What is Rhesus Disease?

Rhesus disease is also known as Haemolytic Disease of the Foetus and Newborn (HDFN). It is a condition caused by an incompatibility between the mother’s blood and that of her unborn child and, in severe cases, can increase the risk of foetal heart disease and stillbirth. Once one of the major causes of perinatal mortality, the implementation of routine anti-D immunoglobulin injections for those women most at risk, means that incidence is now thought to be less than 0.1% in developed countries.

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What causes HDFN?

HDFN occurs when anti-D antibodies in the mother’s blood recognise the baby’s red blood cells as foreign particles and destroy them. It can only happen when the mother is rhesus negative, the baby is rhesus positive and the mother has been previously sensitised to rhesus positive blood. But, what does that actually mean?

Most people are aware of the four major blood groups, A, B, AB and O. We all fall into one of these categories and the specific one will determine which blood we can donate and/or receive during a blood transfusion. However, fewer people are probably aware that their blood is either rhesus positive (RhD positive), or rhesus negative (RhD negative), depending on whether or not they express the rhesus D antigen on the surface of their red blood cells. Current estimates put the prevalence of RhD positive:RhD negative at 85%:15%. Most of the time it will not matter whether you are positive or negative; however, if you are RhD negative and you fall pregnant with a baby that is RhD positive there is a chance that your unborn child will develop rhesus disease.

It is important to note that this can only happen if the mother has already been exposed, or sensitised, to RhD positive blood, which will usually have occurred during a previous pregnancy, most frequently if there is bleeding during the delivery. If sensitisation has occurred, upon detection of ‘foreign’ RhD positive blood, the mother’s immune system will immediately respond, producing antibodies that can cross the placenta and enter the baby’s bloodstream. The initial pregnancy is usually unaffected because by the time the antibodies are produced the baby will have been delivered.

What are the consequences for my unborn child?

The baby will likely develop anaemia and jaundice is common. In very severe cases, a condition called hydrops fetalis can develop, which is when the baby’s organs are unable to compensate for the anaemia; fluid accumulates and the baby is at risk of heart failure. This condition is associated with the pregnancy complication polyhydramnios.

Fortunately, severe complications are very rare these days, mainly due to the discovery that certain people have blood that contains a specific antigen, which can be used to make anti-D immunoglobulin. This immunoglobulin can be used to prevent women becoming sensitised to RhD positive blood. All women undergo blood tests during the early stages of pregnancy and one of the things that these test for is rhesus status. Women who are found to be RhD negative will routinely be offered an anti-D immunisation at approximately 28 weeks of pregnancy. This has reduced the risk of RD negative women becoming sensitised to RhD positive blood to less than 1%.

What increases the risk of a woman becoming sensitised?

Certain scenarios increase a mother’s risk of becoming sensitised, including, bleeding during pregnancy, undergoing invasive tests, such as an amniocentesis, and experiencing a miscarriage or ectopic pregnancy. These scenarios, which all occur before week 28 of pregnancy, increase the risk of sensitisation because the routine anti-D immunisation will not yet have been given. As such, in these scenarios, doctors will be keen to administer an earlier anti-D injection. If given within 72 hours of the event, the mother will not have time to produce any antibodies and, thus, sensitisation will be avoided.

What about if I am already sensitised?

If the mother is already sensitised then anti-D injections will be ineffective and instead she will be carefully monitored throughout the pregnancy. Early identification of potential problems can mean prompt treatment. One of the symptoms of anaemia in an unborn child is a thinning of the blood. This means the blood moves more quickly, a change that can be easily identified using a Doppler ultrasound. In severe cases, it is even possible to carry out a blood transfusion on an unborn child (intrauterine foetal blood transfusion), using a needle which is carefully inserted through the abdomen into the umbilical cord.

A final thought

Perhaps the take home message should be to highlight the value of donating blood. The serendipitous discovery that a small number of people express a rare antigen that can be used to make an effective anti-D immunisation, has saved countless lives.

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Sources:

  • Basu, S, et al. “Hemolytic Disease of the Fetus and Newborn: Current Trends and Perspectives.” Asian Journal of Transfusion Science, vol. 5, no. 1, Jan. 2011, pp. 3–7., doi:10.4103/0973-6247.75963.
  • Costumbrado J, Mansour T, Ghassemzadeh S. Rh Incompatibility. [Updated 2020 Jan 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459353/.
  • Eder, A F. “Update on HDFN: New Information on Long-Standing Controversies.” Immunohematology, vol. 22, no. 4, 2006, pp. 188–195.
  • Hydrops Fetalis.” Stanford Children’s Health, www.stanfordchildrens.org/en/topic/default?id=hydrops-fetalis-90-P02374.
  • “Overview: Rhesus Disease.” NHS, www.nhs.uk/conditions/rhesus-disease/. Page last reviewed: 11/06/2018.
  • Urbaniak, S.j., and M.a. Greiss. “RhD Haemolytic Disease of the Fetus and the Newborn.” Blood Reviews, vol. 14, no. 1, Mar. 2000, pp. 44–61., doi:10.1054/blre.1999.0123.
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