From anemia refers to a reduction in red cell mass or hemoglobin. It is then usually diagnosed when the Hb or Hct value is> 2 standard deviations below the average age. Some doctors suspect a relative anemia even if a Hb or hematocrit is observed above this point, but the demand for oxygen can not be met. Anemia and polycythemia are the most common hematological disease of the newborn.
Diagnosis. Pre- and perinatal changes of erythropoiesis are discussed in Perinatal physiology.) Under anemia refers to a reduction in red cell mass or hemoglobin. It is then usually diagnosed when the Hb or Hct value is> 2 standard deviations below the average age. Some doctors suspect a relative anemia even if a Hb or hematocrit is observed above this point, but the demand for oxygen can not be met. Anemia and polycythemia are the most common hematological disease of the newborn. Both the Hb and the hematocrit value quickly change the course of development of the newborn, and so will the norm values ??change (see Table: Age-dependent values ??for hemoglobin and hematocrit). However, the laboratory results can also by other variables such. B. gestational age and the extraction point (capillary versus venous) can be influenced. Finally, the child’s position in relation to the placenta before Nabelschnurabklemmung may be relevant (a lower position leads to a transfusion in the newborn, a higher position to a blood loss). Age-related values ??for hemoglobin and hematocrit age Hb (g / dL) Hct (in%) 28 weeks 32 weeks 14.5 45 15 47 16.5 birth 51 days 1-3 18.5 56 2 weeks 16.6 53 Etiology The causes of anemia in newborns include Physiological processes blood loss Decreased erythropoiesis Increased red blood cell destruction (hemolysis) Physiological anemia The physiological anemia is the most common cause of anemia in the newborn period. Normal physiological processes often lead to a normocytic normochromic anemia in frost or premature infants. Such physiological anemia usually do not require extensive investigation or treatment. In newborns, the increase in oxygenation performs the normal spontaneous breathing after birth to an abrupt increase in the oxygen concentration in the tissues and thus a negative feedback to the Erythropoetinfreisetzung and erythropoiesis. Both the reduced erythropoiesis and the shorter life span (90 days vs. 120 days in adults) of neonatal red blood cells lead to a decrease in Hb concentration during the first 2 to 3 months of life. The value is typically 9-11 g / dl. During the following weeks, then the value remains stable, then to rise slowly in 4 to 6 months of age according to the re-stimulation by existing erythropoietin again. A Physiological anemia is more pronounced in preterm infants and also occurs to mature neonates earlier and with a lower value in comparison. This condition is also known as anemia of prematurity. A mechanism similar to the one that causes anemia in newborns, leading to anemia in preterm infants during the first 4-12 weeks. A lower production of erythropoietin, a shorter life span of red blood cells (35-50 days), rapid growth and frequent phlebotomy contribute to a faster and lower hemoglobin level (8-10 g / dl) in preterm infants. An anemia of prematurity occurs most often in infants <32 weeks of gestation on. Almost all children acutely ill and extremely preterm (<28 weeks of gestation) develop anemia, which is hard enough to have a red blood cell transfusion during their first hospital stay to erfordern.Blutverlust Anemia may also be pre-, peri- and post-natal blood loss caused , Since the volume of blood of newborns is low (in preterm infants from 90 to 105 ml / kg, the mature child 78-86 ml / kg), low blood loss of, can already. B. 15-20 ml lead to anemia. A chronic blood loss can be compensated physiologically usually, so that these children are clinically stable than those with acute blood loss. Prenatal bleeding may be caused by fetomaternal hemorrhage Fetofetale transfusion in twins umbilical cord malformations placental abnormalities Diagnostic methods fetomaternal transfusion arise spontaneously or as a result of maternal trauma, amniocentesis, an external head phrase or a placental mass. A total of 50% of pregnancies are affected, in most cases, but only with a very low blood volume (about 2 ml); to a "massive" loss of blood, d. H. > 30 ml, it comes in 3 out of 1,000 pregnancies. The fetofetale transfusion is the uneven distribution of blood between twins; affects about 13-33% of monozygotic twin pregnancies monochorioten. If it is a significant transfusion volume may occur during donor to a pronounced anemia and heart failure, whereas the receiver can develop polycythemia and hyperviscosity syndrome. Among the umbilical cord abnormalities include Insertio velamentosa, vasa praevia and abdominal or placental insertion; hemorrhage may be caused by shear or tearing, and is often solid, fast and life threatening. The most common are two reasons for a loss of blood through the placenta previa are the placenta and placental abruption that. Diagnostic procedures that can lead to hemorrhage, are amniocentesis, chorionic villi and the extraction of blood samples from the umbilical cord. Perinatal bleeding may be caused by falling birth (ie fast and spontaneous birth, which means that there is a hemorrhage due to the rupture of the umbilical cord) Obstetric accidents (z. B. incision of the placenta during caesarean section, birth trauma) coagulation disorders Kephalhämatome as a result measures such as vacuum extraction or forceps delivery are usually harmless, by contrast, subgaleal bleeding can quickly spread into the soft tissues and absorb as much blood, causing anemia, to shock and eventually death. Newborns with cerebral hemorrhage can lose enough blood in their intracranial vault to cause anemia and sometimes hemodynamic disturbances – in contrast to older children who have a lower heart-body ratio, and in which cerebral hemorrhages are limited in volume, because the associated cranial sutures do not allow it to expand the skull. Thus, increases in older children the intracranial pressure and stops the bleeding. Much less common is a plan of the liver, spleen or adrenal performs as part of the birth of internal bleeding. Intraventricular hemorrhage, most often in preterm infants (intracranial haemorrhage) may just as subarachnoid and subdural bleeding lead to a significant decrease in hematocrit. Severe bleeding in the newborn (vitamin K deficiency) occur within a few days after an uneventful birth as a result of a temporary physiological deficiency of vitamin K-dependent coagulation factors (Factors II, VII, IX and X). These factors are transported through the placenta to only a small extent and since vitamin K is synthesized by the intestinal bacteria, very little of which is generated in the first sterile intestine of the newborn. Vitamin K deficiency bleeding comes in three forms: Early Classic (in the first 24 hours) (1 week of age) Late (. 2-12 weeks of age) The early form is the maternal ingestion of a medicament, which enables production of vitamin K inhibits (e.g., certain anticonvulsants, isoniazid, rifampicin, warfarin. prolonged use of broad spectrum antibiotics of the mother, which suppress the colonization of intestinal bacteria) caused. The classic form occurs in newborns who received no vitamin K supplementation after birth. The late form occurs in breast-fed babies who received no vitamin K supplementation after birth. Administering from 0.5 to 1 mg of vitamin K i.m. Immediately after birth, the coagulation factors activated. This is a hemorrhagic disease of the newborn is prevented. Other causes of bleeding in the first few days, other coagulopathies (eg. As hemophilia), disseminated intravascular coagulation (DIC) during sepsis or Gefäßfehlbildungen.Verminderte erythropoiesis disorders Erytrhopoese are innate Acquired by the extremely rare congenital defects are the Blackfan -Diamond anemia and Fanconi anemia, the most common. The Blackfan-Diamond anemia is characterized by macrocytic red blood cells, lack of erythrocyte precursor cells in the bone marrow and lack of reticulocytes in peripheral blood; other cell lines are not affected. Often, but not always, it is part of a syndrome with other congenital abnormalities such as microcephaly, cleft palate, eye malformations of the thumb and a short net-like neck. Up to 25% of affected children are anemic at birth, 10% have a low birth weight. Up to 25% of affected children are anemic at birth, and 10% have a low birth weight. The cause faulty stem cell differentiation is suspected. Fanconi anemia is an autosomal recessive disease of the precursor cells in the bone marrow; there is a macrocytosis and reticulocytopenia with a progressive failure of all hematopoietic cell lines. The diagnosis is usually done after the neonatal period. The cause is a genetic defect by which the cell’s own mechanisms for repairing damaged DNA and to eliminate cell-damaging toxic free radicals are not working properly. Another congenital anemia is the Pearson’s syndrome, a rare multisystem disease with failures of the mitochondria, which may be a refractory sideroblastic anemia, pancytopenia and also variable to liver, kidney and pancreatic insufficiency or lead -versagen; Other anemias are the kongentitale congenital dyserythropoietic anemia, which is typically macrocytic and is chronic due to a pathological ineffective production of red blood cells, and finally the hemolysis of red blood cells due to defects. Acquired lesions are those that occur after birth. The most common causes are infections malnutrition infections such as malaria, measles, syphilis, HIV, CMV, adenovirus, bacterial sepsis may affect erythropoiesis in the bone marrow. The congenital parvovirus B19 and human herpes virus-6 infections can lead to a complete cessation of erythropoiesis. The lack of certain trace elements and vitamins such as iron, copper, folic acid and vitamins E and B12 can not lead at birth to anemia in the first months of life, but usually. The incidence of iron deficiency, the most common nutritional deficiency is higher in less developed countries, which is due on the one hand due to malnutrition, the other by the sole and exclusive breastfeeding. Iron deficiency is also found in such newborns often whose mothers have an iron deficiency, as well as in premature infants who did not receive transfusions and their diet was not supplemented accordingly; if there is insufficient supply iron stores in preterm infants 10-14 weeks erschöpft.Hämolyse hemolysis can be caused by autoimmune disorders of the erythrocyte membrane enzyme deficiency hemoglobinopathies infections In all cases there is a hyperbilirubinemia, which can lead to jaundice and kernicterus. The immune-mediated hemolysis occurs as a result of intolerance of infantile and maternal blood. First, having to fetal red blood cells with their surface antigens (mostly rhesus [Rh] and AB0, but also Kell, Duffy and other minor antigens), which differ from the maternal red cell antigens enter the maternal circulation and the production of specific antibodies (IgG) directed against the fetal red blood cells, stimulate. This occurs mostly during the pregnancy or birth of the first-born child; the most common is the constellation Rh-negative (antigen-D-negative) the mother and Rh-positive fetus. With a further Rh-positive pregnancy IgG antibodies cross the placenta and cause fetal and neonatal hemolysis (fetal erythroblastosis). Intrauterine hemolysis can be so difficult pronounced that hydrops or the fetal is the result. Postnatal there is a significant anemia and hyperbilirubinemia with a continuous hemolysis, as the maternal IgG antibodies persist according to their durability (half-life about 28 days). Because of widespread prophylactic administration of anti-D IgG to prevent sensitization only <0.11% of pregnancies Rhesus negative mothers are affected. AB0-incompatibility can cause hemolysis by a similar mechanism. AB0 incompatibility usually occurs in mothers with blood group 0th Mothers with blood groups A, B or AB produce anti-A or anti-B antibodies, which are predominantly IgM and will not be transported across the placenta. Hemolysis by AB0 incompatibility is less severe than that caused by Rh sensitization, although some children develop quite significant hemolysis and hyperbilirubinemia usually. Hemolysis resulting from an AB0-incompatibility can occur even at first pregnancy occasionally. Mothers are often sensitized by antigens in foods or bacteria, which causes an initial IgM response. Although the IgM does not go into the placenta, this awareness causes amnesic response, resulting in an IgG production if there is an exposure to fetal blood during pregnancy. Erythrocyte membrane defects change the shape and deformability of the red blood cells, thereby leading to early elimination from the organism. The most common diseases are hereditary spherocytosis and hereditary elliptocytosis ? ?. Enzyme deficiency of glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase are the most common leading to hemolysis enzyme defects. G6PD deficiency is a gender-specific disease that occurs in people of Mediterranean, Oriental, African and Asian ancestry and affects> 400 million people worldwide. It is believed that this disorder protects against malaria and it has an estimated allele frequency of 8% in malaria areas. Pyruvate kinase deficiency is an autosomal dominant inherited disease that occurs in all ethnic groups. Pyruvate kinase deficiency is rare and occurs in about 51 out of a million Europeans and Americans humans. Hemoglobinopathies are characterized by missing or structurally altered globin chains. At birth, 55-90% of the neonatal hemoglobin from 2 Alpha 2 and gamma-globin chains (fetal hemoglobin or HbF [alpha2gamma2]) are assembled. After birth, the formation of gamma chains decreases (to <2% under the age of 2-4 years), the formation of ? chains doing about it, until adult hemoglobin (HbA [alpha2beta2]) predominates. Alpha-thalassemia is a genetic disease with a reduced formation of alpha globin chains; it is the most common hemoglobinopathies that results in the neonatal anemia. Beta-thalassemia is a hereditary disease with a reduction in the formation of beta-globin chains. Since ?-globin at birth is scarce anyway, beta-thalassemia and structural changes of the beta globin chain are not clinically recognizable already postnatally (Hb S, Hb C [eg, sickle cell anemia.]); Symptoms occur only when the fetal Hb has fallen at an age of three to four months to sufficiently low levels. Intrauterine infection by certain bacteria, viruses, fungi and protozoa (v. A. Malaria) can also cause hemolytic anemia. In malaria Plasmodium parasite invades the red blood cells and causes it to burst. It finally comes to an immune-mediated destruction of parasitized and an excessive removal of non-infected erythrocytes. The associated dyserythropoiesis in the bone marrow leading to undue compensatory erythropoiesis. Intravascular hemolysis extravascular phagocytosis and dyserythropoiesis lead to anemia. Symptoms and signs The symptoms and findings, whatever its cause, similar but vary in severity and the frequency with which it comes to anemia. Newborns are pale and tachycardic in severe anemia and tachypneic generally; occasionally a bruit is auscultation. In an acute blood loss may lead to hypotension, at a hemolysis for jaundice. Clarification history The history should focus on maternal factors (eg. As bleeding, congenital red cell disorders, nutritional deficiencies, drugs), the family history with regard to hereditary diseases that can cause neonatal anemia (eg., Alpha-thalassemia, enzyme deficiencies, Erythrozytenmembran- disorders, red cell aplasia) and obstetric factors focus (z. B. infections, vaginal bleeding, obstetrical procedures, mode of birth, blood loss, treatment and appearance of umbilical cord pathology of the placenta, fetal stress, number of fetuses). Certain non-specific maternal factors may be additional notes. Splenectomy can reveal a possible preloading with hemolysis, red cell membrane disorder or autoimmune anemia; cholecystectomy, however, can provide an indication of a bias with hemolysis induced gallstones. Significant neonatal factors gestational age at birth, the age of onset, gender and ethnic Zugehörigkeit.Körperliche investigation Tachycardia and hypotension are indicate an acute and significant blood loss. Is jaundice before, it is suspected to hemolysis, either systemically (caused by AB0-incompatibility or G6PD deficiency) or localized (caused by degradation sequestered blood at a Cephalhematoma). Hepatosplenomegaly suggests hemolysis, a congenital infection or heart failure. Hematoma, bruising and petechiae are evidence of bleeding diathesis. Congenital malformations can the suspicion of a bone marrow disease nahelegen.Tests Anemia may be suspected prenatally if by ultrasound, a rising middle cerebral blood flow or fetal hydrops shows, which by definition is abnormal or pathological massive accumulation of fluid in two or more body cavities ( z. B. pleura, peritoneum, pericardium) can be seen. An enlargement of the heart, the liver and the spleen may also be detected. After birth, the hemoglobin and hematocrit levels can be checked for suspected anemia. If they are low, the following tests are performed: number of reticulocytes blood smear exam If the reticulocyte count low (it is usually increased when Hb and hematocrit are low), the anemia caused by an acquired or congenital dysfunction of the bone marrow and the child should be examined for causes of bone marrow depression. The following tests shall be performed: titer or PCR tests for congenital infection (rubella, syphilis, HIV, CMV, adenovirus, parvovirus, human herpesvirus 6) folic acid and vitamin B12 levels of iron and copper levels If these tests no cause of identify anemia, Knochenmarkbiobsie, genetic testing for congenital disorders of red cell production, or both may be necessary. When the Retikulozytenanzahl increased or normal (proper bone marrow reaction), the anemia caused by blood loss or hemolysis. If no blood loss is evident or when signs of hemolysis on the peripheral smear were observed or the bilirubin level is increased (which can occur with hemolysis), a direct antiglobulin test (DAT [Coombs test]) should be performed. Is the direct antiglobulin test (DAT) is positive, the suspicion of anemia by Rh, AB0 or ??other blood group incompatibility is obvious. The DAT test is always positive for Rh incompatibility, but sometimes negative in AB0 incompatibility. Toddlers can have an active hemolysis by AB0 incompatibility, while a negative DAT value; However, in these cases should microspherocytes can be detected in the peripheral blood smear, and the direct antiglobulin (Coombs) test is usually positive. Is the direct antiglobulin test (DAT) is negative, the mean corpuscular volume may be (MCV) further insight. A significantly low average volume of red blood cells indicates ?-thalassemia or, less commonly, iron deficiency caused by chronic intrauterine blood loss. Both can be differentiated by the red blood cell distribution width (EVB) that is often normal in thalassemia and increases in iron deficiency. In a normal or high MCV and a pathological morphology in blood smears may be a red cell membrane defect, microangiopathy, disseminated intravascular coagulation (DIC), or a hemoglobinopathy. Infants with hereditary spherocytosis often have an increased mean corpuscular hemoglobin concentration (MCHC). When the blood smear is normal, there is a suspicion of a loss of blood, an enzyme defect or infection; a corresponding clarification on fetomaternal circulation, is necessary. A fetomaternal blood loss can be diagnosed by the detection of fetal red blood cells in maternal blood. The most common test is the Kleihauer-Betke Säureeluations technique; the fluorescent antibody technique and the Agglutinintest apply. In the Kleihauer-Betke technique, a citrate phosphate buffer eluted with a pH value of 3.5 adult hemoglobin, but not fetal red blood cells; characterized fetal erythrocytes can be stained with eosin and visualized under a microscope, whereas the adult red blood cells appear as lysed erythrocytes. The Kleihauer-Betke technique is not useful if the mother has a hemoglobinopathy. Treatment The treatment required perinatal anemia depends on the degree of anemia and the medical consequences associated with it. Mild anemia in otherwise healthy premature infants requires no special treatment generally; a treatment depends on the diagnosed underlying disease. Some patients need a transfusion, if necessary, exchange transfusion with packed red blood cells. Transfusion The transfusion is indicated for severe anemia. A transfusion should be considered in infants considered if symptoms of anemia are present or if it is suspected a limited supply of oxygen in the tissue. The decision for transfusion should be made taking into account the symptoms of age and severity of the disease. The hematocrit value alone should not be the deciding factor for transfusion because some infants may be asymptomatic at low values, while others may be at higher values ??symptomatic. The limits for the indication for transfusion vary; an accepted policy is described in transfusion guidelines for infants <4 months. Transfusion guidelines for infants <4 months Hkt criteria * for transfusion of red blood cells <45% congenital cyanotic heart defect using ECMO ventilation <35% using O2 crested at> 35% FiO2 application of CPAP or mechanical ventilation with mean airway pressure> 6 8 cm H2O <30% application of additional O2 using a CPAP or mechanical ventilation Significant changes in heart rate or respiratory rate <20% Low Retikulozytenanzahl and symptoms of anemia (eg. As tachycardia, tachypnea, poor diet) * At least one of these criteria must also be present. outside the normal range, for example,> 6 episodes of apnea within 12 hours, with 2 episodes of apnea require within 24 h mask ventilation (with administration of therapeutic doses of methylxanthines), a heart rate> 180 / h min 24, clinically significant bradycardia and a respiratory rate> 80 / h min for 24 hours. CPAP = Beatmumgsform combining the spontaneous breathing of the patient with a permanent pressure; ECMO = extracorporeal membrane; FiO2 = fractional inspired O2. Adapted from Roseff SD, Luban NLC, Manno CS: Guidelines for assesing appropriateness of pediatric transfusion. Transfusion42 (11): 1398-1413, 2002. If possible, even before the first transfusion, if not already done, maternal and fetal blood should be monitored for blood type and Rh factor and atypical red cell antibodies and a Coombs test the child’s red blood cells are made. The blood for transfusion should be with both the blood group and the Rh factor in the newborn as well as with all AB0 and Rh antibodies that can be detected in the mother’s or child’s blood, same or compatible. Since newborns rarely make antibodies against erythrocytes of persistent transfusion requirements re antibody screening before the age of 4 months is required. The erythrocyte concentrates used for transfusion is requested filtered (leukocyte depleted) and irradiated, and then added in increments of 10-20 ml / kg of the same donor blood; sequential transfusions of the same blood minimize the exposure of the receiver and thus transfusion complications. Blood cytomegalovirus negative donors should werden.Austauschtransfusion considered for very premature infants into consideration in the exchange transfusion are alternately taken from the newborn blood transfused portions and packed red blood cells; the indication for replacement is in some cases of hemolytic anemia with an increase in serum bilirubin and in some cases, severe anemia with heart failure and in cases where infants are normovolemic with chronic blood loss. By this method, the serum antibody titers and the bilirubin levels are reduced and minimizes excess liquid. Serious side effects (eg, thrombocytopenia;. Necrotising enterocolitis, hypoglycemia, hypocalcemia, shock, pulmonary edema, or both [caused by changes in fluid balance]) are not uncommon, so this measure should only be performed by experienced personnel. The guidelines, when exchange transfusion performed to differ and are not evidenzbasiert.Weitere therapeutic measures, the administration of recombinant human erythropoietin is not routinely recommended, u. a. because it could not be proven that this transfusion frequency may be reduced in the first two weeks of life. An iron therapy is to cases of repeated blood loss (z. B. bleeding, gastrointestinal bleeding, frequent blood sampling) is limited. Oral administration of iron is preferable; gelegentlich kommt es bei der parenteralen Verabreichung von Eisen zu einer Anaphylaxie, sodass die Therapie von einem Hämatologen überwacht werden sollte. Die Behandlung seltener Anämieformen richtet sich nach der Grunderkrankung (z. B. Corticosteroide bei der Blackfan-Diamond-Anämie, Vitamin B12 bei Vitamin-B12 -Mangel). Wichtige Punkte Unter Anämie versteht man eine Verringerung der roten Zellmasse oder des Hämoglobins. Sie wird bei Neugeborenen in der Regel dann diagnostiziert, wenn der Hb- oder Hkt-Wert bei > 2 Standardabweichungen unter dem Altersdurchschnitt liegt. Zu den Ursachen der Anämie bei Neugeborenen gehören physiologische Prozesse, Blutverlust, verringerte Erythrozytenproduktion und erhöhte Erythrozytenzerstörung. Physiologische Anämie ist der hauptsächliche Grund von Anämie in der neonatalen Phase und erfordert keine generelle eingehende Untersuchung oder Behandlung. Neugeborene mit Anämie sind in der Regel blass und bei einer schweren Anämie auch tachykard und tachypnoisch. Die erforderliche Behandlung richtet sich nach dem Grad der Anämie und den damit verbundenen medizinischen Folgen. Eine leichte Anämie bei ansonsten gesunden frühgeborenen Kindern erfordert in der Regel keine spezielle Behandlung; eine Behandlung richtet sich nach der diagnostizierten Grunderkrankung.