Blood particles in focus

Anti-D for Rhesus Negative Women

There are four main blood groups: A, B, AB and O and alongside your blood group is the Rhesus factor with the ‘D antigen’ being an important substance that stimulates your immune system to produce antibodies.

The Rhesus factor (usually abbreviated to ‘Rh’) is a molecule that is found on the surface of our red blood cells. Where people have this molecule called the ‘D antigen’ on the surface of their red blood cells they are referred to as being ‘Rhesus D positive’ (Rh D +). It is estimated that around 85 in 100 people in the general population are Rh D positive.

If the ‘D antigen’ is not present on the red blood cells then these individuals are referred to as being ‘Rhesus D negative’ (Rh D -).

Around 15 in every 100 people are Rh D negative.

A person’s Rhesus factor is genetically determined ie it is inherited from their parents. This means that a baby can inherit either its mother’s or father’s Rhesus factor, so a Rhesus negative mother can carry a baby that has inherited its father’s Rhesus positive blood type.


What are the implications of being Rhesus negative in pregnancy?

During pregnancy tiny amounts of the developing baby’s blood can sometimes cross the placenta and enter the mother’s blood stream – this is referred to as ‘sensitisation’ or ‘isoimmunisation’. While it is unusual for this to happen, because mother and baby have separate blood circulatory systems, there are some circumstances where the mother’s and baby’s blood can come into contact (see list below). If this happens and the blood of a Rhesus D positive baby transfers to a Rhesus D negative mother; the mother’s immune system will view the baby’s blood as a ‘foreign invader’ (‘antigen’) that needs to be destroyed.

The mother’s immune system will produce antibodies which destroy all the baby’s blood cells in her circulatory system. The mother’s immune system is very efficient and remembers how to produce these antibodies again but much more quickly and in much larger numbers. Therefore, if the Rhesus negative mother and Rhesus positive baby’s blood types come into contact with each other again, lots of antibodies will be produced quickly to destroy the baby’s blood cells.

This becomes a problem when these antibodies cross the placenta and begin to attack and destroy the baby’s circulating blood cells whilst they are still developing inside their mother’s uterus (womb). Where this happens, it can cause a number of life-threatening conditions in the baby – anaemia, jaundice, and, in severe cases, permanent damage to the baby’s brain and their nervous system. These conditions are collectively termed, ‘Haemolytic Disease of the Newborn’ (HDN).


Can HDN be prevented?

A blood sample is taken at your ‘Booking’ appointment in early pregnancy to check your Blood Group and Rhesus factor. This is important even if you book late in pregnancy. It means that if you are found to be Rhesus D negative, your midwife and doctor will be very aware of this during your pregnancy and can take steps to ensure your body’s immune system does not produce antibodies against this baby, or any future babies. This is done by giving you an injection of Anti-D immunoglobulin into the muscle of your upper arm.

Close-up of a vial with a medical injectionImmunoglobulin is a major part of the body’s immune response system.

The Anti-D immunoglobulin neutralises any Rhesus D positive antigens that have entered the mother’s blood stream during pregnancy. By neutralising these antigens it prevents the mother’s immune system from ‘learning’ to make Rhesus D antibodies. An injection of Anti-D immunoglobulin should be given whenever there is an actual or suspected risk of sensitisation/isoimmunisation. As part of this, the Rhesus negative mother will be asked to consent to a blood test called a ‘Kleihauer’.


What is a Kleihauer?

The Kleihauer involves taking a small sample of the mother’s blood to check for the presence of antibodies and fetal blood cells within the mother’s blood stream. This is done before she is given an additional injection of Anti-D immunoglobulin – NB. The Anti-D should be given as soon as possibly and always within 72 hours of any actual or potential sensitising event.


When can sensitisation/isoimmunisation occur?

There are specific circumstances where the baby’s blood may enter its mother’s blood stream and sensitisation (isoimmunisation) occurs. They include:

  • Miscarriage (usually after 12 weeks’ of pregnancy)
  • Termination of pregnancy (TOP)
  • Vaginal bleeding
  • During Amniocentesis or Chorionic Villus Sampling (CVS) which can cause trauma to the placenta
  • Antepartum haemorrhage (APH)
  • Ectopic pregnancy
  • Abdominal trauma or injury eg a road traffic collision or fall
  • External Cephalic Version (ECV) – Turning a breech baby
  • At the time of your baby’s birth – when it is almost certain that yours and your baby’s blood will come into contact with each other
  • Intrauterine death.

Should actual or potential sensitisation/isoimmunisation occur, it is important that you inform your midwife or doctor immediately so that they can arrange for you to have a Kleihauer test and be given the injection of Anti-D immunoglobulin without delay.


What is Anti-D immunoglobulin?

Anti-D immunoglobulin is a blood product that is obtained from the blood plasma of human donors who have been sensitised to Rhesus D positive cells. The anti-D that we use within UK maternity services is imported from countries where there are no reported cases of Variant CJD and the donor’s blood has been thoroughly screened and has tested negative to the blood-borne viruses: HIV and Hepatitis B & C. The immunoglobulin is also treated to deactivate any viruses, so the risk of contracting a virus from an injection of Anti-D remains extremely low. The Anti-D injection has been used for almost 50 years in the UK and is considered to be safe for both you and your baby. The research evidence in support of Anti-D immunoglobulin injections indicates that the benefits of preventing sensitisation/isoimmunisation far outweigh the small risks.

Studies show that Anti-D is a very simple and highly effective means of destroying fetal blood cells in the mother’s blood stream before the immune system produces antibodies to destroy them.

Because Anti-D immunoglobulin is a blood product there is a very stringent process that is followed to ensure that women are able to give their informed consent; that the anti-D is prescribed by a doctor and its administration is checked by two midwives and documented in the woman’s hand-held maternity records.


Are there any side-effects associated with Anti-D immunoglobulin?

It is very rare for an injection of Anti-D immunoglobulin to cause an allergic response. Those rare reactions that have been reported include the following:

  • Localised discomfort/inflammation at the injection site
  • Itching and rashes
  • Mouth ulcers
  • Joint pains/flu-like symptoms
  • Dizziness and shaking
  • Very rarely, shortness of breath and swelling in the face.

For these reasons, your midwife and doctor will always recommend that the injection is given in a GP surgery, Health Centre or Hospital and that you remain there for 20 minutes after having the injection. Your midwife and doctor will also ask you to let them know immediately if you begin to feel unwell or experience any side-effects after having the injection.

Antenatal prophylaxis (preventative treatment)

Studies show that a small number of women – one to two in every 100 pregnancies, will become sensitised/isoimmunised without any obvious sensitising event having taken place. This has prompted the recommendation that prophylactic Anti-D immunoglobulin (preventative treatment to stop something happening) is given routinely to all Rhesus D negative women during pregnancy – this is called Routine Antenatal Anti-D Prophylaxis (RAADP)

The National Institute for Health and Clinical Excellence (NICE) recommends that Rhesus D negative women are routinely offered an injection of Anti-D immunoglobulin during the third trimester of pregnancy. This aims to ensure that Anti-D will be available in the woman’s circulatory system to provide maximum protection during the last 12 weeks of her pregnancy. This is because it is more likely that small amounts of blood from the baby will pass into the mother’s blood stream at this time.


How is Routine Antenatal Anti-D Prophylaxis (RAADP) offered?

There are currently two ways that women receive RAADP:

  • A one-dose treatment – where women receive an injection of Anti-D immunoglobulin sometime during the 28th – 30th week of their pregnancy
  • A two-dose treatment – where women receive two injections: one during the 28th week of pregnancy and the second during the 34th

There doesn’t appear to be any difference in the effectiveness of either approach; however, maternity services may choose to adopt the one-dose treatment because it ensures more effective use of their resources and time. Your midwife and doctor will explain which approach is favoured by your own local maternity services.

The Care Pathway for women consenting to Routine Antenatal Anti-D Prophylaxis (RAADP):

  • A routine blood test is offered at 28-30 weeks to check for the presence of antibodies and an injection of Anti-D immunoglobulin is given
  • Should there be any subsequent sensitising events; a further injection of Anti-D will be given after every known or suspected sensitising event
  • Bloods are taken after the birth – A Kleihauer (from the mother) and a sample of cord blood (from the baby) taken once the placenta has been delivered
  • If the baby’s blood type is found to be Rhesus D positive; the mother is given an injection of Anti-D immunoglobulin within 72 hours post birth. This helps to ensure that no Rhesus D antibodies are present in the mother’s blood stream to harm her or any future babies.

stk25191nwlInformed Choice

Some women will make an informed decision not to have prophylactic Anti-D during pregnancy. However, should a sensitising event occur they will always be advised to have an injection of Anti-D after each known ‘event’. The only circumstances in which you may not need the anti-D injection are where you have chosen to be sterilised, or you are certain that you won’t be having any more children. However, if there is any possibility that you will become pregnant again your midwife and doctor will always recommend that you have the Anti-D injection.

Anti-D immunoglobulin after your baby’s birth

As previously mentioned, once your baby has been born, a sample of your baby’s blood will be taken from the section of umbilical cord attached to the placenta. This blood sample is sent to a laboratory to check your baby’s Blood Group and Rhesus factor. If you are Rhesus D negative and your baby is found to be Rhesus D positive, and you haven’t already been sensitised, you will be offered an injection of Anti-D immunoglobulin within 72 hours of giving birth. The injection acts by coating your baby’s blood cells to disguise them from your body’s immune system. This prevents anti bodies being made to destroy the baby’s blood cells before they degrade naturally.

The information provided in this article is, by its nature, rather complex. We therefore recommend that you discuss this topic in greater detail with your own midwife or doctor, to ensure your understanding and are able to make informed decisions.

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