Icterus neonatorum haemolyticus
Definition and introduction
What is Icterus neonatorum haemolyticus (Morbus haemolyticus neonatorum)? Difference to physiological neonatal jaundice. Prevalence and significance.
Icterus neonatorum haemolyticus, also known as Morbus haemolyticus neonatorum (MHN), is a specific form of neonatal jaundice caused by pathological haemolysis, i.e. the accelerated breakdown of erythrocytes (red blood cells). In contrast to physiological neonatal jaundice, which occurs in around 60% of all mature babies and up to 80% of premature babies and is caused by a temporary immaturity of liver function, MHN is characterised by an immunologically induced destruction of the child's erythrocytes. In physiological jaundice, the bilirubin concentration in the blood is also increased, but to a lesser extent and without underlying haemolysis. The prevalence of MHN varies greatly depending on ethnicity and the presence of risk factors such as rhesus or AB0 incompatibilities between mother and child. In countries with effective rhesus prophylaxis programmes, the incidence of Rh-related MHN has fallen significantly. Nevertheless, MHN remains a significant clinical problem, as untreated it can lead to serious complications such as kernicterus (bilirubin encephalopathy), an irreversible damage to the brain caused by high bilirubin levels. Early detection and adequate treatment of MHN are therefore crucial to prevent long-term neurological damage and ensure the health of affected newborns.
Aetiology and pathogenesis
Causes of haemolysis in the newborn. Rhesus incompatibility (Rh incompatibility): Mechanism of antibody formation, role of maternal antibodies (IgG), sensitisation, effects on the foetus. AB0 incompatibility: frequency, severity, differences to Rh incompatibility. Rare causes: Other blood group incompatibilities (e.g. Kell, Duffy), enzyme defects (e.g. glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency), erythrocyte membrane defects (e.g. spherocytosis, elliptocytosis).
Icterus neonatorum haemolyticus is caused by increased haemolysis of the fetal or neonatal erythrocytes. Rhesus incompatibility (Rh incompatibility) is a significant cause. In this case, a Rh-negative mother, sensitised by a previous pregnancy with a Rh-positive child or a transfusion with Rh-positive blood, forms IgG-type antibodies against the Rh-D antigen of the foetal erythrocytes. These maternal IgG antibodies cross the placental barrier and bind to the foetal erythrocytes, leading to their destruction in the foetal spleen and liver. Sensitisation of the mother can already occur during the first pregnancy, although antibody production usually only takes place to a relevant extent after birth and therefore mainly affects subsequent pregnancies. AB0 incompatibility is more common than Rh incompatibility, but is generally less severe. It occurs when the mother has blood group 0 and the child has blood group A or B. The maternal anti-A or anti-B antibodies (usually IgG) can also cross the placenta and cause haemolysis in the foetus. In contrast to Rh incompatibility, sensitisation may already have occurred before pregnancy through contact with A- or B-like antigens in the environment. Other blood group incompatibilities, for example against Kell or Duffy antigens, are less common. In addition to immunological causes, genetic defects in the erythrocytes can also lead to haemolysis. These include enzyme defects such as glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) or pyruvate kinase deficiency, which impair the energy supply to the erythrocytes. Erythrocyte membrane defects, such as spherocytosis or elliptocytosis, also lead to an increased susceptibility to haemolysis due to the altered shape and stability of the cells.
Diagnostics
The diagnosis of Icterus neonatorum haemolyticus involves a multi-stage procedure, starting with a detailed medical history. The mother's blood group and rhesus factor are of particular importance here, as well as information about previous pregnancies, especially those with subsequent neonatal jaundice or necessary transfusions. The clinical examination focuses on the assessment of jaundice, whereby the Cramer scheme is used to estimate the bilirubin level based on the spread of the yellow colouration from cranial to caudal. Attention is also paid to hepatomegaly, splenomegaly and the presence of oedema, which could indicate hydrops fetalis. As part of the laboratory tests, the blood group and rhesus factor of both the newborn and the mother are determined. The direct Coombs test (direct antiglobulin test) is used to detect antibodies that are bound to the newborn's erythrocytes, while the indirect Coombs test detects free antibodies in the mother's serum. It is essential to determine the bilirubin levels, differentiated according to total, direct and indirect bilirubin, in order to assess the severity of the jaundice. In addition, haemoglobin, haematocrit and the reticulocyte count are determined in order to determine the extent of the anaemia and the compensatory erythropoiesis. A blood smear is used to look for morphological abnormalities in the erythrocytes, such as spherocytes or elliptocytes, which may indicate membrane defects. If rare causes are suspected, such as glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), further screening tests can be carried out.
Clinical manifestations
Jaundice, or icterus, is the main symptom of Icterus neonatorum haemolyticus. It is manifested by a yellowish discolouration of the skin and sclera, resulting from the accumulation of indirect bilirubin in the tissue. The course and severity of jaundice are variable and depend on the cause and extent of haemolysis. In the case of rhesus incompatibility, jaundice can already develop intrauterine, whereas in the case of AB0 incompatibility it often only occurs postnatally. Anaemia often develops in parallel with jaundice, with symptoms ranging from pallor and tachycardia to shortness of breath, depending on the degree of haemoglobin loss. In severe cases, especially in the case of untreated rhesus incompatibility, hydrops fetalis can develop, characterised by generalised oedema, ascites and pleural effusions. This is caused by severe anaemia and the resulting cardiac insufficiency. The prognosis of hydrops fetalis is unfavourable. The most feared complication of Icterus neonatorum haemolyticus is kernicterus, also known as bilirubin encephalopathy. It occurs when unconjugated bilirubin, due to its lipophilicity, crosses the blood-brain barrier and is deposited in the basal ganglia, the hippocampus and other regions of the brain. Risk factors for the development of kernicterus are high bilirubin levels, prematurity, asphyxia, hypoalbuminaemia and infections. In the acute phase, kernicterus manifests itself through lethargy, drinking weakness, muscle hypotonia and seizures. In the chronic stage, irreversible neurological damage such as choreoathetosis, hearing impairment, visual paralysis and mental retardation result. Rarer complications of Icterus neonatorum haemolyticus include ascites and pleural effusions, which can occur particularly in the context of hydrops fetalis.
Therapy
The primary aim of treatment for neonatal haemolytic jaundice is to quickly and effectively reduce the bilirubin level in the newborn's serum in order to prevent the dreaded complication of kernicterus, irreversible damage to the brain caused by bilirubin deposits. Phototherapy is a cornerstone of the treatment. It uses blue light in the wavelength range of 400-500 nm to convert the indirect (unconjugated) bilirubin in the skin into water-soluble isomers, which can then be excreted via the bile and urine. The indication for phototherapy depends on the gestational age of the child, the age in hours and the bilirubin level, with appropriate nomograms being used for decision-making. Possible complications include dehydration, skin rashes and, in rare cases, bronze baby syndrome. Close monitoring of temperature, fluid balance and bilirubin levels is essential during phototherapy. If the bilirubin level rises rapidly or exceeds critical thresholds, especially if phototherapy is not sufficiently effective, an exchange transfusion may be necessary. In this invasive procedure, the newborn's blood is gradually replaced with donor blood, removing bilirubin, antibodies and sensitised erythrocytes. The exchange transfusion is associated with risks such as infections, thrombosis, electrolyte disturbances and, in rare cases, cardiovascular complications, which is why it should only be carried out in specialised centres. Intravenous immunoglobulins (IVIG) can be used to support Rh and AB0 incompatibility. They work by blocking the Fc receptors of the macrophages and thus reducing haemolysis. Supportive measures, such as ensuring adequate fluid intake, are also important to promote the excretion of bilirubin and prevent dehydration. Prevention is a key aspect of therapy. Rhesus prophylaxis, consisting of the administration of anti-D immunoglobulin to Rh-negative mothers after the birth of a Rh-positive child or after invasive prenatal procedures, prevents sensitisation of the mother and thus the development of antibodies that could endanger future pregnancies.
Prognosis
The prognosis of Icterus neonatorum haemolyticus is highly dependent on the severity of the haemolysis and the timing of the start of treatment. Early diagnosis and adequate treatment are crucial to prevent serious complications. Cases that are left untreated or treated too late can lead to kernicterus, an irreversible damage to the brain caused by bilirubin. The risks and long-term consequences of kernicterus are manifold and include choreoathetosis (involuntary movements), hearing impairment, gaze palsy (paralysis of the eye muscles) and mental retardation. These neurological deficits significantly impair the quality of life of the affected children and require lifelong therapeutic interventions. Early detection through screening for hyperbilirubinaemia and the rapid initiation of phototherapy or exchange transfusion are therefore of central importance in order to ensure a favourable outcome and minimise long-term morbidity. Close monitoring of bilirubin levels and customisation of therapy are essential to reduce the potential risks and promote the best possible development of the child.
Prevention
Prevention plays a crucial role in avoiding Icterus neonatorum haemolyticus, especially due to Rhesus incompatibility. Rhesus prophylaxis, consisting of the administration of anti-D immunoglobulin to Rh-negative mothers, is an established and effective measure. Rhesus prophylaxis is indicated for all Rh-negative women who are expecting a Rh-positive child or who are at risk of a foetomaternal transfusion. The timing of administration is crucial: anti-D immunoglobulin is administered as standard in the 28th week of pregnancy in order to prevent sensitisation of the mother by any fetal erythrocytes that may have already entered her circulation. It is also administered after invasive procedures during pregnancy, such as amniocentesis or chorionic villus sampling, and after events that are associated with an increased risk of foetomaternal transfusion, such as miscarriage, extrauterine pregnancy or blunt abdominal trauma. Immediately after the birth of a Rh-positive child, rhesus prophylaxis is administered again to prevent sensitisation for future pregnancies. In addition to active prophylaxis, informing parents about the risks and symptoms of haemolytic neonatal disease is of great importance. This includes information about the possible consequences of rhesus incompatibility, the importance of regular check-ups and the need to seek medical help immediately if symptoms such as jaundice, poor drinking or lethargy occur in the newborn. Comprehensive information enables parents to be actively involved in prevention and early detection and thus minimise the risk of serious complications for their child.
Current research and developments
New therapeutic approaches. Improved diagnostics. Importance of genetic counselling. Outlook for future prevention strategies.
Research into Icterus neonatorum haemolyticus is currently focussing on several promising areas. New therapeutic approaches include research into drugs that could inhibit bilirubin production or accelerate bilirubin breakdown, which would reduce the need for phototherapy or exchange transfusions. In the field of diagnostics, improved, non-invasive methods for measuring bilirubin are being developed that enable more precise and gentle monitoring of bilirubin levels. The importance of genetic counselling is increasing, especially in families with a known history of enzyme defects such as G6PD deficiency or hereditary spherocytosis, in order to better assess the risk of haemolysis in the newborn and take preventive measures. Future prevention strategies could be based on a more comprehensive genetic analysis of the parents in order to identify risk constellations at an early stage and develop individualised prevention plans. Another research focus is on optimising rhesus prophylaxis in order to further reduce the sensitisation rate and improve the effectiveness of anti-D immunoglobulin administration.
Icterus neonatorum haemolyticus and frequency nosodes
Icterus neonatorum haemolyticus occurs at different frequencies, which can vary depending on geographical location, ethnicity and the presence of specific risk factors. The frequency of this disease is particularly high in populations where there is a higher rate of rhesus incompatibility or AB0 incompatibility. Epidemiological studies have shown that the prevalence of Icterus neonatorum haemolyticus is higher in developing countries where access to prenatal care and effective treatment may be limited. Genetic factors may also play a role, as certain ethnic groups are predisposed to develop immunological reactions that cause haemolysis. Accurate recording and monitoring of the incidence of Icterus neonatorum haemolyticus is crucial in order to plan preventive measures and optimise healthcare for affected newborns.
