Description
- The physiologic nadir of hemoglobin in newborns occurs at 8–12 weeks. It is the result of a decrease in erythropoietin in response to the transition from a relatively hypoxic state in utero to a hyperoxic state in room air. It is usually asymptomatic and gradually increases to adult values within the first 2 years of birth.
- Anemia of prematurity (AOP), however, is a pathologic and exaggerated response to decreased erythropoietin seen in premature infants (<37 weeks).
- Reduced hemoglobin, with lowest hemoglobin levels 6–7 g/dL in extremely low birth weight (ELBW) infants
- Signs and symptoms of anemia manifest
- Independent risk factor related to apnea
- Spontaneous resolution by 6 months of age
- Starts earlier and lasts longer than in normal newborns
- Normocytic and normochromic red blood cells (RBCs)
- This patient population is at-risk for several other causes of anemia, including shortened RBC life span and enhanced blood loss. Thus, the premature infant's impaired ability to increase erythropoietin levels further compounds the levels of anemia.
Epidemiology
Incidence
- Inversely proportional to:
- Gestational age
- Birth weight
- Advancements in technology have resulted in a new group of preterm infants that previously could not survive; thus increasing the incidence of AOP.
Etiology/Risk Factors
- Decreased RBC production that can be associated with prematurity (1,3,4).
- Inadequate synthesis of erythropoietin in response to hypoxia that results in suboptimal erythropoiesis.
- Nutritional deficiencies: Iron, folate, protein, B12
- Decreased RBC life span that can be associated with prematurity (increased destruction):
- Immune hemolytic anemia: Rh or ABO incompatibility, maternal autoimmune disorders, drug-induced
- Enzyme abnormalities: Glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency
- RBC membrane defects: Spherocytosis, stomatocytosis
- Hemoglobinopathies: Thalassemia
- Increased blood loss that can be associated with prematurity
- Frequent laboratory testing in critically ill infants (iatrogenic) can exacerbate AOP and increase the need for transfusions.
- Fetomaternal or fetoplacental hemorrhage
- Placenta previa, placental abruption
- Internal bleeding: Intracranial, intra-abdominal, pulmonary
Physiology/Pathophysiology
- The fetal environment has several adaptations to accommodate the degree of hypoxia and maximize oxygen delivery to the brain and heart (3,5).
- Hypoxic pulmonary vasoconstriction is maintained through decreased production of nitric oxide (minimal pulmonary blood flow with oxygenation and ventilation occurring at the placenta).
- High pulmonary artery pressures lead to high right heart pressures. This maintains the right-to-left shunt through the foramen ovale (FO).
- Increased circulating prostaglandins that maintain the patency of the ductus arteriosus (DA) and the ductus venosus (DV).
- Fetal hemoglobin has a strong affinity for oxygen to facilitate efficient extraction across the placenta. The P50 is ~19 mm Hg, compared to adult hemoglobin (~27 mm Hg).
- Transition to the extrauterine environment involves decreased shunting secondary to increased oxygen tensions and rapid right and left heart pressure changes. With the neonate's first several breaths, circulating oxygen tensions rise rapidly with resultant increases in bradykinin and nitric oxide and decreased pulmonary vascular resistance; blood flow increases through the pulmonary vasculature. Additionally, circulating prostaglandins decrease rapidly and result in closure of the ductus arteriosus. The relatively hyperoxic environment suppresses erythropoietin production (3).
- Erythropoietin: In utero, it is produced by the liver and kidneys in response to transcription factor hypoxia inducible factor-1 (HIF-1). In the premature infant, it is believed that there is a relative insensitivity by the hepatic oxygen sensor to hypoxia and anemia, resulting in inadequate synthesis of HIF-1.
- Delay surgery, if possible. When surgery must proceed, consider blood transfusion prior to arrival to the operating room or during the case. Type and cross matched, leukocyte-reduced, and CMV-negative blood should be administered.
- Minimize laboratory blood draws to those absolutely needed; additionally, decrease the volume drawn
- Maintain a thermoneutral environment. The combination of cold and hypoxia can result in patent ductus arteriosus (PDA) shunting.
Outline