Introduction – what does RhD negative mean?
Just as every human being is unique, so are the characteristics of your blood. People can belong to one of four blood groups: A, B, AB & O. They are also either rhesus (RhD) positive or rhesus (RhD) negative. Together these are usually shortened, for example to “A positive” or “O negative”. In the UK around 85% of people are RhD positive and 15% RhD negative. People who are RhD negative do not have the rhesus D antigen on their red blood cells. Whether a person is RhD positive or RhD negative is determined by their genes, that is, it is inherited from their parents.
The following information is for pregnant women and people who have been advised by their healthcare professional that their blood type is RhD negative. It provides advice on how having this blood type affects your pregnancy, and what tests and treatments are available to you during pregnancy and after the birth of your baby. The information in this leaflet is based on current guidance from NICE (National Institute for Health and Care Excellence) and NHS Blood and Transplant (NHSBT). There is a useful A-Z of terms at the end of this information sheet.
Why does RhD status matter in pregnancy?
Your rhesus status matters if you are RhD negative and become pregnant with a baby who is RhD positive. This is also known as “incompatibility”. This can only happen if the baby’s biological father or sperm donor is RhD positive. However, not all babies born to an RhD positive biological father or sperm donor will be RhD positive, because the biological father or sperm donor may have both RhD positive and RhD negative genes. Your rhesus status is not a problem if you are RhD positive and your baby is RhD negative.
During pregnancy it is possible that your baby’s blood cells could enter your bloodstream in an event known as a feto-maternal haemorrhage (FMH). Should a large enough amount of blood cells from an RhD positive baby enter your blood, you will react to the D antigen in your baby’s blood as though it is a foreign substance and antibodies will be produced against it. This is known as sensitisation or “alloimmunisation” and it depends on how big the volume of FMH is and the level of your immune response to this.
The most common time when your baby’s blood cells may enter your bloodstream is at the time of birth. However, it can happen at other times in pregnancy, for example during a miscarriage or abortion, or following a medical procedure such as amniocentesis. It can also occur following an episode of vaginal bleeding or an injury to your bump. An event that could cause an FMH where you produce antibodies against the D antigen is called a ‘potentially sensitising event’.
Once sensitisation has occurred it is irreversible. This can affect future pregnancies because the antibodies now present in your blood can cross the placenta and attack the blood cells of an RhD positive baby. This can cause babies to have a condition called haemolytic disease of the fetus and newborn (HDFN) – also known as “Rhesus disease”. HDFN is sometimes very mild but can still cause jaundice. This is treatable but requires a longer postnatal stay for your baby and in some cases a blood transfusion. However, HDFN can be very serious and lead to severe anaemia and jaundice which can cause babies to be stillborn, die after birth or have severe, permanent disabilities. The antibodies remain in your blood so this is why HDFN can occur in future pregnancies once sensitised.
Today HDFN is an uncommon condition as it can be easily prevented through the administration of prophylactic anti-D injection given at 28 weeks and after birth. This reduces the chance of sensitisation to 0.35%. Anti-D is also recommended as a treatment if you experience a potentially sensitising event. It is important to know that without anti-D sensitisation cannot be prevented and once sensitised, anti-D treatment is no longer effective. Sensitisation is permanent and cannot be undone.
What is anti-D prophylaxis?
Prophylaxis is the word given to a medicine that is used to prevent something happening harmful condition developing. Anti-D prophylaxis involves giving you special antibodies to prevent your body from producing your own antibodies against RhD positive blood cells. Thereby it prevents sensitisation and in turn prevents the development of HDFN.
These special antibodies are taken from part of the blood called plasma which is collected from non-UK blood donors whose plasma have high levels of anti-D. The production of these anti-D antibodies is very strictly controlled and processed. This ensures that the chance of a known virus being passed from the donor to the person receiving them is extremely low. As with all medications and blood products, there is a very low risk of allergic reaction. Therefore, if you receive anti-D you should wait in the clinic where it was given for at least 20 minutes afterwards to ensure you don’t experience an adverse reaction.
What are my options if I have an RhD negative blood type?
Anti-D is only needed if an RhD negative woman or person is pregnant with an RhD positive baby. In about one in three pregnancies, the baby will be RhD negative and an anti-D injection would therefore not be necessary. By identifying an unborn baby’s blood group, we can reduce the amount of unnecessary anti-D injections that are given.
The Rosie hospital, together with NHS Blood and Transplant (NHSBT), can now offer a simple screening test to predict your baby’s blood type – called fetal RhD screening. This involves taking a blood sample from you from 11+2 weeks onwards. At this point of pregnancy, some of your baby’s DNA (genetic information) will be detectable in your blood stream making it possible to predict whether your unborn baby is RhD negative or RhD positive.
It is important that you are aware that this is the ONLY information about your baby’s DNA that is screened for during this test. The screening can also be carried out even if you have a multiple pregnancy (twins or more).
We recommend that the fetal RhD screening blood test is taken immediately after you have your dating/combined screening scan between 11+2 and 14+1 weeks. You must have a signed consent form with you for this test and your estimated due date should be updated on this following your scan. The consent form should have been sent to you when we wrote to tell you that your blood type is RhD negative. If you have not received this, please contact 01223 217664. The blood test can be taken in the Rosie phlebotomy department in clinic 21, level 1 of the Rosie. It can be done at the same time as the “combined screening” test for Edward’s, Patau’s and Down’s syndromes if you have also chosen to have these tests too.
We offer the fetal RhD screening test until 25 weeks. This is to make sure there is time to arrange an anti-D injection at 28 weeks should you require this.
All these tests are optional – it is your choice whether to take these tests or not. If you are unsure about what to do please speak to your midwife or obstetrician. There are further sources of information and support also listed below.
Benefits of fetal RhD screening
If your unborn baby is predicted to be RhD negative then you require no further treatment or tests. This means you avoid having unnecessary anti-D injections and it takes away any worry you may feel about your baby or future babies being at risk of developing HDFN.
Risks of fetal RhD screening
There is a very small chance that the fetal RhD screening predicts the wrong blood type. The chance of this happening is about 0.1%, or 1 in 1,000 unborn babies that are screened. Therefore, after your baby’s birth we will double-check your baby’s blood type by taking a sample of blood from the umbilical cord to confirm that your baby is RhD negative. The result is usually available in about 2 hours, so it shouldn’t delay you going home.
If an unexpected result comes back indicating your baby is RhD positive, we will discuss the implications of this with you. We will recommend that we take a blood test from you to check if an FMH has occurred and also take a blood sample from your baby to confirm their blood type. We would also offer you an anti-D injection within 72 hours of the birth. Even if the screening test is proven to be wrong, the chance of sensitisation having occurred during pregnancy without prophylactic anti-D is only 1% (assuming you then receive the anti-D injection following birth and confirmation of your baby being RhD positive).
What if the screening predicts that my baby is RhD positive or I decide that I don’t want the test to find out my baby’s blood type?
You may decide you don’t wish to have fetal RhD screening done, or you may have found out that your baby’s blood type is predicted to be RhD positive. Rarely an inconclusive result comes back which means it wasn’t possible to predict your baby’s blood type. In all of these scenarios we recommend routine anti-D prophylaxis. About 2% of babies predicted to be RhD positive will in fact be RhD negative. However, if DNA testing had not taken place, an anti-D injection would have been offered anyway and the injection does not harm your baby.
Routine antenatal anti-D prophylaxis (RAADP)
If you are told that your baby’s blood type is predicted to be RhD positive, if you decline fetal RhD screening, or if you have an inconclusive result, you will be offered an appointment to attend clinic 21 for RAADP at 28 weeks’ pregnancy.
You will be offered a single injection of 1,500 international units of Rhophylac 300® (a brand of anti-D approved by NICE). This is given into the muscle of the upper arm. To be effective this must be given between 28-30 weeks of pregnancy, as the risk of sensitisation is highest in the third trimester. It is vital that you still attend your appointment for RAADP at 28-30 weeks even if you have been given anti-D earlier in your pregnancy.
It is your choice whether you wish to receive anti-D during and after birth. Please discuss any concerns or questions you may have with your midwife or obstetrician.
Can the anti-D injection cause any adverse effects?
Common side effects: Soreness at the injection site is common. The soreness can last for a few hours to a day or two.
Uncommon side effects: A mild fever, headache or rash.
Very rare: Risk of allergic reaction to anti-D injections is very rare but for this reason anti-D injections are only given at the Rosie hospital or birth centre. 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.
For your unborn baby: There is very limited research on the effect of anti-D injections on the unborn baby. No significant short-term negative effects have been found and the available evidence does not suggest harm to the baby of the current or future pregnancies.
There is a 0.37% failure rate of anti-D injections according to the NICE Health Technology Assessment.
What happens if I have a potentially sensitising event?
If you are RhD negative and you have a potentially sensitising event (such as an injury to your bump or vaginal bleeding) during any stage of pregnancy, it is recommended that an FMH blood test is taken (depending on how pregnant you are) and you will be offered additional anti-D prophylaxis. This must be within 72 hours of the sensitising event.
Even if you wish to have fetal RhD screening, you could have a potentially sensitising event before you get the result of your baby’s blood type. It is therefore very important that you contact the early pregnancy unit 01223 217636 before your dating scan) or maternity assessment 01223 217217 if you have any vaginal bleeding or injury to your bump (unless you have already been told that your baby is predicted to be RhD negative).
For women with bleeding disorders anti-D may be administered by intravenous routes.
Postnatal anti-D prophylaxis
If you are RhD negative, after you have given birth, a blood sample is taken to test your baby’s blood group and RhD status. This sample is usually taken from the part of the umbilical cord that is attached to the placenta. Occasionally, when this is not possible, a neonatologist or midwife caring for your baby will ask your permission to take a small blood sample directly from your baby, usually from the heel of the foot. If your baby’s blood group is found to be RhD positive, you will be offered a further injection of anti-D. This is known as postnatal anti-D prophylaxis. This dose is the same as the antenatal dose – 1,500 international units of Rhophylac 300® administered into the upper arm muscle within 72 hours of the birth.
An FMH blood sample also needs to be taken from you (unless your baby was predicted to be RhD negative), usually within two hours of the birth, to identify the amount of fetal blood cells that may have crossed into your blood during the birth. Laboratory processing of these samples can take a couple of days, but as all RhD negative mothers with an RhD positive baby will be given routine postnatal anti-D prophylaxis, this will not delay you going home.
If the results of this blood test show that the FMH is larger than the standard postnatal anti-D dose can deal with, then you will be contacted by one of the hospital midwives and a time arranged for you to come back to the hospital as soon as possible for further anti-D. A follow-up blood sample will also be needed to ensure that no fetal blood cells remain in your circulation.
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 RhD negative. Please show them this information and your fetal RHD screening test results.
A to Z of useful terms
- Amniocentesis: a test sometimes carried out in pregnancy to check on the baby’s progress in the womb. A small sample of the fluid surrounding your baby is taken for laboratory tests.
- Anaemia: levels of red cells in the blood which are below normal.
- Antibodies: are produced by your immune system to fight against infections or anything foreign which enters your blood.
- Anti-D: an antibody which attacks red blood cells that are D positive. The cause of HDFN.
- Anti-D (immunoglobulin) injection: ready-made anti-D which is given to stop you making your own anti-D. The plasma used to make anti-D injections in England is imported from countries with effective infectious disease screening programmes. Please see the manufacturer’s current anti-D injection patient information leaflet for information on safety with regard to infections.
- Blood group and antigens: the ABO blood group is the most commonly known system; it describes whether humans have blood type A, B, AB or O. This indicates whether a person has one, both or neither of the A and B antigens in their blood. For example, a person with type AB has both and a person with type O has neither. The next most important blood group system is the rhesus factor system which contains more than 50 known antigens, one of which is the rhesus D antigen. An antigen can prompt an immune response so that the body produces antibodies.
- Fetal RhD screening: a maternal blood test in pregnancy to predict the rhesus status of her unborn baby. It is done by detecting the baby’s DNA (genetic information) which is present in the mother’s bloodstream and can be tested from 11+2 weeks onwards.
- Feto-maternal Haemorrhage (FMH): this is when the blood cells of an unborn baby (fetus) enters the bloodstream of its mother. The blood test to measure this is called a maternal FMH test.
- Haemolytic disease of the fetus and newborn (HDFN): is caused by antibodies in the mother affecting the baby’s red blood cells. This can cause anaemia, jaundice and in severe cases brain damage or death, either while the baby is in the womb or after delivery.
- Incompatibility: When a woman or person has RhD negative blood type and is pregnant with a baby who is RhD positive.
- Jaundice: raised levels of waste products from the breakdown of red blood cells. It gives a yellow colour to a baby’s skin and eyes.
- Plasma: the liquid part of blood. Prophylactic anti-D is made from the plasma of specially selected blood donors.
- Potentially sensitising event: this is when there is the potential for a feto-maternal haemorrhage occurring which could lead to sensitisation.
- Prophylactic anti-D: ready-made anti-D given to D negative women to stop them making harmful anti-D. See also ‘anti-D (immunoglobulin) injection’.
- Prophylaxis: medicines given to prevent a harmful condition developing.
- Red Cell Antibodies: antibodies are produced by your immune system to fight against infections or anything foreign which enters your blood. Red cell antibodies are your body’s natural defence against red blood cells which are different from your own. Antibodies can
- destroy red blood cells.
- Rhesus disease: is now known as Haemolytic Disease of the Fetus and Newborn (HDFN) caused by the anti-D antibody.
- Rhesus positive or Rhesus negative: other names for ‘D positive’ or ‘D negative’ blood groups, also referred to as RhD positive or RhD negative.
- Rhesus status: whether your blood group type is rhesus positive or negative.
- Routine antenatal prophylaxis (RAADP): injections of ready-made anti-D offered to women who are D negative to stop them making anti-D. This is given during late pregnancy as well as after incidents which may cause your baby’s red cells to leak into your blood.
- Sensitisation (also known as alloimmunisation): this is when an FMH has occurred and the mother’s body has made anti-D antibodies in response to the baby’s RhD positive blood cells entering her blood stream.
Further information and support
NICE (2008) Routine antenatal Anti-D prophylaxis (RAADP) for women who are rhesus D negative. Technology appraisal guidance 156. London: National Institute of Health and Care Excellence. Available at: https://www.nice.org.uk/guidance/ta156
NICE (2016) High-throughput non-invasive prenatal testing for fetal RHD genotype. Diagnostics guidance 25. London: National Institute of Health and Care Excellence. Available at: High-throughput non-invasive prenatal testing for fetal RHD genotype
Qureshi H, Massey E, Davies T, Robson S, White J, Jones J and Allard S (2014) British Committee for Standards in Haematology guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn. Transfusion Medicine, 24:1, pp8-20.
White J, Qureshi H, Massey E, Needs M, Byrne G, Daniels G, Allard S and British Committee for Standards for Haematology (2016) Guideline for blood grouping and red cell antibody testing in pregnancy. Transfusion Medicine, doi: 10.1111/tme.12299.
Wickham, Sara (2021) Anti-D Explained. Avebury: Birthmoon Creations.
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