Neonatal AnemiaKirsten E. Crowley, MDJune 2005

DefinitionsAnemia: Central venous hemoglobin < 13 g/dL or capillary hemoglobin < 14.5 g/dL in infant > 34 weeks and 0-28 days oldAverage value for central venous hemoglobin at birth for > 34 weeks GA is 17 g/dLReticulocyte count in cord blood 3-7%Average mean corpuscular volume 107 fL

Physiologic anemia of infancyIn healthy term infants, hemoglobin levels begin to decline around the third week of lifeReach a nadir of 11 g/dL at 8-12 weeks

Differences in premature infantsAt birth they have slightly lower hemoglobin levels, and higher MCV and retic countsThe nadir is lower and is reached soonerAverage nadir is 7-9 g/dL and is reached at 4-8 weeks of ageRelated to a combination of decreased RBC mass at birth, increased iatrogenic losses from lab draws, shorter RBC life span, inadequate erythropoietin production, and rapid body growth

PathophysiologyAnemia in the newborn results from three processesLoss of RBCs: hemorrhagic anemiaMost common causeIncreased destruction: hemolytic anemiaUnderproduction of RBCs: hypoplastic anemia

Hemorrhagic anemiaAntepartum period (1/1000 live births)Loss of placental integrityAbruption, previa, traumatic amniocentesisAnomalies of the umbilical cord or placental vesselsVelamentous insertion of the cord in twins, communicating vessels, cord hematoma, entanglement of the cordTwin-twin transfusion syndromeOnly in monozygotic multiple births13-33% of twin pregnancies have TTTSDifference in hemoglobin usually > 5 g/dLCongestive heart disease common in anemic twin and hyperviscosity common in plethoric twin

Hemorrhagic anemiaIntrapartum periodFetomaternal hemorrhage (30-50% of pregnancies)Increased risk with preeclampsia-eclampsia, need for instrumentation, and c-sectionC-section: anemia increased in emergency c-sectionTraumatic rupture of the cordFailure of placental transfusion due to cord occlusion (nuchal or prolapsed cord)Obstetric trauma causing occult visceral or intracranial hemorrhage

Hemorrhagic anemiaNeonatal periodEnclosed hemorrhage: suggests obstetric trauma or severe perinatal distressCaput succedaneum, cephalhematoma, intracranial hemorrhage, visceral hemorrhageDefects in hemostasisCongenital coagulation factor deficiencyConsumption coagulopathy: DIC, sepsisVitamin K dependent factor deficiencyFailure to give vit K causes bleeding at 3-4 days of ageThrombocytopenia: immune, or congenital with absent radiiIatrogenic blood loss due to blood draws

Hemolytic anemiaImmune hemolysis: Rh incompatibility or autoimmune hemolysisNonimmune: sepsis, TORCH infectionCongenital erythrocyte defectG6PD, thalassemia, unstable hemoglobins, membrane defects (hereditary spherocytosis, elliptocytosis)Systemic diseases: galactosemia, osteopetrosisNutritional deficiency: vitamin E presents later

Hypoplastic anemiaCongenital Diamond-Blackfan syndrome, congenital leukemia, sideroblastic anemiaAcquiredInfection: Rubella and syphilis are the most commonAplastic crisis, aplastic anemia

Clinical presentationDetermine the following factorsAge at presentationAssociated clinical featuresHemodynamic status of the infantPresence or absence of comensatory reticulocytosis

Presentation of hemorrhagic anemiaAcute hemorrhagic anemiaPallor without jaundice or cyanosis and unrelieved by oxygenTachypnea or gasping respirationsDecreased perfusion progressing to hypovolemic shockDecreased central venous pressureNormocytic or normochromic RBC indicesReticulocytosis within 2-3 days of event

Presentation of hemorrhagic anemiaChronicPallor without jaundice or cyanosis and unrelieved by oxygenMinimal signs of respiratory distressCentral venous pressure normalMicrocytic or hypochromic RBC indicesCompensatory reticulocytosisEnlarge liver d/t extramedullary erythropoiesisHydrops fetalis or stillbirth may occur

Presentation of hemolytic anemiaJaundice is usually the first symptomCompensatory reticulocytosisPallor presents after 48 hours of ageUnconjugated hyperbilirubinemia of > 10-12 mg/dLTachypnea and hepatosplenomegaly may be present

Presentation of hypoplastic anemiaUncommonPresents after 48 hours of ageAbsence of jaundiceReticulocytopenia

Presentation of other formsTwin-twin transfusionGrowth failure in the anemic twin, often > 20%Occult internal hemorrhageIntracranial: bulging anterior fontanelle and neurologic signs (altered mental status, apnea, seizures)Visceral hemorrhage: most often liver is damaged and leads to abdominal massPulmonary hemorrhage: radiographic opacification of a hemithorax with bloody tracheal secretions

DiagnosisInitial studiesHemoglobinRBC indicesMicrocytic or hypochromic suggest fetomaternal or twin-twin hemorrhage, or a-thalassemiaNormocytic or normochromic suggest acute hemorrhage, systemic disease, intrinsic RBC defect, or hypoplastic anemiaReticulocyte countelevation suggests antecedent hemorrhage or hemolytic anemia while low count is seen with hypoplastic anemia

DiagnosisInitial studies continuedBlood smear looking for spherocytes (ABO incompatibility or hereditary spherocytosis)elliptocytes (hereditary elliptocytosis)pyknocytes (G6PD)schistocytes (consumption coagulopathy)Direct Coombs test: positive in isoimmune or autoimmune hemolysis

Other diagnostic studiesBlood type and Rh in isoimmune hemolysisKleihauer-Betke test on maternal blood looking for fetomaternal hemorrhageCXR for pulmonary hemorrhageBone marrow aspiration for congenital hypoplastic or aplastic anemiaTORCH: bone films, IgM levels, serologies, urine for CMVDIC panel, platelets looking for consumptionOccult hemorrhage: placental exam, cranial or abdominal ultrasoundIntrinsic RBC defects: enzyme studies, globin chain ratios, membrane studies

ManagementSimple replacement transfusionIndications: acute hemorrhageUse 10-15 ml/kg O, RH- packed RBCs or blood cross-matched to mom and adjust hct to 50%Give via low UVC or central UVC if time permitsDraw diagnostic studies before transfusionongoing deficit replacementmaintenance of effective oxygen-carrying capacityHct < 35% in severe cardiopulmonary diseaseHct < 30% in mild-moderate cardiopulmonary disease, apnea, symptomatic anemia, need for surgeryHct < 21%

ManagementExchange transfusionIndicationsChronic hemolytic anemia or hemorrhagic anemia with increased central venous pressureSevere isoimmune hemolytic anemiaConsumption coagulopathyNutritional replacement: iron, folate, vitamin E

Prophylactic managementErythropoietinIncreased erythropoiesis without significant side effectsDecreases need for late transfusionsWill not compensate for anemia due to labsNeed to have restrictive policy for blood sampling and micromethods in the labNutritional supplementation: iron, folate, vitamin E