How to save 40,000 women a year from having an unnecessary blood product…

small_3309781374It 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 the publication of even more recent research has meant that I wanted to take the opportunity to update it.

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. And if you’d like me to keep you updated with birth-related research, click here to sign up for my free monthly newsletter containing research, blog posts and other updates from me.

 

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.

References

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

 

The Research

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.

photo credit: blood bottles by patrick h. lauke via photopin cc

14 comments for “How to save 40,000 women a year from having an unnecessary blood product…

  1. Anna
    March 10, 2014 at 5:02 pm

    I am a midwife and declined my 28week anti d. My decision was based on low silent sensitisation rate and little information available. I was also Poorly around this time and felt my immune system had enough to do.

    • March 12, 2014 at 7:49 am

      Hi Anna, thanks for your comment. The lack of information is really shocking, particularly when one thinks about how many women are offered this each year…
      Sara

  2. Natalie
    March 12, 2014 at 12:08 am

    Hi, thanks for this post – really interesting. What are the “potential side effects and risks for both mum and baby” and how likely are they? I was given Anti-D without my knowledge (never mind my consent) after an ectopic pregnancy, and was simply booked in and given Anti-D (without any discussion – and at the time I didn’t know to ask) when subsequently pregnant with both of my children. This represents care from 3 different hospitals in London, between 2006 and 2010.

  3. Raven
    September 16, 2014 at 7:08 am

    So if the chance of a “silent” baby death is nearly unheard of and can be fixed before it happens if it happens, what are the symptoms of when it does happen? Is it something that would send that most staunch anti-allopathic to the emergency room immediately, or is it mere camping and vision loss and fatigue/trouble walking, which will not have them in a medical facility at all but rather will have them chanjjng positions or eating kidney beans.

    Also, is there a test to find out whether or not you (the mother) was already given this shot right after their last baby was born, or is there no possible way to know that if you can’t remember?

    • September 16, 2014 at 10:08 am

      I’m not sure if I’m misunderstanding your question, Raven, but the ‘silent’ in ‘silent sensitisation’ isn’t referring to ‘baby death’, but to a woman becoming sensitised (or isoimmunised). Lots more on that starting here: http://www.sarawickham.com/topic-resources/anti-d-resources-1-getting-started/

      So I can’t really answer your first paragraph, because I think we might be talking about slightly different things.

      As far as your second question is concerned, as this is a blood product it has to be specially acquired and should be carefully recorded in your notes, so (assuming you would already have checked your notes if you had a copy) the best way of finding out would be to check with your care provider 🙂

  4. Raven
    September 16, 2014 at 7:10 am

    Have to post again with something random, because air didn’t check the box for replies.

  5. Claire
    October 11, 2015 at 1:16 pm

    I have chosen this as my dissertation topic following caring for a rhesus negative lady in labour who had her antenatal care in Sweden, wish me luck!

    • Emily
      August 11, 2016 at 7:57 am

      Claire what were your findings when finishing your dissertation?

  6. November 18, 2016 at 9:12 am

    As an Rh -ve woman, mother to four Rh +ve babies and now a student midwife I have several points of interest on this. I was given anti-d after the birth of my first and second babies in 2005/2007 without knowing what I was getting or why. I had a little more knowledge with the third and purely based on not wanting a blood product unnecessarily, I declined 28 week prophylaxis which had started being offered between pregnancy 3 and 4. However, wanting a physiological third stage and waiting for cord pulsation to finish (home birth) I was then told there was not a drop left for testing and ‘the baby needs to be bled’. I refused and requested prophylaxis for myself instead which I had to attend the ward for. Same situation for baby number 4, but rather than giving me anti-d, blood was taken and I was told it wasn’t required. I assume they tested for sensitisation.

    One major concern I have is that given the strength of evidence on optimal cord clamping, that babies are being deprived of this based on its potential Rh factor – (another student reported a case of this recently, where not even the local policy of a designated minute was given) – where not only is the mother potentially receiving two lots of unnecessary blood product, but the baby is being compromised. I think routine anti-d needs to be urgently replaced with fetal RHD testing on both counts.

  7. Nora
    November 18, 2016 at 3:56 pm

    I am Rhesus neg and so is my partner. I offered this as an explanation as to why I declined Anti-D. The midwife told me it is still recommended that I get it because *she* could not be sure my partner is actually the father of my child. Never mind that I am. So did my GP. When I kept declining I was repeatedly asked if I was aware of the risks and put under pressure to get Anti-D.
    A test for Antibodies was done on my baby without asking me. Of course he was Rh neg as well.
    This paternalistic approach is simply outrageous.

    • Nora
      November 18, 2016 at 4:05 pm

      Sorry, actually meant so say simply taking the complete picture into account rather than just going “according to guidelines” would already save many women from getting unnecessary Anti-D and even save money for unnecessary tests. Surely we can trust mothers to know if they are certain about the paternity of their baby or that they would take any uncertainty into account w.r.t. their decision about Anti-D.

  8. November 19, 2016 at 7:56 am

    This is a really interesting one Sara, I come from a family of rhesus negative women we have all had anti d during pregnancy and I don’t believe any of us have been given any other option or had the risks / benefits explained, it has been prescribed and given without question. All four of my children were also rhesus negative so it would seem I didn’t really need it at all.

  9. Danielle
    November 6, 2017 at 2:33 pm

    Just wanted to say thank you for your articles! I’m pregnant with my third and they have offered me the specialised blood test (I’m in Oxfordshire). I’ll be declining the shot during pregnancy, as I did with my first two pregnancies, and I will decide after the birth if I will have it then.

    Again thank you for writing these articles.

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