Randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams: neurocognitive development at 5.3 years' corrected age.

Background: Iron deficiency in early childhood may impair neurodevelopment. In a masked, randomized, controlled trial of early versus late enteral iron supplementation in preterm infants with birth weights of <1301 g, early iron supplementation reduced the incidence of iron deficiency and the number of blood transfusions.

Objective: We sought to examine whether early enteral iron supplementation improves neurocognitive and motor development in these infants.

Methods: Children who participated in the above mentioned trial were evaluated by applying the Kaufmann Assessment Battery for Children and the Gross Motor Function Classification Scale at the age of school entry.

Results: Of the 204 infants initially randomized, 10 died and 30 were lost to follow-up. A total of 164 (85% of the survivors) were evaluated at a median corrected age of 5.3 years. In this population (n = 164), the mean (+/-SD) mental processing composite in the early iron group was 92 (+/-17) versus 89 (+/-16) in the late iron group. An abnormal neurologic examination was found in 17 of 90 versus 26 of 74, and a Gross Motor Function Classification Scale score of >1 was found in 2 of 90 versus 5 of 74, respectively. Fifty-nine of 90 children in the early iron group were without disability, compared with 40 of 74 in the late iron group. Severe disability was found in 5 of 90 versus 6 of 74 children and 67 of 90 versus 49 of 74 qualified for regular schooling, respectively.

Conclusions: Early enteral iron supplementation showed a trend toward a beneficial effect on long-term neurocognitive and psychomotor development and showed no evidence for any adverse effect. Because the initial study was not designed to evaluate effects on neurocognitive development, the power was insufficient to detect small but potentially clinically relevant improvements. Additional studies are required to confirm the trend towards a better outcome observed in the early iron group.