Early BCG Vaccination, Hospitalizations, and Hospital Deaths

Analysis of a Secondary Outcome in 3 Randomized Trials from Guinea-Bissau

Frederik Schaltz-Buchholzer, S Biering-Sørensen, N Lund, I Monteiro, P Umbasse, A B Fisker, A Andersen, A Rodrigues, P Aaby, C S Benn

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Background: This study was performed to examine the effects of early BCG vaccination on the risk, cause, and severity of infant hospitalizations. The analysis included 3 trials randomizing low-weight neonates to early BCG vaccination (intervention) versus no BCG vaccination (usual practice in low-weight neonates, control), with hospitalizations as secondary outcome.

Methods: Hospitalization data were collected at the pediatric ward of the National Hospital. Effects of BCG vaccination on hospitalization risk were assessed in Cox models providing overall and major disease-group incidence rate ratios (IRRs). Severity was assessed by means of in-hospital case-fatality rates and compared by group as cohort study risk ratios (RRs).

Results: Among 6583 infants (3297 in BCG group, 3286 controls), there were 908 infant hospitalizations (450 BCG, 458 controls) and 135 in-hospital deaths (56 BCG, 79 controls). The neonatal (28 days), 6-week, and infant (1-year) BCG versus control hospitalization IRRs were 0.97 (95% confidence interval [CI], .72-1.31), 0.95 (.73-1.24), and 0.96 (.84-1.10). Corresponding BCG versus control case-fatality rate RRs were 0.58 (95% CI, .35-.94), 0.56 (.35-.90), and 0.72 (.53-.99). BCG vaccination tended to reduce neonatal and infant sepsis hospitalization rates (IRR, 0.75 [95% CI, .50-1.13] and 0.78 [.55-1.11], respectively), and it reduced the neonatal in-hospital sepsis mortality rate (RR, 0.46; 95% CI, .22-.98). There were no confirmed hospitalizations for tuberculosis.

Conclusions: BCG vaccination did not affect hospitalization rates but reduced in-hospital mortality rates significantly, primarily by preventing fatal cases of sepsis. The observed beneficial effects of BCG on the in-hospital mortality rate were entirely nonspecific.

Clinical Trials Registration: NCT00146302, NCT00168610, and NCT00625482.

Original languageEnglish
JournalThe Journal of Infectious Diseases
Volume219
Issue number4
Pages (from-to)624-632
ISSN0022-1899
DOIs
Publication statusPublished - 29. Jan 2019

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Guinea-Bissau
Mycobacterium bovis
Hospital Mortality
Confidence Intervals
Odds Ratio
Incidence
Newborn Infant
Weights and Measures
Proportional Hazards Models

Keywords

  • Bacille Calmette-Guérin; infant mortality; infant morbidity; in-hospital case-fatality; neonatal mortality; neonatal morbidity; non-specific (heterologous) effects of vaccines; sepsis; tuberculosis

Cite this

@article{180e6a1419454d9e829e86b2a14e3844,
title = "Early BCG Vaccination, Hospitalizations, and Hospital Deaths: Analysis of a Secondary Outcome in 3 Randomized Trials from Guinea-Bissau",
abstract = "Background: This study was performed to examine the effects of early BCG vaccination on the risk, cause, and severity of infant hospitalizations. The analysis included 3 trials randomizing low-weight neonates to early BCG vaccination (intervention) versus no BCG vaccination (usual practice in low-weight neonates, control), with hospitalizations as secondary outcome.Methods: Hospitalization data were collected at the pediatric ward of the National Hospital. Effects of BCG vaccination on hospitalization risk were assessed in Cox models providing overall and major disease-group incidence rate ratios (IRRs). Severity was assessed by means of in-hospital case-fatality rates and compared by group as cohort study risk ratios (RRs).Results: Among 6583 infants (3297 in BCG group, 3286 controls), there were 908 infant hospitalizations (450 BCG, 458 controls) and 135 in-hospital deaths (56 BCG, 79 controls). The neonatal (28 days), 6-week, and infant (1-year) BCG versus control hospitalization IRRs were 0.97 (95{\%} confidence interval [CI], .72-1.31), 0.95 (.73-1.24), and 0.96 (.84-1.10). Corresponding BCG versus control case-fatality rate RRs were 0.58 (95{\%} CI, .35-.94), 0.56 (.35-.90), and 0.72 (.53-.99). BCG vaccination tended to reduce neonatal and infant sepsis hospitalization rates (IRR, 0.75 [95{\%} CI, .50-1.13] and 0.78 [.55-1.11], respectively), and it reduced the neonatal in-hospital sepsis mortality rate (RR, 0.46; 95{\%} CI, .22-.98). There were no confirmed hospitalizations for tuberculosis.Conclusions: BCG vaccination did not affect hospitalization rates but reduced in-hospital mortality rates significantly, primarily by preventing fatal cases of sepsis. The observed beneficial effects of BCG on the in-hospital mortality rate were entirely nonspecific.Clinical Trials Registration: NCT00146302, NCT00168610, and NCT00625482.",
keywords = "Bacille Calmette-Gu{\'e}rin; infant mortality; infant morbidity; in-hospital case-fatality; neonatal mortality; neonatal morbidity; non-specific (heterologous) effects of vaccines; sepsis; tuberculosis",
author = "Frederik Schaltz-Buchholzer and S Biering-S{\o}rensen and N Lund and I Monteiro and P Umbasse and Fisker, {A B} and A Andersen and A Rodrigues and P Aaby and Benn, {C S}",
year = "2019",
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language = "English",
volume = "219",
pages = "624--632",
journal = "Journal of Infectious Diseases",
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Early BCG Vaccination, Hospitalizations, and Hospital Deaths : Analysis of a Secondary Outcome in 3 Randomized Trials from Guinea-Bissau. / Schaltz-Buchholzer, Frederik; Biering-Sørensen, S; Lund, N; Monteiro, I; Umbasse, P; Fisker, A B; Andersen, A; Rodrigues, A; Aaby, P; Benn, C S.

In: The Journal of Infectious Diseases, Vol. 219, No. 4, 29.01.2019, p. 624-632.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Early BCG Vaccination, Hospitalizations, and Hospital Deaths

T2 - Analysis of a Secondary Outcome in 3 Randomized Trials from Guinea-Bissau

AU - Schaltz-Buchholzer, Frederik

AU - Biering-Sørensen, S

AU - Lund, N

AU - Monteiro, I

AU - Umbasse, P

AU - Fisker, A B

AU - Andersen, A

AU - Rodrigues, A

AU - Aaby, P

AU - Benn, C S

PY - 2019/1/29

Y1 - 2019/1/29

N2 - Background: This study was performed to examine the effects of early BCG vaccination on the risk, cause, and severity of infant hospitalizations. The analysis included 3 trials randomizing low-weight neonates to early BCG vaccination (intervention) versus no BCG vaccination (usual practice in low-weight neonates, control), with hospitalizations as secondary outcome.Methods: Hospitalization data were collected at the pediatric ward of the National Hospital. Effects of BCG vaccination on hospitalization risk were assessed in Cox models providing overall and major disease-group incidence rate ratios (IRRs). Severity was assessed by means of in-hospital case-fatality rates and compared by group as cohort study risk ratios (RRs).Results: Among 6583 infants (3297 in BCG group, 3286 controls), there were 908 infant hospitalizations (450 BCG, 458 controls) and 135 in-hospital deaths (56 BCG, 79 controls). The neonatal (28 days), 6-week, and infant (1-year) BCG versus control hospitalization IRRs were 0.97 (95% confidence interval [CI], .72-1.31), 0.95 (.73-1.24), and 0.96 (.84-1.10). Corresponding BCG versus control case-fatality rate RRs were 0.58 (95% CI, .35-.94), 0.56 (.35-.90), and 0.72 (.53-.99). BCG vaccination tended to reduce neonatal and infant sepsis hospitalization rates (IRR, 0.75 [95% CI, .50-1.13] and 0.78 [.55-1.11], respectively), and it reduced the neonatal in-hospital sepsis mortality rate (RR, 0.46; 95% CI, .22-.98). There were no confirmed hospitalizations for tuberculosis.Conclusions: BCG vaccination did not affect hospitalization rates but reduced in-hospital mortality rates significantly, primarily by preventing fatal cases of sepsis. The observed beneficial effects of BCG on the in-hospital mortality rate were entirely nonspecific.Clinical Trials Registration: NCT00146302, NCT00168610, and NCT00625482.

AB - Background: This study was performed to examine the effects of early BCG vaccination on the risk, cause, and severity of infant hospitalizations. The analysis included 3 trials randomizing low-weight neonates to early BCG vaccination (intervention) versus no BCG vaccination (usual practice in low-weight neonates, control), with hospitalizations as secondary outcome.Methods: Hospitalization data were collected at the pediatric ward of the National Hospital. Effects of BCG vaccination on hospitalization risk were assessed in Cox models providing overall and major disease-group incidence rate ratios (IRRs). Severity was assessed by means of in-hospital case-fatality rates and compared by group as cohort study risk ratios (RRs).Results: Among 6583 infants (3297 in BCG group, 3286 controls), there were 908 infant hospitalizations (450 BCG, 458 controls) and 135 in-hospital deaths (56 BCG, 79 controls). The neonatal (28 days), 6-week, and infant (1-year) BCG versus control hospitalization IRRs were 0.97 (95% confidence interval [CI], .72-1.31), 0.95 (.73-1.24), and 0.96 (.84-1.10). Corresponding BCG versus control case-fatality rate RRs were 0.58 (95% CI, .35-.94), 0.56 (.35-.90), and 0.72 (.53-.99). BCG vaccination tended to reduce neonatal and infant sepsis hospitalization rates (IRR, 0.75 [95% CI, .50-1.13] and 0.78 [.55-1.11], respectively), and it reduced the neonatal in-hospital sepsis mortality rate (RR, 0.46; 95% CI, .22-.98). There were no confirmed hospitalizations for tuberculosis.Conclusions: BCG vaccination did not affect hospitalization rates but reduced in-hospital mortality rates significantly, primarily by preventing fatal cases of sepsis. The observed beneficial effects of BCG on the in-hospital mortality rate were entirely nonspecific.Clinical Trials Registration: NCT00146302, NCT00168610, and NCT00625482.

KW - Bacille Calmette-Guérin; infant mortality; infant morbidity; in-hospital case-fatality; neonatal mortality; neonatal morbidity; non-specific (heterologous) effects of vaccines; sepsis; tuberculosis

U2 - 10.1093/infdis/jiy544

DO - 10.1093/infdis/jiy544

M3 - Journal article

VL - 219

SP - 624

EP - 632

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 4

ER -