Maternal Bacille Calmette-Guérin Scars and Mortality Risk for Male and Female Newborns: Observational Study From Guinea-Bissau

Author:

Schaltz-Buchholzer Frederik12ORCID,Nielsen Sebastian12ORCID,Sørensen Marcus Kjær1ORCID,Gomes Gabriel Marciano1,Hoff Simon13ORCID,Toft Anna Memborg13,Stjernholm Elise Brenno1,Monteiro Ivan1,Aaby Peter1ORCID,Benn Christine Stabell124ORCID

Affiliation:

1. Bandim Health Project, INDEPTH Network , Bissau , Guinea-Bissau

2. Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark and Odense University Hospital

3. Department of Public Health, GloHAU, Center for Global Health, Aarhus University

4. Danish Institute of Advanced Study, University of Southern Denmark , Odense

Abstract

Abstract Background Maternal priming with bacille Calmette-Guérin (BCG) has been associated with reduced mortality in male offspring. We investigated this association in a cohort of healthy BCG-vaccinated neonates. Methods This observational study within a randomized controlled trial comparing different BCG strains was conducted in Guinea-Bissau from 2017 to 2020. As part of trial inclusion procedures, on the day of discharge from the maternity ward, maternal BCG scar status was evaluated by visual inspection, followed by offspring BCG and polio vaccination. Through mortality data collected at telephone interviews at 6 weeks and 6 months of age, we assessed all-cause mortality risk in Cox proportional hazards models adjusted for maternal schooling and BCG strain, providing adjusted mortality rate ratios (aMRRs). Results In total, 64% (11 070/17 275) of mothers had a BCG scar, which was not associated with admission risk, admission severity, or all-cause mortality for females and the overall sample. By 6 months of age, the mortality rate (MR) was 4.1 (200 deaths/4919 person-years) for the maternal BCG scar cohort and 5.2 (139/2661) for no maternal scar (aMRR, 0.86; 95% Confidence Interval [CI], .69–1.06). In males, 6-month MRs were 4.3 (109 deaths/2531 person-years) for maternal BCG scar vs 6.3 (87/1376) for no scar (aMRR, 0.74; 95% CI, .56–.99). In females, 6-month MRs were 3.8 (91 deaths/2388 person-years) vs 4.0 (52/1286), respectively (aMRR, 1.04; 95% CI, .74–1.47; for interaction with sex, P = .16). Conclusions While we cannot rule out an association in females, being born to a mother with a BCG scar reduced the risk of death during early infancy for BCG-vaccinated males, reproducing findings from previous studies.

Funder

University of Southern Denmark

Augustinusfonden

MICA-Fonden

Research Center for Vitamins and Vaccines

Danish National Research Foundation

European and Developing Countries Clinical Trials Partnership

Publisher

Oxford University Press (OUP)

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