Haemolytic Disease of the Newborn
Created | Updated Jun 5, 2009
Midwives and doctors have known about haemolytic disease of the newborn (HDN; also known as erythroblastosis foetalis or rhesus disease) since the early 17th Century. The root of the disease was unknown until the 1930s, when it was observed that infants with the condition had abnormally immature blood cells in their circulatory system. With advances in knowledge regarding blood groups in the 1940s and 1950s, the cause of HDN was finally pinned down to an incompatibility between the rhesus blood group of the mother and foetus.
Why does it happen?
The road to HDN begins when a mother with a rhesus-negative blood group becomes pregnant with a rhesus-positive foetus. If this first pregnancy proceeds normally (ie the pregnancy is not ectopic1 and there is no damage to the placenta) then the foetus is unlikely to be at risk of HDN. However, during delivery of the infant, there is a good chance that the mother's bloodstream will be exposed to blood from the foetus. The rhesus proteins are recognised as foreign and antibodies are produced to direct the immune system to destroy them. More importantly, these antibodies remain in the mother's blood - this creates a condition described as sensitised to rhesus proteins. The first infant is safe, but future pregnancies now carry a risk.
If the mother becomes pregnant again with a rhesus-positive foetus, the anti-rhesus antibodies can cross the placenta into the bloodstream of the foetus and attack red blood cells. This second foetus will then develop some, or all, of the symptoms of HDN.
It is important to note that if a rhesus-negative woman has been exposed to rhesus proteins before becoming pregnant for the first time, then a first pregnancy with a rhesus-positive foetus is at risk. This is why preventative measures should be taken with all rhesus-negative women who become pregnant (see below).
As knowledge of blood groups has progressed, it is now known that blood groups other than rhesus can cause HDN. Immune responses to these groups, such as Duffy, Kell and MNS, are much rarer than those to rhesus proteins.
Infants born with HDN usually develop jaundice - a condition in which there is an accumulation of chemicals ('bile pigments'2) formed by the breakdown of haemoglobin, within 24 hours after birth. This symptom is accompanied by an enlarged liver and spleen3. In severe cases, there is tissue swelling4 all over the body caused by fluid leaking out of blood vessels. The destruction of blood cells by the immune system also means that these infants are anaemic.
Around half of affected newborns do not require any treatment and will recover naturally. Some 25% are born at or near full-term and become extremely jaundiced. Without treatment, these infants will die or suffer kernicterus - damage to the brain and other organs caused by build up of bile pigments. The remaining 25% become severely affected while still in the uterus.
If the foetus is known to be affected before 20 - 22 weeks of pregnancy, treatment is by plasmapheresis. Blood is taken from the mother, and the plasma - which contains the anti-rhesus antibodies - removed. The remainder of the blood, together with a solution of protective antibodies that prevent further damage in the foetus, is returned to the mother.
After 22 weeks, the foetus is developed enough for direct transfusion to be carried out. In the past, the transfusion was given into the peritoneum, the membrane surrounding the intestines and other abdominal organs. With modern ultrasound techniques, the transfusion can be given directly into the foetal circulation. O-negative blood5 is transfused in regular batches until the haemoglobin level of the foetus has returned to normal. The transfusion is then repeated when necessary until the foetus is delivered.
After birth, further treatment may be required. Treatment may also be needed by infants with milder forms of the disease who did not need treatment in the uterus. Treatments used include phototherapy, which helps to treat jaundice by breaking down bile pigments in the skin, or blood transfusion.
Fortunately, HDN is preventable. If a rhesus-negative woman becomes pregnant, she is given protective antibodies after 28 weeks of pregnancy. A second dose is given after birth if the baby is rhesus-positive. These antibodies bind to any rhesus proteins that enter the mother's bloodstream, thereby hiding them from the mother's immune system until they are naturally broken down and removed from the body.
Using rhesus immunisation, it is highly unlikely that the mother will become sensitised to rhesus proteins during the birth of a rhesus-positive child. Therefore, if the mother should again become pregnant with a rhesus-positive foetus, there is little chance of HDN developing. Since the development of these preventative techniques, the incidence of HDN is around one in every 1000 births (0.1%). Of those foetuses who do develop the condition, only 10% require transfusion while still in the uterus.