Anemia

The basic classification of neonatal anemia includes the following items:

• hemorrhagic anemia => blood loss (antenatal – perinatal – postnatal)
• hemolytic anemia (congenital vs. acquired) => increased destruction
• aplastic anemia => decreased production
• anemia of prematurity => specific to preterm infants

Erythropoiesis

Hemoglobin production begins around the third week of pregnancy in the cytoplasm of embryonic red blood cells in the yolk sac. Hematopoietic stem cells then colonize other organs and hematopoiesis takes up in the liver, kidneys, thymus, connective tissue (from 6 weeks) and later happens predominantly in the medullary cavity (from 11 weeks; at 24 weeks overtakes the red blood cell production in other parts).

Erythropoietin is produced in liver (from 11 weeks) and later predominantly in kidneys (its production increases after 34 weeks of gestation and in hypoxic conditions). There are significant differences in blood count between newborns (see below) and older children:

• normoblasts (first 3 days of life)
• shorter half-life of erythrocytes (preterm 60 days, term 90 days, adults 120 days)
• erythropoietin concentration plummets after birth
• fetal hemoglobin (80% of hemoglobin (HbF) in fetal red blood cells) => increased affinity to oxygen (2 α-subunits and 2 γ-subunits, whereas HbA (97% of total hemoglobin in adults) is composed of 2 α- and 2 β-subunits)
• fetal erythrocytes more resistant to alkaline environment (principle of Apt test or alkali denaturation test, to distinguish between maternal and neonatal blood => added NaOH does not hemolyze erythrocytes)
• dynamic changes in hemoglobin, hematocrit, red blood cell counts during early postnatal period
  1. → initial hemoconcentration = decrease in plasma volume as part of physiologic weight loss, causing an increase in the concentration of red blood cells, hemoglobin
  2. → later decline in hemoglobin = up to 8-12 weeks of life (physiologic anemia, early anemia of infancy)

AGE	TERM (Hb)	PRETERM (Hb)
1-3 days	140 – 220	120 – 180
2 weeks	130 – 170	110 – 150
2 months	90 – 130	70 – 90

Hemorrhagic anemia

Twin-twin transfusion syndrome (feto-fetal transfusion)

• complication of monochorionic, diamniotic pregnancy (in 20% of cases)
• pathological anastomoses between fetuses in the shared placental bed
• donor => anemia, oligohydramnios, growth restriction, hypoxia
• recipient => polycythemia, polyhydramnios, hydrops, cardiac failure

Feto-maternal transfusion

• 8% of pregnancies (esp. with preeclampsia)
• usually presents as chronic anemia
• Kleihauer-Betke test = maternal peripheral blood film reveals fetal erythrocytes (alternative is to determine fetal hemoglobin concentration in the maternal blood)

Placental transfusion not performed

• placental transfusion involves a shift of placental blood to a newborn within a limited amount of time immediately after delivery and may be achieved in two different ways: passive delayed cord clamping (DCC) and active umbilical cord milking (UCM)
• These enhanced placental transfusion techniques can help us achieve greater blood volume at birth (up to 10-15 ml/kg to the total of 90 ml/kg) which can be significant especially in very low birth weight infants
• improved circulation stability in the first 24 hours of life (blood pressure, urine output) => decreased risk for intraventricular hemorrhage
• diminished need for blood transfusions during the first weeks of life (improved iron reserve)
• Not performed: urgency to commence resuscitation, improper technique, monochorionic pregnancy

Placental or umbilical cord problems

• placental abruption, trauma (amniocentesis), anomalies
• abnormal umbilical cord position
• vasa praevia

Birth trauma

• birth injury that can be associated with more significant blood loss: cephalhematoma, subgaleal hemorrhage, adrenal hemorrhage, liver hematoma

Hemorrhagic states

• hemophilia
• morbus hemorrhagicus neonatorum (hemorrhagic disease of newborn)

Hemolytic anemia

Congenital (corpuscular) hemolytic anemia

• erythrocyte membrane defects (spherocytosis)
• enzymatic deficits (pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase (G6PD) deficiency)
• hemoglobinopathy (sickle cell disease, α-thalassemia)

Acquired (extra-corpuscular) hemolytic anemia

• hemolytic disease of newborn
• autoimmune hemolytic anemia of mother
• sepsis
• disseminated intravascular coagulopathy (DIC)

Aplastic anemia

Congenital aplastic anemia

• Diamond-Blackfan anemia
• Fanconi’s anemia

Acquired hypoplastic anemia

• sepsis (fetal infection by parvovirus B19, cytomegalovirus)
• nutrition deficits (vitamin B₁₂, folic acid – B₉)
• medullary inhibition (medication, leucemia)

Anemia of Prematurity

Multiple factors affect this specific anemia of preterm newborns:

• lower initial hemoglobin concentration
• shorter half-life of red blood cells
• low level of erythropoietin
• low iron storage reserves and capacity
• frequent blood tests
• infections

Diagnosis

Medical history

• anemia and jaundice in family members
• gallbladder and bile duct stones
• splenectomy (hereditary spherocytosis, G6PD deficiency)
• ethnic origin (thalassemia)
• medication (antimalarials, antipyretics, vitamin K analogues, sulphonamides) that can cause G6PD deficiency
• pregnancy (placenta praevia, placental abruption)

Clinical signs

• based on the severity of anemia and the swiftness of blood loss => diminished tissue oxygenation (oxygen-carrying capacity is reduced)
• general symptoms: tachycardia, tachypnea, jaundice, hepatosplenomegaly, failure to thrive, apneas, apathy, poor feeding, pale color of skin and mucosa
• acute anemia: hypovolemia, hypotension, cardiac insufficiency
• chronic anemia: usually well tolerated for a long time

Laboratory findings

• decreased hemoglobin, hematocrit and red blood cells for given age
• peripheral blood film (spherocytosis)
• reticulocyte count
• blood group and Coombs test
• maternal antibodies
• coagulation tests
• serology and virology tests
• iron and ferritin (sideropenic anemia = iron deficiency anemia at later age)

Imaging

• cranial ultrasound (intraventricular hemorrhage)
• ultrasound of other organs (liver hematoma, adrenal hemorrhage)

Therapy

Acute

• volume therapy (hypovolemia, hypotension)
• red blood cell transfusion (20 ml/kg)

Chronic

• based on the origin of anemia
• nutritional support (folic acid, iron drops)
• red blood cell transfusion

References

① Aher S, Malwatkar K, Kadam S. Neonatal anemia. Semin Fetal Neonatal Med. 2008;13(4):239-247. doi:10.1016/j.siny.2008.02.009