|
from previous page 76-91 % with a false positive rate of 5 %.
This combination became the standard recommendation for those wishing to undergo prenatal testing in Australia. Most of those with an abnormal screening test result would proceed to diagnostic testing such as amniocentesis.
However, 10-20 amniocenteses would need to be performed to confirm one affected pregnancy, which carried a small, but acknowledged risk, of miscarriage.
Non-invasive prenatal testing Fetal cells cross the placenta during pregnancy and stem cells from previous pregnancies have been detected in maternal bone marrow many decades after delivery. 12 However, cell-free fetal DNA from the placenta is present in the maternal circulation only for the duration of that pregnancy. 13
Maternal plasma is a mix of cell-free DNA from both mother and fetus, with the mother contributing about 85-90 %. In non-invasive prenatal testing( NIPT), blood is collected from the mother to allow all this DNA to be sequenced and the chromosomal origin of each fragment identified by comparing it with the human genome. The number of fragments corresponding to the chromosomes of interest are counted and compared with a standard reference chromosome.
In pregnancies where the fetus carries an extra chromosome, the number of fragments derived from that chromosome are proportionately higher than in a euploid pregnancy.
NIPT should not be performed before 10-12 weeks’ gestation because there is insufficient fetal DNA for reliable results prior to that.
Even if NIPT is performed at the recommended time, about 3 % of samples will need retesting. This is usually because of insufficient fetal DNA being identified, but can also be the result of haemolysis and, very rarely, assay failure. 14
Increasing maternal weight, exercise prior to testing and maternal infection can all increase the maternal fraction of cell-free DNA and make the test less reliable.
NIPT can detect trisomy 21, 18 and 13, as well as the more common sex chromosomal abnormalities such as Turner and Klinefelter syndromes. While this covers about 80-90 % of the anomalies that would be detected using traditional cytogenetic karyotyping, NIPT will not detect other chromosomal abnormalities or the more subtle deletions
|
PHOTO: Dr Wolfgang Moroder CC-BY-SA bit. ly / 2h6xfk0 |
TABLE 1. ASSOCIATION BETWEEN MATERNAL AGE AND ABNORMALITIES
Maternal age at delivery( years)
and translocations that may be picked up on a chromosomal microarray.
However, some pathology centres now offer the option of screening for a range of rare specific deletions such as DiGeorge, Prader-Willi, Wolf-Hirschhorn and Cri du Chat syndromes at an
Incidence of Down syndrome
additional cost. Such testing might be considered if these conditions have affected a previous pregnancy.
Incidence of any chromosomal abnormality
ANYONE CONTEMPLATING NON- INVASIVE PRENATAL TESTING MUST BE COUNSELLED ON ITS LIMITATIONS. IN SHORT, IT DOES NOT GUARANTEE A HEALTHY BABY.
Counselling parents— the pros and cons of NIPT NIPT is more sensitive( 93- 99 %) and more specific( more than 99 %) than conventional
first-trimester screening. This means significantly fewer women will be referred for amniocentesis.
Another advantage of NIPT is that it does not require referral to a specialist ultrasound centre and may be more accessible for women living in rural and regional Australia. 15
However, it’ s not covered by Medicare and costs about $ 500, with a turnaround time of about a week.
Anyone contemplating NIPT must be counselled on the limitations of the test. It cannot pick up all chromosomal abnormalities and is not designed to detect structural or sensory abnormalities. In short, it does not guarantee a healthy baby.
NIPT can also be unreliable
|
because of mosaicism, which develops when the fetus and placenta have different DNA or the mother has unusual DNA.
Analysis using NIPT is possible in a known twin pregnancy, but has not been validated for triplets and beyond.
It is also important to discuss what decisions might be made if the result is abnormal. It would generally be advised to confirm an abnormal NIPT result with amniocentesis.
It is worth discussing the risk, albeit small, of pregnancy loss associated with diagnostic testing and exploring considerations about termination if aneuploidy is confirmed.
Is this the end of conventional firsttrimester screening? Probably not, at least in the short term. Conventional first-trimester screening is not as accurate as NIPT. However, it does detect a broader range of problems, including some major structural abnormalities, and may also provide the first alert to multiple pregnancy.
For those with a low-risk outcome on conventional testing, NIPT probably has little added benefit.
A key role for NIPT comes when first-trimester screening predicts an increased risk of chromosomal abnormality, such as a result that is between 1:50 and 1:300. Many clinicians now suggest NIPT as the next logical step, although this would be at the patient’ s expense.
|
These women would only be referred for diagnostic testing if the NIPT was abnormal or unreportable.
The current advice for those with a high risk of fetal abnormality on conventional first-trimester screening, such as greater than 1 in 50, is to consider moving straight to diagnostic testing. 16
Yet another model would see universal NIPT at 10 weeks followed by an ultrasound scan at 12 weeks. Those with an abnormality on either test would be referred for diagnostic testing, but an equivocal result still leaves time for conventional nuchal translucency / serum testing. 17
Ongoing issues Much of the published advice on NIPT comes from the US, driven by a private system in which second trimester screening is still the norm.
In Australia, where there is a draft recommendation for doctors to discuss NIPT with all pregnant women, we urgently need more local data on the attitudes and preferences of both patients and clinicians.
There remains an inherent inequity while access to NIPT is restricted to those who can afford it.
It is important to tease out the difficulties of ensuring informed consent in a society that tends to accept that any available testing must be beneficial but struggles when the results are inconsistent or incorrect.
Lastly, there is the underlying issue of how the community accepts difference and supports parents who make a decision to continue with a pregnancy that is considered high risk for chromosomal abnormality.
One 1999 international review suggested that the rate of termination following a diagnosis of Down syndrome was up to 92 %. 18 Australian findings are similar, with only 5 % of women choosing to continue a pregnancy after Down syndrome is confirmed on prenatal testing. 19
Yet a 2013 Dutch survey suggested that the availability of NIPT may lead to more women who would never consider termination undergoing screening with the hope that they are better able to prepare for a special needs child. 20
Such apparently contradictory findings highlight the complex and difficult considerations surrounding the advancing field of prenatal diagnostics. ●
Dr Foran is a sexual health physician and a lecturer with the University of NSW’ s school of women’ s and children’ s health.
References on request.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||