BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15 Months of Age in Danish Children

A Randomized Clinical Multicenter Trial

Lone Graff Stensballe, Henrik Ravn, Nina Marie Birk, Jesper Kjærgaard, Thomas Nørrelykke Nissen, Gitte Thybo Pihl, Lisbeth Marianne Thøstesen, Gorm Greisen, Dorthe Lisbeth Jeppesen, Poul-Erik Kofoed, Ole Pryds, Signe Sørup, Peter Aaby, Christine Stabell Benn

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis might reduce the non-tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization.

Methods: A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses.

Results: In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.85-1.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86-1.16). Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45-0.94); the HR for children who had a non-BCG-vaccinated mother was 1.10 (95% CI, 0.93-1.29) (P = .01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54-0.99] in children born by cesarean section vs 1.10 [95% CI, 0.92-1.30] in other children; P = .02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95% CI, 0.95-3.43), whereas the HR was 0.94 (95% CI, 0.82-1.08) for children born at term (P = .05).

Conclusion: BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration.

OriginalsprogEngelsk
TidsskriftPediatric Infectious Diseases Society. Journal
Vol/bind8
Udgave nummer3
Sider (fra-til)213-220
ISSN2048-7193
DOI
StatusUdgivet - sep. 2019

Fingeraftryk

Multicenter Studies
Randomized Controlled Trials
Confidence Intervals
Intention to Treat Analysis
Mothers
Child Mortality
Premature Birth
Denmark
Control Groups

Citer dette

Stensballe, Lone Graff ; Ravn, Henrik ; Birk, Nina Marie ; Kjærgaard, Jesper ; Nissen, Thomas Nørrelykke ; Pihl, Gitte Thybo ; Thøstesen, Lisbeth Marianne ; Greisen, Gorm ; Jeppesen, Dorthe Lisbeth ; Kofoed, Poul-Erik ; Pryds, Ole ; Sørup, Signe ; Aaby, Peter ; Benn, Christine Stabell. / BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15 Months of Age in Danish Children : A Randomized Clinical Multicenter Trial. I: Pediatric Infectious Diseases Society. Journal. 2019 ; Bind 8, Nr. 3. s. 213-220.
@article{ca563d64d9a843b8a9e2d40f04a219fc,
title = "BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15 Months of Age in Danish Children: A Randomized Clinical Multicenter Trial",
abstract = "Background: The bacillus Calmette-Gu{\'e}rin (BCG) vaccine against tuberculosis might reduce the non-tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization.Methods: A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses.Results: In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95{\%} confidence interval (CI), 0.85-1.15]). The PP analysis yielded an HR of 1.00 (95{\%} CI, 0.86-1.16). Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95{\%} CI, 0.45-0.94); the HR for children who had a non-BCG-vaccinated mother was 1.10 (95{\%} CI, 0.93-1.29) (P = .01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95{\%} CI, 0.54-0.99] in children born by cesarean section vs 1.10 [95{\%} CI, 0.92-1.30] in other children; P = .02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95{\%} CI, 0.95-3.43), whereas the HR was 0.94 (95{\%} CI, 0.82-1.08) for children born at term (P = .05).Conclusion: BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration.",
keywords = "Bacillus Calmette-Gu{\'e}rin (BCG), Children, Hospitalization for infection, Nonspecific effect of immunization",
author = "Stensballe, {Lone Graff} and Henrik Ravn and Birk, {Nina Marie} and Jesper Kj{\ae}rgaard and Nissen, {Thomas N{\o}rrelykke} and Pihl, {Gitte Thybo} and Th{\o}stesen, {Lisbeth Marianne} and Gorm Greisen and Jeppesen, {Dorthe Lisbeth} and Poul-Erik Kofoed and Ole Pryds and Signe S{\o}rup and Peter Aaby and Benn, {Christine Stabell}",
year = "2019",
month = "9",
doi = "10.1093/jpids/piy029",
language = "English",
volume = "8",
pages = "213--220",
journal = "Pediatric Infectious Diseases Society. Journal",
issn = "2048-7193",
publisher = "Heinemann",
number = "3",

}

Stensballe, LG, Ravn, H, Birk, NM, Kjærgaard, J, Nissen, TN, Pihl, GT, Thøstesen, LM, Greisen, G, Jeppesen, DL, Kofoed, P-E, Pryds, O, Sørup, S, Aaby, P & Benn, CS 2019, 'BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15 Months of Age in Danish Children: A Randomized Clinical Multicenter Trial', Pediatric Infectious Diseases Society. Journal, bind 8, nr. 3, s. 213-220. https://doi.org/10.1093/jpids/piy029

BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15 Months of Age in Danish Children : A Randomized Clinical Multicenter Trial. / Stensballe, Lone Graff; Ravn, Henrik; Birk, Nina Marie; Kjærgaard, Jesper; Nissen, Thomas Nørrelykke; Pihl, Gitte Thybo; Thøstesen, Lisbeth Marianne; Greisen, Gorm; Jeppesen, Dorthe Lisbeth; Kofoed, Poul-Erik; Pryds, Ole; Sørup, Signe; Aaby, Peter; Benn, Christine Stabell.

I: Pediatric Infectious Diseases Society. Journal, Bind 8, Nr. 3, 09.2019, s. 213-220.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15 Months of Age in Danish Children

T2 - A Randomized Clinical Multicenter Trial

AU - Stensballe, Lone Graff

AU - Ravn, Henrik

AU - Birk, Nina Marie

AU - Kjærgaard, Jesper

AU - Nissen, Thomas Nørrelykke

AU - Pihl, Gitte Thybo

AU - Thøstesen, Lisbeth Marianne

AU - Greisen, Gorm

AU - Jeppesen, Dorthe Lisbeth

AU - Kofoed, Poul-Erik

AU - Pryds, Ole

AU - Sørup, Signe

AU - Aaby, Peter

AU - Benn, Christine Stabell

PY - 2019/9

Y1 - 2019/9

N2 - Background: The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis might reduce the non-tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization.Methods: A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses.Results: In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.85-1.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86-1.16). Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45-0.94); the HR for children who had a non-BCG-vaccinated mother was 1.10 (95% CI, 0.93-1.29) (P = .01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54-0.99] in children born by cesarean section vs 1.10 [95% CI, 0.92-1.30] in other children; P = .02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95% CI, 0.95-3.43), whereas the HR was 0.94 (95% CI, 0.82-1.08) for children born at term (P = .05).Conclusion: BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration.

AB - Background: The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis might reduce the non-tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization.Methods: A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses.Results: In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.85-1.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86-1.16). Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45-0.94); the HR for children who had a non-BCG-vaccinated mother was 1.10 (95% CI, 0.93-1.29) (P = .01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54-0.99] in children born by cesarean section vs 1.10 [95% CI, 0.92-1.30] in other children; P = .02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95% CI, 0.95-3.43), whereas the HR was 0.94 (95% CI, 0.82-1.08) for children born at term (P = .05).Conclusion: BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration.

KW - Bacillus Calmette-Guérin (BCG)

KW - Children

KW - Hospitalization for infection

KW - Nonspecific effect of immunization

U2 - 10.1093/jpids/piy029

DO - 10.1093/jpids/piy029

M3 - Journal article

VL - 8

SP - 213

EP - 220

JO - Pediatric Infectious Diseases Society. Journal

JF - Pediatric Infectious Diseases Society. Journal

SN - 2048-7193

IS - 3

ER -