in brief

In Brief

Anemia in Infancy

Jennifer Cobelli Kett, MD cells that express embryonic hemoglo- Blood loss, a common cause of Children’s National Medical Center bin. At 6 weeks’ gestation, the liver be- in the neonatal period, may be acute or Washington, DC comesthepredominantsiteofRBC chronic and can result from umbilical production, and the cells produced pri- cord abnormalities, placenta previa, pla- marily express fetal hemoglobin. Not until cental abruption, traumatic delivery, or Author Disclosure 6 months’ gestation does the bone mar- internal in the infant. In one-half Dr Kett has disclosed no financial row become the major site of hematopoi- of all , fetal–maternal hemor- relationships relevant to this article. esis. Throughout fetal life, erythrocytes rhage can be demonstrated by the iden- This commentary does not contain decrease in size and increase in number: tificationoffetalcellsinthematernal increases from 30% to 40% circulation. Blood also can be transfused a discussion of an unapproved/ during the second trimester to 50% to from one fetus to another in monochor- investigative use of a commercial 63% at term. In late gestation and after ionic twin gestations. In some pregnan- product/device. birth, RBCs gradually switch from the cies, these losses can be severe. production of fetal hemoglobin to adult The accelerated destruction of RBCs hemoglobin. may be either immune or nonimmune Anemia and Pallor. Kolb EA, Levy AS. In: After birth, RBC mass normally de- mediated. Isoimmune hemolytic anemia McInerny TK, Adam HM, Campbell DE, clines in response to an increase in the is caused by ABO, Rh, or minor blood Kamat DM, Kelleher KJ, eds. American availability of oxygen and downregu- group incompatibility between the Academy of Textbook of lation of erythropoietin. RBC count mother and fetus. Maternal immuno- Pediatric Care. Elk Grove Village, IL: decreases until oxygen delivery is inade- globulin G antibodies to fetal antigens American Academy of Pediatrics; quate for metabolic demand and eryth- can cross the placenta and enter the 2009:1395–1405 Diseases of the Blood. In: Behrman RE, ropoietin production is stimulated again. fetal bloodstream, causing hemolysis. Kliegman RM, Jenson HB, eds. Nelson In healthy term infants, the RBC nadir, These disorders have a wide clinical Textbook of Pediatrics. 17th ed. a physiologic response to postnatal spectrum, ranging from mild, self-limited Philadelphia, PA: Saunders; 2004: life and not a hematologic disorder, hemolytic to lethal hydrops fe- 1599–1678 typically occurs at 8 to 12 weeks of talis. Because maternal antibodies may The Blood and Hematopoietic System. life and at a hemoglobin level of 9 to take months to clear, affected infants In: Martin RJ, Fanaroff AA, Walsh MC, 11 g/dL. can experience prolonged hemolysis. eds. Fanaroff and Martin’s Neonatal- Preterm infants also experience a de- ABO incompatibility usually occurs Perinatal Medicine: Diseases of the crease in hemoglobin concentration af- when type O mothers carry fetuses that Fetus and Infant. 8th ed. Philadelphia, ter birth, with a decline that typically is are type A or B. Because A and B anti- PA: Mosby; 2006:1287–1356 more abrupt and more profound than in gens are widely distributed in the body, term infants, reaching hemoglobin lev- ABO incompatibility typically is less se- Anemia is the reduction in red blood cell els of 7 to 9 g/dL at 3 to 6 weeks of age. vere than and is not affected (RBC) number, hematocrit, or hemoglobin This anemia of prematurity is likely the by birth order. In contrast, Rh hemolytic concentration to a value >2SDsbelow result of lower hemoglobin levels at disease occurs infrequently during the the age-specific mean. Anemia in infancy, birth, decreased RBC lifespan, and a first because sensitization which may result from increased erythro- suboptimal erythropoietin response, and typically is caused by maternal exposure cyte loss or inadequate RBC production, may be more pronounced in the smallest to Rh-positive fetal cells around the time raises unique considerations. and most premature infants. Anemia of of delivery. With the widespread use of Understanding the development of prematurity may be exaggerated by non- Rh immunoglobulin, life-threatening Rh the hematopoietic system may be help- physiologic factors, including frequent incompatibility is now rare. ful in the evaluation of neonates with blood sampling for laboratory tests, and Abnormalities of RBC structure, en- anemia. Erythropoiesis begins in the yolk may be accompanied by significant clin- zyme activity, or hemoglobin produc- sac at 2 weeks’ gestation, generating ical symptoms. tion also can cause hemolytic anemia

186 Pediatrics in Review Vol.33 No.4 April 2012 in brief

because the abnormal cells are removed are normal or slightly increased. Fanconi physical examination, with special at- more rapidly from the circulation. He- anemia is a congenital syndrome of bone tention to cardiovascular status, jaun- reditary spherocytosis is one such disor- marrow failure, although it is often un- dice, organomegaly, and any physical der, caused by a cytoskeletal protein recognized until later in childhood. Other anomalies. The initial laboratory evalua- defect that results in fragile, inflexible congenital anemias include the congen- tion should include a complete blood cells. Glucose-6-phosphate dehydroge- ital dyserythropoietic anemias and the count with red cell indices, a reticulocyte nase deficiency, an X-linked enzyme sideroblastic anemias. count, a peripheral blood smear, and di- disorder, typically causes an episodic Iron deficiency is a common cause rect antiglobulin test (Coombs’ test). hemolytic anemia that occurs in re- of microcytic anemia in infants and These results may help to direct addi- sponse to infection or oxidant stress. children, and it typically peaks at 12 tional testing. Treatment will be guided The thalassemias are hereditary disor- to 24 months of age. Preterm infants by the clinical severity of the anemia ders caused by defects in hemoglobin have less stored iron and may become and the underlying illness. Transfu- synthesis and are classified as alpha deficient earlier. Infants who experi- sions may be required to restore ade- or beta according to the affected globin ence increased iron loss from frequent quate tissue oxygenation and expand chain. They range in severity from silent laboratory sampling, surgical procedures, circulating blood volume, and certain carrier states to fatal , hemorrhage, or anatomic abnormalities clinical conditions may require exchange depending on the type of thalassemia, also may become deficient sooner. In- transfusion. number of affected genes, amount of testinal blood loss caused by exposure globin production, and ratio of alpha- to cow milk also may place infants at Comments: Prematurely born in- to beta-globin produced. higher risk. Lead poisoning can be the fants are at particular risk for iron defi- Sickle cell anemia is another disor- cause of a microcytic anemia similar to ciency because they have not had the der of hemoglobin production. Children iron deficiency anemia. benefit of a full third trimester of ges- born with sickle trait are largely unaf- Both vitamin B12 and folate defi- tation, during which an infant born at fected, whereas those who have sickle ciency can cause macrocytic anemia. term has been able to leach from the cell disease may experience hemolytic Because human milk, pasteurized cow mother (unless she is severely depleted) anemia associated with a wide range milk, and infant formulas provide suf- enough iron to maintain sufficiency un- of clinical effects. The onset of symptoms ficient folic acid, a deficiency of this til the infant has slightly more than occurs as the amount of fetal hemo- vitaminisuncommonintheUnited doubled his or her birth weight. Full- globin declines and abnormal hemo- States. Of note, goat milk is not an ad- term infants, unless they are actively globin S rises, typically after 4 months equate source of folate. Vitamin B12 de- losing blood, are not at high risk for of age. ficiency also is rare but may occur in iron-deficiency anemia in the first Infants and young children may ex- human milk–fed infants born to moth- months of age, but premature infants perience serious bacterial infections, ers with low B12 stores, especially those with their insufficient iron stores cer- dactylitis, hepatic or splenic sequestra- who follow strict vegan diets or have tainly are. tion, aplastic crises, vaso-occlusive cri- pernicious anemia. Malabsorptive syn- What is even more significant is the ses, acute chest syndrome, priapism, dromes, necrotizing enterocolitis, and fact that when the body is depleted of stroke, and other complications. Other other intestinal anomalies may put in- iron stores, the consequences go be- hemoglobinopathies include hemoglo- fants at higher risk for these deficien- yond anemia. Iron is critical to a wide bin E, the most common hemoglobinop- cies, as can certain drugs or congenital range of physiologic functions beyond athy worldwide. Hemolytic anemia also disorders. hemoglobin’s role as a carrier of oxygen. can be caused by infection, hemangio- Other disorders of inadequate RBC Mitochondrial electron transport, neu- mas, vitamin E deficiency, and dissemi- production may be the result of chronic rotransmitter function, and detoxifica- nated intravascular coagulation, among disease, infection, malignancy, or tran- tion, as well as catecholamine, nucleic other disorders. sient erythroblastopenia of childhood, acid, and lipid metabolism all depend Impaired RBC production may be the a transient, acquired, normocytic ane- on iron, and its deficiency results in a result of acquired or congenital disor- mia believed to be the result of damage systemic disorder that can have long- ders. Diamond-Blackfan anemia is a rare to erythroid precursors by viruses. Al- term consequences, especially during a congenital macrocytic anemia in which though infants can be affected, most time of rapid brain growth. the bone marrow demonstrates few ery- cases occur at 2 to 3 years of age. throid precursors, although the white The evaluation of an anemic infant Henry M. Adam, MD blood cell and platelet counts generally must include a thorough history and Editor, In Brief

Pediatrics in Review Vol.33 No.4 April 2012 187