Iron supplementation in premature infants using the zinc protoporphyrin to heme ratio: short- and long-term outcomes

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The objective of this study was to determine the effect of incrementally higher doses of iron on the zinc protoporphyrin to heme ratio (ZnPP/H) and serum ferritin, and developmental outcomes in premature infants at risk for iron deficiency.


Infants eligible for this prospective, randomized blinded trial were between 27 and 30 completed weeks of gestation, older than 1 week of age and tolerating 100 ml kg−1 per day of enteral feedings. The control group was treated with 2.2 mg kg−1 per day of ferrous sulfate and the treatment group was treated with 3 to 12 mg kg−1 per day based on the ZnPP/H. Infants had follow-up with Bayley exams at 6 and 24 months corrected age. Statistical evaluation included Student's t-tests and Fisher's exact test.


Eighty-one infants were enrolled (40 control, 41 treatment). The average total iron dose for the control group was 2.2 mg kg−1 per day and for the treatment group was 10.4 mg kg−1 per day (P<0.05). The ZnPP/H was not different between the two groups. The ferritin at the end of the study was decreased in the control group but remained stable in the treatment group (control initial 202 ± 109 ng ml−1, final 168 ± 141 ng ml−1 (P<0.05); treatment initial 187 ± 131 ng ml−1, final 176±118 ng ml−1). At 24 months, infants with psychomotor development index <85 occurred in 25% of the subjects in the control group and in 7% of subjects in the treatment group in a post hoc analysis (odds ratio, 4.2; 95% confidence interval, 0.7 to 43, P = 0.07).


The ZnPP/H may not be a reliable marker of iron status when used in a short period of time during iron supplementation. Infants treated with a lower dose of ferrous sulfate had a decreasing serum ferritin and a trend toward increased motor delays at 24 months.

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