Parental Bacillus Calmette-Guérin vaccine scars decrease infant mortality in the first six weeks of life: A retrospective cohort study.

Background: Live attenuated vaccines have been observed to have particularly beneficial effects for child survival when given in the presence of maternally transferred immunity (priming). We aimed to test this finding and furthermore explore the role of paternal priming.

Methods: In an exploratory, retrospective cohort study in 2017, parental Bacillus Calmette-Guérin (BCG) scars were assessed for infants from the Bandim Health Project (BHP) who had participated in a 2008-2013 trial of neonatal BCG vaccination. Parental scar effects on mortality were estimated from birth to 42 days, the age of the scheduled diphtheria-tetanus-pertussis (DTP) vaccination, in Cox proportional hazard models adjusted with Inverse Probability of Treatment Weighting.

Findings: For 66% (510/772) of main trial infants that were still registered in the BHP area, at least one parent was located. BCG scar prevalence was 77% (353/461) among mothers and 63% (137/219) among fathers. In the first six weeks of life, maternal scars were associated with a mortality reduction of 60% (95%CI, 4% to 83%) and paternal scars with 49% (-68% to 84%). The maternal scar association was most beneficial among infants that had received BCG vaccination at birth (73% (-1% to 93%)). Although priming was less evident for paternal scars, having two parents with scars reduced mortality by 89% (13% to 99%) compared with either one or none of the parents having a scar.

Interpretation: Parental BCG scars were associated with strongly increased early-life survival. These findings underline the importance of future studies into the subject of inherited non-specific immunity and parental priming.

Funding: Danish National Research Foundation; European Research Council; Novo Nordisk Foundation; University of Southern Denmark.