Later this year, the Department of Health will announce that a new screening technology, Non Invasive Prenatal Testing, or NIPT, will be offered as an additional test for Down syndrome and other conditions. NIPT is a simple blood test which works by detecting fragments of DNA from the placenta which are circulating in the mother’s blood. By the tenth week of pregnancy, this ‘fetal fraction’ is detectable, and can be analysed to predict the genotype of the fetus. Compared to existing non-invasive tests, NIPT gives fewer false positive results, but still only about 78% of positives are actually affected pregnancies, which is why a confirmatory invasive test is still required.
If NIPT is such a good test, you would think that it would be offered as initial screening to all pregnant women. But that would cost a lot more. Instead, NIPT will be offered as a second stage of screening to women who have a risk higher than 1 in 150 of having an affected pregnancy. Only women who screen positive on NIPT will be offered the invasive test, such as amniocentesis, which will give them diagnostic confirmation. The major benefit of NIPT is that it will reduce the number of women who have amniocentesis by more than three thousand. This will reduce NHS costs, but more importantly, it will also avoid the dozens of miscarriages which result from amniocentesis each year. The downside is the potential delay of several weeks before these women at high risk receive a final confirmation of the status of the pregnancy.
I am chairing a Nuffield Council on Bioethics working group looking at ethical and social aspects of NIPT, and we will make recommendations within six months. But here are my own personal thoughts about these issues. And this is very personal, given that I have a genetic condition myself, achondroplasia or restricted growth, which I inherited from my father, and passed on to both my children. My dad was a doctor, I am an academic, my daughter is a social worker and my son is a civil servant. Our stature never stopped any of us flourishing.
I support a woman’s right to choose, and I support the right of prospective parents to test, and indeed to terminate, if that’s their wish. But my concern about all prenatal screening is whether people are getting balanced information about life with disability. At present, two thirds of pregnant women accept the offer of screening. That’s reassuring, because it suggests people are making their own minds up, rather than being pressured to avoid the birth of an affected child. But of those who are diagnosed with a pregnancy affected by Down syndrome, up to ninety per cent terminate.
I worry that the NHS puts a lot of energy and expense into ensuring that these tests are scientifically robust, but less resources into achieving balanced information and sufficient counselling. I also worry that because the decision about NIPT is free from the worry of miscarriage, it’s possible that people will think less deeply about it, and end up having to make a decision later they do not feel prepared for.
Advocates for people with Down syndrome argue that having the condition does not prevent you having a good life, although it‘s hard for families as they struggle for support to bring up their child. While Down syndrome comes in more or less severe versions, there are people with the condition who live independently, get married, and have jobs. Most importantly, all the people with Down syndrome I have ever met have a great capacity for happiness and love.
NIPT is a technology that is being driven by the commercial sector. Already, couples are opting to buy NIPT in pregnancy. Even when NIPT is offered as a second level screen in the NHS, some couples will opt to buy it as a first level screen. This causes inequities. Most importantly, commercial providers are competing to offer more and more information through these blood tests. Not only are there fears that commercial providers will make misleading claims about their tests, there is also anxiety that these expanded tests may actually increase uncertainty. For example, NIPT companies can tell you about minor DNA changes – called microdeletions – which have a high false positive rate. This means that a confirmatory amniocentesis will be required after the commercial test. The irony is that that a test which was introduced to reduce the number of amniocenteses may actually begin to increase them.
So far, I’ve been discussing NIPT as a screening test in the general population for Down syndrome and other trisomies. But already, NIPT brings benefits to those rare families who affected by inherited genetic conditions, such as my own condition, achondroplasia, or cystic fibrosis or muscular dystrophy. For conditions which are inherited via the father, NIPT is diagnostic. This means that shortly after ten weeks, it will be possible for families to know whether the developing fetus is carrying the genetic mutation that causes one of these conditions. I think that’s a real benefit. Families at higher risk will be able to know earlier, and without risk of losing their pregnancy to miscarriage.
But in the longer term, it’s possible that all families, not just those at higher risk, will be able to learn about single gene conditions like these. That’s because everyone has genetic spelling mistakes in their genome. For example, two thirds of cases of achondroplasia arise as new mutations. A child with the condition is born out of the blue, as with my father’s birth.
In order to test for these very rare random occurrences, you would need to offer Whole Genome Sequencing alongside NIPT. Or maybe, instead of sequencing the whole genome, you’d test for the top 100 random mutations via a process called panel testing. It seems to me very likely that within the next five years, these services will be routinely offered via the private sector. And as we have seen, what happens in the private sector often eventually becomes offered in the NHS, to avoid inequities of provision.
There was no prenatal testing in 1927, when my father was born. His birth was a shock to his parents, nobody knew the cause of his dwarfism. In 1966, my own parents knew there was a 50% chance that I would be affected, but could do nothing about it. In 1988, when my daughter was born, we were told she would be short, but refused the offer of abortion. Today, as she contemplates starting a family, she will be offered information about achondroplasia, as well as Down syndrome and other conditions. You might think that knowledge is power – but that other proverb, ignorance is bliss, sometimes feels more relevant.