Blood groups and red cell antibodies in pregnancy
What are blood groups?
Red blood cells are the most common cells in your blood stream. They carry the oxygen you breathe around your body. Your red cells have natural proteins on the surface which make up your blood groups. These blood groups are inherited from your parents.
The four main blood groups are group O, group A, group B and group AB. But you also have another blood group called D (also known as “RhD”).
So, for example, you could be Group A, D positive, or Group A, D negative. In addition to ABO and D groups everyone has other, minor blood groups. Two of the minor blood groups that can be important in pregnancy are ‘c’ (little c) and ‘K’ (Kell).
What are red cell antibodies?
Antibodies are your body’s natural defence against anything which is different from yourself. For example, a virus, vaccine or a different blood group. They are part of your immune system and protect your body against harmful invasions like infections.
You may form antibodies if blood cells with a different blood group from your own enter your blood stream. This can happen because of a blood transfusion or during pregnancy.
How are these antibodies made during pregnancy?
A few of your baby’s blood cells may ‘leak’ into your blood during pregnancy. This usually happens when the baby is born.
If your baby’s blood group is different from your own, your immune system may produce antibodies. This is rare. Only about three in 100 pregnant women develop antibodies, and most of these are harmless. The illustrations over the page show how this happens.
Why are blood groups and red cell antibodies important when I’m pregnant?
There are three main reasons:
1. If you need a blood transfusion.
If you need a blood transfusion the blood selected for you must be the correct blood group. It must also be the correct match for any antibodies you have.
2. To ensure you and your baby get the right treatment.
If tests show that you have made antibodies to your baby’s blood you may need extra treatment.
How could red cell antibodies affect my baby?
Antibodies are generally harmless, but they can move from your blood stream into your baby’s blood. Your baby’s red cells could be damaged if they have the blood group which matches these antibodies. The illustrations on the previous page show how this can happen.
In most cases the baby is not harmed. However, certain antibodies, particularly if they are strong, could destroy the baby’s red cells. This condition is called haemolytic disease of the fetus and newborn (HDFN) previously called Rhesus disease. HDFN can cause anaemia, jaundice and in severe cases brain damage or death, either while the baby is in the womb or after delivery.
The antibody called anti-D causes the most common form of HDFN. The antibodies remain in the mother’s blood and they could also damage the red cells of a subsequent baby, if he or she has the same blood group as the first.
Is there a test to see if my baby would be affected by the antibodies I have?
Yes, there is a test called Fetal Blood Group Genotyping, to determine your baby’s blood group type specific to the antibodies you have, however this test is not available for all antibodies. If your baby’s blood type is the same as yours, your baby will not be affected by the antibody you have and you will not have to have the tests outlined in the next paragraphs. Please discuss having this test with your obstetrician or your midwife.
What will happen if I have antibodies to my baby’s blood cells?
If you have antibodies you may be offered regular blood tests to measure the levels.
Your baby may be monitored by ultrasound scan during your pregnancy. This is just a precaution, and generally no treatment is needed. However, if the antibody levels rise very high, your baby may need to be delivered early. Your baby may also be tested soon after birth to make sure he or she is not anaemic.
Sometimes babies will need a blood transfusion in the womb. This is very rare and is performed in specialist hospital departments. This is called an intrauterine transfusion.
What are the risks to me and my baby if my baby needs a transfusion in the womb?
Your obstetrician will discuss with you the need of transfusing your baby in the womb, if the scan and laboratory tests show that your baby is at a high risk of HDFN. The risk to your baby, of not having this transfusion, is very high at this stage and could result in severe harm to your baby.
Any intervention incurs risks; please discuss these with your obstetrician prior to the procedure. It is not within the scope of this leaflet to outline these particular risks.
Which antibodies cause most problems?
Anti-D is the antibody most likely to cause problems as it is the commonest antibody that can cause HDFN in your baby. Anti-D can form if your blood group is D negative and your baby’s is D positive. There is a way to prevent anti-D antibodies forming, see point 3. To find out if you are D negative in the next section.
Anti-c (‘little c’) and anti-K (Kell) are other antibodies which can cause HDFN.
3. To find out if you are D negative
If I am D negative, how am I affected?
It is important that you have a blood group test early in your pregnancy. If you are D negative you will be told about treatment during your pregnancy to prevent the formation of anti-D. This is important; if you form anti-D in this pregnancy it might affect a subsequent baby who has a D positive blood group.
How can I avoid making anti-D?
If you are D negative you can avoid making the antibody by receiving anti-D injections of a ‘ready-made’ antibody. This harmless antibody removes your baby’s red cells from your blood before your own body is able to make an antibody to fight these red cells.
What are anti-D injections and what are its associated risks?
Anti-D injections are made from plasma. Plasma is the fluid part of blood, which transports blood cells around the body. The plasma used in anti-D injections is collected from specially selected blood donors. It is also known as ‘prophylactic anti-D’ or ‘anti-D immunoglobulin’. It has been used successfully for over 30 years.
Can anti-D injection cause any adverse effects?
Common side effects: Soreness at the injection site is common. The soreness lasts for a few hours to a day or two.
Uncommon side effects: a mild fever, headache or rash. Very occasionally women can experience an allergic reaction to anti-D injections. If you have any concerns, please speak to your midwife or obstetrician.
Transmission of infection from anti-D injections has never occurred in the UK despite thousands of doses having been administered to pregnant women every year since the late 1960s. A very small risk of infection from the plasma donors cannot however be completely ruled out.
What is the failure rate of anti-D injections?
The failure rate is 0.37% according to the NICE Health Technology Assessment 2003.
Please speak to your midwife or obstetrician, if you have any concerns.
Do all D negative mothers need anti-D?
Anti-D injections are only needed if a D negative woman is pregnant with a D positive baby. In about one in three pregnancies, the baby will be D negative, and the anti-D injection would be unnecessary.
By identifying the unborn baby’s blood group, we can ensure that only women who need it will receive anti-D.
Please see below: When will I need treatment?
When the unborn baby’s blood group is known to be D negative, injections will not be needed. If healthcare staff do not know the baby’s D blood group, then an anti-D injection would be recommended.
Please speak to your midwife or obstetrician, if you would like to have a test which determines your unborn baby’s D group. Please note that this test is now available at most hospitals in England at the time of publication.
When will I need treatment?
If you are D negative and need anti-D injections (see above ‘Do all D negative mothers need anti-D) you will need treatment at the following times:
During pregnancy – routine treatment
If you are D negative you should be offered ‘anti-D’ during the last three months of your pregnancy. This is called ‘routine antenatal prophylaxis’. It is normally given as an injection at 28 and 34 weeks of pregnancy. However, you may be offered just one larger dose at 28 weeks.
During pregnancy – after an incident
There are some incidents which can cause your baby’s cells to leak into your blood:
- Hospital treatment for miscarriage or threatened miscarriage
- Termination of pregnancy
- Injury to your abdomen, such as a seat belt injury or a fall
- Vaginal bleeding
- Some tests such as amniocentesis (when a small sample of the fluid surrounding your baby is taken)
- Turning your baby from breech (bottom first) position by a doctor or midwife.
You will need an injection of anti-D after any of these events when you are 12 weeks pregnant or more. You should receive the injection within three days of any of these incidents, but it can work up to ten days later. Your doctor or midwife will advise you. The injection will not affect your baby.
After childbirth
Your baby will be tested after birth. If the baby is D positive it is important that you are offered an injection of anti-D within three days of giving birth. Ask your midwife or obstetrician for more information.
What if I do not want to receive anti-D injections?
When you are offered anti-D injections, either during your pregnancy or following the birth of your baby, you can choose whether or not to accept them. Receiving the injections of anti-D is recommended in order to protect any more babies you might have against HDFN. Speak to your midwife or obstetrician if you need more information.
Further Information
If you have questions about the information in this leaflet, or if there are things that worry you, please ask your obstetrician or midwife.
You may also find these websites useful:
D negative Mother's blood test to check her unborn baby's blood group
Why is it important to know my D blood type (previously known as “Rhesus D”, “RhD” or “Rhesus”)?
Identifying your blood group and detecting red cell antibodies in pregnant women is important to prevent haemolytic disease of the fetus and newborn (HDFN).
In addition to the four main blood types/blood groups, O, A, B and AB there is another clinically significant blood group/type called D. People may be D positive or D negative. A person’s blood group is usually shortened to, for example, A positive or A negative (the terms ‘positive’ and ‘negative’ relate to the D blood group status). 15% of people have a D negative blood group.
What is Haemolytic Disease of the Fetus and Newborn (HDFN)?
HDFN, previously known as rhesus disease, is a blood disorder in a fetus (an unborn baby) or a newborn baby. HDFN may develop when a mother and her unborn baby have different blood types (called ‘incompatibility’). The mother produces substances called antibodies that attack the developing baby’s red blood cells.
The D status only matters if a D negative mother is carrying a D positive baby. If any of the red blood cells from the D positive baby get into the blood of the D negative mother, her immune system may recognise the D protein on the surface of the baby’s red cells as a ‘foreign’ substance and produce D antibodies. Women who are D positive do not produce D antibodies.
Anti-D antibodies can cross from the mother’s blood into the unborn baby’s blood and destroy the baby’s red blood cells causing anaemia, jaundice and in severe cases brain damage or even death of the baby while in the womb or after delivery.
The antibodies remain in the mother’s blood and they may also damage the red cells of a subsequent D positive baby.
How can haemolytic disease of the fetus and newborn (HDFN) be prevented?
HDFN is prevented by giving anti-D injections to mothers who are D negative and have no D antibodies. This treatment can usually prevent HDFN and has been routine practice for many years.
What is anti-D and what are its associated risks?
Anti-D injections are made from plasma. Plasma is the fluid part of blood, which transports blood cells around the body. The plasma used in anti-D injections is collected from blood donors.
Can anti-D injection cause any adverse effects?
Common side effects: Soreness at the injection site is common. The soreness lasts for a few hours to a day or two.
Uncommon side effects: a mild fever, headache or rash. Very occasionally women can experience an allergic reaction to anti-D injections. If you have any concerns, please speak to your midwife or obstetrician.
Transmission of infection from anti-D injections has never occurred in the UK despite thousands of doses having been administered to pregnant women every year since the late 1960s. The possibility of a very small risk of infection from the plasma donors cannot however be completely ruled out. Please speak to your midwife or obstetrician, if you have any concerns.
Do all D negative mothers need anti-D?
Anti-D injections are only needed if a D negative woman is pregnant with a D positive baby. In about one in three pregnancies, the baby will be D negative, and the anti-D injection would be unnecessary.
By identifying the unborn baby’s blood group, we can ensure that only women who need it will receive anti-D.
Anti-D is offered if it is possible that some of the baby’s blood may have passed into the pregnant woman’s blood, for example, if there is vaginal bleeding, if there has been an injury to the pregnant woman of any kind, or if a doctor or midwife needs to undertake some form of investigation or treatment for the mother or baby during pregnancy, such as amniocentesis. When the unborn baby’s blood group is known to be D negative, injections will not be needed. If healthcare staff do not know the baby’s D blood group, then an anti-D injection would be recommended.
Determining the unborn baby’s blood group (fetal blood group)
A small amount of the unborn baby’s DNA is present in the mother’s blood. By detecting the baby’s DNA in the mother’s blood, it is possible to determine the unborn baby’s D blood group. This is the fetal RHD screening test.
NHS Blood and Transplant is now able to offer this screening test to hospitals in the UK and Ireland.
Can I have this test if I carry twins?
You can have the fetal RHD screening test if you carry more than one baby. If at least one of your babies is D positive you will need anti-D.
Where and when can I have a fetal RHD screening test to determine my baby’s blood group?
A sample of your blood for the fetal RHD screening test can be taken by your community midwife from 11 weeks plus 2 day’s gestation (usually 15 weeks) onwards.
How will the results affect my treatment?
Unborn baby is D positive
If your blood test report shows that your unborn baby is D positive, or the result is inconclusive, you will be offered an anti-D injection. However, 2.0% of these babies may in fact be D negative. This is of no concern as anti-D prophylaxis would have been offered in all cases if DNA testing had not taken place and the injection will not harm your baby.
Unborn baby is D negative
If the unborn baby is predicted to be D negative, we suggest you do not have anti-D injections before or after giving birth.
How accurate is the fetal RHD screening test?
If the unborn baby is predicted to be D negative there is a very small chance (0.1%, or 1:1000) that the baby might be found to be D positive after birth. In this case you will be given an anti-D injection at that time
What is the risk when my baby was predicted D negative but tests D positive at birth?
Only 1% of D negative women become sensitised if they receive anti-D injections at birth only and do not receive anti-D at 28 weeks. The possibility of getting sensitised is reduced to 0.35% when you receive anti-D injections at 28 weeks and at birth.
What is the failure rate of anti-D injections?
The failure rate is 0.37% according to the NICE Health technology assessment 2003.
What if I attend a different hospital?
When you attend another hospital, they may wish to offer you anti-D even if your baby is D negative. Please show them this leaflet and your fetal RHD screening test results.
What options do I have?
When you have the test results, you can request to have the anti-D injection even if the result predicts that the unborn baby is D negative.
Equally you can decline to have anti-D injection(s) even if we recommend it in cases where your unborn baby is predicted to be D positive.
To understand the implications of the results from your fetal RHD screening test and your treatment options, we recommend discussing your wishes with your midwife, doctor or other lead clinician who is responsible for your care.
Further Information
If you have questions about the information in this leaflet, or if there are things that worry you, please ask your doctor or midwife.
You may also find these websites useful:
Protecting women and babies with anti-D immunoglobulin
Blood Groups
Just as every human being is unique, so are the factors in your blood. People can have one of four blood groups: A, B, AB and O, which are formed by substances carried on the red blood cells.
There is another important difference in people’s blood called ‘Rh factor’, or D-type, which is a protein found on the red blood cells. Blood group and D-type are inherited from both parents.
People who are ‘Rh’ positive have what is known as the D antigen on the surface of their red blood cells – they are said to be D-positive.
People who are ‘Rh’ negative do not have the D antigen on their blood cells – they are D-negative.
In Europe around 85% of people are D-positive and 15% D-negative.
Why is the ‘Rh’ D-type important in pregnancy?
Unborn babies inherit their blood type from BOTH parents. This is important because pregnant women with D-negative blood can carry babies who have D-positive blood, having inherited the factor from the father.
It is important to realise that not ALL babies who have D-positive fathers will have D-positive blood.
Inside the womb, the placenta usually acts as a barrier between the red blood cells of the mother and baby. However, even in normal pregnancies small amounts of the baby’s blood may cross over into the mother’s blood stream. The most common time for a baby’s blood cells to get into the mother’s blood is at the time of birth.
But it can happen at other times, for example during a miscarriage or termination of pregnancy, or if something happens during the pregnancy such as having an amniocentesis, chorionic villus sampling, vaginal bleeding or after abdominal injury such as following a fall, a blow to the abdomen or trauma from a seat belt.
If any of the blood cells from a D-positive baby get into the blood of a D-negative woman, she recognises the D antigen on the baby’s blood cells as a foreign protein and may produce antibodies to it.
This is called ‘sensitisation’, and anything that could cause the mother to produce antibodies against the D antigen is called a ‘potentially sensitising event’.
As a general rule the first child that triggers this sensitisation does not suffer any adverse consequences, as it will already have been born by the time antibodies have developed.
However, if the woman becomes pregnant again with a D-positive baby, antibodies may cross into the baby’s bloodstream and attack the baby’s red blood cells.
This is called ‘haemolytic disease of the fetus and newborn’ or ‘HDFN’.
HDFN can be mild, but if more severe can lead to anaemia, heart failure, jaundice, brain damage, or even to the death of the baby.
With further pregnancies and further D-positive babies the risk of earlier and more severe HDFN increases and the outcomes can be more serious. This is why a preventative measure such as the use of anti-D prophylaxis is so important.
There are about 65,000 births of D-positive babies to D-negative mothers in England and Wales each year and it is estimated that, without routine preventative treatment, there would be over 500 problem pregnancies each year, leading to the deaths of over 30 babies and more than 20 brain damaged children.
Prophylaxis with anti-D immunoglobulin
Prophylaxis means giving a medicine to prevent something happening. Anti-D prophylaxis means giving a medicine called anti-D immunoglobulin to prevent a D-negative woman producing antibodies against D-positive blood cells and so to prevent the development of HDFN in an unborn baby.
Thanks to prophylaxis with anti-D immunoglobulin, sensitisation during pregnancy and after childbirth can now largely be prevented.
Anti-D immunoglobulin is given as an injection, usually into the muscle of the upper arm (intramuscular injection) or sometimes into a blood vein (intravenous injection).
What exactly is anti-D immunoglobulin?
Anti-D immunoglobulin is made from the clear part of the blood, called plasma, and is sourced from donors in countries outside of the UK. As with all blood products, donors are screened very carefully and the plasma is treated during manufacture so that the chance of passing on any infection is very low.
Anti-D prophylaxis during pregnancy
a) Potentially Sensitising Events
In the event of potentially sensitising events such as the examples listed below, additional injections of anti-D immunoglobulin may be necessary.
- Impending or actual miscarriage.
- Ectopic pregnancy.
- Termination of pregnancy (abortion).
- Vaginal bleeding.
- Obstetric interventions such as chorionic villus sampling, amniocentesis, or external cephalic version (ECV) in a breech presentation.
- Abdominal injury e.g. after a fall, blow to the abdomen or a traffic accident.
In order to reduce the possible effects of a sensitising event, it is crucial to report any events such as vaginal bleeding or abdominal injury to your midwife or doctor as soon as possible.
b) Routine prophylaxis
Generally, all pregnant women who are D-negative and who have not already been sensitised (those who have antibodies to the D-antigen) are advised to have prophylaxis with an anti-D immunoglobulin, even if they have already received anti-D for a sensitising event. This is known as ‘routine antenatal anti-D prophylaxis’, or ‘RAADP’. Depending on the dose given, you will either receive a single injection of 1500IU between the 28th and 30th week of pregnancy, or two lower dose injections, one at 28 and one at 34 weeks.
Anti-D prophylaxis after childbirth
After birth, your baby’s blood group will be tested. If your baby is found to be D-positive, you will receive a further injection of anti-D immunoglobulin, ideally within 3 days of delivery for it to be effective. This is known as ‘postnatal prophylaxis’. If baby’s blood group has not been tested, or if there is any doubt as to the result, then you should receive anti-D.
Does every D-negative pregnant woman need prophylaxis?
There are certain circumstances when this treatment may not be necessary:
- If you have opted for sterilisation after birth, though it may still be routinely offered.
- If you are certain that the father of the child is D-negative.
- If it is certain you will not have another child after the current pregnancy.
- If your antenatal clinic offers a screening test looking at your baby’s DNA in your blood that can show whether the baby is D-negative.
What should I do next?
If you are pregnant and have been informed that you are D-negative, the person responsible for delivering your antenatal care (midwife, obstetrician or GP) should discuss anti-D prophylaxis with you and explain the options available so that you can make an informed choice about your treatment.
Anti-D prophylaxis following miscarriage, termination of pregnancy or stillbirth
The loss of any pregnancy, for whatever reason, is traumatic for all those involved and there are many competing concerns following such a difficult time. However, it is still important to receive anti-D immunoglobulin, to reduce the risk of sensitisation and problems in following pregnancies. This is the case even when it is not possible to determine the baby’s blood group.
Your midwife, nurse or doctor should discuss anti-D prophylaxis with you so that you are able to make an informed choice as to your treatment. Generally, anti-D prophylaxis is advised for:
- Any woman undergoing expectant, surgical or medical management of miscarriage (including molar pregnancy).
- Any woman undergoing expectant, medical or surgical management of ectopic pregnancy.
- Any woman undergoing medical or surgical termination of pregnancy (abortion).
- At diagnosis of intrauterine death and again following delivery of the baby.
Remember – If in doubt, do not be afraid to ASK!
You may also find the following websites useful: