How to save 40,000 women a year from having unnecessary Anti-D…

How many women receive unnecessary Anti-D?

It is now more than fifty 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. We began to offer Anti-D in other situations as well. One of the most controversial of these is the recommendation in some areas that all rhesus negative women are routinely offered Anti-D once or twice (depending on the local policy) during their pregnancy. But this means that we’re giving a lot of unnecessary Anti-D.

I first wrote this blog post in 2014 but have updated it since the publication of even more recent research and while writing my new book on this topic, Anti-D Explained.

 

Why the controversy?

Routine antenatal Anti-D is offered because it is thought that a small number of women will experience something called ‘silent’ sensitisation. But I need to go back a step to explain what that means.

Anti-D prevents a problem called sensitisation. (If you are totally new to this area and need something that will walk you through the issues and the evidence, we’ve got a resources page coming when my book is published!) So Anti-D usually offered in response to a potentially sensitising event (PSE). That is, something occurs which can make the baby’s blood enter the mother’s bloodstream. Like a bump to a woman’s abdomen, or an invasive medical procedure.

But it is thought that, occasionally, the situation that could cause a woman to become sensitised may occur without there being an obvious sensitising event. This led to the offering of routine antenatal Anti-D. It’s one of those “just in case” things. But this is controversial for a number of reasons.

First, the chance of ‘silent’ sensitisation is low. This raises questions about the justifiability of routine Anti-D, 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. When Anti-D is warranted, it can save the lives of future babies. But we need to consider the health of the current baby too, of course!

Moreover, many of the women who receive routine antenatal Anti-D do not need it. That’s because they are carrying a rhesus negative baby. And the problem that Anti-D is given to prevent simply wouldn’t happen for these women. That’s why the issue of unnecessary Anti-D needs discussion.

In the UK, this proportion is estimated to be around a third of rhesus negative women (Finning et al 2008). But this figure will vary in other countries because the percentage of people who carry the rhesus factor varies according to ancestry. In simple terms, about 40,000 women in the UK each year receive unnecessary Anti-D. They are given a medicine made from blood that they do not need.

 

But there’s a solution – at least for some

But for the past few years this has been even more unnecessary. That’s because there now exists a highly accurate test which shows whether the unborn baby is rhesus positive or rhesus negative. Finning et al‘s (2008) 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. (There’s also lots more on this in my book.)

No test can be right all the time but, partly because the chance 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 pregnant women. It significantly reduces the number of women offered unnecessary Anti-D. Yes, those who have a rhesus positive baby still need to weigh up the decision. But it removes the decision and worry entirely for a good proportion of rhesus negative women.

There are other ways of testing a baby’s rhesus group. For instance, this can also be done as part of a NIPT test. But there are wider issues to consider with that.

 

More research confirms this

In 2016, another study was published in the British Medical Journal by de Haas et al (2016). The results confirmed 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”.

Laboratory-based research by Vivanti et al (2016) also 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. Or to be eligible for NIPT testing. But, as I said, that’s a wider form of screening and has bigger implications and more things to consider than the simple rhesus test.

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. It’s important that women, families midwives and birth workers know that such options exist. So please share the link to this post with anyone who you think might be interested.

 

How to find out more

If you’d like to know more about unnecessary Anti-D or, in fact, anything else relating to Anti-D, my book is called Anti-D Explained. It has been written to help women and families understand the issues and the evidence. It’s due out in June 2021.

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.

 

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

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