Extremely low birth weight infants have decreased blood levels of Vitamin A. This Vitamin A
deficiency may increase the risk of infections and chronic lung disease in these infants.
This study will examine the effects of Vitamin A supplementation in premature babies born
weighing less than 1500 grams (3.3 lbs).
Vitamin A and its derivative retinoic acid (RA) have been recognized as important factors in
potentiating the immune response and protecting against infection. In developing nations,
Vitamin A deficiency is associated with infectious gastroenteritis and increased
susceptibility to a number of infections, such as measles. RA is an important regulator of
cell growth and differentiation and can augment IgM production from core blood mononuclear
cells in response to a polyclonal B-cell activator. This augmentation in immunoglobulin
secretion is mediated by the effects of RA on both T and B cells, in part through the
production of certain cytokines (e.g., IL-6 and IL-10) important in the terminal
differentiation of B-cells to plasma cells. In animal models, correction of Vitamin A
deficiency improves immune response to vaccination.
Infants with extremely low birth weight have low plasma and tissue concentrations of Vitamin
A. Vitamin A supplementation of pre-term infants reduces chronic lung disease and the risk
of sepsis. Because the immune system of the pre-term infant is immature, the response of
pre-term infants to Hepatitis B vaccine is diminished compared to full-term babies. This
study will determine whether Vitamin A supplementation of pre-term infants will enhance the
response of these infants to immunization with Hepatitis B vaccine. The study will also
evaluate the effect of Vitamin A supplementation on survival, chronic lung disease, and
Low birth weight pre-term infants will be randomized to receive either Vitamin A
supplementation or placebo. The Vitamin A treatment group will receive 5,000 IU of Vitamin
A (retinyl palmitate) by intramuscular injection 3 times weekly for 28 days starting on
postnatal day 2. To avoid pain and discomfort, the placebo group will receive a sham
procedure rather than a placebo saline injection. The staff of the neonatal intensive care
unit will retain the responsibility for decisions regarding the use of other therapies, such
as parental fluids, mechanical ventilation, glucocorticoids, hyperalimentation, and blood
replacement. All infants will be assessed for potential Vitamin A toxicity. While in the
neonatal intensive care unit, infants will have blood tests at Days 0, 14, 30, and 60.
After discharge from the neonatal intensive care unit, patients return for clinic assessment
and blood samples at Months 4, 6, and 9. Infants will be given Hepatitis B vaccine at 2, 4,
and 6 months chronological age. Primary outcome measures will include Hepatitis B antibody
levels, chronic lung disease, rate of infection while in the neonatal intensive care unit,
and the incidence and severity of infections during the first 9 months of life.
- Born at less than 32 weeks gestation
- Weigh less than 1500 g (3.3 lbs) and more than 500 g (1.1 lbs)