Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses
Brief Summary: Vitamin A supplementation (VAS) significantly reduces all-cause mortality when given after 6 months of age, but has a null or detrimental effect when given between 1-5 months. Studies of neonatal VAS (NNVAS) have produced conflicting findings. These age-pattern variations might result from immunological interactions between VAS and vaccines. The potential efficacy of NNVAS is being retested in 3 large new intervention trials with mortality as endpoint. Complementary mechanistic studies in animals and in human infants in The Gambia (this proposal) and Bangladesh have been commissioned to run in parallel.

The investigators will use a 2-arm double blind RCT to test whether NNVAS modulates the early ontogeny of human immune development. Neonates, recruited through a peri-urban clinic in The Gambia, will receive either 50,000 International Units (IU) VAS orally within 48 hours of birth (intervention group, n=100) or a placebo (control group, n=100). Male and female neonates will be randomized separately at enrolment for later analyses by sex. All infants will be followed up from birth to age 1 year. A broad panel of immunological outcomes will examine whether NNVAS: a). normalises thymic development (thymic index by ultrasound); b). skews mycobacterial and recall antigen responses towards a Th2 profile; c). diminishes Th1 and Th17 reactivity to mycobacterial and recall antigens; d). diminishes the tuberculin skin test (TST) response; e). causes increased innate immune reactivity; f). increases the frequency of circulating regulatory T cells (Tregs) expressing gut homing receptors; g). enhances B cell immune responses after routine vaccination (increase of B cell numbers and activation status); h). increases circulating IgA in mucosal immune compartment, especially oral polio vaccine (OPV) specific IgA post-vaccination; i). decreases bacterial translocation, by improving mucosal barrier function; and j). decreases markers of infection or inflammation. Growth and morbidity will also be assessed.


Options:
A: Inclusion Criteria:

* singleton birth,
* birth weight ≥1,500g,
* mother over 18 years willing to participate and residency within the study area.
* Birth vaccinations and vitamin A supplement must be administered within 48 hours of birth.

Exclusion Criteria:

* Infants having a congenital disease,
* a serious infection at birth
* an inability to feed (initially assessed by the lack of the suck reflex),
* mothers who are seriously ill at time of enrolment (defined as bed bound for more than 24 hours),
* mother participating in other studies,
* mothers who are HIV positive.
B: Inclusion Criteria:

* Infant receiving OPV and BCG within 48 hr of birth

Exclusion Criteria:

* Mother is less than 18 years of age
* Infant is part of a multiple birth
* Infant will likely not remain in the study area for the next 4 months
* Infant has a condition precluding vaccination
* Infant is unable to breastfeed or drink other fluids
* Birth weight is less than 1.5 kg
C: Inclusion Criteria: Belonging to the study area

Exclusion Criteria:Overt illness, signs of vitamin A deficiency, previous BCG vaccination
D: Inclusion Criteria:

* Previous enrolment in NCT00146302
* Living within Bandim Health Project study area

Exclusion Criteria:

* Children with known history of anaphylaxis
* Children with skin infections or severe skin conditions for who SPT could not be reliably performed
* Children currently taking anti-histamine medication

Answer: A