Background: Randomized controlled trials (RCTs) indicate that Bacille Calmette-Guérin (BCG) vaccination provides broad beneficial non-specific protection against infections. We investigated the effect on in-hospital mortality of providing BCG immediately upon admission to a neonatal intensive care unit (NICU), rather than BCG-at-discharge. The pre-trial NICU mortality was 13% and we hypothesized that BCG would reduce mortality by 40%.

Methods: Parallel-group, open-label RCT initiated in 2013 in Guinea-Bissau. NICU-admitted neonates were randomized 1:1 to BCG+Oral Polio Vaccine (OPV) immediately (intervention) versus BCG+OPV at hospital discharge (control; usual practice). The trial was discontinued due to decreasing in-hospital mortality and major NICU restructuring. We assessed overall and disease-specific mortality by randomization allocation in Cox Proportional Hazards models providing Mortality Rate Ratios (MRRs).

Results: We recruited 3,353 neonates and the overall mortality was 3.1% (52/1676) for BCG-vaccinated neonates versus 3.3% (55/1677) for controls, MRR=0.94 (0.64-1.36). For non-infectious causes of death the MRR was 1.20 (0.70-2.07) and there tended to be fewer deaths from infections in the BCG group (N=14) than among controls (N=21), MRR=0.65 (0.33-1.28).

Conclusions: Providing BCG+OPV to frail neonates was safe and might protect against fatal infection in the immediate newborn period. Deaths due to prematurity and perinatal complications were unaffected by BCG.