Reference Ranges of Reticulocyte Haemoglobin Content in Preterm and Term Infants: A Retrospective Analysis

Abstract

Background: Despite iron supplementation, some preterm infants develop iron deficiency (ID). The optimal iron status parameter for early detection of ID has yet to be determined. Objective: To establish reference ranges for reticulocyte haemoglobin content (Ret-He) in preterm and term infants and to identify confounding factors. Methods: Retrospective analyses of Ret-He and complete blood count in infants with a clinically indicated blood sample obtained within 24 h after birth. Results: Mean (SD) Ret-He was 30.7 (3.0) pg in very preterm infants with a gestational age (GA) of <30 weeks (n = 55), 31.2 (2.6) pg in moderately preterm infants (GA 30-36 weeks, n = 241) and 32.0 (3.2) pg in term infants (GA ≥37 weeks, n = 216). The 2.5th percentile of Ret-He across all GA groups was 25 pg, with a weak correlation between Ret-He and GA (r = 0.18). Moreover, only weak/no correlations were found between Ret-He and C-reactive protein (r = 0.18), interleukin 6 (IL-6) (r = 0.03) and umbilical artery pH (r = -0.07). There was a slight variation in Ret-He with mode of delivery [normal vaginal delivery: 32.3 (3.2) pg, secondary caesarean section (CS): 31.4 (3.0) pg, instrumental delivery: 31.3 (2.7) pg and elective CS: 31.2 (2.8) pg]. Conclusion: GA at birth has a negligible impact on Ret-He, and the lower limit of the normal reference range in newborns within 24 h after birth can be set to 25 pg. Moreover, Ret-He seems to be a robust parameter which is not influenced by perinatal factors within the first 24 h after birth.

Reticulocyte Haemoglobin Content Declines More Markedly in Preterm than in Term Infants in the First Days after Birth

“…For all infants with a Ret-H e value below the reference range of <25 pg [3], we checked if the MCV values were within the GA-specific reference ranges [2]. Out of 10 infants with a Ret-H e of <25 pg, 8 had MCV values within the reference range, 1 had an MCV value below the reference range, and 1 had an MCV value above the reference range.…”

“…However, the postnatal changes in Ret-H e , which are more pronounced in preterm than in term infants, need to be taken into account when using Ret-H e as an iron status parameter within the first days after birth. The reference range (2.5th and 97.5th percentile) for Ret-H e in term and preterm infants within 24 h of birth is 25-37 pg [3]. The postnatal decline in Ret-H e observed in this study population was substantial, but future studies are needed to answer the question whether this finding is actually of clinical relevance and should therefore influence treatment decisions.…”

“…The original study had the aim of establishing GA-specific reference ranges for Ret-H e and identifying possible confounding factors directly after birth [3]. …”

“…Other common parameters such as ferritin or mean corpuscular volume (MCV) are highly influenced by either coexisting inflammatory conditions or the physiological shift from foetal to adult erythropoiesis, thus limiting their applicability during neonatal intensive care [2]. Ret-H e reference ranges in the first 24 h after birth are slightly lower in very preterm than in term infants [3]; this may even become more pronounced in the days that follow. It is known from recent studies that Ret-H e quickly drops after birth [4,5], but to what extent and if this is influenced by gestational age (GA) is less clear.…”

Defining Normal Healthy Term Newborn Automated Hematologic Reference Intervals at 24 Hours of Life

“…14 Yet, GA has a negligible impact on RET-He levels. 15 Platelet counts mildly increase with GA and the IPF decreases. [16][17][18] Reviewing the work of Mouzinho et al 19 and Manroe et al 20 with healthy newborns revealed that neutrophil counts in low-birthweight preterm newborns weighing less than 1500 g were lower and had a wider range of distribution than in larger, term newborns.…”