Advances in Prenatal Testing
Recently, there have been major advances in prenatal testing. I have detailed below the three changes which may affect your pregnant patient requiring prenatal screening and testing.
Human Placental Growth Factor (HPlGF) and AFP in conjunction with Nuchal Translucency Assessment
At The Wesley Fetal Medicine Unit and Sunnybank Fetal Medicine Unit, we are now accredited to screen for early onset pre-eclampsia, preterm delivery and IUGR. The screening test is done in conjunction with the 12- 13½ week nuchal translucency assessment. We are also taking this opportunity to do an early morphology assessment of the fetus.
Ideally, the blood is taken at 10.5 – 11 weeks gestation. If this timeframe is missed, the bloods should be taken as soon as possible after 11 weeks gestation. The biochemistry is also used in twin pregnancies, except in cases where there is fetal demise of one twin.
We will now be assessing the level of Human Placental Growth Factor (HPlGF) and AFP in conjunction with the screen for early onset pre-eclampsia, pre-term delivery and IUGR. The First Trimester Blood request form will be sent to your patient by us when they schedule their appointment for the 12 to 13½ week screening test. If it is your preference to provide your patient with the pathology request form, please be sure to include HPlGF and AFP in addition to PAPP-A and free Beta HCG. Following the screen, the patient will be put into a high risk or low risk group for early onset pre-eclampsia, preterm delivery or growth restriction.
The Fetal Medicine Foundation has published a randomised controlled trial, showing that the incidence of early onset pre-eclampsia (26 week to 32 weeks gestation) can be reduced by a factor of 10, if low dose aspirin therapy is commenced prior to 16 weeks gestation. This assessment at the 12 – 13 weeks will be a major step forward in improving perinatal outcomes.
Non-invasive Prenatal Testing (NIPT)
It is important to realise that the NIPT is a screening test, not a diagnostic test. The results are given as risk of aneuploidy – not as a diagnosis of aneuploidy. In order to confirm that a fetus with a “high risk” of aneuploidy does have a chromosome anomaly, an amniocentesis would need to be performed.
There is then, confusion in the community about the role of free fetal DNA testing in maternal serum. When is the best time for this test to be done? The test is available from 10 weeks gestation. If the test fails to produce a result, the patient can elect to have the test repeated. The re-collection rate is between 1% and 5%. However, the overall failure rate of this test to produce a result is 1% or less. The turn- around time is between 10 and 14 days. The following would represent a practical strategy for screening a patient:-
This order of care is preferred, as not every patient will need the NIPT, thereby saving the patient the cost. For patients that want every test, no matter what, the fetal DNA test could be done from 10 weeks gestation, followed by the 12 –13 ½ week scan.
At the moment there are a number of fetal DNA screening tests available. These tests only look for Trisomy 13, 18, 21 and sex chromosome variations. They can now test for deletions and micro-deletions, but these screenings are not accurate. The NIPT has a low positive predictive value for low incidence diseases and a high false positive rate. Translocations or abnormalities involving other chromosomes cannot be predicted using NIPT at this stage. The cost of the NIPT is currently $450. There is no Medicare rebate.
If you wish to refer a patient, they must have a scan prior to the blood test and be fully counselled.
It is important that the patient still has a 12 -13 week nuchal translucency screen for the following reasons:
1. The fetal anatomy still needs to be checked for structural defects.
2. Although the NIPT screens for trisomies 13, 18, 21 and the sex chromosomes, it does not detect translocations or other chromosome defects..
3. A thickened nuchal translucency at 12 -13 weeks may be an early indication of fetal heart defects.
4. The biochemistry (PAPP-A, free Beta HCG, AFP and HPlGF), taken at this stage, can help to identify patients who are at a high risk for pregnancy complications.
There is a new test available in conjunction with Amniocentesis. This is Prenatal Microarray. As well as checking for the number of chromosomes, it can also test for micro-deletions and micro-duplications. These small changes in genetic material may be associated with genetic syndromes and this test will check for more than 150 including, DiGeorge syndrome, Angelman syndrome, Prader-Willi syndrome and Williams syndrome. Microarray analysis may potentially show gene anomalies, the implications of which may not be easily explained. We are in the very early days of this evolving technology.
The risk of miscarriage through amniocentesis is low. A recent study has shown that when a CVS is performed at a tertiary centre, the rate of miscarriage is 0.22% or about 1:500. The study also found that the rate of miscarriage for amniocentesis was also much lower when performed at a tertiary centre, being 0.11% or about 1:1000. (Ann Tabor. World Conference in Fetal Medicine 2016)
The risk of miscarriage is determined by:
-the skill of the operator
-the gauge of the needle
-the number of times the needle passes into the uterus.
1. HPlGF and AFP added to PAPP-A and free Beta HCG - A new screen for early onset pre-eclampsia, pre-term delivery and IUGR is now available in conjunction with the first trimester screening test.
2. NIPT does not replace first trimester screening. NIPT looks at chromosomes 21, 18, 13 and the sex chromosomes only. It does not look at micro-deletions, translocations etc.
3. With the recent advances in ultrasound resolution, we are now able to see many important structural anomalies at the 12-13 week ultrasound.
4. Prenatal Microarray is available from 14 weeks through amniocentesis to patients requiring testing for micro-deletions and micro-duplications.
5. The miscarriage rate for amniocentesis and CVS performed at a tertiary centre is much lower than previously thought.
Patient attends NT screening
test at 12- 13 ½ weeks
Low risk aneuploidy
Better than 1:1000
Moderate risk aneuploidy 1:100 – 1:1000
High risk aneuploidy
1:2 – 1:100
Amniocentesis or CVS
Fetal DNA testing
at 19 – 20 weeks
Morphology Scan at
19 - 20 weeks