Neonatal anemia
Introduction
Neonatal anemia is defined by a hemoglobin or hematocrit concentration of greater than 2 standard deviations below the mean for postnatal age.1 The etiology of neonatal anemia is commonly subdivided into three major categories: blood loss, decreased production, and increased destruction of erythrocytes (Box 1). Hematopoiesis in the fetus and neonate is in a constant state of flux and evolution as the newborn adapts to a new milieu.
Fetal erythropoiesis occurs sequentially during embryonic development in three different sites: yolk sac, liver, and bone marrow.2 Yolk-sac formation of red blood cells (RBCs) is maximal between 2 and 10 weeks of gestation. Myeloid (bone marrow) production of RBCs begins at around week 18 and, by the 30th week of fetal life, bone marrow is the major erythropoietic organ. At birth, almost all RBCs are produced in the bone marrow, although a low level of hepatic erythropoiesis persists through the first few days of life. RBC production in extrauterine life is controlled in part by erythropoietin (EPO) produced by kidney.
Hemoglobin, hematocrit, and RBC count increase throughout fetal life. Extremely large RBCs with an increased content of hemoglobin (Hb) are produced early in fetal life. The size and Hb content of these cells decrease throughout gestation, but the mean corpuscular hemoglobin concentration (MCHC) does not change significantly. During the neonatal period, the newborn leaves the relatively hypoxic in-utero environment and emerges into a different physiologic setting.
Section snippets
Physiologic anemia of infancy
When infants take their first breath, considerably more oxygen is available for binding to Hb, and Hb oxygen saturation increases from approximately 50% to 95% or more. The normal developmental switch from fetal to adult Hb synthesis actively replaces high-oxygen-affinity fetal Hb with low-oxygen-affinity adult hemoglobin, which can deliver a greater fraction of Hb-bound oxygen to the tissues. Therefore, immediately after birth the increase in blood oxygen content and tissue oxygen delivery
Anemia of prematurity
The physiologic anemia seen in preterm infants is more profound and occurs earlier than anemia of infancy. Various causes contribute to this condition. An important component in the first few weeks of life is blood loss due to sampling for the many laboratory tests that premature infants undergo. The erythropoietic response is also suboptimal, a significant problem because demands on erythropoiesis are heightened by the short survival of the RBCs from premature infants (approximately 40–60 days
Blood loss
Blood loss in neonates can occur before, during, or after delivery, and can account for 5–10% of all cases of severe neonatal anemia.16 Anemia frequently follows fetal blood loss, bleeding from obstetric complications, and internal hemorrhages associated with birth trauma.
Iatrogenic anemia due to repeated removal of blood for laboratory testing is common in premature infants. Most affected infants are asymptomatic but when losses approach 20% of total blood volume, signs and symptoms of
Diagnosis
Bleeding in the newborn is usually obvious because external bleeding can be perceived. It becomes difficult if the bleeding is not obvious. Rapidly developing anemia with hyperbilirubinemia and reticulocytosis, and absence of specific signs of the different types of hemolytic anemia, should lead to the diagnosis of internal bleeding. Thus the presence of signs of regeneration, without evidence of blood destruction, should lead to the suspicion of bleeding inside the body. A Kleihaur Betke's
Issues in transfusion
The goal of transfusion in infants with anemia of prematurity is to ‘restore or maintain oxygen delivery without increasing oxygen consumption’.38 Transfusion practices vary markedly across units and there is a lack of evidence-based studies to guide practice.39 None of the clinical signs has been consistently useful – either alone or as a group – in determining when to transfuse an infant with low hemoglobin of (physiologic) anemia of prematurity and iatrogenic losses. The decision to
Donor issues
A concern for infants who might need multiple transfusions is exposure to multiple donors. The use of multiple donors increases the risk of infection and transfusion reactions. Donor exposure can be reduced for infants who need small-volume transfusions (<15–20 ml/kg) by using stored packed red blood cells (PRBCs) from a single unit (Table 1). This unit is divided into multiple aliquots that are reserved for a specific infant. This procedure has reduced donor exposure to one or two donors for
Prevention of late nutritional anemia
Both term and preterm infants should be discharged from the hospital on supplemental iron, either as iron-fortified formulas or as an oral supplement of 2–3 mg/kg per day elemental iron for breastfed infants. Enteral iron supplementation is feasible and probably safe in infants with birth weight <1301 g.44 Iron supplementation can reduce the incidence of iron deficiency and the number of late blood transfusions.
Iron deficiency can occur in very low birthweight infants despite early
A diagnostic approach to the newborn with anemia
The establishment of an accurate diagnosis is essential to directing the appropriate therapeutic interventions. Thorough history taking and physical examination are the primary steps in identifying the condition and establishing an etiology, but further investigations in the form of laboratory testing are often required to differentiate the many possible causes.
References (52)
- et al.
Erythrocyte disorders in infancy
- et al.
Anemia of prematurity: determinants of the erythropoietin response
J Pediatr
(1984) Anemia of prematurity: the prospects for avoiding blood transfusions with recombinant erythropoietin
Adv Pediatr
(1993)- et al.
Premature infants require additional folate and vitamin B12 to reduce the severity of the anemia of prematurity
Am J Clin Nutr
(1994) - et al.
Vitamin E deficiency: a previously unrecognized cause of hemolytic anemia in the premature infant
J Pediatr
(1967) - et al.
Nutritional anemia in infancy
Clin Perinatol
(1995) Life-span of the fetal red blood cell
J Pediatr
(1967)- et al.
Assessment of anemia in newborn infants
Clin Perinatol
(1984) - et al.
Haemolytic disorders of infancy
Clin Haematol
(1978) - et al.
Iron in fetal and neonatal nutrition
Semin Fetal Neonatal Med
(2007)
Variation in blood transfusions among newborn intensive care units. SNAP II Study Group
J Pediatr
The use of erythropoietin in neonates
Clin Perinatol
Changing practices of red blood cell transfusion in infants with birth weights less than 1000 g
J Pediatr
Neonatal anaemia secondary to blood loss
Clin Haematol
The blood and hematopoietic system
Oral vitamin E supplementation for the prevention of anemia in premature infants, a controlled trial
Pediatrics
A randomized, controlled trial of the effects of adding vitamin B12 and folate to erythropoietin for the treatment of anemia of prematurity
Pediatrics
Effects of a combined therapy of erythropoietin, iron, folate, and vitamin B12 on the transfusion requirements of extremely low birth weight infants
Pediatrics
Erythropoietin for anemia in a preterm Jehovah's baby
Early Hum Dev
Double blind trial of recombinant human erythropoietin in preterm infants
Arch Dis Child
Meta-analysis of controlled clinical trials studying the efficacy of rHuEPO in reducing blood transfusions in the anemia of prematurity
Transfusion
Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants
Cochrane Database Syst Rev
Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants
Cochrane Database Syst Rev
Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants
Cochrane Database Syst Rev
Post-hemorrhagic anemia ad shock in the newborn: a review
Pediatrics
Quantitative studies of the human neonatal circulation. III. Observations on the newborn infant's central circulatory response to moderate hypovolemia
Acta Paediatr Scand
Cited by (68)
Optimizing haemoglobin measurements in VLBW newborns: Insights from a comparative retrospective study
2024, Early Human DevelopmentHematology of childhood and adolescence
2023, Encyclopedia of Child and Adolescent Health, First EditionNon-essential heavy metals and protective effects of selenium against mercury toxicity in endangered Australian sea lion (Neophoca cinerea) pups with hookworm disease
2022, Environment InternationalCitation Excerpt :Irrespective of hookworm status, significant positive associations for RBC, PCV, HGB and MCHC with higher Hg concentrations were seen in N. cinerea pups. The highest Hg concentrations in pups were immediately postpartum, when red blood cell parameters are at their peak, prior to the development of the ‘physiological anaemia of infancy’ (Halvorsen and Bechensteen, 2002) seen during the early stages of lactation and the early neonatal period (Aher et al., 2008; Weinhouse et al., 2017) and before the clinical impacts of hookworm infection are seen. Similar to the finding in N. cinerea, a significant positive association between red blood cell parameters and higher Hg concentrations were seen in Atlantic bottlenose dolphins (Tursiops truncatus), while absolute lymphocyte, eosinophil and platelet values decreased (Schaefer et al., 2011).
Transfusion in Neonatal Patients: Review of Evidence-Based Guidelines
2021, Clinics in Laboratory MedicineMedical physiological parameter for lead/vaccine testing
2021, The Design and Development of Novel Drugs and Vaccines: Principles and ProtocolsEpidemiological, therapeutic and prognostic of anemia amongst premature newborn babies in Centre Hospitalier d'Essos, Yaounde, Cameroon
2020, Journal de Pediatrie et de Puericulture