Postnatal RhD prophylaxis prevents most RhD immunisations, which are due to intrapartum fetomaternal haemorrhage. This prophylaxis will not, however, prevent immunisations caused by fetomaternal haemorrhage in pregnancy, or major haemorrhage. Antenatal RhD prophylaxis should thus be able to reduce the immunisation rate further.
In 1989, Birgitta Trolle published a Danish intervention study in which RhD-negative pregnant women were given both antenatal and postnatal anti-RhD prophylaxis (22). While there were six immunisations in the control group (n = 291) that received only postnatal prophylaxis, there were none in the intervention group (n = 322). Other, larger studies have confirmed that a combination of antenatal and postnatal prophylaxis is more effective than postnatal prophylaxis alone, but the degree of risk reduction varies with the study design (23) – (25).
A significant problem with extending antenatal prophylaxis to all RhD-negative women, as practised in some countries including the USA, is that about 38 % of the women will be carrying an RhD-negative foetus and so not require prophylaxis (26). Giving prophylaxis to these women seems unethical. It is unnecessary treatment, and anti-RhD immunoglobulin must still be made by immunising RhD-negative men, who are paid to undergo the procedure and then donate plasma for use in manufacturing these drugs. Globally, there is a shortage of such immunoglobulin.
In the last few years, methodology has been developed for genomic RhD typing of the foetus using cell-free DNA from maternal blood at gestational weeks 10 – 12 (27). At such an early stage in the pregnancy, the amount of cell-free foetal DNA in maternal blood is quite small. This can lead to false-negative results (2.4 %); that is, an RhD-positive foetus could be typed as RhD-negative because of the low quantity of foetal DNA (27). The mother would not then receive the necessary antenatal prophylaxis. The method, which was introduced in Denmark in 2010 and in the Netherlands in 2011, does however have specificity and sensitivity of over 98 % when typing is performed in gestational weeks 25 – 27 (28, 29). A similar method has recently been established at the Norwegian National Advisory Unit on Blood Group Serology at Oslo Blood Bank. In Norway, the Guidelines in Obstetrics from 2014 recommend RhD typing of the foetus from a maternal blood sample in week 25 (30). This is beyond the abortion time-limit, such that the result can only be used as grounds for RhD prophylaxis and not as grounds for late abortion. There are therefore no ethical concerns over the typing.
Even if the analysis is performed in gestational weeks 25 – 27, there may still be a few false negative results (0.087 %) (28). However, postpartum prophylaxis will be given if RhD typing reveals the newborn to be RhD-positive. It is therefore important to keep the umbilical cord blood samples of newborns during the introductory period as these will hold the answer key. The guidelines recommend giving prophylaxis with anti-RhD immunoglobulin in week 29. The Norwegian Directorate of Health has approved the new method, and the regional health authorities, through the National System for the Introduction of New Health Technologies (methods) within the Specialist Health Service, have decided that it is to be adopted (31).
The typing method established at the Norwegian National Advisory Unit on Blood Group Serology, Oslo University Hospital, Ullevål, is based on amplification of exons 7 and 10 of the RHD gene and has sensitivity of 100 % and specificity of 98.9 % (unpublished data).
When immune anti-RhD is detected, the woman will be monitored with respect to HDFN and given appropriate treatment, in accordance with current practice. It is also important to keep in mind that HDFN may occur as a result of other blood group immunisations.
The prophylaxis programme must be maintained for the foreseeable future as the risk of immunisation will always be present in an RhD-negative woman carrying an RhD-positive foetus. With this strategy, we expect to see a further significant reduction in RhD immunisation in pregnancy.