Abstract
Bacille Calmette-Guérin (BCG) vaccination lowers the risk of severe infection; we tested whether effects are modulated by maternal BCG in a large cohort of BCG-vaccinated newborns from Guinea-Bissau. Maternal BCG scar status were inspected at enrolment in a BCG trial conducted from 2014 to 17 in Bissau, Guinea-Bissau. We tested associations with background factors for potential confounding; maternal age affected effect estimates >5% and accordingly, all analyses were adjusted for maternal age. Hospitalization data was collected prospectively and assessed in Cox-models providing adjusted Incidence Rate Ratios (aIRRs). In-hospital risk of death (case-fatality) risk was assessed using binomial regression providing adjusted Risk Ratios (aRRs). 60% (6,309/10,598) of mothers had a scar. The maternal-scar/no-scar admission aIRR was 0.96 (0.81-1.14) from 0 to 6 weeks and 1.12 (0.97-1.28) for 6 weeks-3 years. The 6-week in-hospital case-fatality infection aRR was 0.59 (0.34-1.05); 0.40 (0.17-0.91) for males and 0.86 (0.38-1.94) for females. Protection was especially evident against sepsis, the overall 6-week aRR=0.49 (0.26-0.91); no effect was observed for non-infectious deaths or after 6 weeks of age. Effects were similar across BCG strains and multivariate models adjusted for socioeconomic status did not affect estimates. Among BCG-vaccinated newborns, there was a trend for fewer in-hospital deaths from infection associated with maternal BCG priming, especially for males. Providing BCG to adults without a vaccination scar might enhance their offspring's capacity to handle severe infections. Brief 40-word summary: Within a trial comparing BCG strains for their overall effects on morbidity and mortality in Guinea-Bissau, vertical priming with BCG (represented by the maternal BCG scar) was associated with beneficial sex-differential effects on offspring survival.
Highlights
The early-life mortality remains high in developing countries and nearly half of under-5 deaths occur in the neonatal period.[1]
A Danish randomized controlled trials (RCTs) of neonatal Bacille Calmette-Guérin (BCG) versus no-BCG found no overall effect on admission risk between 0-15 months, except within the subgroup born to BCGvaccinated mothers, where BCG was associated with a 35% (6-55%) reduced risk of infectious disease admissions, compared to unvaccinated controls.[10]
The main trial analysis included 12,021 neonates of which 10,777 were recruited after initiation of maternal BCG scar assessments, which were performed for 98% (10,598/10,777); 60% (6,309/10,598) of mothers had a scar (Table 1)
Summary
The early-life mortality remains high in developing countries and nearly half of under-5 deaths occur in the neonatal period.[1] Neonatal sepsis caused by a range of different bacterial agents, against which specific vaccines are not available, is a leading cause of death.[2] A strategy to reduce early-life infection severity is the at-birth provision of live vaccines such as Oral Polio Vaccine (OPV) and Bacille Calmette-Guérin (BCG).[3] In a series of randomized controlled trials (RCTs) conducted by the Bandim Health Project (BHP, www.bandim.org) in Guinea-Bissau, BCG provided at hospital discharge a few days after birth reduced infectious disease mortality risk by 40% (95% Confidence Interval (CI): 11-60%)[4], due to protection against neonatal sepsis.[5,6] A recent RCT from Uganda reported protective non-specific effects (NSE) of at-birth BCG against non-tuberculosis infectious diseases.[7]. A retrospective study has indicated that maternal BCG is associated with a 60% (4-83%) reduction in all-cause mortality by 6 weeks of age.[12]
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