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.
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
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
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.