Anemia of prematurity overview

# Overview
Anemia of prematurity is a normochromic, normocytic anemia commonly seen in premature infants cared for in the neonatal intensive care unit. Normally, all the newborns develop anemia during the first few weeks of their life after birth. Decreased erythropoietin production, increased erythropoietin metabolism, and shortened RBC lifespan leads to anemia in newborns. Term infants tolerate it well and do not require any treatment. This physiological anemia in newborns resolves with increasing age. Whereas, premature infants develop anemia rapidly and more profoundly. Blood loss during phlebotomy and other illness related to prematurity contribute to the development of anemia of prematurity. Severity of symptoms varies with the blood hemoglobin levels. Treatment involves blood transfusion and recombinant human erythropoietin therapy.

# Historical perspective

# Classification
There is no established system for the classification of anemia of prematurity.

# Pathophysiology
Anemia of prematurity occurs as a result of a combination of increased blood loss or red blood cell destruction, decreased erythropoietin production, increased erythropoietin metabolism, deficient iron stores, and decreased RBC lifespan. Phlebotomy is the major contributing factor of anemia of prematurity. Term infants tolerate anemia well and do not develop any symptoms and resolve with increasing age. Whereas, in preterm infants these factors exaggerate to cause a severe form of anemia more rapidly.

# Causes
Common causes of anemia of prematurity include preterm birth, blood loss during phlebotomy, increased destruction of red blood cells, and decreased production of red blood cells. Iron, vitamin B6, vitamin E, and folate deficiencies are less common causes of anemia of prematurity.

# Differentiating Anemia of prematurity from other diseases
Anemia of prematurity should be differentiated from anemia due to increased red blood cell destruction, increased blood loss, and decreased red blood cell production. It should also be differentiated from other causes of normocytic normochromic anemia.

# Epidemiology and Demographics

## Age
Anemia of prematurity is a common problem in neonatal intensive care unit (NICU). It usually affects preterm and low birth weight infants born before 32-weeks of gestation. The risk of anemia of prematurity is inversely proportional to birth weight and gestational age at time of birth.

## Gender
Men and women are equally likely to develop anemia of prematurity

## Race
There is no racial predilection for anemia of prematurity

# Risk factors
Anemia of prematurity is a serious problem in preterm infants. Common risk factors in the development of anemia of prematurity are preterm birth, low birth weight, and excess blood loss during phlebotomy. Less common risk factors are family history of anemia, anemia and nutritional deficiencies in mother during pregnancy, multiple gestations, complications during pregnancy and delivery, blood loss during pregnancy and delivery, and twin-to-twin transfusion.

# Natural History, Complications, and Prognosis
Anemia of prematurity can be asymptomatic or produce abnormal clinical signs and symptoms depending on the hemoglobin levels. Mild symptoms usually resolve spontaneously without treatment. Severe symptoms require treatment with blood transfusion and erythropoietin. Untreated anemia of prematurity can lead to poor growth, apnea, and cardiovascular instability. The prognosis of anemia of prematurity is good with prompt diagnosis and early treatment.

# Diagnosis

## History and Symptoms
Majority of patients with anemia of prematurity are either asymptomatic or develop vague and non-specific symptoms. They usually present with pallor and lethargy. Decreased activity, breathing difficulties, feeding difficulties, and difficulty in gaining weight are common symptoms. Less common symptoms are tachycardia, heart murmurs, and metabolic acidosis.

## Physical Examination
Patients with anemia of prematurity usually appear pale and lethargic. Physical examination of patients with anemia of prematurity is usually remarkable for pallor, decreased activity, and poor growth.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of anemia of prematuriy are reduced hemoglobin, hematocrit, and reticulocyte count in the blood. Normocytic, normochromic RBCs and red blood cell precursors are seen predominantly on the peripheral smear of patients with anemia of prematurity.

## Ultrasound
There are no ultrasound findings associated with anemia of prematurity. Cranial USG and abdominal USG can be done to exclude other causes of anemia.

## Other Imaging Findings
There are no other imaging findings associated with anemia of prematurity.

## Other Diagnostic Studies
There are no other diagnostic studies associated with anemia of prematurity.

# Treatment

## Medical Therapy
Blood transfusion is the mainstay in the treatment of anemia of prematurity. Treatment of infants with anemia of prematurity depends on the severity of symptoms. Asymptomatic patients are managed with close monitoring and supportive care. Whereas, blood transfusion and recombinant erythropoietin therapy are required to treat infants with symptomatic anemia of prematurity.

## Primary Prevention
Effective measures for the primary prevention of anemia of prematurity include limiting blood loss during phlebotomy, cord blood sampling for the laboratory investigations, and improving placental transfusion.

## Secondary Prevention
There are no established measures for the secondary prevention of anemia of prematurity.