Most parents do tests to reassure themselves that the fetus is at low risk for some (not ALL) common chromosomal abnormalities that can be detected on screening tests. However some of these screening tests may also come back as positive. Some of these positive screening tests, when tested further, will reveal that the fetus indeed has chromosomal abnormalities. Other positive screening tests turned out to be false positives which often cause anxiety.
It is therefore important to understand the parents' goals of chromosomal or genetic screening for the fetus. Detection of fetal abnormalities often allow parents to be mentally, emotionally and financially prepared, and also allow parents adequate time to make further decisions after the current pregnancy. Is your goal of screening then to detect if the fetus has Trisomy 21, 18 or 13? Or is your goal to detect as many as possible of fetal abnormalities that are moderate to severe? Not all chromosomal or genetic abnormalities can be detected with screening or diagnostic tests.
Therefore you would need to make a decision on which range of chromosomal and / or genetic fetal abnormalities you want to screen for. You would need to understand the different types of chromosomal and / or genetic abnormalities to decide which tests to do.
1. Large chromosomal abnormalities that are visible to the microscope are at least 5-10 MB in size.
a) Common chromosomal abnormalities which are usually random events that increase with increasing mother's age
i) Trisomy 21 or Down syndrome - Occurs in about 1:600-700 live births, increasing with mother's age (from 1:2000 for a 20-year-old mother to 1:100 for a 40-year-old mother). It ranges from mild to severe, with normal lifespan for the mild cases, with mild to severe intellectual disabilities and typical facial appearance, often with heart defects, and other abnormalities.
ii) Trisomy 18 and Trisomy 13 (Edwards and Patau syndromes) - Occurs in 1:5,000 for Trisomy 18 and 1:10,000 for Trisomy 13. Severe disorders with multiple abnormalities with > 90% dying while in the womb or within the first year of birth; < 10% survive longer than 1 year.
b) Sex chromosomal abnormalities (including 47XXX, 47 XXY, 47XYY) - Occurs in about 1:1,000 for each of the 3 sex chromosomal abnormalities. Most of these individuals are normal, but some may have deficits in social or intellectual skills. Individuals with 47XXY are often infertile. Some experts question if there is a need to screen for this group of conditions which does not usually result in serious manifestations while other experts advocate screening for this as early intervention after birth have been shown to improve outcomes (when compared to those who were not diagnosed at birth and hence did not have the early interventions).
c) 45XO (Turner syndrome) - More than 90% of Turner syndrome fetuses miscarry. Those born alive (about 1:2,000 to 5,000 live births) tend to be short with early menopause, may have difficulty to conceive and occasionally have developmental delay or behavioural problems. For the milder Turner syndrome children, early interventions like growth hormone and low dose estrogen have been shown to improve adult height, and cognitive and behavioural functions.
d) Triploidy - Occurs in 1-2% of pregnancies. This is a condition where there are 3 copies of every chromosome instead of the normal 2. Most embryos with triploidy miscarry early. Severe disorder with multiple abnormalities including the brain and skeleton, usually small in size with very little amniotic fluid and / or enlarged placenta.
e) Other chromosomal abnormalities - These are typically not detected by routine screening tests but are fortunately rare and account for < 30% of all the large chromosomal abnormalities.
2. Smaller chromosomal abnormalities are invisible to the microscope and range between 0.6 to 5-10 MB in size. These include microdeletion and microduplication syndromes. Depending on the specific condition, these may cause variable effects on the intellectual function, multiple structural abnormalities, and autistic spectrum disorders. Advances in technology now allow many conditions in this category to be diagnosed though some experts question if there is a need to screen for this group of conditions as current technologies only allow a small number of the rare microdeletions to be screened, and the screening tests have uncertain detection rates and low positive predictive values (i.e. probability that the fetus is affected if the test is high risk), and many may have a wide spectrum of severity of manifestations that may not be predicted accurately even if the genetic condition has been confirmed. This group of disorders does not appear to vary with mother's age, and appears to occur at about 0.84% prevalence. This group includes:
a) 22q11.2 deletion syndrome - This is the commonest micro deletion syndrome, occurring in about 1:2000 pregnancies, also known as DiGeorge syndrome. It may be associated with mild to moderate intellectual disability and schizophrenia, heart abnormalities, feeding difficulties, problems with immunity, and low calcium levels.
b) 4 other common deletion syndromes - They include 1p36 deletion syndrome, Prader-Willi syndrome, Angelman syndrome and Cri-du-chat syndrome. These are relatively rare, accounting for about 1:5000 to 1:20000 pregnancies.
c) Other microdeletion or microduplication syndromes - they could be grouped into 2 groups:
i) abnormal or pathogenic - Some of these conditions may be known to be associated with early onset of intellectual disability, multiple structural abnormalities and / or autism spectrum disorders. Other conditions may be associated with variable onset and severity (ranging from mild to severe) of disorder. Up to 1% of the population may have a microduplication or microdeletion syndrome.
ii) variation of unknown significance (VUS) where parents' blood may have to be further checked. Depending on whether the parents also carry the same microdeletions / microduplications, referral to a geneticist is usually required to discuss the possible outcomes of the baby.
3. Single gene disorders
These are single gene disorders that could be as small as 3000 bases. There are many of these. Many are inherited from parents either from both parents who may be silent carriers or from one parent as a dominant gene. Some could even be random mutations (i.e. spontaneous changes in the absence of similar changes in either parents). In general, it is difficult to screen for such diseases in the absence of a positive family history of genetic diseases.
Among locals, we often screen for thalassaemia as it is one of the commonest genetic disorder that could result in severe disease to the baby. One strategy employed in some countries involve expanded carrier screening for a panel of (but not ALL) genetic syndromes among the parents. This expanded carrier screening should either be performed before trying for a baby, or early in pregnancy as the results often take a few weeks to be back. If both parents are found to be carriers for the same genetic disease, invasive diagnostic tests may be performed to check if the fetus is affected.
One could choose no further test (which may be appropriate especially if abortion is not an option), an invasive diagnostic test such as chorionic villus sampling or amniocentesis (which is associated with 0.1-0.3% risk of miscarriage from the procedure) if one desires the highest detection rate for most chromosomal abnormalities, or a screening blood test at 10-12 weeks which evaluates the risk further (allowing detection of some, especially the common ones, but not all) before deciding if an invasive test is necessary. The test to choose for this category depends on individuals’ views on this.
This is a suggestion of an algorithm that may help you choose which test to do.