Monitoring Iron Supplementation

Miller SM, McPherson RJ, and Juul SE. Iron Sulfate Supplementation Decreases Zinc Protoporphyrin to Heme Ratio in Premature Infants. J Pediatr (Jan 2006); 148:44-48. [Full Text] [PDF] [Editorial])

Objectives: To test the utility of zinc protoporphyrin to heme ratio (ZnPP/H) as an indicator of iron status in premature infants and to evaluate the effect of oral iron supplements on oxidative injury. We hypothesized that iron sulfate supplementation would decrease the ZnPP/H in preterm infants.

Study design: Infants eligible for this prospective study were: hospitalized, 24 to 32 weeks of gestation, 7 to 60 days old, feeding ≥ 70mL/kg/d, with a ZnPP/H ≥ the mean for age. Iron dose was determined by the ZnPP/H. Iron status and oxidative injury were evaluated at study entry and completion. Concurrent control subjects met entry criteria but were not enrolled and were not treated with iron during the study interval. Statistical evaluation included repeated measures analysis of variance and Z-score conversions.

Results: Entry ZnPP/H of iron-treated subjects (n = 16) and control subjects (n = 16) were not different. The ZnPP/H of iron-treated infants was lower at study end (P < .05) but did not change in control infants. Iron treatment (3 to 12 mg/kg/day) was not associated with changes in conventional measures of iron status nor in measures of oxidative injury.

Conclusions: Iron sulfate supplementation (3-12 mg/kg/d) decreases ZnPP/H, is tolerated, and is not associated with increased oxidative injury.

Comments: Iron deficiency is a universal problem in premature infants. It not only causes anemia, but it is also associated with cognitive deficits later in life. Serum transferrin is NOT a sensitive indicator of tissue iron depletion in preemies. When iron is not available, the body makes ZnPP instead of heme. The ratio of ZnPP to heme turns out to be a very sensitive measure of iron status in premature infants. As explained in the accompanying editorial, the measurement of ZnPP/H requires only 50 microliters of blood, is inexpensive, and takes only a few minutes to run. Based on the results of this preliminary study, it appears that would benefit from higher levels of iron supplementation than we currently use. ABK.

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