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Rhesus disease (haemolytic disease of the foetus and newborn (HDFN)) : Symptoms, Causes, Diagnosis and Treatment

What is Rhesus disease?

Rhesus disease is a condition where antibodies in a pregnant woman's blood destroy her baby's blood cells. Rhesus disease doesn't harm the mother, but it can cause the baby to become anaemic and develop jaundice.

Rhesus disease is one of the diseases which can cause jaundice.

Rhesus disease can only happen if a mother's blood type is Rhesus negative and her baby's blood type is Rhesus positive. The mother's immune system produces antibodies that react against her baby's blood. The baby's red blood cells break down. The medical word for this process is haemolysis. It leads to more bilirubin being produced than normal and a high chance of jaundice.

A mother's blood type is routinely checked at the beginning of pregnancy. All women who are Rhesus negative have extra blood tests during pregnancy to check if they are making Rhesus antibodies. The baby's blood group is not known at this stage. It is checked after birth. If a baby is at risk of Rhesus disease, there are several treatments.

Rhesus disease is also known as haemolytic disease of the foetus and newborn (HDFN). Rhesus disease belongs under the category of Blood disease. Generally Female are the victim of the Rhesus disease. Seriousness of this disease is Serious.

Symptoms of Rhesus disease are :

  • Lack of energy
  • whites of your eyes
  • Yellowing of the skin
  • swollen skin
  • Abdominal swelling
  • A faster heartbeat
  • A rapid or fast heartbeat is when your heart is beating faster than normal. A normal heart rate is 60 to 100 beats per minute. Tachycardia is considered a heart rate of greater than 100 beats per minute.
    If you are exercising, or performing any kind of activity, your heart will normally beat faster. This allows your heart to pump blood throughout your body, to provide oxygen to the tissues.
    If you are experiencing fear, anxiety or stress, your heart rate will increase.

    People who can feel their heartbeat, or flutter, may be experiencing palpitations. This may be due to stress, anxiety, medications, or it may be a sign of a serious heart condition. If you experience palpitations, you should report this to your healthcare provider.

  • Difficulty in breathing
  • Experiencing breathing difficulty describes discomfort when breathing and feeling as if you can?t draw a complete breath. This can develop gradually or come on suddenly. Mild breathing problems, such as fatigue after an aerobics class, don?t fall into this category.

    Breathing difficulties can be caused by many different conditions. They can also develop as a result of stress and anxiety.

    It?s important to note that frequent episodes of shortness of breath or sudden, intense breathing difficulty may be signs of a serious health issue that needs medical attention. You should discuss any breathing concerns with your doctor.


    Rhesus disease can be caused due to:

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

    Rhesus disease can only occur in cases where all of the following happen:

    • 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)

    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 (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're RhD positive or negative depends on how many copies of the RhD antigen you've 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'll 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, every baby will have RhD positive blood. If the father only has one copy of the RhD antigen, there's 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 aren't 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's been bleeding during 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 a 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's 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. les.nhs.uk/encyclopaedia/r/article/rhesusdisease/#top)

    What kind of precaution should be taken in Rhesus disease?

    Rhesus disease can largely be prevented by having an injection of a medication called anti-D immunoglobulin.

    This can help to 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.

    Anti-D immunoglobulin

    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 won't produce antibodies.

    You'll be offered anti-D immunoglobulin if it's thought there's 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's likely that 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 (RAADP)

    There are currently two ways you can receive 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 doesn't 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 RAADP be given?

    RAADP is recommended for all pregnant RhD negative women who haven't been sensitised to the RhD antigen, even if you previously had an injection of anti-D immunoglobulin.

    As RAADP doesn't offer lifelong protection against rhesus disease, it will be offered every time you become pregnant if you meet these criteria.

    RAADP won't work if you?ve already been sensitised. In these cases, you'll 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're RhD negative and your baby is RhD positive, and you haven't already been sensitised, you'll 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 won't have a chance to produce antibodies and will significantly decrease the risk of your next baby having rhesus disease.

    Treatment for the Rhesus disease


    Rhesus disease is usually diagnosed during the routine screening tests you're offered during pregnancy.

    Blood tests

    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're 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 and you'll be 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's a risk that 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. This is because your baby won't be at risk of rhesus disease if both the mother and father have RhD negative blood.

    Checking your baby's blood type

    It's 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's usually possible to get a reliable result from this test after 11 to 12 weeks of pregnancy, which is long before the baby is at risk from the antibodies.

    If your baby is RhD negative, they're not at risk of rhesus disease and no extra monitoring or treatment will be necessary. If they're found to be RhD positive, the pregnancy will be monitored more closely so that 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 routinely, to see if they're 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'll 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 an ultrasound scan called a Doppler ultrasound.

    If a Doppler ultrasound shows your baby's blood is flowing faster than normal, a procedure called foetal 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's 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 IUT are only carried out in specialist units, so you may need to be referred to a different hospital to the one where you are planning to have your baby.

    Diagnosis in a newborn baby

    If you're RhD negative, blood will be taken from your baby's umbilical cord when they're born. This is to check their blood group and see if the anti-D antibodies have been passed into their blood. This is called a Coombs test.

    If you're known to have anti-D antibodies, your baby's blood will also be tested for anaemia and jaundice.


    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 don't 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're born if phototherapy isn't effective.

    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.

    Alternatively, they may be placed on a blanket containing optical fibres through which light travels and shines onto the baby's back (fibre optic 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.

    Blood transfusions

    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 to remove some of the bilirubin in the baby?s blood and also removes the antibodies that cause rhesus disease.

    It's 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.

    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 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'll 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's a small risk of miscarriage during an intrauterine foetal blood transfusion, so it's usually only used in particularly severe cases.

    Intravenous immunoglobulin

    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 that it's injected into a vein.

    Intravenous immunoglobulin helps to 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 delay the need for treatment with intrauterine foetal blood transfusions. yclopaedia/r/article/rhesusdisease/#top)

    Possible complication with Rhesus disease

    Complications from Rh disease in your baby may include:

    • Anemia. In some cases, anemia is severe. Your baby?s spleen and liver may be enlarged.

    • Jaundice

    • Hydrops fetalis. This happens when your baby's organs aren?t able to handle the anemia. Your baby?s heart will start to fail. This will cause large amounts of fluid buildup in your baby's tissues and organs. Babies with this condition are at risk for being stillborn.

    After birth, your baby may have the following:

    • Severe jaundice. Your baby?s liver can?t handle the large amount of bilirubin. This causes your baby?s liver to grow too big. He or she will still have anemia.

    • Kernicterus. The most severe form of too much bilirubin. It?s due to the buildup of bilirubin in your baby?s brain. This can cause seizures, brain damage, and deafness. It can even cause death.


    1 https://www.nhs.uk/conditions/rhesus-disease/complications/ 2 https://www.marchofdimes.org/complications/rh-disease.aspx 3 https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=90&ContentID=P02498 4 https://www.pregnancybirthbaby.org.au/rhesus-d-negative-in-pregnancy 5 https://111.wales.nhs.uk/encyclopaedia/r/article/rhesusdisease/ 6 https://www.nidirect.gov.uk/conditions/rhesus-disease 7 https://www.kidshealth.org.nz/rhesus-disease