Can Earlier BCG Vaccination Reduce Early Infant Mortality? A Randomised Trial

Background: BCG and oral polio vaccines (OPV) at birth are associated with beneficial non-specific effects, reducing neonatal mortality by more than what can be explained by prevention of the target diseases. BCG is recommended at birth, but is often given much later, especially in rural areas. In two RCTs in Guinea-Bissau, BCG-at-birth reduced neonatal mortality in low birthweight (<2500g; LBW) children by 48% (95%CI: 18-67%) and in children with a birthweight >2500g (NBW), OPV+BCG vs BCG was associated with a 32% (95%CI: 0-55%) lower mortality.

WHO recommends home visits shortly after birth to reduce mortality, but vaccinations are not normally provided. If the vaccines indeed have profound effects on innate immunity and neonatal mortality in both LBW and NBW children many lives could be saved if BCG and OPV was provided earlier. Urban and rural clusters are randomised to home visits with and without vaccinations. All children participating in the study will be offered routine vaccines at village visits by the BHP team in the rural area. In the urban area, BCG and OPV will be provided at follow-up visits if the child has not yet received the vaccines. Thereby the study will provide earlier vaccination for all children.

Hypothesis: BCG+OPV at birth provided at village visits shortly after birth will reduce early infant mortality by 40%.

Methods: The study will be conducted in Biombo, Oio and Cacheu in rural Guinea-Bissau and in six suburban districts in the capital of Guinea-Bissau. In Guinea-Bissau home visits are not yet implemented as part of the routine program. Pregnant women will be offered to participate in the study at the time of pregnancy registration, which is conducted as part of the routine registration in the rural and urban health and demographic surveillance systems, respectively. Community key informants or mothers will communicate information on births to the BHP study team, and a study nurse will visit every new-born child shortly after a CKI or mother calls, if possible on the same day. Clusters will be randomised to receive immediate vaccination of their children shortly after birth or at the first visit by the BHP team in the rural area and at 2-months follow-up visits in the urban area.

Statistical analyses: The primary analysis of early infant non-accidental mortality will be assessed on a PP analysis stratifying for factors used in the randomization (Region, pre-study mortality level (high/low)) and sex, thus allowing different baseline hazards for boys and girls. To account for clustering we will employ cluster-robust variance estimates.