Rh-negative mothers who have become sensitised to the D-antigen in an Rh-positive fetus develop anti-D antibodies which can cross the placenta and attack the blood of Rh-positive fetuses in subsequent pregnancies. This leads to the condition usually referred to as Rhesus Isoimmunisation 1 2, but also referred to as Haemolytic Disease of the Newborn and Erythroblastosis fetalis. This condition primarily involves haemolysis of red blood cells before and after birth. In severe cases fetal anaemia develops, causing congestive cardiac failure ("hydrops fetalis"). The other consequence of haemolysis is release of haemoglobin which is rapidly converted to unconjugated bilirubin (SBR). The fetus is protected because of placental removal of bilirubin, but following birth the rapidly rising SBR places the baby at risk of kernicterus.
Incidence and risk factors:
The incidence of Rhesus isoimmunisation has dramatically declined since the implementation of prophyaxis (treatment of Rh-negative mothers with anti-D antibody following birth of an Rh- positive baby, or in association with miscarriages, termination, ectopic pregnancies and other invasive proceedures). Once very common, we now treat about only 5 cases/year. Factors which increase the risk of kernicterus for a given SBR level include:
Consequences of disease
Positive Coombs Tests without maternal sensitization
Occasionally the situation arises where rhesus-negative mothers who receive anti-D immunoglobulin prophylaxis close to the baby's birth, have a baby with a positive Coombs test, with antibodies identified as anti-D. These cases have only been seen in the last couple of years since propylactic anti-D has been routinely given. This is passively transferred antibody, and may be associated with significant jaundice. However, no such cases at RPA have led to the need for exchange transfusion.
Other causes of haemolytic jaundice
Other haemolytic antibodiesAntibodies similar to anti-D but much less common may cause a similar clinical picture to rhesus isoimmunisation. These include anti-C, anti-Kell, anti-Duffy, etc. They are usually managed along similar lines to rhesus disease.
Diagnosis is straight forward when the blood groups are appropriate and the Direct Coombs Test is positive. It can be difficult when the evidence points towards ABO, but the Direct Coombs Test is negative. In this case the diagnosis is likely if the mother's plasma contains anti-A or anti-B IgG antibody, and the same antibody is detectable on the baby's RBC's. This assumes other etiologies have been excluded.
Glucose-6-phosphate dehydrogenase deficiencyG6PD is a cytoplasmic enzyme that catalises the first step in the hexose monophosphate pathway producing NADPH, and is responsible for the generation and maintenance of reduced glutathione. This protects the red blood cell membrane from the deleterious effects of oxidation.
The G6PD gene lies on the X chromosome, and over 300 mutants have been described. The normal variety is GdB, and the severe form, first described in the mediterranean region and later in SE asia, is called GdMed. This has nearly zero activity in all cells. Because of the high gene frequency in some regions, homozygous affected females are not uncommon.
G6PD deficiency is associated with severe, rapidly rising jaundice, following one of a number of documented triggers. The most important in our experience are firstly naphthalene ("moth balls"), and secondly fava beans ("broad beans"). Other triggers include infection and drugs. For a full list, see triggers. Early, aggressive phototherapy is warranted, but exchange transfusion is still often required.
References1. Hsia DY-Y, Allen FH, Gelliss SS, Drummond LK. Erythroblastosis fetalis, VIII: studies of serum bilirubin in relation to kernicterus. N Engl J Med. 1952; 247:668-671
2. Mollison PL, Cutbush M. Haemolytic disease of the newborn. In: Gairdner D, ed. Recent Advances in Pediatrics. New York, NY: P Blakiston & Son; 1954:110
3. Brodersen R, Stern L. Deposition of bilirubin acid in the central nervous system: a hypothesis for the development of kernicterus.Acta Pediatr Scand. 1990; 79:12-19
4. Brown AK, Kim MH, Wu PYK, Brylaa DA. Efficacy of Phototherapy in Prevention and Management of Neonatal Hyperbilirubinemia. Pediatrics 1985; 75(Suppl): 393-400
5. Alcock GS, Liley H. Immunoglobulin infusion for isoimmune haemolytic jaundice in neonates. (Cochrane Review). In: The Cochrane Library, Issue 2, 2003. Oxford: Update Software.
Last Reviewed: May, 2003