Effect of vitamin A supplementation on morbidity of low-birth-weight neonates

Low-birth-weight (LBW) infants (< 2,500 g) are at increased risk of respiratory infection in the first few months of life and have low liver stores of vitamin A. As retinol is essential for respiratory epithelial cell differentiation, deficiency could result in pathological changes in the respiratory epithelium, with respiratory problems.

A randomised, double-blind, placebo-controlled trial to investigate the effect of vitamin A supplementation on the incidence and severity of respiratory infections in LBW infants during their first year of life.

One hundred and thirty LBW infants (gestational age < 36 weeks and birth weight 950-1,700 g) were enrolled in the study. The infants were randomly allocated to a vitamin A or placebo group. Infants in the vitamin A group received 25,000 IU of vitamin A (retinyl palmitate, Arovit drops, Roche, Basle, Switzerland) on study days 1, 4 and 8. Study day 1 was between 36 and 60 hours after delivery. Infants in the placebo group received a placebo (formulated by Roche) with a similar appearance and packed in the same dropper bottles as the vitamin A drops.

Vitamin A supplementation markedly improved serum retinol levels. After the last vitamin A dose, the vitamin A group had higher mean serum retinol concentrations than the placebo group (45.77 +/- 17.07 micrograms/dl v. 12.88 +/- 6.48 micrograms/dl, P = 0.0001). There was no evidence of improvement in neonatal or post-neonatal respiratory problems associated with vitamin A supplementation. Vitamin A and placebo groups did not differ in the occurrence or duration of respiratory distress or the need for head-box oxygen. There were also no significant differences in the cumulative probability of developing lower or upper respiratory tract infection through the first year of life. There was a slight suggestion of an increase in the risk of hospitalisation with pneumonia associated with vitamin A supplementation. The cumulative probability of being hospitalised with pneumonia by 6 months of age was 24.6% (7 hospitalisations) in the vitamin A group compared with 7.4% (2 hospitalisations) in the placebo group (log rank test P = 0.04). After adjusting for risk factors this difference was no longer significant.

Vitamin A supplementation in LBW neonates may not reduce incidence or severity of respiratory infections. These results do not negate the importance of improving vitamin A status in children as an important public health measure to reduce morbidity and mortality from other childhood infections.