Neonatal Haematology. Irene RobertsЧитать онлайн книгу.
blood cell metabolism in the fetus and neonate
There are major differences between the metabolism of fetal or neonatal red blood cells and that of adult red blood cells. These differences affect not only the functional properties of the red cells of healthy fetuses and neonates but also the clinical impact of inherited and acquired red cell disorders. Both the glycolytic pathway and the pentose phosphate pathway are affected (see Table 1.1). Overall, glycolysis and glucose consumption are lower in neonatal red blood cells than in adult red blood cells. This occurs despite the increased activity of most glycolytic pathway enzymes, such as glucose‐6‐phosphate dehydrogenase (G6PD), pyruvate kinase and lactate dehydrogenase (LDH), and is thought to be the result of reduced phosphofructokinase activity. Neonatal red cells also have less ability to generate the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) via the pentose phosphate pathway and have lower levels of glutathione peroxidase than adult red blood cells. The net result is that neonatal red blood cells are more susceptible than adult cells to oxidant‐induced injury.46
In addition, neonatal red blood cells have a lower level of methaemoglobin reductase (about 60% of that in adult red blood cells). Methaemoglobin levels are therefore slightly higher in neonates than in adults (mean 4.3 g/l in preterm neonates, 2.2 g/l in term neonates and 1.1 g/l in adults).35 Neonates are also more likely to develop methaemoglobinaemia because they are susceptible to the toxic effects of chemicals, such as nitric oxide and local anaesthetics, that oxidise haemoglobin‐derived iron more rapidly than the maximal possible rate of methaemoglobin reduction (see Chapter 2, Case 2.7).
Iron metabolism in the fetus and neonate
Although stores of iron are adequate at birth in term babies born to well‐nourished mothers, this is not always the case in preterm neonates. This is because the majority of fetal total body iron is stored during the third trimester. Estimates have shown that total body iron increases from 35–40 mg at 24 weeks’ gestation to 225 mg at term, with the result that preterm neonates, especially those with IUGR, are born with lower iron stores than term neonates.47,48 These amounts of iron are equivalent to 6 months iron store for a term neonate49 but only around 2 months for extremely preterm neonates unless they are given supplementary iron. In addition, preterm neonates have an increased requirement for iron both because of their rapid growth rate and because of frequent phlebotomy.50,51 Therefore, preterm neonates generally develop iron deficiency after 2–4 months if the recommended daily intakes are not maintained.52 Administration of iron supplements to preterm babies leads to a slightly higher haemoglobin concentration (Hb) and improved iron stores, thereby reducing the risk of subsequent iron deficiency anaemia.53 The recommended iron intake of preterm infants with a birthweight of 1500–2000 g is 2 mg/kg/day from 2 to 4 weeks of life using iron‐containing human milk fortifier or preterm formula milk and/or iron supplements until at least 6 months of age.54 For very low birthweight neonates, a higher daily iron intake (2–3 mg/kg/day) is usually recommended, starting at 2 weeks of age.54
The regulation of iron status in the neonate, even in those who are born extremely preterm, has recently been shown to depend on the action of hepcidin, erythroferrone (ERFE), ferroportin and EPO, as in adults.55,56 Thus, hepcidin falls when iron deficiency develops, facilitating increased iron absorption, while hepcidin is upregulated when iron stores are sufficient, triggering degradation of the iron exporter ferroportin, which results in inhibition of iron absorption and mobilisation.57 Like serum ferritin, hepcidin levels increase with gestational age and in parallel with the increasing iron stores.58 Hepcidin and pro‐hepcidin levels in term and preterm infants vary in response to inflammation, infection and red blood cell transfusion.59–61 ERFE, an erythroid hormone, acts as a direct suppressor of hepcidin expression in the liver in response to EPO. Little is known about the role of ERFE in regulating iron metabolism in neonates but some preliminary data suggest that although the components of the EPO–ERFE–hepcidin–ferroportin axis are present in neonates,55 ERFE‐mediated suppression of hepcidin is impaired, at least in preterm neonates.62
Normal values for red blood cell parameters in the fetus and neonate
Haemoglobin concentration and red blood cell indices
Typical normal values for red cell variables in the fetus and neonate are shown in Tables 1.2 and 1.3.63–68 At birth, the Hb in term infants is high (140–215 g/l), which compensates for the low oxygen concentration in the fetus. The range of normal values for Hb and haematocrit have been updated to reflect the changes in neonatal medicine, including the lower limit of gestation of neonates admitted for neonatal intensive care. Jopling et al. published the results of a retrospective study of archived laboratory measurements of Hb and haematocrit from approximately 25 000 neonates analysed on the same equipment in a single group of hospitals between 2002 and 2008.69 They found an approximately linear increase in both Hb and haematocrit between 22 weeks’ and 40 weeks’ gestation calculated from samples collected within 6 hours of birth. In contrast to adults, no differences in Hb or haematocrit were seen between male and female neonates.
Table 1.2 Impact of gestational age at birth on the principal blood count parameters in healthy neonates*
| Gestation at birth | Term (≥37 weeks) | 30–36 weeks | 26–29 weeks | <26 weeks |
|---|---|---|---|---|
| Erythropoiesis | ||||
| Hb (g/l) | 140–215 | 130–215 | 115–200 | 115–185 |
| Hct (l/l) | 0.43–0.65 | 0.40–0.42 | 0.30–0.58 | 0.30–0.57 |
| MCV (fl) | 98–115 | 100–117 | 103–130 | 104–133 |
| MCH (pg) | 32.5–39 | 33.5–40.5 | 33.5–43 | 34.5–44.5 |
| NRBC | ||||
| /100 WBC | ≤5 | ≤25 | ≤25 | ≤25 |
| ×109/l | <1.0 | 1.0–2.0 | 2.0–3.0 | 2.0–3.0 |
| Leucocytes (×10 9 /l) |
|