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

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 - Nissen, Thomas Nørrelykke

AU - Pihl, Gitte Thybo

AU - Thøstesen, Lisbeth Marianne

AU - Kofoed, Poul-Erik

AU - Pryds, Ole

AU - Ravn, Henrik

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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 7days 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 15months 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 15months 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 7days 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 15months 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 15months of age in this Danish study population.

KW - BCG Vaccine

KW - Child, Preschool

KW - Denmark

KW - Female

KW - Follow-Up Studies

KW - Hospitalization

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Male

KW - Perinatal Care

KW - Risk Factors

KW - Socioeconomic Factors

KW - Tuberculosis

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

U2 - 10.1136/archdischild-2016-310760

DO - 10.1136/archdischild-2016-310760

M3 - Journal article

C2 - 27443836

SN - 0003-9888

VL - 102

SP - 224

EP - 231

JO - Archives of Disease in Childhood

JF - Archives of Disease in Childhood

IS - 3

ER -