Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birthweight infants

Vitamin A is a group of fat-soluble compounds used by the body for regulation and promotion of growth and differentiation of many cells, including cells in the retina of the eye and the cells that line the lung. Preterm infants have low vitamin A levels at birth. This may contribute to an increased risk of developing chronic lung disease, and hence a requirement for oxygen. It is possible that additional vitamin A supplement may reduce complications of prematurity, including abnormal development of the retina (retinopathy), bleeding in the brain (intraventricular haemorrhage), and damage to the gut from inflammation (necrotising enterocolitis) as well as reducing respiratory infections. Too much vitamin A is potentially harmful as it can raise intracranial pressure and cause skin and mucous membrane changes (injury or lesions), and vomiting. Nine trials were included in this review, eight comparing vitamin A with a control (placebo or no supplementation) and one comparing different vitamin A regimens. Supplementing very low birthweight infants with vitamin A by intramuscular injection or in the milk formula was associated with a trend toward a reduced number of deaths or oxygen requirement at one month of age compared to placebo. For surviving infants with birthweight less than 1000 g (three trials, 824 infants of which at least 96% had a birthweight < 1000 g), fewer infants required oxygen at 36 weeks' postmenstrual age compared to the control; the number needed to treat for one to benefit was 13 (95% confidence interval 7 to 100). Three trials with information on retinopathy of prematurity suggested a trend towards reduced incidence in infants receiving vitamin A supplementation. The one trial that investigated neurodevelopmental status at 18 to 22 months of age correcting for prematurity found no evidence of benefit or harm associated with vitamin A supplementation compared to control. No adverse effects of vitamin A supplementation were reported, but it was noted that intramuscular injections of vitamin A were painful.