It is now more than 40 years since some countries introduced a policy wherein anti-D is offered to rhesus negative women who have given birth to a rhesus positive baby. In that time, a number of related developments have also occurred, and one of the most controversial of these is the recommendation in some areas that all rhesus negative women are offered anti-D once or twice (depending on the local policy) during their pregnancy.
I first wrote this blog post in 2014 but have updated it since the publication of even more recent research.
Antenatal anti-D is controversial for a number of reasons. The chance of ‘silent’ sensitisation is low, which raises questions about the justifiability of prophylaxis, especially where there are potential side effects and risks for both mum and baby. There isn’t nearly enough research about how anti-D may affect the unborn baby. Moreover, a proportion of the women who receive antenatal anti-D do not need it because they are carrying a rhesus negative baby, and therefore the problem that anti-D is given to prevent simply didn’t exist in the first place for these women. In the UK, this proportion is estimated to be around a third of rhesus negative women (Finning et al 2008), although this figure will vary in other countries because the percentage of people who carry the rhesus factor varies according to ethnic origin. In simple terms, about 40,000 women in the UK each year receive a blood product that they do not need.
But for the past few years this has been even more unnecessary, because we now have a highly accurate test that can be carried out on women’s blood which shows whether the unborn baby is rhesus positive or rhesus negative. This test is known as fetal RhD genotyping and, in 2008, Finning et al’s study confirmed that this test was feasible and that the false negative rate was extremely low, at 0.2%. This has been further confirmed in a 2014 study by Manzanares et al, and I’ve added some even more recent data below.
No test can be right all the time but, because the risk of silent sensitisation is also very low, this test is really close. In fact, if a rhesus negative woman has this test, is told that her baby is rhesus negative and decides not to have routine antenatal anti-D as a result, her chances of becoming sensitised are only one in 86,000. When we take into account the fact that anti-D itself is not 100% effective (although it is close), it is little wonder that countries such as Denmark and The Netherlands are offering this test to all rhesus negative women so as to reduce the number of women unnecessarily exposed to anti-D.
In 2016, another study was published in the British Medical Journal by de Haas et al (2016) and the results confirm that, “fetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use”. Meanwhile, laboratory-based research by Vivanti et al (2016) has further confirmed the accuracy of this test.
In the UK, to my knowledge, the only chance most women have of getting this test on the NHS is to be pregnant in one of the small number of areas where research into this is underway. (But if you’re in an area where it’s available, please comment so that we can gather more knowledge on this). The issues are being debated in the literature, and the economic argument that the testing is not economically justified Szczepura et al (2011) is set against the claim that it may be unethical not to offer this test to all rhesus negative woman (Kent et al 2014).
I think this is too big a debate to leave to the literature, and am keen to raise more awareness of this among women, midwives and birthworkers, so I hereby invite you to share this with anyone who you think might be interested.
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If you are new to the site and would like to know more about anti-D, click here for the first part of a series of posts explaining this or click here to see my book on the topic.
Finning K, Martin P, Summers J et al (2008). Effect of high throughput RHD typing of fetal DNA in maternal plasma on use of anti-RhD immunoglobulin in RhD negative pregnant women: prospective feasibility study. BMJ 2008;336:816.
de Haas et al (2016). Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands. BMJ 355 doi: http://dx.doi.org/10.1136/bmj.i5789
Kent J, Farrell A-M and Soothill P (2014). Routine administration of Anti-D: the ethical case for offering pregnant women fetal RHD genotyping and a review of policy and practice. BMC Pregnancy and Childbirth 2014,14:87 doi:10.1186/1471-2393-14-87.
Manzanares S, Entrala C, Sanchez-Gila M et al (2014). Noninvasive Fetal RhD Status Determination in Early Pregnancy. Fetal Diagnosis and Therapy 35(1): 7-12.
Szczepura A, Osipenko L Freeman K (2011). A new fetal RHD genotyping test: Costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales. BMC Pregnancy and Childbirth 2011, 11:5 doi:10.1186/1471-2393-11-5.
Vivanti A et al (2016). Diagnostic accuracy of fetal rhesus D genotyping using cell-free fetal DNA during the first trimester of pregnancy. AJOG 215(5): 606.e1–606.e5
This is the summary of the de Haas et al (2016) study:
Objective To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD.
Design Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined.
Setting Nationwide screening programme, the Netherlands. Tests are performed in a centralised setting.
Participants 25 789 RhD negative pregnant women.
Main outcome measures Sensitivity, specificity, false negative rate, and false positive rate of fetal RHD testing compared with serological cord blood typing; proportion of technical failures; and compliance to the screening programme.
Results A fetal RHD test result and serological cord blood result were available for 25 789 pregnancies. Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%). In two cases these were due to technical failures. False positive fetal RHD testing results were registered for 225 samples (0.87%, 0.76% to 0.99%). Weak RhD expression was shown in 22 of these cases, justifying anti-D immunoglobulin use. The negative and positive predictive values were 99.91% (95% confidence interval 99.82% to 99.95%) and 98.60% (98.40% to 98.77%), respectively. More than 98% of the women participated in the screening programme.
Conclusions Fetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use.