BCG vaccination at birth and early childhood hospitalisation: A randomised clinical multicentre trial

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

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Resumé

Background The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting.

Methods Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses.

Results 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics.

Conclusions BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15 months of age in this Danish study population.
OriginalsprogEngelsk
TidsskriftArchives of Disease in Childhood
Vol/bind102
Udgave nummer3
Sider (fra-til)224-231
ISSN0003-9888
DOI
StatusUdgivet - mar. 2017

Fingeraftryk

Mycobacterium bovis
Multicenter Studies
Randomized Controlled Trials
Pregnant Women
Parental Consent
Intention to Treat Analysis
Denmark
Random Allocation
Proportional Hazards Models
Immune System
Outcome Assessment (Health Care)
Newborn Infant
Population

Citer dette

Stensballe, Lone Graff ; Sørup, Signe ; Aaby, Peter ; Benn, Christine Stabell ; Greisen, Gorm ; Jeppesen, Dorthe Lisbeth ; Birk, Nina Marie ; Kjærgaard, Jesper ; Nørrelykke Nissen, Thomas ; Thybo Pihl, Gitte ; Thøstesen, Lisbeth ; Kofoed, Poul-Erik ; Pryds, Ole ; Ravn, Henrik . / BCG vaccination at birth and early childhood hospitalisation : A randomised clinical multicentre trial. I: Archives of Disease in Childhood. 2017 ; Bind 102, Nr. 3. s. 224-231.
@article{2c67359f2e634a8882bfc80d18bfe7ea,
title = "BCG vaccination at birth and early childhood hospitalisation: A randomised clinical multicentre trial",
abstract = "Background The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting.Methods Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses.Results 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95{\%} CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics.Conclusions BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15 months of age in this Danish study population.",
keywords = "Bacillus Calmette-Gu{\'e}rin (BCG, hospitalisation, infant, non-specific effect, vaccine, Follow-Up Studies, Humans, Risk Factors, Child, Preschool, Perinatal Care, Infant, Male, Socioeconomic Factors, BCG Vaccine, Denmark, Female, Hospitalization/statistics & numerical data, Tuberculosis/prevention & control, Infant, Newborn",
author = "Stensballe, {Lone Graff} and Signe S{\o}rup and Peter Aaby and Benn, {Christine Stabell} and Gorm Greisen and Jeppesen, {Dorthe Lisbeth} and Birk, {Nina Marie} and Jesper Kj{\ae}rgaard and {N{\o}rrelykke Nissen}, Thomas and {Thybo Pihl}, Gitte and Lisbeth Th{\o}stesen and Poul-Erik Kofoed and Ole Pryds and Henrik Ravn",
year = "2017",
month = "3",
doi = "10.1136/archdischild-2016-310760",
language = "English",
volume = "102",
pages = "224--231",
journal = "Archives of Disease in Childhood",
issn = "0003-9888",
publisher = "B M J Group",
number = "3",

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Stensballe, LG, Sørup, S, Aaby, P, Benn, CS, Greisen, G, Jeppesen, DL, Birk, NM, Kjærgaard, J, Nørrelykke Nissen, T, Thybo Pihl, G, Thøstesen, L, Kofoed, P-E, Pryds, O & Ravn, H 2017, 'BCG vaccination at birth and early childhood hospitalisation: A randomised clinical multicentre trial', Archives of Disease in Childhood, bind 102, nr. 3, s. 224-231. https://doi.org/10.1136/archdischild-2016-310760

BCG vaccination at birth and early childhood hospitalisation : A randomised clinical multicentre trial. / Stensballe, Lone Graff; Sørup, Signe; Aaby, Peter; Benn, Christine Stabell; Greisen, Gorm; Jeppesen, Dorthe Lisbeth; Birk, Nina Marie; Kjærgaard, Jesper ; Nørrelykke Nissen, Thomas; Thybo Pihl, Gitte; Thøstesen, Lisbeth; Kofoed, Poul-Erik; Pryds, Ole; Ravn, Henrik .

I: Archives of Disease in Childhood, Bind 102, Nr. 3, 03.2017, s. 224-231.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - BCG vaccination at birth and early childhood hospitalisation

T2 - A randomised clinical multicentre trial

AU - Stensballe, Lone Graff

AU - Sørup, Signe

AU - Aaby, Peter

AU - Benn, Christine Stabell

AU - Greisen, Gorm

AU - Jeppesen, Dorthe Lisbeth

AU - Birk, Nina Marie

AU - Kjærgaard, Jesper

AU - Nørrelykke Nissen, Thomas

AU - Thybo Pihl, Gitte

AU - Thøstesen, Lisbeth

AU - Kofoed, Poul-Erik

AU - Pryds, Ole

AU - Ravn, Henrik

PY - 2017/3

Y1 - 2017/3

N2 - Background The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting.Methods Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses.Results 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics.Conclusions BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15 months of age in this Danish study population.

AB - Background The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting.Methods Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses.Results 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics.Conclusions BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15 months of age in this Danish study population.

KW - Bacillus Calmette-Guérin (BCG

KW - hospitalisation

KW - infant

KW - non-specific effect

KW - vaccine

KW - Follow-Up Studies

KW - Humans

KW - Risk Factors

KW - Child, Preschool

KW - Perinatal Care

KW - Infant

KW - Male

KW - Socioeconomic Factors

KW - BCG Vaccine

KW - Denmark

KW - Female

KW - Hospitalization/statistics & numerical data

KW - Tuberculosis/prevention & control

KW - Infant, Newborn

U2 - 10.1136/archdischild-2016-310760

DO - 10.1136/archdischild-2016-310760

M3 - Journal article

C2 - 27443836

VL - 102

SP - 224

EP - 231

JO - Archives of Disease in Childhood

JF - Archives of Disease in Childhood

SN - 0003-9888

IS - 3

ER -