Paucity of clinical trials in iron deficiency: lessons learned from study of VLBW infants.

Pediatricians and hematologists alike should take keen interest in the report by Taylor and Kennedy in this issue of Pediatrics of a randomized, placebo-controlled study of daily oral iron supplementation in very low birth weight (VLBW) infants ,36 weeks’ postgestational age. Study subjects, managed according to relatively liberal transfusion guidelines, derived no benefit from the additional iron supplement of 2 mg/kg with regard to hematocrit (the primary outcome), reticulocyte count, or transfusion requirements. This result supports the concept that the need for 2 mg/kg per day of iron for low birth weight infants can be met by using iron-fortified formula or breast milk alone without medicinal iron supplementation. Two previous studies in this field were noted by Taylor and Kennedy to be inconclusive, whereas another investigation suggesting the need for iron supplementation was limited to infants whose birth weights were between 2000 and 2500 g. Taylor and Kennedy’s study, although well designed and well executed, does not provide the final word regarding the optimal method and timing of iron delivery to VLBW infants. The report failed to describe the specific types of iron used in the multivitamin with iron supplement and in the iron-fortified mother’s milk used in the study. Different forms of iron (Table 1) have different absorption profiles and toxicities. Moreover, both the benefits and potential adverse effects of medicinal iron supplements require additional study in VLBW infants, especially in settings in which transfusions are used less frequently and where outcomes other than hematocrit at 36 weeks’ postgestational age are assessed. The implications of this well-designed clinical trial involving VLBW infants are relevant to all infants and young children facing the risks of iron deficiency. Iron is required for all living cells, and a deficiency of this vital element therefore interferes appreciably with their function, regardless of whether they are erythroid progenitors, neurons, or cardiomyocytes. Thus, all pediatricians should be knowledgeable about optimal means to prevent iron deficiency by using effective feeding strategies in normal and VLBW neonates as well as later in infancy when iron requirements remain high due to continued rapid growth. Emphasis on prevention and early diagnosis of iron deficiency is critically important in older infants and toddlers just as it was in the VLBW infants studied by Taylor and Kennedy.1 Yet despite the many reports and recommendations from the American Academy of Pediatrics and others, prevention of iron deficiency is often not achieved. Too many exclusively breastfed infants fail to receive adequate supplemental iron after 5 or 6 months of age, and excessive quantities of whole cow’s milk constitute a large part of the diet of AUTHOR: George R. Buchanan, MD