Zinc Protoporphyrin-to-Heme Ratio and Ferritin as Measures of Iron Sufficiency in the Neonatal Intensive Care Unit

Abstract

Objectives: To evaluate ferritin and zinc protoporphyrin-to-heme (ZnPP/H) ratios as biomarkers of iron status in neonates, determine how specific clinical events affected these measures, and assess how iron status changed during hospitalization.

Study design: We performed a retrospective study of all infants with paired ferritin and ZnPP/H measurements between October 2014 and May 2016. Concordance of these measurements, effects of sepsis, red blood cell transfusion, erythropoietin treatment, and iron supplementation were assessed. Iron status was measured over time.

Results: A total of 228 patients (mean birth weight 1.3 kg, median gestational age 29 weeks) were evaluated. Mean log ZnPP/H values in infants with and without sepsis were not significantly different (4.98 µmol/mol vs 4.97 µmol/mol, adjusted P = .103), whereas log-transformed ferritin values increased significantly during infection (5.23 ng/mL vs 4.04 ng/mL, adjusted P < .001). Ferritin also increased more significantly than ZnPP/H following red blood cell transfusion (ferritin: mean 5.03 ng/mL vs 4.0 ng/mL, P < .001; ZnPP/H: mean 4.85 µmol/mol vs 4.98 µmol/mol, P < .001). The mean iron supplementations at 30, 60, and 90 days were 5.4, 6.9, and 7.4 mg/kg/day, respectively. Ferritin values decreased with advancing postnatal age (adjusted P < .001), with 66% of ferritin values less than 76 ng/mL. Treatment with erythropoietin increased ZnPP/H, but not ferritin levels.

Conclusions: Ferritin is more significantly affected by inflammatory events such as sepsis and transfusion than ZnPP/H, thus, ZnPP/H may be a more reliable marker of iron status in this population. Infants showed worsening iron sufficiency over time despite supplementation above American Academy of Pediatrics guidelines.

Keywords: NICU; ferritin; iron; iron sufficiency; neonates; zinc protoporphyrin-to-heme ratio.