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. 2021 Aug 12:39:101049.
doi: 10.1016/j.eclinm.2021.101049. eCollection 2021 Sep.

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

Mlt Berendsen  1   2   3 , F Schaltz-Buchholzer  1   2 , P Bles  2   3 , S Biering-Sørensen  2 , K J Jensen  4   5 , I Monteiro  2 , I Silva  2 , P Aaby  1   2 , C S Benn  1   6
Affiliations

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

Mlt Berendsen et al. EClinicalMedicine. .

Abstract

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.

Keywords: Bacille Calmette-Guérin; Heterologous effects; Immunological inheritance; Non-specific effects of vaccines; Parental priming; Vertical boosting.

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Conflict of interest statement

MLTB and FSB received support from the University of Southern Denmark in the form of a scholarship. CSB holds an ERC starting grant and PA holds a research professorship from Novo Nordisk. PB, SBS, KJJ, IM, and IS declare no conflict of interest.

Figures

Fig 1
Fig. 1
Study design of the original trial and flowchart of study participants. In the original trial infants were randomized to BCG-at-birth or standard practice (‘delayed’ BCG). The BCG vaccination at 6 weeks in the control group is an indication from when most children in the control group would start receiving BCG, not the age to which the control group was randomized. Abbreviations: BCG, bacillus Calmette-Guérin; BHP, Bandim Health Project; HDSS, Health and Demographic Surveillance System.
Fig 2
Fig. 2
Kaplan-Meier curve of survival probability by parental BCG scar status. Adjusted mortality rate ratios (aMRRs) for maternal BCG scar (A) and paternal BCG scar (B) estimated in a Cox proportional hazards model with time since randomization as the underlying time variable. Models were adjusted by stabilized Inverse Probability of Treatment Weighting (sIPTW) based on the variables maternal schooling, electricity, indoor toilet and age of the child at inclusion. Observations were censored at migration or 42 days of age, whatever came first. Numbers at risk and numbers censored (bracketed) are rounded to the nearest integer because of the sIPTW. Abbreviations: BCG, Bacillus Calmette-Guérin.
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