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By Dr J Kabyemela, MD

Anti-D and non anti-D antibodies in pregnancy

This is a notoriously tricky subject to explain or understand but the basic tenet is simple and straightforward. When the mother’s immune system is exposed to foreign blood cells dissimilar to hers, it reacts by producing antibodies for the purpose of destroying those foreign cells. These antibodies stay in circulation. If and when she becomes pregnant, these antibodies can cross the placenta and attack the baby’s blood cells. That is unless the baby’s cells are similar to the mothers. This reaction can then cause destruction of the baby’s blood cells causing a condition called Haemolytic Disease of the Fetus and the Newborn (HDFN)

Whilst many people are aware of the main blood group system, the so-called ABO blood groups as well as the division into Rhesus Positive and Rhesus negative categories, not many know that there are many more blood group systems. In fact, there are 29. In those 29 groups, there are more than 300 blood antigens (protein components) that have been identified to date and many of these can provoke antibody reaction. Apart from the well-known anti-D, the two other important potential causes of HDFN are anti-c and anti-Kell.

Other antibodies that have been known to cause haemolytic disease of the fetus and newborn (HDFN) include anti-e, anti-Ce, anti-Fya, anti-Jka, anti-Cw and anti-Lea. There are a few others. In fact there are antibodies that have been identified but which have shown no inclination to cause this reaction (destruction of the baby’s red blood cells). These include anti-Lutheran, anti-Doa, anti-Dob, anti-Cob, anti-Xg and several others.


Around 1 -2% of women in the Western world are found to have irregular antibodies in pregnancy. The vast majority of these are not clinically significant.

Severe haemolytic disease of the fetus and newborn is seen in about 8 out of every 100,000 pregnancies so it is quite low. It means, a district hospital averaging 3000 deliveries a year may see one case every 4 years or so. Only 1 in 25 babies will require transfusion either in utero or soon after birth (exchange transfusion), with 80% of them being for anti-D.

Testing for antibodies in pregnancy

Different countries have different protocols for doing this. However, most of these hinge on early detection of antibodies in pregnancy to identify those at risk. Testing for blood antibodies therefore forms part of the pregnancy booking protocol normally carried out in the first trimester. In the UK, if significant antibodies such as anti-D, anti-c or anti-Kell are identified, surveillance of the level of antibodies is put in place. This will involve a blood test every 4 weeks until 28 weeks. Testing frequency is increased to every two weeks thereafter until delivery. If the antibody titre (concentration) is steadily rising and there appears to be a significant risk of haemolytic disease of the fetus, the mother will need to be at a hospital with facilities and expertise to deal with this. Fetal transfusion and very early (preterm) delivery may be required.

Rhesus Disease

When an individual is described as Rhesus Positive or Negative, it actually means, her blood cells carry the Rhesus antigen D (Positive) or does not (Negative). Because Rhesus D status is the commonest cause of haemolytic disease of the fetus and newborn (HDFN) accounting for roughly 80% of all; the ‘D’ has somehow disappeared from the description. However, that is slightly misleading because the Rhesus blood group system has got other antigens namely C and E. The proper description therefore ought to be Rhesus D Positive and Rhesus D Negative. It is sometimes abbreviated as RhD+ve  and RhD-ve.

This is what happens: When a Rhesus D Negative mother is somehow sensitized by being exposed to Rhesus Positive blood cells, her immune system reacts by producing antibodies meant to hunt down and destroy those cells carrying the foreign antigen. In most cases, sensitization occurs as a result of pregnancy where the baby is Rhesus D Positive. If the fetus’ blood cells find their way into the Rhesus D negative mother’s circulation, she reacts by producing anti-D antibodies. The bay in that sensitizing pregnancy will normally not be adversely affected because the concentration of antibodies is usually quite low. It is in subsequent pregnancies where there is potential for trouble. If she carries another pregnancy where the baby is also Rhesus D Positive, production of these antibodies is likely to be accelerated. The antibodies do cross the placenta into the baby’s circulation. If the concentration of antibodies is high, the destruction of the fetal red blood cells may be to such an extent that the baby develops anaemia which could lead to heart failure, hydrops and even death. This is why, once the presence of anti-D antibodies has been identified, close regular monitoring is essential. That is unless the fetus is confirmed to be Rhesus D negative in which case it will not be at risk. Ways of establishing the Rhesus D status of the baby is explained further down.

Preventing sensitization for Rhesus D Negative mothers

In modern obstetric practise, all Rhesus D Negative mothers are administered an anti-D injection at 28 weeks of gestation. This is to prevent sensitization. This means, even if the mother is carrying a Rhesus D Positive baby and the fetal blood cells enter her circulation, there will be anti-D antibodies there to destroy these cells. Her own immune system will therefore not react. It is a very effective preventive measure which has drastically reduced cases of Rhesus disease in the western world.

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Rhesus Disease in Pregnancy