Early BCG Vaccination, Hospitalizations, and Hospital Deaths: Analysis of a Secondary Outcome in 3 Randomized Trials from Guinea-Bissau

Background: This study was performed to examine the effects of early BCG vaccination on the risk, cause, and severity of infant hospitalizations. The analysis included 3 trials randomizing low-weight neonates to early BCG vaccination (intervention) versus no BCG vaccination (usual practice in low-weight neonates, control), with hospitalizations as secondary outcome. Methods: Hospitalization data were collected at the pediatric ward of the National Hospital. Effects of BCG vaccination on hospitalization risk were assessed in Cox models providing overall and major disease-group incidence rate ratios (IRRs). Severity was assessed by means of in-hospital case-fatality rates and compared by group as cohort study risk ratios (RRs). Results: Among 6583 infants (3297 in BCG group, 3286 controls), there were 908 infant hospitalizations (450 BCG, 458 controls) and 135 in-hospital deaths (56 BCG, 79 controls). The neonatal (28 days), 6-week, and infant (1-year) BCG versus control hospitalization IRRs were 0.97 (95% confidence interval [CI], .72-1.31), 0.95 (.73-1.24), and 0.96 (.84-1.10). Corresponding BCG versus control case-fatality rate RRs were 0.58 (95% CI, .35-.94), 0.56 (.35-.90), and 0.72 (.53-.99). BCG vaccination tended to reduce neonatal and infant sepsis hospitalization rates (IRR, 0.75 [95% CI, .50-1.13] and 0.78 [.55-1.11], respectively), and it reduced the neonatal in-hospital sepsis mortality rate (RR, 0.46; 95% CI, .22-.98). There were no confirmed hospitalizations for tuberculosis. Conclusions: BCG vaccination did not affect hospitalization rates but reduced in-hospital mortality rates significantly, primarily by preventing fatal cases of sepsis. The observed beneficial effects of BCG on the in-hospital mortality rate were entirely nonspecific. Clinical Trials Registration: NCT00146302, NCT00168610, and NCT00625482.