What is Anemia of Prematurity?
All newborn infants manifest a decrease in hemoglobin. In the uterus, the tissue is in a relatively hypoxic state whereas after birth there is a relatively hyperoxic state. This leads to an increased oxygen concentration in the tissue which leads to a decrease in erythropoietin concentration.
In the term infant, this physiological anemia is observed 8-12 weeks after birth.
Anemia of prematurity is an exaggerated, pathologic response of the preterm infant to this change.
Anemia of prematurity is a normocytic, normochromic, hyporegenerative anemia characterized by low serum erythropoietin. Nutritional deficiencies of iron, vitamin E, vitamin B 12, and folate may exaggerate the degree of anemia.
Anemia of prematurity resolves in many premature infants within 3-6 months of birth.
In others, however, medical care is required.
The risk of anemia of prematurity is inversely related to gestational maturity and birthweight.
Causes of Anemia of Prematurity
Three factors are responsible for the development of anemia of prematurity
- Inadequate red blood cell production
- Shortened red blood cell (RBC) lifespan
- Blood loss
Inadequate RBC production
Erythropoietin is synthesized in fetal liver but gradually shifts toward the kidney with an increase in gestational age. However, the liver remains the major source of erythropoietin till the end of gestation.
Fetal erythrocytes are first synthesized in the liver and then move to bone marrow gradually so that by 40 weeks of gestation, bone marrow is the center for erythropoiesis.
Read more about Bone Marrow-Structure, Composition, and Functions
There is a difference between erythropoietin produced by the liver and kidney in the level of stimulus required for their production.
Anemia and hypoxia required to stimulate erythropoietin production are far greater for the fetal liver than for the fetal kidney. The liver may not be stimulated for erythropoietin production until the hemoglobin concentration of 6-7 g/dL is reached.
Moreover, erythropoietin, endogenously produced or exogenously administered is rapidly eliminated by neonates, therefore leading to lesser stimulation of bone marrow for the production of red blood cells.
The deficiency of iron or other substrate or co-factors required for red blood cell production would lead to inefficient production. Moreover, rapid growth of an infant may prevent the appropriate increase in hemoglobin concentration as the demand keeps continuously rising.
Shortened Red Blood Cell Life Span or Hemolysis
Adult red blood cells circulate for 100-120 days. The lifespan of a neonatal red blood cell is only one half to two thirds that of an adult red blood cell. However, red blood cells of immature infants may survive only 35-50 days due to various factors of formation and metabolism.
This further contributes to the development of anemia.
Any blood loss during delivery either due to fetal-placental transfer, repeated sampling, etcetera may contribute to anemia.
In contrast, delayed cord clamping so as to let more blood pass to the fetus from the placenta may lessen the degree of anemia of prematurity.
Presentation of Anemia of Prematurity
- Poor weight gain despite adequate calorie intake
- Tachycardia – increase in heart rate
- Tachypnea – increase in breathing rate
- Flow murmurs
- Decreased activity and lethargy
- Difficulty with oral feeding
There could be an increase in apneic [stoppage of breathing] and bradycardic [decrease in heart rate] episodes.
Increased cellular anaerobic metabolism may lead to the accumulation of lactic acid.
- Low hemoglobin values, usually <10g/dL, may reach as low as 6-7 g/dL
- White blood cell count is normal
- Platelet values are normal in anemia of prematurity
- Red blood cell indices are normal ( normochromic, normocytic) for age.
Relative to the degree of anemia, reticulocyte count is low. If the reticulocyte count is elevated, it is not most likely to be anemia of prematurity.
Red blood cell morphology as observed under the light microscope is normal. Prominence of red blood precursors may be visualized.
Coombs test is important to detect an immune-mediated hemolytic process related to maternal-fetal blood group incompatibility. Rh typing of the mother and child should be done as well.
Read more about Rh Immune Globulin
Serum bilirubin, if elevated would suggest a hemolytic type of anemia.
Raised lactic acid levels may guide the need for blood transfusion.
Management of Anemia of Prematurity
As most of the newborns are not symptomatic, observation is indicated in most of the cases who do not have symptoms, are not very ill and are receiving adequate nutrition.
Supportive nutritional treatment like vitamin E, vitamin B-12, folate, and iron can be supplemented.
Hematocrit levels are checked periodically till the hemoglobin levels rise.
Packed red blood cell transfusions
Packed red blood cell transfusions are the mainstay of therapy in patients who require transfusion.
The frequency of blood transfusion varies with gestational age and degree of illness.
There are many problems associated with blood transfusions. These are
- Hematological complications
- Immunologic complications
- Metabolic complications
- Late onset necrotizing enterocolitis
- Infection (hepatitis, cytomegalovirus, human immunodeficiency virus, syphilis)
- Fluid overload and electrolyte imbalances
- Posttransfusion graft versus host disease
Therefore, the number of transfusions and the number of donors should be reduced as much as possible.
When required, it becomes pertinent to discuss the need for transfusion with the family of the child. The risks associated therein along with the advantages and disadvantages of erythropoietin administration should also be discussed.
How to Reduce Donor Number for Transfusion
Infants may be assigned a specific unit of blood from a single donor which would suffice for treatment. This limits exposure to a single donor.
Recombinant Erythropoietin Treatment
Subcutaneous administration of erythropoietin is preferred because intravenous administration leads to an increased loss in the urine.
Studies have suggested an association between erythropoietin administration and retinopathy of prematurity.
The erythropoietin treatment protocol is yet to be devised and still, it is not accepted as standard therapy for an infant with anemia of prematurity.
Epoetin alfa is used to stimulate erythropoiesis and decrease the need for erythrocyte transfusions in high-risk preterm neonates. It induces the release of reticulocytes from the bone marrow into the bloodstream.
Iron, folate and vitamin E are prescribed, as needed.