Frederik Schaltz-Buchholzer1, Christian Bjerregård Øland2, Mike Berendsen3, Morten Bjerregaard-Andersen2, Elise Brenno Stjernholm2, Christian N Golding2, Ivan Monteiro2, Peter Aaby2, Christine Stabell Benn4. 1. Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau; Bandim Health Project, OPEN, Institute of Clinical Research, Uni. Southern Denmark and Odense University Hospital, Odense, Denmark. Electronic address: fschaltz-buchholzer@health.sdu.dk. 2. Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau. 3. Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau; Bandim Health Project, OPEN, Institute of Clinical Research, Uni. Southern Denmark and Odense University Hospital, Odense, Denmark; Department of Internal Medicine, Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands. 4. Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau; Bandim Health Project, OPEN, Institute of Clinical Research, Uni. Southern Denmark and Odense University Hospital, Odense, Denmark; Danish Institute of Advanced Science, Uni. Southern Denmark, Odense, Denmark. Electronic address: cbenn@health.sdu.dk.
Abstract
OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.