Effect of Iron Supplementation on Psychomotor Development of Non-anemic Exclusively or Predominantly Breastfed Infants: Randomized, Double-blind, Placebo-controlled Trial.

INTRODUCTION Iron is a nutrient of essential importance to the human organism. It takes part in energy production, oxygen transportation, and DNA synthesis and is indispensable for the development of the central nervous system. Iron is required for the myelination and production of neurotransmitters. It has been well documented that iron deficiency anemia (IDA) impairs child development. If the diagnosis of IDA is delayed, the deficits may be irreversible. Iron deficiency (ID) is the most common single nutrient deficiency and may affect 12% of children < 3 years of age in industrialized countries. ID has the potential to negatively influence psychomotor development. However, a causal relationship is not as clear as for IDA.

Previous studies have suggested that iron supplementation in healthy infants may enhance psychomotor development. A meta-analysis carried out by our group (Szajewska et al. ) aimed to evaluate the effects of iron supplementation in non-anemic pregnant women and in non-anemic healthy children aged <3 years on the mental performance and psychomotor development of children. The authors identified 7 randomized controlled trials (RCTs), 5 of which referred to supplementation during infancy. The polled results of 3 RCTs (n = 561) showed significant improvement on the Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development at approximately 12 months of age in the iron-supplemented group compared with the control group (mean difference: 4.21; 95% CI 2.31 to 6.12). No significant effect of iron supplementation on the Mental Developmental Index (MDI) or behavior was found. Since the meta-analysis was performed, one relevant new study has been published. In this follow-up study, cognitive and school performance was measured at the age of 9 years. In the original study, infants were randomized to receive daily supplementation of iron, zinc, iron and zinc or placebo from 4 to 6 months of age and an assessment of iron and zinc status, as well as growth, was performed. No statistically significant difference in cognitive performance or school performance was reported between the four groups.

Given that ID is a common problem in small children, measures to prevent ID are being taken. According to Committee of Nutrition of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN CoN), this should be achieved by the promotion of exclusive breastfeeding, the use of iron-fortified formulas when formula feeding is needed, the postponement of the introduction of whole cow milk as the main drink until the end of the first year of life, and the promotion of consumption of complementary foods rich in iron. More recently, the ESPGHAN CoN concluded that there is no convincing evidence that iron supplements should be provided to normal birth weight, exclusively breastfed infants during the first 6 months of life in populations with a low prevalence of IDA among 6-month-olds. In contrast, the American Academy of Pediatrics (AAP) recommends iron supplementation (1 mg/kg) in exclusively breastfed infants beginning at 4 months of age that should be continued until iron from complementary foods is available. Since in partially breastfed infants iron intake is uncertain, those who receive more than one half of their daily feedings as human milk, should also be supplemented with 1mg/kg iron beginning at 4 months.

Interventional studies of good methodological quality evaluating the role of iron supplementation of infants without anemia on their mental and psychomotor development are still needed.

MATERIALS AND METHODS