ANEMIA OF PREMATURITY NEWBORN BABY

Anemia frequently is observed in the infant who is hospitalized and premature. Although many causes are possible, anemia of prematurity (AOP) is the most common diagnosis. AOP is a normocytic, normochromic, hyporegenerative anemia that is characterized by the existence of a low serum erythropoietin (EPO) level in an infant who has what may be a remarkably reduced hemoglobin concentration. Although common, AOP remains a controversial issue for clinicians. Few universally accepted signs or symptoms are attributable to AOP. Even less agreement exists regarding the timing, method, and effectiveness of current therapeutic interventions in individuals with AOP. With an increasing number of transfusion-related complications reported in the last 2 decades, caregivers and families of infants understandably are concerned about the use of blood products. This article reviews the pathophysiology of AOP, the means of reducing blood transfusions, and the current status of recombinant EPO.

Pathophysiology (anemia of prematurity newborn baby) : The 3 basic mechanisms for the development of anemia in any patient are inadequate red blood cell (RBC) production, shortened RBC life span or hemolysis, and blood loss. AOP has its roots in each of these processes.

Inadequate red blood cell production (anemia of prematurity newborn baby)
The first mechanism of anemia is inadequate RBC production. The location of EPO and RBC production changes during gestation of the fetus. EPO synthesis initially occurs in cells of monocyte or macrophage origin that reside in the fetal liver, with production gradually shifting to the peritubular cells of the kidney. By the end of gestation, the liver remains a major source of EPO. In the first few weeks of embryogenesis, fetal erythrocytes are produced in the yolk sac. This site is succeeded by the fetal liver, which, by the end of the first trimester, has become the primary site of erythropoiesis. Bone marrow then begins to take on a more active role in producing erythrocytes. By approximately 32 weeks' gestation, the burden of erythrocyte production in the fetus is shared evenly by the liver and bone marrow. By 40 weeks' gestation, the marrow is the sole erythroid organ. Premature delivery does not accelerate the ontogeny of these processes.

Although EPO is not the only erythropoietic growth factor in the fetus, it is the most important. EPO is synthesized in response to both anemia and hypoxia. The degree of anemia and hypoxia required to stimulate EPO production is far higher for the fetal liver than for the fetal kidney. As a result, new RBC production in the extremely premature infant (whose liver remains the major site of EPO production) is blunted despite what may be marked anemia. In addition, EPO, whether endogenously produced or exogenously administered, has a larger volume of distribution and is eliminated more rapidly by neonates, resulting in a curtailed time for bone marrow stimulation. Erythroid progenitors of premature infants are quite responsive to EPO when that growth factor finally is produced or administered.

Shortened red blood cell life span or hemolysis Secondly, the average life span of a neonatal RBC is only one half to two thirds that of the RBC life span in an adult. Cells of the most immature infants may survive only 35-50 days. The shortened RBC life span of the neonate is a result of multiple factors, including diminished levels of intracellular ATP, carnitine, and enzyme activity; increased susceptibility to lipid peroxidation; and increased susceptibility of the cell membrane to fragmentation.

Blood loss Finally, blood loss may contribute to the development of AOP. If the neonate is held above the placenta for a time after delivery, a fetal-placental transfusion may occur. More commonly, because of the need to closely monitor the tiny infant, frequent samples of blood are removed for various tests. Because the smallest patients may be born with as little as 40 mL of blood in their circulation, withdrawing a significant percentage of an infant's blood volume in a short period is relatively easy. In one study, mean blood loss in the first week of life was nearly 40 mL. Taken together, the premature infant is at risk for the development of AOP because of limited synthesis, diminished RBC life span, and increased loss of RBCs.

Frequency (anemia of prematurity newborn baby): In the US: Frequency of AOP is related inversely to the gestational age and/or birthweight of the population. As many as 80% of infants with very low birthweight (VLBW) and 95% of infants with extremely low birthweight (ELBW) receive blood transfusions during their hospitalizations.

Mortality/Morbidity (anemia of prematurity newborn baby): Although a premature infant is unlikely to be allowed to become so anemic as to die, complications from necessary blood transfusions ultimately can be responsible for the death of a patient. Anemia is blamed for a variety of signs and symptoms, including apnea, poor feeding, and inadequate weight gain.

Race: Race has no influence on the incidence of AOP.

Sex: Although the presence of testosterone in the male infant is believed to be at least partially responsible for a slightly higher hemoglobin level at birth, this effect is of no significance with regard to individuals with AOP.

Age:
• The more immature the infant, the more likely the development of AOP. AOP typically is not a significant issue for infants born beyond 32 weeks' gestation.
• The nadir of the hemoglobin level typically is observed when the tiniest infants are aged 4-8 weeks.
• AOP spontaneously resolves by the time most patients are aged 3-6 months.

History (anemia of prematurity newborn baby): Few symptoms are universally accepted as attributable to AOP; however, the following are among the symptoms that clinicians attribute to AOP:
• Poor weight gain
• Apnea
• Tachypnea
• Decreased activity
• Pallor
• Tachycardia
• Flow murmurs

Physical (anemia of prematurity newborn baby): Debate regarding the presence or absence of physical findings in the infant with AOP is ongoing. Clinical trials designed to determine the efficacy of blood transfusions in relieving these findings have produced conflicting results.
• Poor growth
o Inadequate weight gain despite adequate caloric intake often is attributed to AOP.
o The response of weight gain to transfusions has been inconsistent in the literature.
• Apnea
o If severe enough, anemia may result in respiratory depression manifested by increased periodic breathing and apnea.
o While some studies have demonstrated a decrease in frequency of these symptoms subsequent to blood transfusions, others have found similar results with simple crystalloid volume expansion.
• Decreased activity: Lethargy frequently is attributed to anemia, with subjective improvement subsequent to transfusion.
• Metabolic acidosis
o Significant anemia can result in decreased oxygen-carrying capacity less than the needs of the tissue, resulting in increased anaerobic metabolism with production of lactic acid.
o Blood transfusions have been documented to decrease lactic acid levels in otherwise healthy infants who are anemic and premature. Some medical professionals have suggested using lactate levels as an aid in determining the need for transfusion.
• Tachycardia
o Infants with AOP may respond by increasing cardiac output through increased heart rates, presumably in response to inadequate oxygen delivery to the tissues caused by anemia.
o Blood transfusions have been associated with a lowering of the heart rate in infants who are anemic.
• Tachypnea
• Flow murmurs

Causes (anemia of prematurity newborn baby):
• AOP results from a combination of relatively diminished RBC production, shortened RBC life span, and blood loss.
• Nutritional deficiencies of vitamin E, vitamin B-12, and folate may exaggerate the degree of anemia.

Lab Studies (anemia of prematurity newborn baby):
• Complete blood count
o The CBC demonstrates normal white blood cell (WBC) and platelet lines.
o The hemoglobin is less than 10 g/dL but may descend to a nadir of 6-7 g/dL; the lowest levels generally are observed in the smallest infants.
o RBC indices are normal (eg, normochromic, normocytic) for age.
• Reticulocyte count
o The reticulocyte count is low when the degree of anemia is considered as a result of the low levels of EPO.
o The finding of an elevated reticulocyte count is not consistent with the diagnosis of AOP.
• Peripheral blood smear: No abnormal forms are observed.
• Maternal and infant blood typing: In the evaluation of anemia, consider the possibility of hemolytic processes, such as the ABO blood group system and Rh incompatibility.
• Direct antibody test (Coombs): This test may be coincidentally positive; however, with such a finding, ensure that an immune-mediated hemolytic process is not ongoing.
• Serum bilirubin: With an elevated serum bilirubin level, consider other possible explanations for the anemia.