EFFECT OF COBALAMIN SUPPLEMENTATION IN INFANTS: A RANDOMIZED, CONTROLLED TRIAL

Abstract

INTRODUCTION: A metabolic profile that suggests impaired cobalamin status is prevalent in breastfed infants. Whether this profile reflects immature organ systems or cobalamin deficiency has not been clarified. OBJECTIVE: Our goal was to study serum cobalamin levels in breastfed infants. METHODS: This study included 107 apparently healthy infants who at the age of 6 weeks were randomly assigned to receive either an intramuscular injection with 400 μg of cobalamin or no intervention. Concentrations of cobalamin and folate in serum and total homocysteine (tHcy), methylmalonic acid (MMA), and cystathionine in plasma were determined at inclusion and at the age of 4 months. RESULTS: There was no significant difference in the concentrations of any vitamin marker between those in the intervention (n = 54) and control (n = 53) groups at 6 weeks (P = .20–.78). At the age of 4 months, infants who were given cobalamin had 75% higher serum cobalamin levels than those of controls. The intervention was associated with a remarkable reduction in median plasma tHcy (from 7.46 to 4.57 μmol/L) and MMA (from 0.58 to 0.20 μmol/L) (P < .001) levels, whereas both metabolite levels were essentially unchanged during follow-up in the control-group infants. CONCLUSIONS: Cobalamin supplementation of infants changed all markers of impaired cobalamin status (low cobalamin, high MMA and tHcy, and slightly elevated folate concentrations) toward a profile observed in cobalamin-replete older children and adults. Thus, high MMA and tHcy levels, reported for a large fraction of infants, do not reflect immature metabolism but, rather, insufficient cobalamin to fully sustain cobalamin-dependent reactions. Clinicians and researchers should address the possible developmental and clinical consequences of metabolic evidence of cobalamin deficiency in infants.