Irene Roberts - Neonatal Haematology

Hb, haemoglobin concentration; Hct, haematocrit; MCH, mean cell haemoglobin; MCV, mean cell volume, NRBC, nucleated red blood cell.

Table 1.3 Impact of postnatal age on Hb and Hct values in healthy term and preterm neonates *

*Values are based on reference ranges in Christensen et al . 2009. 63

Hb, haemoglobin concentration; Hct, haematocrit;

In the absence of red cell transfusion, the Hb and haematocrit fall over the first few weeks of life due to the physiological reduction in red blood cell production. In term babies, the average Hb falls from 180 g/l at birth to 140 g/l at the age of 4 weeks, 69reaching a nadir of around 100 g/l at 2 months of age. Studies of healthy preterm infants carried out almost 50 years ago reported a more rapid fall in Hb than in term babies, reaching a mean of 65–90 g/l at 4–8 weeks postnatal age (reviewed in reference 35). However, these differences are difficult to interpret because of the variable clinical course of preterm infants and the effects of red cell transfusion, particularly in neonates of less than 26 weeks’ gestation at birth. More recently, data from non‐transfused neonates have confirmed the lower Hb nadir in preterm neonates, with a mean Hb 28 days after birth of approximately 105 g/l in neonates with a gestational age at birth of 29–36 weeks and 130 g/l for term neonates. 69

The mean cell volume (MCV) of red blood cells in healthy neonates at birth is higher than that in older children and adults and is inversely proportional to gestational age ( Table 1.2). 63,68The average MCV of a term neonate is about 105 fl, while extremely preterm neonates with a gestational age of less than 26 weeks typically have an MCV averaging about 120 fl. 63Similarly, the mean cell haemoglobin (MCH) at birth is higher in preterm neonates than in term neonates, averaging 40 pg in a preterm neonate of less than 26 weeks’ gestation and about 36 pg in a term neonate. 63The MCV, but not MCH, has been reported to be significantly lower in black preterm compared with white preterm neonates, although this may reflect a higher prevalence of α thalassaemia trait in these neonates as this was not specifically investigated. 70In contrast to the MCV and MCH, the mean cell haemoglobin concentration (MCHC) does not change significantly during gestation 70and, unlike in older children, changes in MCHC are not very useful for diagnostic purposes in neonates. In term babies, the MCV and MCH fall slowly over the first few weeks of life, with a lower limit of normal of 77 fl and 26 pg, respectively. 63The same pattern is seen in preterm neonates although the high frequency of red cell transfusions means that reliable data are not available.

Two newly available automated red cell parameters generated as part of a full blood count, MicroR and HYPO‐He, have recently been evaluated in neonates. 71In adult red blood cells, MicroR provides an automated measure of the percentage of red blood cells with an MCV of <60 fl and HYPO‐He measures the percentage of red blood cells with an MCH of <17 pg. Bahr and colleagues created new reference ranges for neonates based on analysis of more than 11 000 blood counts and used them to show that a combination of MicroR and HYPO‐He was more sensitive than MCV/MCH in identifying iron deficiency at birth. 71Further validation of these results in prospective studies and assessment of the impact of gestational age will be needed to determine the value of these new parameters in the diagnosis of neonatal iron deficiency and anaemia.

The reticulocyte count falls rapidly after birth as erythropoiesis declines. In term babies it then starts to increase at 7–8 weeks of age, reaching 35–200 × 10 9/l (1–1.8%) at 2 months of age; in preterm babies it increases at 6–8 weeks of age. 35Neonatal reticulocytes, like mature neonatal red blood cells, have a larger volume and lower Hb than adult reticulocytes. 35Manual reticulocyte counts have now largely been replaced by automated reticulocyte counts based on cell size and ribonucleic acid (RNA) content. Automated reticulocyte counts also provide a measure of the fraction of reticulocytes with the highest RNA content (Immature Reticulocyte Fraction [IRF]), which has been used in neonates to determine whether or not there is increased erythropoietic activity, for example in response to EPO treatment or as a diagnostic aid to haemolysis. 72–74

Normal ranges for the numbers of circulating nucleated red blood cells (NRBC) in neonates have been compiled by Christensen et al . 66and are generally higher in preterm neonates (2–3 × 10 9/l) than in term neonates (about 1 × 10 9/l) (see Table 1.2). Although modern analysers are increasingly able to generate accurate absolute NRBC counts, a useful guide from examination of blood films is that the presence of up to 5 NRBC/100 white blood cells in a term baby and up to 25 NRBC/100 white blood cells in a preterm baby can be considered normal for the first 1–2 days of life. In fact, there seems to be no difference between results obtained when the manual and automated methods are compared. 75The number of NRBC in the peripheral blood falls rapidly over the first week of life and these cells are no longer seen after the second week of life. By contrast, circulating erythroblasts are increased in a variety of conditions in neonates and their presence can therefore be useful diagnostically because they usually indicate increased erythropoiesis driven either by anaemia or by chronic intrauterine hypoxia, for example due to IUGR ( Table 1.4and Fig. 1.10). It should be noted that NRBC also appear in the peripheral blood as part of a leucoerythroblastic picture, most typically in response to acute perinatal hypoxia ( Fig. 1.11). 76,77

Even in freshly taken samples, the morphology of neonatal red blood cells is distinctly different to that of adult cells. 35,78The most typical morphological feature that differs from what is observed at other times of life is the presence of echinocytes (see Fig. 1.8). In healthy neonates, the proportion of echinocytes in blood films made from samples collected during the first week of life is inversely proportional to gestational age at birth. Echinocytes gradually disappear from the peripheral blood film over the first few weeks of life so that even very preterm neonates will have few circulating echinocytes by 4 weeks of age ( Fig. 1.12). This, together with the universal presence of echinocytes in very preterm neonates, strongly suggests that the changes reflect the unique differences in the cell membrane and metabolism of fetal red blood cells. Indeed, echinocytes are not a useful indicator of red cell pathology in neonates. Instead, other morphological indicators of red cell pathology, such as spherocytes, elliptocytes, target cells and occasionally acanthocytes, are a more reliable diagnostic guide (see Chapter 2).

Table 1.4 Causes of increased numbers of circulating nucleated red blood cells (erythroblasts) in term and preterm neonates

*The increase in circulating erythroblasts is even higher in Down syndrome neonates with transient abnormal myelopoiesis than in Down syndrome neonates in general.