Rhesus factor disease

Causes of rhesus disease

Rhesus disease is caused by a specific mix of blood types between a pregnant mother and her unborn baby.

Rhesus disease is only possible if:

  • The mother is rhesus negative (RhD negative).
  • The baby is rhesus positive (RhD positive).
  • Sensitisation (see below) has previously occurred.

Blood types

There are several different types of human blood known as blood groups with the four main ones being A, B, AB and O. Each of these blood groups can either be RhD positive or negative.

Whether someone is RhD positive or RhD negative is determined by the presence of the rhesus D antigen (RhD). An antigen is a protein molecule found in blood (see antigens and antibodies below). People who have this antigen are RhD positive, and those without it are RhD negative. In the UK, around 85% of the population are RhD positive.

How are blood types inherited?

Your blood type depends on the genes that you inherit from your parents. Whether you are RhD positive or negative depends on how many copies of the RhD antigen you have inherited. For example, you could inherit one copy of the RhD antigen from your mother or father, a copy from both of them or none at all.

You will be RhD positive if you have inherited either a single copy of the RhD gene (called heterozygote Dd) from one of your parents, or two copies (called homozygote DD); one from each of your parents. To be RhD negative you must have inherited no copies of this gene (called homozygote dd).

If your blood is mixed with a different blood type, it will have a reaction to it. Each type contains different antigens, and, in response to antigens from a different blood type, your blood will produce antibodies.

RhD-positive baby

If a woman who is RhD negative (homozygote dd) has an RhD-positive male partner (heterozygote Dd, or homozygote DD) there is a chance their baby will be RhD positive.

If the male partner has two copies of the D antigen (homozygote DD), the baby will definitely inherit one copy of the D antigen and will be RhD positive.

RhD-negative baby

If the male partner has one copy of the D antigen (heterozygote Dd), there is a 50% chance the baby will be RhD positive, and a 50% chance that they will be RhD negative. An RhD-negative baby will not get rhesus disease because their red blood cells will not have the RhD antigen, so the antibodies will have nothing to recognise and attack.

What are antigens and antibodies?

Antigens are protein molecules found on the surface of red blood cells in plasma. Plasma is the liquid that makes up your blood. Blood groups are identified by the antigens and antibodies that are present in the blood.

Antibodies are your body's natural defence against any foreign antigens that enter your blood. An antibody is a protein that is produced by the body to destroy disease-carrying organisms and toxins. If your blood comes into contact with blood that carries different antigens, your body will produce antibodies to those antigens. The antibodies will destroy the foreign blood cells.

The first time your blood comes into contact with another type of blood and has this response, it is called sensitisation.


An RhD-positive baby will only have rhesus disease if the RhD-negative mother has been sensitised to RhD-positive blood. 

Sensitisation happens when a mother who is RhD negative is exposed to RhD-positive blood for the first time and has an immune response to it.

During the immune response, the woman’s body recognises that the RhD positive blood cells are foreign and prepares to attack them. Her body does this by designing a specific antibody to target the D antigens in the RhD-positive blood cells. Once the design is ready, her body can start producing the antibody.

However, at this stage there will probably not be enough time to start producing the antibody before the RhD-positive blood is naturally filtered out of her system. Therefore, during sensitisation, it is unlikely that any foreign blood cells will actually be destroyed by the antibodies.

The next time RhD-positive blood cells enter the woman’s blood, the design will be ready and the correct antibodies can be produced straight away. This time, enough antibodies will be produced to start destroying the foreign blood cells. If this occurs, the baby will develop rhesus disease.

How does sensitisation occur?

The most likely time that RhD-positive blood cells could have entered the mother’s blood is during an earlier pregnancy with a baby who was RhD positive.

During pregnancy, sensitisation can happen if:

  • Small numbers of foetal blood cells cross into the mother’s blood during a normal pregnancy.
  • Blood of the mother and baby come into contact during delivery.
  • There has been bleeding in the pregnancy.
  • An invasive procedure has been necessary during pregnancy – such as amniocentesis, or chorionic villus sampling (CVS).
  • The mother has had an abdominal injury.

Sensitisation can also occur after a previous miscarriage, or ectopic pregnancy, or if an RhD negative woman has received a transfusion of RhD positive blood.

Last updated: 12 July 2012

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