Anemia is a disorder in which red blood cells are decreased in the blood.
For newborns of age 0-28 days, that value is as follows: [new born should have completed at least 34 weeks of intrauterine life]
- Central venous hemoglobin < 13 g/dL
- Capillary hemoglobin < 14.5 g/dL
What are Normal Average Values for Newborn
The average value for central venous hemoglobin at birth for > 34 weeks gestational age is 17 g/dL Reticulocyte count in cord blood is 3-7% and average mean corpuscular volume is 107 fL.
What is Physiological Anemia of Newborn
This is related to the following factors
- Decreased red blood cell mass at birth
- Increased losses from lab sample draws
- Shorter life span of RBCs
- Inadequate erythropoietin production
- Rapid body growth
Premature infants have slightly lower hemoglobin levels at birth and higher mean corpuscular volume [MCV] and reticulocyte counts. The nadir, in this case, is lower and reaches earlier than in normal infants. Average nadir is 7-9 g/dL and is reached at 4-8 weeks of age.
Pathophysiology and Causes of Anemia of Newborn
Three processes are responsible for anemia of newborn – loss of blood or hemorrhage, breakdown of blood cells in the body for one or other reason and inadequate production of red blood cells by bone marrow.
The anemia resulting from loss of red blood cells or hemorrhage is called hemorrhagic anemia. It is the most common cause of anemia of newborn.
Anemia due to increased destruction of red blood cells is called hemolytic anemia.
When anemia is due to underproduction of red blood cells, it is called hypoplastic anemia.
Depending on whether the cause is before birth, during birth or after birth, three types of groups of causes are responsible for hemorrhagic anemia of newborn
Antepartum Events Causing Hemorrhagic Anemia of Newborn
These events occur before birth and affect 1/1000 live births. These are
- Loss of placental integrity
- Abruptio placentae
- Placenta previa
- Traumatic amniocentesis
- Umbilical cord or placental vessel anomalies
- Velamentous insertion of the cord in twins
- Communicating vessels
- Cord hematoma
- Entanglement of the cord
- Twin-twin transfusion syndrome: This occurs in multiple pregnancies sharing one placenta and affects as much as 30% pregnancies in some studies. Due to single placental sharing, the blood supply may become connected resulting in unequal supply of blood. One fetus develops anemia and the other develops hyperviscosity.
Intrapartum [During delivery] Events Causing Hemorrhagic Anemia of Newborn
- Fetomaternal hemorrhage
- Increased risk with preeclampsia-eclampsia
- Need for instrumentation
- Cesarean Section
- Traumatic rupture of the cord
- Failure of placental transfusion due to cord occlusion
- Obstetric trauma causing occult visceral or intracranial hemorrhage
Causes of Hemorrhagic Anemia after Birth
- Obstetric trauma or severe perinatal distress
- Caput succedaneum
- Intracranial hemorrhage
- Visceral hemorrhage
- Defects in hemostasis
- Congenital coagulation factor deficiency
- Consumption coagulopathy as in DIC, sepsis
- Vitamin K dependent factor deficiency [ If vitamin K is not given to such children, bleeding may occur at 3-4 days of age]
- Thrombocytopenia: immune, or congenital with absent radii
- Iatrogenic blood loss due to blood draws
In this, there is increased destruction of red blood cells leading to the reduction in red blood cells.
- Immune hemolysis: Rh incompatibility or autoimmune hemolysis
- Nonimmune hemolysis- sepsis, TORCH infection
- Congenital erythrocyte defect
- Unstable hemoglobins
- Membrane defects (hereditary spherocytosis, elliptocytosis)
- Systemic diseases: galactosemia, osteopetrosis
- Nutritional deficiency: vitamin E presents later
There is decreased production of blood cells by the body.
- Diamond-Blackfan syndrome
- Congenital leukemia
- Sideroblastic anemia
- Infection: Rubella and syphilis are the most common
- Aplastic crisis, aplastic anemia
Presentation of Anemia of Newborn
Most infants with mild or moderate anemia have no symptoms.
Moderate anemia may result in lethargy or sluggishness and poor feeding.
Severe anemia, for example in newborns who have suddenly lost a large amount of blood may cause pallor, rapid heart rate, low blood pressure, along with rapid, shallow breathing.
In cases where the anemia results from rapid hemolysis, there is also an increased level of bilirubin, and the newborn may present with jaundice.
Acute hemorrhagic anemia
- Pallor without jaundice
- Cyanosis which is unrelieved by oxygen
- Tachypnea or gasping respirations
- Decreased perfusion progressing to hypovolemic shock
- Decreased central venous pressure
- Normocytic or normochromic RBCs on peripheral smear examination
- Reticulocytosis within 2-3 days of the event
Chronic hemorrhagic anemia
This occurs when there is a chronic loss of blood
- Pallor without jaundice or cyanosis and unrelieved by oxygen
- Minimal signs of respiratory distress
- Central venous pressure normal
- Microcytic or hypochromic RBC indices
- Compensatory reticulocytosis
- Enlarged liver due to extramedullary erythropoiesis. Liver tries to compensate for the loss by upping the production
- Hydrops fetalis or stillbirth may occur
Presentation of hemolytic anemia
- Jaundice is usually the first symptom. Jaundice occurs due to an increase in bilirubin following increased breakdown of hemoglobin
- Compensatory reticulocytosis
- Pallor could be seen after 48 hours of age
- Unconjugated hyperbilirubinemia of > 10-12 mg/dL
- Tachypnea and hepatosplenomegaly may be present
Presentation of hypoplastic anemia
It is an uncommon type of presentation and usually presents after 48 hours of age. There is an absence of jaundice and in contrast to other two types, number of reticulocytes is also decreased.
In twin-twin transfusion, there would be a growth failure in the twin who is anemic.
In intracranial hemorrhage, there would be bulging anterior fontanelle and neurologic signs like altered mental status, apnea and seizures.
In case of visceral hemorrhage, an abdominal mass can be palpated.
Pulmonary hemorrhage leads to opacification of a hemithorax on x-ray.
- RBC indices
Microcytic or hypochromic red blood cells suggest fetomaternal or twin-twin hemorrhage, or thalassemia. If red blood cells are normocytic or normochromic, it suggests acute hemorrhage, systemic disease, some kind of intrinsic RBC defect, or hypoplastic anemia
- Reticulocyte count
If reticulocytes are increased in number, it shows hemorrhage or hemolytic anemia. Lower count of reticulocyte [reticulocytopenia] is seen in hypoplastic anemia.
- Peripheral blood smear
- If spherocytes are seen, it suggests ABO incompatibility or hereditary spherocytosis
- Elliptocytes when visualized suggest hereditary elliptocytosis
- Pyknocytes are seen in G6PD deficiency
- Schistocytes are seen in consumption coagulopathy
- Direct Coombs test is positive in autoimmune hemolysis
Other investigations sought may vary from case to case
- Blood type and Rh factor in isoimmune hemolysis
- Kleihauer-Betke test on maternal blood – It is also called Acid elution test. It is a blood test used to measure the amount of fetal hemoglobin to look for fetomaternal hemorrhage
- X-ray of chest to rule out pulmonary hemorrhage
- Bone marrow aspiration is indicated in congenital hypoplastic or aplastic anemia
- Tests for TORCH infections – TORCH stands for toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and HIV
The tests done are skeletal x-rays to look for bone changes, serology and urine examination
- To look for consumption coagulopathy, Disseminated intravascular coagulation (DIC) panel is done
- Cranial or abdominal ultrasound is done to look for hemorrhage
- In case of intrinsic defects in red blood cells, enzyme studies, globin chain ratios and membrane studies are done.
Treatment of Anemia of Newborn
Most infants have mild anemia and do not require any treatment.
Note: Before any therapy blood sample for lab studies should be withdrawn
- Newborns who have rapidly lost large amounts of blood, often during labor and delivery, are treated with intravenous fluids followed by a blood transfusion.
- Very severe anemia caused by hemolytic disease may also require a blood transfusion, but the anemia is more often treated with an exchange blood transfusion, which lowers the bilirubin level as well as increases the red blood cell count.
In an exchange transfusion, a small amount of the newborn’s blood is gradually removed and replaced with equal volumes of fresh donor blood.
Indications for Blood Transfusion
- Acute hemorrhage
- Ongoing deficit replacement
- Maintenance of effective oxygen-carrying capacity
- Hct < 35% in severe cardiopulmonary disease
- Hct < 30% in mild-moderate cardiopulmonary disease, apnea, symptomatic anemia, need for surgery
- Hct < 21%
Indications for Exchange transfusion
- Chronic hemolytic anemia or hemorrhagic anemia with increased central venous pressure
- Severe isoimmune hemolytic anemia
- Consumption coagulopathy
Erythropoietin increases erythropoiesis and decreases the need for late transfusions.
Supplements: Nutritional supplementation like iron, folate, vitamin E should be given
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