Vitamin A Supplementation for Extremely-Low-Birth-Weight Infants

Infants with extremely low birth weights (≤1,000 g) have low plasma and tissue concentrations
of vitamin A, and vitamin A deficiency may predispose these infants to chronic lung disease.
A meta-analysis of clinical trials of vitamin A supplementation for preterm infants revealed
a 17% increase in the rate of survival without chronic lung disease, which approached
statistical significance.

This multi-site, randomized trial was conducted to determine the safety and effectiveness of
a higher dose of vitamin A than that used in previous trials in extremely-low-birth-weight
(ELBW) infants. We hypothesized that vitamin A supplementation would increase the rate of
survival without bronchopulmonary dysplasia and reduce the risk of sepsis.

Infants with birth weights from 401-1000g and who received mechanical ventilation or
supplemental oxygen at 24-96 hours of age were enrolled. Subjects were randomized to either
the vitamin A or a control group. Infants in the Vitamin A group were given a dose of 5000 IU
(0.1 ml) intramuscularly on Mondays, Wednesdays, and Fridays for four weeks. Control infants
received a sham procedure rather than placebo injections.

Serum vitamin A was measured in a central laboratory at base line and at 28 days in the first
300 infants. On study day 28 (two to three days after the last treatment and immediately
after a blood sample was collected), the relative dose-response was evaluated.

Inclusion Criteria:

- Infants wtih birth weights from 401-1,000g

- Receiving mechanical ventilation or supplemental oxygen at 24-96 hours of age

Exclusion Criteria:

- Major congenital anomalies

- Congenital nonbacterial infection

- Infants diagnosed with a terminal illness (as indicated by a pH below 6.80 or by the
presence of hypoxia with bradycardia for more than two hours)

- Infants who were to receive vitamin A in a parenteral fat emulsion or in doses
exceeding recommendations for multivitamin preparations