | Early-BCG versus no-BCG, follow-up at 2, 6 and 12 months | HDSS health centres (100%) | LBW, healthy, no severe malformations | Denmark | 104 | 37 | 30 | 30 | 3.3 (1/30) |
| LBW II (II)†18 | 2004–2009 | HDSS health centres (5%) HNSM (95%) | LBW, healthy, no severe malformations | Denmark | 2320 | 971 | 776 | 776 | 4.4 (34/776) | |
| LBW III (III)†3 | 2009–2013 | HDSS health centres (10%) HNSM (90%) | LBW, healthy, no severe malformations | Denmark | 4158 | 1712 | 1387 | 1385 | 3.0 (42/1385) | |
| BCGIMED (IV)‡19 | 2013–2018 | Immediate versus BCG-at-discharge, follow-up at 2, 6 and 12 months | HNSM nursery (100%) | Nursery admission. Not moribund and no severe malformations. | Denmark, Japan | 3354 | 2883 | 1863 | 1859 | 1.5 (27/1859) |
| BCGSTRAIN (V)§14 | 2014–2018 | BCG-Denmark versus BCG-Russia, BCG-Japan versus BCG-Russia, follow-up at 2 and 6 months, 6–12 months HDSS follow-up | HNSM (100%) | Healthy neonates born at HNSM with no severe malformations | Denmark, Japan, Russia | 12 021 (2529 HDSS) | 2500 | 1978 | 1962 | 0.8 (15/1962) |
| RCTs I–V combined | 2002–2018 | – | HDSS health centres (4%) HNSM (96%) | – | Denmark, Japan, Russia | 12 465 | 8103 | 6034 | 6012 | 2.0 (119/6012) |
RCT I recruited participants exclusively at HDSS health centres; RCTs II–III both recruited at HDSS health centres and HNSM where most inclusions took place, and RCTs IV–V recruited exclusively at HNSM. The RCT IV (BCGIMED) study strain was BCG-Denmark from October 2013 to June 2016 and BCG-Japan from July 2016 to August 2017 due to a halt of the BCG-Denmark production. Infants from both randomisation groups were eligible for the present study if BCG had been provided within 1 week after birth. RCT V14 (BCGSTRAIN) compared different BCG strains provided to low-weight and normal-weight neonates at discharge from HNSM and was divided into two phases due to the production halt: in phase I (December 2014–June 2016), neonates were randomised to BCG-Denmark (Copenhagen 1331 strain, Statens Serum Institut (SSI), Copenhagen, Denmark) versus BCG-Russia (Moscow 361-I strain, Serum Institute of India, Pune, India). In phase II (July 2016–October 2017), neonates were randomised to BCG-Japan (Tokyo 172-1 strain, Japan BCG Laboratory, Tokyo, Japan) versus BCG-Russia (Moscow 361-I strain, Serum Institute of India, Pune, India).
*The families of four infants requested that home-visits were discontinued at later visits; these four infants are not included in the cohort.
†RCTs of early BCG versus no-BCG to neonates with low weight (<2500 g) on the day of inclusion.
‡RCT of providing BCG immediately on admittance to the maternity ward nursery versus BCG provided at discharge.
§RCT of BCG-Denmark versus BCG-Russia (phase I, 5677 neonates) and BCG-Japan versus BCG-Russia (phase II, 6344 neonates); approximately 20% of the cohort were HDSS residents and could thus be included for the present study.
BCG, Bacille Calmette-Guérin; HDSS, Health Demographic Surveillance System; HNSM, Hospital Nacional Simão Mendes; LBW, low birth weight; RCT, randomised controlled trial.