Zinc supplementation in infants born small for gestational age reduces mortality: A prospective, randomized, controlled trial

Background. Low birth weight infants have been noted to have low zinc conce ntrations in cord blood, and zinc deficiency in childhood is associated wit h reduced immunocompetence and increased infectious disease morbidity. This study investigates whether zinc supplementation of infants born full term and small for gestational age affects mortality. Methods. A randomized, double-blind, controlled trial with 2-by-2 factorial design enrolled 1154 full-term small for gestational age infants to receiv e in syrup 1 of the following: riboflavin; riboflavin and zinc (5 mg as sul fate); riboflavin, calcium, phosphorus, folate, and iron; or riboflavin, zi nc, calcium, phosphorus, folate, and iron. A fixed dosage of 5 mL per child was given daily from 30 to 284 days of age. Household visits were made 6 d ays per week to provide the syrup and conduct surveillance for illness and death. When a child's death was reported, parental reports and medical reco rds were used to ascertain the cause. The effects of zinc and of the combin ation of iron, folate, calcium, and phosphorus were analyzed by intent to t reat. The mortality analysis was performed using a survival analytic approa ch that models time until death as the dependent variable; all models had 2 terms as independent variables: 1 for the zinc effect and 1 for the vitami n and mineral (calcium and phosphorus, folate and iron) effect. Results. Zinc supplementation was associated with significantly lower morta lity, with a rate ratio of 0.32 (95% confidence interval: 0.12-0.89). Calci um, phosphorus, folate, and iron supplementation was not associated with a mortality reduction, although a statistically nonsignificant trend toward r eduction was observed with a rate ratio of 0.88 (95% confidence interval: 0 .36-2.15). Conclusion. Zinc supplementation in small for gestational age infants can r esult in a substantial reduction in infectious disease mortality.