Maternal blood screening tests / Fetal scans in pregnant women for Genetic disorders : What, Why & When?
When women become pregnant, the couple is elated with excitement. However, once they reach a doctor’s office, fetal health screening program begin which can lead to some anxiety. Health care professionals discuss a combination of maternal blood screening tests [Double, Triple, Quadruple marker screenings and Non-invasive prenatal test (NIPT)] as well as fetal ultrasound scans (Nuchal translucency and anomaly scans)]. This can be confusing for the parents to be. In order to learn more about individual testing and what may be appropriate for them, pre and post-test counselling should be offered by genetic consultants/counsellors. The counselling should be patient-specific and should depend on patient’s value systems, cultural and religious beliefs. The information regarding different screening and diagnostic tests should be explained in a non biased way, so that patients can make an informed decision. In addition, post-test counselling is also essential to explain what do the test results mean and to discuss available options in case of high risk pregnancies. Such counselling would minimise anxiety associated with the test results. This blog will discuss various options in detail so that expecting parents may be more informed.
Pre and post screening genetic counselling is essential to ease anxiety and to guide the couple for appropriate testing
Maternal Blood Screening Tests: What are they for?
These are screening tests used to identify high risk pregnancies for detection of genetic disorders and other anomalies of the fetus. These disorders occur in 1 in 800-1000 pregnancies. Since these are rare disorders, the couple needs to understand that most of the findings during screening are of low risk.
What are genetic disorders?
Genetic disorders are caused due to defects or copy number changes of the genes. In general, they manifest as physical and mental disabilities. They can be inherited.
High risk or abnormal screening test results mean?
Screening tests are meant to identify high risk pregnancies with genetic abnormalities, but they are not meant to confirm disease. This is because these tests are done on mother blood samples. The screening tests are recommended for all pregnant women. However, only a few pregnant women need to undergo diagnostic tests to confirm or rule out the screening test results. Diagnostic tests are confirmatory with high certainty as they are performed directly on fetal tissue.
Do screening tests cover all genetic disorders?
No. There are about 7000 types of Genetic disorders that have been identified so far. There are screening tests only for a few genetic disorders, mostly to screen for chromosomal / aneuploidy disorders such as Downs, Patau and Edwards syndromes as well as non-genetic disorders like neural tube defects. In general, the primary focus of the screening test is Down's syndrome because of the following reasons: 1. this is one of the most common disorders and other aneuploidy disorders are relatively rare 2. Downs syndrome patients can now live into their 40s to 50s even with intellectual disability along with other health problems while other aneuploidy disorders are non-compatible with life and in addition their screening test accuracy is not as high as that of Downs syndrome.
What screening tests are currently available ?
A combination of maternal serum screening tests from mother blood including double, triple, quadruple marker and NIFT (non-invasive fetal test) coupled with Fetal NT scan and anomaly scans.
Are the above Genetic disorders hereditary (passed from parents and previous generations) ?
Rarely. However, sometimes parents carry balanced chromosomal translocations and while parents have no disorders, there is a high risk of their children being affected. The balanced translocations are observed in 1 in 500 people approximately. To identify one person with such genetic problem, around 500 people need to be screened. Preconception couple karyotype is recommended to identify such problems.
Over 7000 types of Genetic Disorders known so far. However, pregnancy / prenatal screening tests are available only for a few, such as chromosomal aneuploidy disorders.
What are the options for a couple who wants to have the above screening performed?
There are multiple genetic screening strategies which are recommended depending on maternal and gestational age, couple’s cultural and religious believes.
Option 1: between 11-13th week of pregnancy, a combination of double marker (two maternal serum markers) and NT scan (NT is subcutaneous fluid-filled space between the back of the fetal neck and the overlying skin) is offered. Taking mothers age into account the risk score is calculated and reported as either low risk or high risk. This option is relatively accurate. Moreover, since it is done during early pregnancy, there will be enough time for further testing in case of high risk score of genetic disorders or if other neural tube defects are reported.
Option 2: In case the first option is missed, in second trimester (18 to 20th week pregnancy), a combination of quadruple maternal screening (four maternal serum markers) and Anomaly scan or TIFF (Targeted imaging for fetal anomalies) scan is an option. The combined findings are expressed as risk score.
Option 3. In recent years another screening test, NIPT is also available since 2012 in India. This can be done from mother blood sample after 11th week of pregnancy. The advantage is that at very early stage it can be done and it is a higher efficiency screening test than other screening tests (biochemical screening or ultrasound studies). However it can not predict neural tube defects, abnormal pregnancy outcomes like pre-eclampsia.
Option 4: Instead of screening tests, after assessing individual risk such as maternal age and family history, one may opt for direct diagnostic testing from fetal sample, which is the gold standard. The fetal sample is obtained from invasive procedures such as Chorionic sampling or Amniocentesis. The advantage of this is that it is a confirmatory test. However, earlier there was a concern regarding potential miscarriages. Recent studies have indicated that the risk of miscarriage and other complications of invasive procedures are much lower than observed earlier.
There are other strategies available such as integrated / sequential / nasal bone scan marker with better detection rates. In Indian context, these approaches may not be suitable, however this may be discussed with your doctor.
Maternal & gestational age, other risk factors and family values will be taken into account for guiding the couple in selection of appropriate screening and diagnostic tests
If the above screening tests indicate high risk pregnancy, what is the next step?
The low risk test results within the standard range can ease your anxiety. If intermediate or high risk score is obtained, depending on the screening test risk score, maternal age and gestational age as well as financial affordability, you will be informed of various options. The same kind of recommendation will not fit all. Based on the above scenario, one may be recommended to go for an anomaly scan and/or NIFT or an invasive procedure such as chorionic villus sampling or amniocentesis.
How is fetal tissue obtained for testing and what are the diagnostic tests done for confirming or ruling out the genetic disorder?
Fetal tissues are obtained by invasive procedures such as Chorionic Villi Sampling (done at 11 to 13 week pregnancy) and
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| Fetal Sampling by Amniocentesis |
Amniocentesis (done at 16 to 20 weeks of pregnancy). Then the fetal tissue is tested by diagnostics tests including Karyotype, FISH, Microarray, QF-PCR etc.
What is the role of fetal scans in diagnosis of genetic disorders?
Fetal scans are done to identify structural anomalies of the fetus. In combination with maternal serum screening tests, the scans give risk scores that indicate possibility of Downs syndrome and other aneuploidy disorders.
First trimester NT scan is done at 11-13 weeks of pregnancy and is effective for screening aneuploidies especially Downs syndrome.
Second trimester scan, called anomaly scan is done at 18 to 20 weeks of pregnancy to identify structural abnormalities which may suggest genetic disorders. Sometimes these may have to be then confirmed by invasive diagnostic procedures. Apart from structural anomalies, this scan also identify soft markers which may raise anxiety in the couple, although they indicate very low risk especially when they are isolated markes. Hence, soft markers diagnosis needs genetic counselling to discuss options before pursuing diagnostic testing.
The scans are fetal imaging tests, however, definitive diagnosis cannot be determined on the basis of ultrasound alone as many of the chromosomal syndromes have similar sonographic findings
Take home message:
Prenatal maternal screening tests are not diagnostic tests and just indicates increased risk of a genetic disorder.
All patients should be offered both screening and direct diagnostic tests. All patients have the right to accept or decline testing after counselling
It is important to understand that in order to identify 3 to 4 aneuploidy cases, we would need to screen 1000 pregnancies. In other words, 300 or more women would need to undergo screening tests just to detect one affected fetus. However, for that one couple, it may be very important for them not to have an affected child
The prenatal screening tests in general come back as low risk (less than 1:1000) which means that the likelihood of the fetus being affected is one in 1000 cases. Even if the results come back high risk (<1:250), there is still a good chance that the fetus may not be affected. In a nutshell, the chance of having an affected child is very low. However, these tests are offered to minimize the risk of having babies with birth defects.
Hence, in order to reduce unnecessary anxiety and also to prevent termination of pregnancies before an accurate diagnosis is made, pre-test and post-test counselling is very important.
Contact:
Dr Jayanthi Undamatla
9502709941
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