pediatrics
Perinatal Anemia
Evaluation of Perinatal Anemia
History should focus on maternal factors (eg, bleeding diatheses, hereditary red blood cell [RBC] disorders, nutritional deficiencies, drugs), family history of hereditary disorders that may cause neonatal anemia (eg, alpha-thalassemia, enzyme deficiencies, RBC membrane disorders, RBC aplasias), and obstetric factors (eg, infections, vaginal bleeding, obstetric interventions, mode of delivery, blood loss, treatment and appearance of the cord, placental pathology, fetal distress, number of fetuses). Nonspecific maternal factors may provide additional clues. History of anemia in the parents should be sought. Splenectomy would indicate a possible history of hemolysis, RBC membrane disorder, or autoimmune anemia; cholecystectomy might indicate a history of hemolysis-induced gallstones. Important neonatal factors include Gestational Age at delivery, age at presentation, sex, race, and ethnicity. Tachycardia and hypotension suggest acute, significant blood loss. Jaundice suggests hemolysis, either systemic (caused by Rh or ABO incompatibility or G6PD deficiency) or localized (caused by breakdown of sequestered blood in cephalhematomas). Hepatosplenomegaly suggests hemolysis, congenital infection, or heart failure. Hematomas, ecchymoses, or petechiae suggest bleeding diathesis. Congenital anomalies may suggest a bone marrow failure syndrome. Anemia may be suspected prenatally if ultrasonography shows increased middle cerebral artery peak systolic velocity or hydrops fetalis, which, by definition, is abnormal, excessive fluid in ≥ 2 body compartments (eg, pleura, peritoneum, pericardium); cardiac, hepatic, and splenic enlargement may be present. After birth, if anemia is suspected, a complete blood count is done; if hemoglobin and hematocrit levels are low, initial testing consists of Reticulocyte count Peripheral smear examination If anemia is acute, urgent intervention may be required. If thereticulocyte count is low(it is normally elevated when hemoglobin and hematocrit are low), anemia may be caused by acquired or congenital bone marrow dysfunction, and the infant should be evaluated for causes of bone marrow suppression with Titers or polymerase chain reaction studies for congenital infection (rubella, syphilis, HIV, cytomegalovirus, adenovirus, parvovirus, human herpesvirus 6) Folate and vitamin B12 levels Iron andcopperlevels If these studies do not identify a cause of anemia, a bone marrow biopsy, genetic testing for congenital disorders of RBC production, or both may be necessary. (reflecting an appropriate bone marrow response), anemia may be caused by blood loss or hemolysis. If there is no apparent blood loss or if signs of hemolysis are noted on the peripheral smear or the serum bilirubin level is elevated (which may occur with hemolysis), a Direct Antiglobulin (Direct Coombs) Test (DAT [Coombs test]) should be done. anemia is likely secondary to Rh, ABO, or other blood group incompatibility. The DAT is always positive with Rh incompatibility but is sometimes negative with ABO incompatibility because there is less ABO antigen on the RBC membrane than Rh antigen. Infants may have active hemolysis caused by ABO incompatibility and have a negative DAT; however, in such infants, the peripheral blood smear should reveal microspherocytes, and the Indirect Antiglobulin (Indirect Coombs) Test is usually positive because it identifies plasma ABO antibodies, which, in the presence of adult RBCs (adult RBCs have well discriminated ABO antigens), give a positive test result. If thedirect antiglobulin test is negative,the RBC mean corpuscular volume (MCV) may prove helpful, although because fetal RBCs are normally larger than adult RBCs, it can be challenging to interpret MCV in the neonate. However, a significantly low MCV suggests alpha-thalassemia or, less commonly, iron deficiency due to chronic intrauterine blood loss; these may be distinguished by red cell distribution width (RDW), which is often normal with thalassemia but elevated with iron deficiency. With a normal or high MCV, the peripheral blood smear may show abnormal RBC morphology compatible with a membrane disorder, microangiopathy, disseminated intravascular coagulation,vitamin Edeficiency, or hemoglobinopathy. Infants with hereditary spherocytosis often have an elevated mean corpuscular hemoglobin concentration (MCHC). If the smear is normal, blood loss, enzyme deficiency, or infection should be considered and an appropriate assessment, including testing for fetal-to-maternal hemorrhage, should ensue. Fetal-to-maternal hemorrhage can be diagnosed by testing for fetal RBCs in maternal blood. The Kleihauer-Betke acid elution technique is the most frequently used test, but other tests include fluorescent antibody techniques and differential or mixed agglutination testing. In the Kleihauer-Betke technique, citric acid-phosphate buffer of pH 3.5 elutes hemoglobin from adult but not fetal RBCs; thus, fetal RBCs stain with eosin and are visible on microscopy, whereas adult RBCs appear as red cell ghosts. The Kleihauer-Betke technique is not useful when the mother has a hemoglobinopathy. 