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Other antibodies in pregnancy

The specter of haemolytic disease of the fetus and newborn (HDFN)

Anti-Kell antibodies causing HDFN

The reason why this is not as common as anti-D is because the Kell group of antigens is present in only a small proportion of the population. Only 2% of black people and 9% of white people have blood cells with the antigen. The law of averages mean even if a woman has anti-Kell antibodies, her partner is most likely not to have the antigen that would trigger the reaction in the baby. Remember, the baby has got to inherit the target antigen for the reaction to occur. When paternity is certain, the father can be tested for Kell antigen. Most will be negative. If the father is Kell negative, the four weekly blood tests are not necessary and the mother can have her routine antibody test at 28 weeks like everybody else. For this strategy to be adopted there has got to be no doubt at all about paternity.

The management of pregnancies with anti-Kell antibodies differs significantly from those with other types of antibodies. This is because the serial estimation of antibodies titres is not a reliable indicator of severity of the disease. Of late, Döppler ultrasound of the baby’s brain to monitor blood flow in the middle cerebral artery has been found to be a reliable indicator of fetal anaemia and can help facilitate decision on intrauterine transfusion or timing of delivery.

The use of Middle cerebral artery (MCA) Döppler ultrasound is based on the fact that destruction of the baby’s blood cells (haemolysis) causes anaemia for the fetus. This, in turn, causes the blood volume and velocity to increase as compensatory measures. The increase in the blood flow will be accurately reflected using MCA Döppler ultrasound

Anti-c and anti-E antibodies causing HDFN

Because 4 out of 5 men (80%) carry the ‘c’ antigen on their blood cells, if a woman is found to have anti-c antibodies, there is a high probability that her partner will have the target antigen and therefore the baby too. It is therefore imperative that the standard close surveillance is maintained with 4 weekly blood tests to estimate the antibody titres until 28 weeks and then fortnightly thereafter. Up to 1 in 5 of babies whose mother are found to have anti-c antibodies require exchange transfusion.

Anti-E is not as common as anti-c but in about 10% of affected pregnancies it causes severe haemolytic disease of the fetus and newborn requiring intrauterine transfusion, early delivery and/or exchange transfusion. Anti-c and anti-E have a tendency to occur together. 40% of those with anti-c antibodies also have anti-E.

Duffy antigen system

The ‘Duffy’ antigen system is made up of two antibodies called  Fya and Fyb. It is not common and severe haemolytic disease due to anti-Fya or anti-Fyb antibodies is quite uncommon. The monitoring described with the other antibodies above is nonetheless necessary once the antibodies have been detected.

Kidd antigen system

The Kidd antigen system consists of two antigens, namely, Jka and Jkb.  Only a handful of women have been found to carry this anti-Jka and anti-Jkb antibodies. Though the haemolytic disease of the fetus and newborn (HDFN) caused by these antibodies is usually mild, a handful of severe cases have been reported. Diligent surveillance is therefore required with this as with other antibody types.

Identifying fetus at risk of HDFN

Technology has advanced to a stage where many of the most important causes of HDFN can be investigated and identified using non-invasive techniques.

As stated earlier, the presence of antibodies in maternal blood only indicate that the fetus might be at risk. A fetus that does not carry the target antigen will not be at risk. The trick is therefore to identify those fetuses where the presence of antibodies is a harbinger of possible trouble in the form of HDFN. The use of invasive procedures such as amniocentesis or chorionic villus sampling (CVS) carries with it a risk of provoking miscarriage and therefore obstetricians have traditionally shied away from using these for cases of maternal antibodies. Now, it is possible to isolate cell-free fetal DNA from maternal blood from around 16 -20 weeks of gestation. If the mother had been found to have anti-D, anti-c, anti-E or anti-Kell antibodies, it is possible to accurately establish whether the fetus has the relevant target antigen in around 96% of cases. In those cases where the fetus is found not to have the target antigen, the close surveillance described above is not necessary and she can be reassured and continue with low risk antenatal care. For those babies found to have the relevant target antigen, the close surveillance to ensure their continued wellbeing and to intervene timely if and when required is maintained.

Fetal blood sampling

When there is suspected or confirmed haemolytic disease of the fetus, it may be necessary to accurately estimate the degree of fetal anemia. One way of doing this is by getting a fetal blood sample usually obtained from the site of the cord insertion under ultrasound guidance. This procedure can be difficult especially in the second trimester but even in uncomplicated cases, fetal loss as a direct result of the procedure is around 1 – 3%.

Delivery and its timing

Many of the severely affected fetuses will require repeated intrauterine transfusion. At around 26 weeks, the mother is given a two injection course of steroids (betamethasone or dexamethasone) in anticipation of possible pre-term delivery. A substantial proportion of these babies are delivered pre-term. Sometimes complications occur in the course of transfusing the fetus and an immediate emergency caesarean section becomes necessary. If the condition remains stable, induction of labour or delivery by caesarean section is planned for around 37 – 38 weeks.

Last update: August 29, 2012