How antenatal care is changing

My name is Pranav Pandya, I’m a consultant in fetal medicine at University College Hospital. At the same time I chair the fetal anomaly screening program advisory board. So we are centrally involved in implementation of screening for pregnant women with ultrasound and aneuploidy screening nationally. The standard for screening for Down’s, Edwards, Patau Syndromes in the country at the moment is offering women the option of screening at 11 to 14 weeks. And we know that nationally about 60% of women accept that offer and 40% don’t want screening in the UK at the moment.

Of those women that want screening the majority will have something called the ‘combined test’ which is utilizing the mother’s age ultrasound findings and 2 biochemical markers to give them a risk of having a baby with either Down’s, Edward’s or Patau’s. It is a very good test. The detection rate using this test is about 85%. But one of the disadvantages is that about 3% of women are told that they are at an increased risk and therefore they are offered the option of invasive testing.

And the big disadvantage is, that if they want to know for sure if the pregnancy is effected with a chromosomal abnormality they need to have an invasive procedure which is either something called chorionic villus sampling which is done up to 15 weeks or amniocentesis from 15 weeks and both of these procedures carry a small but real risk of miscarriage of a healthy pregnancy. So the major changes that have been reviewed at the moment are looking at cell-free fetal DNA or non-invasive prenatal testing to see if we can look at the baby’s DNA inside the maternal blood to give women more information about the risk of the baby having Down’s Syndrome.

But the central aim here is to reduce the risk of miscarriage of healthy, normal babies. And I think one of the main messages to get across within NIPT is that the central focus is to reduce miscarriage rates. It is not to do with selecting pregnancies that are affected with a chromosomal abnormality and termination of pregnancy. That is centrally not what we are trying to do. We are well aware, as I said earlier, that 60% of women in this country have screening. We don’t know what will happen with cell-free DNA. Will more women want more screening? Will women want less screening? We don’t know. There is no data out there which will clearly tell us what will happen nationally.

But we also know that in the model that we have at the moment women that have screening that are increased risk are anxious about that risk of miscarriage. They may not decide to have invasive testing, they may wish to avoid invasive testing. So the potential of cell-free fetal DNA or non-invasive testing is to enable women to have a further test which will give them a better idea as to whether the pregnancy is at risk of having either Down’s, Edwards or Patau Syndrome. There are many potential roles of cell-free fetal DNA in maternal circulation. And I think it is very important before any of these tests are implemented to general population that we evaluate how effective and how useful they are.

One of the major advantages I have had in working with the national screening committee is that I’ve appreciated, in some depth, what the implications are from a public health perspective of evaluating an implementation of a test and looking at strengths and weaknesses. And many of us will know that there are a number of criteria which are imperative before you implement a screening test. And one of the central tenants is to do more good than harm. And so if you look at something as simple as aneuploidy screening or the Down’s Syndrome screening program, what the national screening committee are doing are looking at evaluating a roll-out in extending the present model of screening. So, what do I mean by that?

It is not going to be offered to all pregnant women. It will be offered to women who have an increased risk following the combined or the quadruple test. And that group will be given the option of either having invasive testing or cell-free fetal DNA. And from that we will learn Nationally, how good is this test? How well does it work in our laboratories? Is it as good as the publications out there? Many of the publications are sponsored by private companies and therefore we need to appreciate how it will function. What will the failure rate be? How many results will be inconclusive? How many women will choose to have invasive testing? How many women will choose to have cell-free fetal DNA?

And these are the unknowns. How well will it function for trisomy 21, 18, 13? We know that there is a difference in the literature. So I’ve given the example of aneuploidy and how complicated that is. And then when you extend it to other disorders so, for example at the moment we know that cell-free fetal DNA is available clinically in conditions to sex the fetus So there are genetic abnormalities such as congenital adrenal hyperplasia whereby knowing the sex of the fetus at an early stage can change the outcome by offering treatment to female fetuses at an early stage. So there is a real benefit there. And we also know that there are X-link disorders.

So if it is a male fetus then the pregnancy may be at risk and if it is a female fetus the pregnancy wouldn’t be at risk. So here is clear evidence to show that by using cell-free fetal DNA we can minimise the risks. And there are conditions where there is research for example, looking at the role of cell-free fetal DNA in Sickle Cell disease or Thalassemia. These are extremely important conditions. They affect a large population worldwide. And by offering a non-invasive test we can have a major impact. But then there are other conditions where I think the evidence and data is lacking.

So, for example, should we be screening for genetic disorders that may put that child at risk in the future of cancer or of Alzheimer’s or of heart disease? And I think there clearly would be a huge ethical debate about whether it is appropriate to consider those options. And I am very pleased to say that certainly the national screening committee and all of us involved would feel very strongly that we shouldn’t be screening for these genetic disorders which may predispose that individual to problems in the future. So there is a lot of research in this area looking at single gene disorders. And there are certain disorders which can be diagnosed.

So we know that certain skeletal problems problems the bones can be diagnosed using cell-free fetal DNA. And there again it is a huge advantage by minimizing the risk of miscarriage. But those are major advances and I think screening for disorders where we are uncertain what the implications may be, we don’t appreciate what the long-term outcome is we would not look to offering cell-free fetal DNA for those specific disorders.