Dear Editor,
I was delighted to read the article (Lancaster, 2019) in British Journal of Midwifery (BJM), discussing the importance of continuing the conversation around prenatal screening and, in particular, non-invasive prenatal testing (NIPT).
One of the many issues with NIPT is that some of the ways it has been described during commercial marketing are misleading to consumers and professionals. The concern is that women may then make decisions informed by the ‘popular’ view of what NIPT is, rather than the factual. Some of these misleading statements are quite subtle but important.
Where does the DNA come from?
The DNA analysed is a mixture of the mother's DNA and the DNA from the placenta. This is not DNA from the fetus and is one of the reasons that the test may be wrong, due to placental mosaicism. Describing the DNA as ‘fetal’ or ‘from the fetus’ is at best misleading and at worst incorrect, as barely any DNA passes from the fetus through the placenta—certainly not enough to give results for NIPT. It also gives the impression that it is the baby's DNA being directly analysed, which may, in women's minds, imply greater accuracy than is possible with NIPT.
NIPT and other tests
NIPT, the combined test and the quadruple test are all screening tests. It is vital that this is understood. Results from all these screening tests give a high or low chance of the child having one of the three syndromes, with varying levels of accuracy. In contrast, amniocentesis and chorionic villus sampling (CVS) are diagnostic tests and will both give a positive or negative result; therefore, we must be careful that when we make comparisons between tests, we are comparing like for like.
The comparison of NIPT with ‘other second-stage tests’ such as amniocentesis or CVS in the article (Lancaster, 2019: 330) could imply that they are similar tests, capable of giving the same type of result. This is misleading, although clarified later in the article.
It is very common to see NIPT described as ‘safer and more accurate’ than current tests (Ralph and Marshall, 2018). This is incorrect.
It therefore preferable to say: ‘NIPT is more accurate than current screening tests’ and ‘although there is no risk of miscarriage associated with any screening test, there is with diagnostic tests’.
NIPT should not be described as an ‘alternative’ to CVS or amniocentesis, as it cannot give a diagnosis. Furthermore, CVS is not always the best test to offer after NIPT, as it, like NIPT, tests cells from the placenta, meaning that it can equally give incorrect results due to placental mosaicism. Therefore, expectant parents should be advised to wait for the full karyotype, by which time the results of an amniocentesis, which is twice as safe (Akolekar, 2015), may be available anyway.
You may have seen the recent tragic case (McCrave, 2019) of a couple in Ireland who had a termination of pregnancy after receiving a high-chance result for Edwards syndrome, based on a genetic test and an initial positive CVS result (ie not the full karyotype). When the full karyotype was returned, the baby did not have Edwards syndrome after all. The couple were understandably devastated. It seems likely that the couple thought that two high chance results were ‘as good as’ diagnostic, and wanted to have a termination as early as possible. It is not clear if they used NIPT (although the report implied that it was a genetic screen) but this illustrates another reason why it is so important to make a clear distinction between screening and diagnostic tests.
Accuracy?
When quoting figures, health professionals should always consider what a pregnant woman is actually asking. In the case of NIPT, she will most likely want to know the probability of a high-chance result being correct, her positive predictive value. If the woman is 26 years old and has had no other screening, her positive predictive value can be as low as 47% for Down syndrome (and lower for Edwards or Patau syndromes). Even if women only have NIPT on the NHS pathway, a high-chance result from NIPT could still be only 88% likely to be correct (Perinatal Quality.org, 2019). This is much higher than the combined test, but for every 100 women, 12 will not be carrying a baby who has Down syndrome.
Quoting sensitivity figures, ie the percentage of babies with Down syndrome that the test will identify, is much more attractive in marketing the test. Sensitivity is also useful when the National Screening Committee is considering the introduction of a new population screen. However, sensitivity, which is 97% for NIPT in the high-chance population (Taylor-Philips, 2016), does not answer the question women are asking.
Full information
There is also a very small chance of a false negative result from NIPT. This is not often talked about, but it is there, as can be seen by a recent population study in Denmark (Karow, 2018). The importance of alerting women to the possibility of false negatives cannot be stressed enough in this age of litigation for wrongful birth.
Conclusion
I strongly agree with Lancaster (2019) on the importance of discussion around NIPT, and thank her for continuing to raise the issue and for all the work she is doing around a care pathway. It is also essential that professionals, as well as women, are fully informed about screening, and not left with any misconceptions that they may have gathered from advertising. I also strongly agree that it is important to offer expectant parents the opportunity to speak to someone with lived experience of Down syndrome today. It is, of course, impossible to know from any prenatal testing what the life of any one person with Down syndrome will be like—it is impossible to know that for any child. However, the chance to read about life with Down syndrome, or to meet people with this experience, to learn what it is like to be part of this community, should be offered to all women. I was therefore so pleased to see an article (Enoch, 2019) in BJM concerning the charity Positive About Down Syndrome a couple of months ago, a superb resource.