Second-Year Neonatology Fellow Children's Hospital of Richmond at VCU Richmond, Virginia, United States
Background: Iron is an essential mineral critical for brain development. Preterm infants have higher iron needs than term infants and are at a high risk for deficiency, which has potentially irreversible consequences. Traditional methods of identifying iron deficiency in neonates are limited in that they only become abnormal after deficiency has been present for some time. Reticulocyte Hemoglobin (Ret-He) shows promise for identifying iron deficiency earlier. We hypothesized that low Ret-He values would correlate with abnormal neurodevelopment in preterm infants. Objective: To determine how the severity, timing, and duration of low Ret-He impacts neurodevelopmental outcomes in preterm infants. Design/Methods: Infants born at < 37 weeks and admitted to the Children's Hospital of Richmond between 2019-2022 for ≥28 days and attended at least 1 of 3 neonatal follow-up visits were included in this retrospective study. Variables measured included demographics, gestational age (GA), illness severity, comorbidities, developmental support services, Ret-He, and standardized neurodevelopmental test scores (Test of Infant Motor Performance, Alberta Infant Motor Scale, Bayley Scales of Infant and Toddler Development, and Development Assessment of Young Children). Abnormal neurodevelopment (AbND) was defined as <-0.5 standard deviations on any individual test score. Low Ret-He was defined as < 29pg. Descriptive analysis, Mann-Whitney U-test, and repeated measures analysis of variance were used to analyze the data. Results: There were 141 infants in the analysis with a mean GA of 28.6 weeks ±3 (Table 1). There were 46 infants with normal neurodevelopment (NND) and 95 with AbND. Ret-He was low in 90 (64%) infants at some point during hospitalization, and 45 (32%) spent ≥28 days with low Ret-He. Mean Ret-He over 1-20 weeks was 31.1pg ±2.4 in NND infants compared to 29.8pg ±2.2 in AbND infants, p< 0.01 (Figure 2). NND infants had a significantly shorter duration of exposure to low Ret-He, spending a median of 12.7% of weeks with a low Ret-He compared to 25% in AbND Infants, p< 0.05 (Figure 3). The lowest Ret-He recorded in NND infants was a median of 28.8pg (IQR: 27.4, 31.8), compared to 27.2pg (IQR: 25.3, 29.3) in AbND infants, p< 0.01 (Figure 3).
Conclusion(s): Ret-He positively correlated with neurodevelopment scores via multiple measures. Lower average, lowest experienced, and duration of exposure to low Ret-He were all associated with adverse neurodevelopmental outcomes. These encouraging findings underscore the need for further studies on the utility of Ret-He in guiding individualized iron supplementation for preterm infants.