Rhesus factor disease
Rhesus disease is a condition where antibodies in a pregnant woman’s blood destroy her baby's blood cells.
The condition is also known as haemolytic disease of the foetus and newborn.
Rhesus disease only happens when the mother has rhesus-negative blood (RhD negative) and the baby in her womb has rhesus-positive blood (RhD positive). The mother must have also been previously sensitised to RhD-positive blood.
Sensitisation happens when a woman with RhD negative blood is exposed to RhD positive blood, usually during a pregnancy with an RhD positive baby. The woman’s body responds to the RhD positive blood by producing antibodies (infection-fighting molecules) that recognise the foreign blood cells and destroy them.
If sensitisation occurs, the next time the woman is exposed to RhD positive blood her body will produce antibodies immediately. If she is pregnant with an RhD-positive baby, the antibodies can cross the placenta, causing rhesus disease in the unborn baby. The antibodies can continue attacking the baby's red blood cells for a few months after birth.
Rhesus disease does not harm the mother, but it can cause the baby to become anaemic and develop jaundice (yellowing of the skin and whites of the eyes).
Preventing rhesus disease
Rhesus disease is uncommon these days because it can usually be prevented using injections of a medication called anti-D immunoglobulin.
All women are offered blood tests as part of their antenatal screening to determine whether their blood is RhD negative or positive. If the mother is RhD negative, she will be offered injections of anti-D immunoglobulin at certain points in her pregnancy when she may be exposed to the baby’s red blood cells. This anti-D immunoglobulin helps to remove the RhD foetal blood cells before they can cause sensitisation.
If a woman has developed anti-D antibodies in a previous pregnancy (she is already sensitised) then these immunoglobulin injections do not help. The pregnancy will be monitored more closely than usual, as will the baby after delivery.
Treating rhesus disease
If an unborn baby does develop rhesus disease, the treatment will depend on how severe it is. A blood transfusion to the unborn baby may be needed in more severe cases. After delivery, the child is likely to be admitted to a neonatal unit (a hospital unit that specialises in caring for newborn babies).
Treatment for rhesus disease after delivery can include a light treatment called phototherapy, blood transfusions, and an injection of a solution of antibodies (intravenous immunoglobulin) to prevent red blood cells being destroyed.
If rhesus disease is left untreated, severe cases can lead to stillbirth (when a baby dies in the womb before it is born). In other cases, it could lead to brain damage, learning difficulties, deafness and blindness. However, treatment is usually effective and these problems are uncommon these days.
Rhesus disease occurs when antibodies produced by a pregnant woman destory her baby's red blood cells
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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 can only occur if:
the mother has a rhesus negative (RhD negative) blood type
the baby has a rhesus positive (RhD positive) blood type
the mother has previously been exposed to RhD positive blood and has developed an immune response to it (known as sensitisation)
These are explained in more detail below.
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 (RhD) antigen. This is a molecule found on the surface of red blood cells.
People who have the RhD antigen are RhD positive, and those without it are RhD negative. In the UK, around 85% of the population are RhD positive.
How blood types are inherited
Your blood type depends on the genes you inherit from your parents. Whether you are RhD positive or negative depends on how many copies of the RhD antigen you have inherited. You can inherit one copy of the RhD antigen from your mother or father, a copy from both of them, or none at all.
You will only have RhD negative blood if you don't inherit any copies of the RhD antigen from your parents.
A woman with RhD negative blood can have an RhD positive baby if her partner's blood type is RhD positive. If the father has two copies of the RhD antigen, the baby will have RhD positive blood. If the father only has one copy of the RhD antigen, there is a 50% chance of the baby being RhD positive.
An RhD positive baby will only have rhesus disease if their RhD negative mother has been sensitised to RhD positive blood. Sensitisation occurs when the mother is exposed to RhD positive blood for the first time and develops an immune response to it.
During the immune response, the woman’s body recognises that the RhD positive blood cells are foreign and creates antibodies to destroy them.
In most cases, these antibodies are not produced quickly enough to harm a baby during the mother's first pregnancy. Instead, any RhD positive babies the mother has in the future are most at risk.
How does sensitisation occur?
During pregnancy, sensitisation can happen if:
small numbers of foetal blood cells cross into the mother’s blood
the mother is exposed to her baby's blood 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 injures her abdomen (tummy)
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 by mistake (although this is extremely rare).
How sensitisation leads to rhesus disease
If sensitisation occurs, the next time the woman is exposed to RhD positive blood her body will produce antibodies immediately.
If she is pregnant with an RhD-positive baby, the antibodies can lead to rhesus disease when they cross the placenta and start attacking the baby's red blood cells.
Diagnosing rhesus disease
The routine screening tests offered while you're pregnant can usually determine if your baby is at risk of rhesus disease.
A blood test should be carried out early on in your pregnancy to test for conditions such as anaemia, rubella, HIV and hepatitis B.
Your blood will also be tested to determine which blood group you are, and whether your blood is rhesus (RhD) positive or negative (see causes of rhesus disease for more information).
If you are RhD negative, your blood will be checked for the antibodies (known as anti-D antibodies) that destroy RhD positive red blood cells. You may have become exposed to them during pregnancy if your baby has RhD positive blood.
If no antibodies are found, your blood will be checked again at 28 weeks of pregnancy. If there are still no antibodies present at this point, you will offered an injection of a medication called anti-D immunoglobulin to reduce the risk of your baby developing rhesus disease (see preventing rhesus disease for more information).
If anti-D antibodies are detected in your blood during pregnancy, there is a risk your unborn baby will be affected by rhesus disease. For this reason, you and your baby will be monitored more frequently than usual during your pregnancy.
In some cases, a blood test to check the father's blood type may be offered if you have RhD negative blood because your baby will not be at risk of rhesus disease if both the mother and father have RhD negative blood.
Checking your baby's blood type
It is now possible to determine if an unborn baby is RhD positive or RhD negative by taking a simple blood test during pregnancy.
Genetic information (DNA) from the unborn baby can be found in the mother's blood which allows the blood group of the unborn baby to be checked without any risk. It is usually possible to get a reliable result from this test after 11-12 weeks of pregnancy, which is long before the baby is at risk from the antibodies.
If your baby is RhD negative, they are not at risk of rhesus disease and no extra monitoring or treatment will be necessary. If they are found to be RhD positive, the pregnancy will be monitored more closely so any problems that may occur can be treated quickly.
In the future, RhD negative women who haven't developed anti-D antibodies may be offered this test to see if they are carrying an RhD positive or RhD negative baby, to avoid unnecessary treatment.
Monitoring during pregnancy
If your baby is at risk of developing rhesus disease, they will be monitored by measuring the blood flow in their brain. If your baby is affected, their blood may be thinner and flow more quickly. This can be measured using a type of ultrasound scan called a Doppler ultrasound.
If a Doppler ultrasound shows your baby’s blood is flowing faster than normal, a procedure called fetal blood sampling (FBS) can be used to check whether your baby is anaemic. This procedure involves inserting a needle through your abdomen (tummy) to remove a small sample of blood from your baby. The procedure is performed under local anaesthetic, usually on an outpatient basis so you can go home on the same day.
There is a small (usually 1-3%) chance that this procedure could cause you to lose your pregnancy, so it should only be carried out if necessary.
If your baby is found to be anaemic, they can be given a transfusion of blood through the same needle. This is known as an intrauterine transfusion (IUT) and it may require an overnight stay in hospital.
FBS and intrauterine transfusion are not available in all hospitals, so you may need to be referred to a different hospital to the one where you were going to have your baby.
Diagnosis in a newborn baby
If you are RhD negative, blood will be taken from your baby’s umbilical cord when they are born to check their blood group and to see if the anti-D antibodies have been passed into their blood. This is called a Coombs test.
If you are known to have anti-D antibodies, your baby’s blood will also be tested for anaemia and jaundice.
Treating rhesus disease
Treatment for rhesus disease depends on how severe the condition is. In more severe cases, treatment may need to begin before the baby is born.
Around half of all cases of rhesus disease are mild and do not usually require much treatment. However, your baby will need to be monitored regularly in case serious problems develop.
In more severe cases, a treatment called phototherapy is usually needed and blood transfusions may help to speed up the removal of bilirubin (a substance created when red blood cells break down) from the body.
In the most serious cases, a blood transfusion may be carried out while your baby is still in the womb and a medication called intravenous immunoglobulin may be used when they are born if phototherapy is ineffective.
If necessary, the baby may be delivered early using medication to start labour (induction) or a caesarean section so treatment can start as soon as possible. This is usually only done after about 34 weeks of pregnancy.
Phototherapy is treatment with light. It involves placing the newborn baby under a halogen or fluorescent lamp with their eyes covered. Or on a blanket containing optical fibres through which light travels and shines onto the baby's back (fibreoptic phototherapy).
The light absorbed by the skin during phototherapy lowers the bilirubin levels in the baby’s blood through a process called photo-oxidation. This means that oxygen is added to the bilirubin, which helps it to dissolve in water. This makes it easier for the baby’s liver to break down the bilirubin and remove it from the blood.
During phototherapy, fluids will usually be given into a vein (intravenous hydration) because more water is lost through your baby's skin and more urine is produced as the bilirubin is expelled.
Using phototherapy can sometimes reduce the need for a blood transfusion.
In some cases, the levels of bilirubin in the blood may be high enough to require one or more blood transfusions.
During a blood transfusion, some of your baby’s blood is removed and replaced with blood from a suitable matching donor (someone with the same blood group). A blood transfusion normally takes place through a tube inserted into a vein (intravenous cannula).
This process helps remove some of the bilirubin in the baby’s blood and also removes the antibodies that cause rhesus disease.
It is also possible for the baby to have a transfusion of just red blood cells to top up those they already have.
Blood transfusion to an unborn baby
If your baby develops rhesus disease while still in the womb, they may need to be given a blood transfusion before birth. This is known as intrauterine foetal blood transfusion (IUT).
An intrauterine foetal blood transfusion requires specialist training and is not available in all hospitals. You may therefore be referred to a different hospital for the procedure.
A needle is usually inserted through the mother's abdomen (tummy) and into the umbilical cord so that donated blood can be injected into the baby. An ultrasound scanner is used to help guide the needle to the right place.
Local anaesthetic is used to numb the area, but you will be awake during the procedure. A sedative may be given to keep you relaxed and your baby may also be sedated to help stop them moving during the procedure.
You may need more than one intrauterine foetal blood transfusion. Transfusions can be repeated every two to four weeks until your baby is mature enough to be delivered. They may even reduce the need for phototherapy after birth, but further blood transfusions could still be necessary.
There is a small risk of miscarriage during an IUT, so it's usually only used in particularly severe cases.
In some cases, treatment with intravenous immunoglobulin (IVIG) is used alongside phototherapy if the level of bilirubin in your baby’s blood continues to rise at an hourly rate.
The immunoglobulin is a solution of antibodies (proteins produced by the immune system to fight against disease-carrying organisms) taken from healthy donors. Intravenous means it's injected into a vein.
Intravenous immunoglobulin helps prevent red blood cells being destroyed, so the level of bilirubin in your baby’s blood will stop rising. It also reduces the need for a blood transfusion.
However, it does carry some small risks. It's possible that your baby may have an allergic reaction to the immunoglobulin, although it's difficult to calculate how likely this is or how severe the reaction will be.
Concerns over possible side effects, and the limited supply of intravenous immunoglobulin, mean that it's only used when the bilirubin level is rising rapidly despite phototherapy sessions.
Intravenous immunoglobulin has also been used during pregnancy, in particularly severe cases of rhesus disease, as it can help delay the need for treatment with intrauterine foetal blood transfusions.
Complications of rhesus disease
Although rhesus disease is rare and most cases are successfully treated, there are some risks to both unborn and newborn babies.
If rhesus disease causes severe anaemia in an unborn baby, it can lead to:
foetal heart failure
fluid retention and swelling (foetal hydrops)
Blood transfusions given to a baby in the womb (intrauterine transfusions (IUT)), can be used to treat anaemia in an unborn baby. However, this treatment also carries some risks of complications. It can lead to an early labour that begins before the 37th week of pregnancy and there is a 2% risk of miscarriage or stillbirth.
Rhesus disease causes a build up of excessive amounts of a substance called bilirubin. Without prompt treatment, a build-up of bilirubin in the brain can lead to a neurological condition called kernicterus. This can lead to deafness, blindness, brain damage, learning difficulties or even death.
Treatment for rhesus disease is usually effective in reducing bilirubin levels in the blood, so these complications are uncommon.
The risk of developing an infection from the blood used in blood transfusions is low because all the blood is carefully screened. The blood used will also be matched to the baby’s blood type, so the likelihood of your baby having an adverse reaction to the donated blood is also low.
However, there may be a problem with the transfusion itself. For example, the tube (catheter) used to deliver the blood can become dislodged, causing heavy bleeding (haemorrhage) or a blood clot.
Generally, the risks associated with blood transfusions are small and do not outweigh the benefits of treating a baby with anaemia.
Preventing rhesus disease
Rhesus disease can largely be prevented by having an injection of a medication called anti-D immunoglobulin.
This can help avoid a process known as sensitisation, which is when a woman with RhD negative blood is exposed to RhD positive blood and develops an immune response to it. Blood is known as RhD positive when it has a molecule called the RhD antigen on the surface of the red blood cells.
The anti-D immunoglobulin neutralises any RhD positive antigens that may have entered the mother’s blood during pregnancy. If the antigens have been neutralised, the mother’s blood will not start to produce antibodies.
You will be offered anti-D immunoglobulin if it's thought there is a risk that RhD antigens from your baby have entered your blood. For example, if you experience any bleeding, if you have an invasive procedure (such as amniocentesis) or if you experience any abdominal injury.
Anti-D immunoglobulin is also administered routinely during the third trimester of your pregnancy if your blood type is RhD negative. This is because it is likely small amounts of blood from your baby will pass into your blood during this time.
This routine administration of anti-D immunoglobulin is called routine antenatal anti-D prophylaxis, or RAADP (prophylaxis means a step taken to prevent something from happening).
Routine antenatal anti-D prophylaxis
There are currently two ways that you can receive routine antenatal anti-D prophylaxis (RAADP):
a one-dose treatment: where you receive an injection of immunoglobulin at some point during weeks 28 to 30 of your pregnancy
a two-dose treatment: where you receive two injections; one during the 28th week and the other during the 34th week of your pregnancy
There does not seem to be any difference in the effectiveness between the one-dose or two-dose treatments. Your local clinical commissioning group (CCG) may prefer to use a one-dose treatment because it can be more efficient in terms of resources and time.
When will routine antenatal anti-D prophylaxis be given?
Routine antenatal anti-D prophylaxis is recommended for all pregnant RhD negative women who have not been sensitised to the RhD antigen, even if you previously had an injection of anti-D immunoglobulin.
As routine antenatal anti-D prophylaxis does not offer lifelong protection against rhesus disease, it will be offered every time you become pregnant if you meet these criteria.
Routine antenatal anti-D prophylaxis will not work if you’ve already been sensitised. In these cases, you will be closely monitored so treatment can begin as soon as possible if problems develop.
Anti-D immunoglobulin after birth
After giving birth, a sample of your baby's blood will be taken from the umbilical cord. If you are RhD negative and your baby is RhD positive, and you have not already been sensitised, you will be offered an injection of anti-D immunoglobulin within 72 hours of giving birth.
The injection will destroy any RhD-positive blood cells that may have crossed over into your bloodstream during the delivery. This means your blood will not have a chance to produce antibodies and will significantly decrease the risk of your next baby having rhesus disease.
Complications from anti-D immunoglobulin
Some women are known to develop a slight short-term allergic reaction to anti-D immunoglobulin, which can include a rash or flu-like symptoms.
Although the anti-D immunoglobulin taken from the donor blood will be carefully screened, there is a small risk that an infection could be transferred through the blood. However, the evidence in support of routine antenatal anti-D prophylaxis shows that the benefits of preventing sensitisation far outweigh these small risks.