Management of pregnancies with RhD alloimmunisation

Dear Sir

Kumar and Regan in their review eloquently summarise the current
situation in the UK as regards clinical management of pregnancies at risk
of RhD alloimmunisation. This includes routine antenatal prophylaxis with
anti-D immunoglobulin for all women who are RhD negative, which is now
recognised as a cost-effective strategy as opposed to previous
conventional management, i.e. administration of anti-D to women after the
birth of an RhD positive infant and after sensitising events in pregnancy
[1]. But, as further research evidence becomes available, the most cost-
effective means of managing such pregnancies will once again become an
issue of debate.

For example, the authors quote current recommendations from the Royal
College of Obstetricians and Gynaecologists and NICE for administration of
two doses of anti-D immunoglobulin at 28 and 34 weeks of pregnancy.
However, according to recent research [2], and practice in other countries
(USA, Germany and Switzerland), it appears that immunoprophylaxis can be
given safely with just one dose of anti-D immunoglobulin (~300mg) between
28 and 30 weeks. The introduction of such a regime would be cost-
effective, resulting in annual savings of up to £3 million in the UK if it
were to replace two dose prophylaxis. Furthermore, reduction of anti-D
immunoglobulin production would help save donor blood which could be used
for other products. The possibility of alternative (monoclonal
antibodies) production of anti-D is not considered feasible in the next
few years.

More interestingly, the authors mention the emerging use of non-
invasive tests based on fetal DNA in maternal blood to establish fetal Rh
genotype. Their discussion is limited to management of cases of proven
RhD alloimmunisation where use of such tests, in conjunction with
velocimetry, has already superseded serial amniocentesis for monitoring
affected pregnancies. However, with automation and potential
centralisation of testing, these non-invasive tests will become less
expensive and their use as screening tests for all women who are RhD
negative may prove to be more cost-effective than anti-D prophylaxis
administered to these same women. 100% sensitivity rates have been
reported for these tests by a number of European centres [3,4,5], and
screening can save anti-D immunoglobulin costs for those pregnancies found
not to be at risk (ca 40% of RhD negative pregnant women).

As part of the work of the SAFE Network of Excellence, recently
funded by the EC (www.safenoe.org), we are currently investigating the
likely socio-economic consequences of the introduction of a range of non-
invasive prenatal tests based on fetal DNA and fetal cells in maternal
blood. In addition to tests to establish fetal RhD status, the use of new
tests for detection of haemoglobinopathies, cystic fibrosis and
chromosomal abnormalities in the fetus, and for prediction of pre-term
labour and preeclampsia will be assessed.

1. Chilcott J., et. al. The economics of routine antenatal anti-D
prophylaxis for pregnant women who are Rh negative 2004 BJOG 111:903-907.
2. MacKenzie, IZ et al. Efficacy and safety of a new, chromatographically
purified rhesus (D) immunoglobulin Eur J Obstet Gynecol Reprod Biol. 2004
1;117(2):154-61.
3. Costa, J-M, et al Genetic analysis of the fetus using maternal blood.
Gynecol Obstet Fertil 32(7-8)L646- 50.
4. Hromadnikova, et. al. Non-invasive Fetal RhD and RhCE Genotying using
real-time PCR testing of maternal plasma in RhD negative pregnancies.
Journal of Histochemistry and Cytochemistry 53(3): 301-5.
5. van der Schoot, et. al Prenatal typing of Rh and Kell blood group
system antigentL the edge of a watershed. Transfus Med Rev 17: 31-44.

Competing interests:
None declared