Bacille Calmette Guérin Immunisation at Birth and Childhood Morbidity in Danish Children.
Condition: Prospective; Single-blind; Clinical; Trial; Intervention
Intervention: BCG-vaccine (SSI)
Intervention MeSH terms: BCG Vaccine
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 4262.0
Sex: All
Maximum age: 7 Days
Healthy volunteers: No

Summary:

      In high-income societies the use of health care and medication is steadily increasing.
      Children have high morbidity, many visits at the general practitioner, an increasing number
      of hospitalisations, and an increasing use of medication. And, when children are ill, someone
      has to stay home to care for them. An un-explained global increase in the incidence of the
      allergic diseases eczema, wheezing, asthma and allergies means that 25% of high-income
      populations are affected. Cheap preventive measures are highly warranted. Recent studies have
      shown a positive, non-specific effect of early Bacille Calmette Guérin (BCG) immunisation on
      neonatal mortality in low-income countries and suggested a positive, non-specific effect on
      allergic disease in high-income countries. "Non-specific" means that the vaccine effect goes
      beyond prevention of the targeted disease, i.e. the BCG vaccine benefits the health status of
      the immunised individual in ways unrelated to protection against tuberculosis (TB). For
      instance, in a recent randomised trial in West Africa the investigators showed that the BCG
      vaccine at birth was safe in low birth weight (LBW) infants and significantly reduced
      neonatal mortality in these children, with a significant long-lasting effect on infant
      mortality in the smallest newborns with a birth weight <1.5 kg. There is an urgent need to
      explore the huge potential of the BCG's beneficial immune-stimulatory effects among children
      in high-income populations.

      Therefore, the investigators will carry out a large prospective randomised clinical trial in
      Denmark primarily designed to test the hypothesis that infants who get the BCG vaccine at
      birth experience 20% fewer hospitalisations during early childhood.

      Secondary outcomes

        1. To test the hypothesis that infants who get the BCG vaccine at birth are prescribed less
           antibiotics during early childhood than non-BCG-immunised infants.

        2. To test the hypothesis that Danish infants who get the BCG vaccine at birth develop less
           eczema, asthmatic bronchitis/wheeze and food allergy at 3 and 12 months of age:
           self-reported, diagnosed by a physician, or found at clinical examination; and are
           prescribed less anti-eczema/asthma/allergy medication during early childhood than
           non-BCG-immunised infants.

        3. To test the hypothesis that infants who receive the BCG at birth respond in paraclinical
           measures: Specific IgE, thymic gland size, leucocyte count and differentiation, monocyte
           memory, cytokine profiles, and antibody titres following immunisation against
           diphtheria, tetanus, pertussis, pneumococcus, hemophilus.

        4. To test the hypothesis that infants who get the BCG vaccine at birth respond in growth
           measures: weight, length and head circumference.

        5. To test the hypothesis that infants who get the BCG vaccine at birth respond with
           decreased morbidity: common cold, pneumonia, febrile episodes, diarrhoea and vomiting,
           acute otitis media, febrile convulsions.

        6. To test the hypothesis that premature infants with gestational age less than 37 weeks
           who get the BCG vaccine at birth have unaffected psychomotor development measures: Ages
           and Stages scores.

        7. To test the hypothesis that infants who get the BCG vaccine at birth has unaffected
           coverage with the subsequent vaccinations in the Child Vaccination Programme.

        8. To test the above mentioned hypotheses specifically in the strata of premature and
           low-birth-weight Danish infants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All parents planning to give birth at Rigshospitalet, Hvidovre Hospital and Kolding
             Hospital will receive at letter during 2nd/3rd trimester of pregnancy with information
             on the study and be offered inclusion in the study.

        Exclusion Criteria:

          -  Infants born before gestational age 32 weeks and/or birth weight < 1000g, infants with
             known congenital disease, anomaly or malformation, immune deficiency and HIV, will be
             excluded. Non-Danish speaking parents will be excluded.