Rapid Protective Effects of Early BCG on Neonatal Mortality Among Low Birth Weight Boys: Observations From Randomized Trials

Sofie Biering-Sorensen, Kristoffer Jarlov Jensen*, Ivan Monterio, Henrik Ravn, Peter Aaby, Christine Stabell Benn

*Corresponding author for this work

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    Background. Three randomized trials (RCTs) in low-weight (<2.5 kg) infants have shown that Bacille Calmette-Guérin (BCG) vaccine nonspecifically reduces all-cause mortality in the neonatal period. Methods. Using data from 3 RCTs of early BCG (n = 6583) we examined potential sex differences in the timing of the mortality reduction in the neonatal period, presenting metaestimates of the main outcome mortality rate ratios (MRR) for BCG-vaccinated and controls. Results. Among controls, boys had a particularly high mortality during the first week after randomization: male–female MRR 2.71 (95% CI, 1.70–4.50). During the first week, BCG had a marked beneficial effect for boys, reducing mortality 3-fold (MRR [BCG/no BCG] = 0.36 [0.20–0.67]). In weeks 2–4 the effect waned for boys (MRR = 0.91 [0.51–1.69]). In girls, the pattern was opposite with a limited effect in the first week (MRR = 0.85 [0.46–1.54]), but a significant reduction in weeks 2–4 (MRR = 0.56 [0.31–1.00]). This was consistent in all 3 trials. Verbal autopsies linked early benefit to fewer sepsis-related deaths among BCG-vaccinated boys. Discussion. The marked reduction in mortality in the days after BCG vaccination in boys emphasizes the importance of providing BCG soon after birth. Trial registration numbers: ClinicalTrials.gov (NCT00146302) and ClinicalTrials.gov (NCT00625482).
    Original languageEnglish
    JournalJournal of Infectious Diseases
    Issue number5
    Pages (from-to)759-766
    Publication statusPublished - 2018

    Bibliographical note

    © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/
    by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com


    • Bacille Calmette-Guérin vaccine
    • Heterologous immunity
    • Neonatal mortality
    • Nonspecific effects of vaccines
    • Sex differences

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