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

ABSTRACT: 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.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.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.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.NCT01694108, results.

SUBMITTER: Stensballe LG

PROVIDER: S-EPMC5339556 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Stensballe Lone Graff LG Sørup Signe S Aaby Peter P Benn Christine Stabell CS Greisen Gorm G Jeppesen Dorthe Lisbeth DL Birk Nina Marie NM Kjærgaard Jesper J Nissen Thomas Nørrelykke TN Pihl Gitte Thybo GT Thøstesen Lisbeth Marianne LM Kofoed Poul-Erik PE Pryds Ole O Ravn Henrik H

Archives of disease in childhood 20160721 3

<h4>Background</h4>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.<h4>Methods</h4>Pregnant women planning to give birth at three Danish hospitals were invited to ...[more]

PMID: 27443836

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Project description:IntroductionIncreasing evidence suggests that the BCG vaccine has non-specific effects, altering the susceptibility to non-tuberculous infections. Thus, early BCG vaccination may reduce mortality. BCG is recommended at birth but is often delayed. Vaccination opportunities are missed due to multidose vials not being opened for a few children. We will assess the effect of making BCG available at the first health-facility contact on early infant mortality and morbidity in a rural setting in Guinea-Bissau.Methods and analysisIn a cluster-randomised crossover trial, we randomise 23 health centres to two different treatment groups. In half of the health centres, BCG is provided as per current practice; in the remaining health centres, we make BCG available everyday to allow opening a vial of BCG if there is just one eligible child present. The randomisation of centres will be crossed over after 12 months and enrolment will continue for another 12 months.We will use logistic regression models with adjustment for village to assess the effect of making BCG available at the first health-facility contact. The main outcome is non-accidental mortality between day 1 and day 42 after birth. We will adjust for sex, health centre, period (before/after crossover) and level of surveillance (level 1 or level 2). Further analyses include assessment of the effect on hospital admission and a cost-effectiveness evaluation.Ethics and disseminationIf BCG vaccination reduces early infant mortality, missed opportunities and delays of vaccinations expose infants in several low-income countries to unnecessary excess mortality risk. The present trial will provide information on the effect of implementing a feasible intervention, where all children receive BCG at their first health-facility contact. Consent is obtained from all pregnant women registered as part of the trial. The results of the study will be published and communicated to the National Institute of Public Health in Guinea-Bissau.Trial registration numberNCT04658680; Clinicaltrials.gov.

Project description:ObjectiveTo investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates.DesignRandomised, placebo controlled, two by two factorial trial.SettingBissau, Guinea-Bissau.Participants1717 low birthweight neonates born at the national hospital.InterventionNeonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12 months.Main outcome measureMortality, calculated as mortality rate ratios (MRRs), after follow-up to 12 months of age for infants who received vitamin A supplementation compared with those who received placebo.ResultsNo interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality: the MRR of vitamin A supplementation compared with placebo, controlled for randomisation to "early BCG" versus "no early BCG" was 1.08 (95% CI 0.79 to 1.47). Stratification by sex revealed a significant interaction between vitamin A supplementation and sex (P=0.046), the MRR of vitamin A supplementation being 0.74 (95% CI 0.45 to 1.22) in boys and 1.42 (95% CI 0.94 to 2.15) in girls. When these data were combined with data from a complementary trial among normal birthweight neonates in Guinea-Bissau, the combined estimate of the effect of neonatal vitamin A supplementation on mortality was 1.08 (95% CI 0.87 to 1.33); 0.80 (95% CI 0.58 to 1.10) in boys and 1.41 (95% CI 1.04 to 1.90) in girls (P=0.01 for interaction between neonatal vitamin A and sex).ConclusionsThe combined results of this trial and the complementary trial among normal birthweight neonates have now shown that, overall, it would not be beneficial to implement a neonatal vitamin A supplementation policy in Guinea-Bissau. Worryingly, the trials show that vitamin A supplementation at birth can be harmful in girls. Previous studies and future trials should investigate the possibility that vitamin A supplementation has sex differential effects. Trial registration ClinicalTrials.gov NCT00168610.

Project description:Importance:The BCG vaccine is currently the only approved tuberculosis vaccine and is widely administered worldwide, usually during infancy. Previous studies found increased rates of lymphoma and leukemia in BCG-vaccinated populations. Objective:To determine whether BCG vaccination was associated with cancer rates in a secondary analysis of a BCG vaccine trial. Design, Setting, and Participants:Retrospective review (60-year follow-up) of a clinical trial in which participants were assigned to the vaccine group by systematic stratification by school district, age, and sex, then randomized by alternation. The original study was conducted at 9 sites in 5 US states between December 1935 and December 1998. Participants were 2963 American Indian and Alaska Native schoolchildren younger than 20 years with no evidence of previous tuberculosis infection. Statistical analysis was conducted between August 2018 and July 2019. Interventions:Single intradermal injection of either BCG vaccine or saline placebo. Main Outcomes and Measures:The primary outcome was diagnosis of cancer after BCG vaccination. Data on participant interval health and risk factors, including smoking, tuberculosis infection, isoniazid use, and other basic demographic information, were also collected. Results:A total of 2963 participants, including 1540 in the BCG vaccine group and 1423 in the placebo group, remained after exclusions. Vaccination occurred at a median (interquartile range) age of 8 (5-11) years; 805 participants (52%) in the BCG group and 710 (50%) in the placebo group were female. At the time of follow-up, 97 participants (7%) in the placebo group and 106 participants (7%) in the BCG vaccine group could not be located; total mortality was 633 participants (44%) in the placebo group and 632 participants (41%) in the BCG group. The overall rate of cancer diagnosis was not significantly different in BCG vaccine vs placebo recipients (hazard ratio, 0.82; 95% CI, 0.66-1.02), including for lymphoma and leukemia. The rate of lung cancer was significantly lower in BCG vs placebo recipients (18.2 vs 45.4 cases per 100 000 person-years; hazard ratio, 0.38; 95% CI, 0.20-0.74; P = .005), controlling for sex, region, alcohol overuse, smoking, and tuberculosis. Conclusions and Relevance:Childhood BCG vaccination was associated with a lower risk of lung cancer development in American Indian and Alaska Native populations. This finding has potentially important health implications given the high mortality rate associated with lung cancer and the availability of low-cost BCG vaccines.

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

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

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