Reticulocyte hemoglobin content as a marker of iron deficiency in premature newborns with very low birth weight. A simple tool for diagnosing iron deficiency

Abstract

Reticulocyte hemoglobin content (RET-He) is a promising marker of iron deficiency (ID) in newborns. Objective: to determine the diagnostic value of RET-He as a marker of ID in premature newborns with very low birth weight (VLBW). We conducted a single-center retrospective cohort study, which included 66 premature infants admitted to the National Medical Research Center for Obstetrics, Gynecology and Perinatology named the Academician V.I. Kulakov of the Ministry of Healthcare of the Russian Federation. Data were obtained from January 2016 to December 2018. The gestational age ranged from 29 to 32 weeks. Laboratory examination included blood tests on the 1st and 3rd day of life, then every 10–14 days until the day of life, then every 10–14 days the Institute of Neonatology and Pediatrics; discharge from hospital, and the measurements of serum iron, ferritin, transferrin on the 7th until the discharge from hospital. This clinical study was approved by the Biomedical Research Ethics Committee (Minutes No.12 of 17 November 2016) and the Scientific Council (Minutes No.19 of 29 November 2016) of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after the Academician V.I. Kulakov of Ministry of Healthcare of the Russian Federation. RET-He was the highest at birth and declined gradually thereafter in premature newborns reaching the lowest values after 3 weeks of life (median (interquartile range) 28.4 (25.8–34.8) pg (on the 1st day of life – 40.0 (35.7–41.9) pg and 33.5 (29.2–36.6) pg at the time of discharge). A low RET-He level was associated with low reticulocytes, with no changes in hemoglobin. There was a positive correlation between RET-He and MCH. D-He decreased from 1 to 42 days of life as a marker of increasing anemia. There was a negative correlation between RET-He and Hypo-He (p < 0.005). Starting from 42 days of life, or by the time of discharge, 32% of premature infants (n = 21) had a low ferritin level and 77% (n = 51) of premature infants had a low RET-He level, of which 21 infants developed ID (a positive correlation between RET-He and ferritin after 42 days of life (r = 0.34, p = 0.046)). There was no correlation between RET-He and ferritin in newborns without ID. Also, there were no correlations between RET-He and iron and RET-He and transferrin. After 42 days of life, RET-He less than 28.4 pg was a marker of ID (sensitivity 83.3% and specificity 93.7%). Low RET-He, D-He, RBC-Hе and high microR, Hypo-He were the earliest markers of ID in premature infants which predicted a decrease in serum iron and ferritin levels. RET-He, D-Не and Hypo-He are biomarkers with accurate diagnostic value of ID in premature infants with VLBW.