AMNIOCENTESIS AND CHORIONIC VILLUS SAMPLING
Invasive diagnostic procedures like amniocentesis and chorionic villus sampling (CVS) are performed under ultrasound guidance to obtain amniotic fluid and chorionic villi (or placental tissue) respectively to check for certain conditions during the pregnancy.
These procedures are safe when performed by experienced operators though they are associated with procedure-related risks of miscarriage ranging from 0.1-0.3%.
CVS can be performed from 10 weeks onwards. This is normally performed from the abdominal (a.k.a transabdominal) approach, and involves getting a small sample of placental tissue or chorionic villi from a needle inserted abdominally under local anaesthesia. From the transabdominal approach, the main technical difficulty is that placentas that are located behind may not be reached from the front in about 1% of cases. In such cases, delaying the procedure by up to 1 week later or an amniocentesis from 16 weeks onwards may be more appropriate.
Amniocentesis is performed from 16 weeks onwards. It involves getting some amniotic fluid from a needle inserted abdominally under ultrasound guidance. There is no need for local anaesthesia here.
These procedures may be required when:
1. there is increased risk of chromosomal abnormalities from First Trimester Screening / OSCAR, non-invasive prenatal test (e.g. Panorama and Harmony tests), or minor and major abnormalities detected on the Second Trimester Fetal Anomaly Scan.
2. both parents are carriers of recessive genes e.g. thalassaemia, cystic fibrosis.
3. there is a history of chromosomal abnormalities in previous pregnancies.
4. there is a possibility of certain infections in the fetus.
These samples can then be sent to check for:
1. Polymerase chain reaction (PCR)
a) to look for number of specific chromosomes (chromosome number 21, 18, 13, X and Y) within 2-3 working days.
b) to look for certain infections e.g. toxoplasmosis, cytomegalovirus (CMV), chickenpox (varicella zoster virus or VZV), rubella.
2. Chromosome culture or karyotype to examine the chromosomes of the body within 12 -14 days. This test is able to detect the "large" chromosomal abnormalities up to 5MB in resolution, but will not detect smaller chromosomal abnormalities below that resolution. This allows detection of:
a) aneuploidies i.e. abnormalities in the number of chromosomes e.g. Trisomies 21, 18, 13, Turner syndrome, sex chromosomal abnormalities, other rarer types of aneuploidies.
b) structural changes in the chromosomes e.g. deletions, duplications, inversions, translocations.
3. Chromosomal microarray (CMA) test, which is a molecular test, which "chops" up the chromosomes into important areas up to 0.1-0.2MB in resolution (higher resolution than chromosome culture or karyotype), and then measure the number of copies of these areas. This allows detection of similar conditions like in chromosome culture or karyotype (except inversions and balanced translocations), and even microdeletion and microduplication syndromes that are beyond the resolution of chromosome culture or karyotype. This still means that smaller genetic defects smaller than this resolution cannot be detected. Microdeletion and microduplication syndromes cause a spectrum of conditions ranging from mild to severe, and may include variable effects on the intellectual function, multiple structural abnormalities and/or autism spectrum disorders. Possible results from a CMA test include:
a) normal - This is very reassuring but does not include functional disorders (e.g non-chromosomal causes of mental retardation / autism spectrum disorders, hearing loss, visual loss), structural abnormalities (the major ones of which ultrasound scan may be able to detect) and diseases caused by smaller genetic disorders (e.g. single gene disorders like thalassaemia).
b) abnormal or pathogenic - Some of these conditions are known to be associated with early-onset diseases and therefore likely to be severe, while other conditions may be of variable onset and of variable severity. Whilst the diagnosis of the aneuploidy / microdeletion / microduplication may be definite, the prediction of the severity of the manifestations of the disorder may not be as clear.
c) variation of unknown significance - Some microdeletion or microduplication may not be clearly known to cause disorders. Where there are no data to suggest that diseases may be associated with such a microdeletion or microduplication, the laboratories do not report them in general. Where there are only a few cases with abnormalities associated with such a microdeletion or microduplication but such associations are not strong, the laboratories may report them. Such a report may cause undue anxiety in the parents.
d) incidental findings - Rarely incidental findings from CMA studies may reveal that:
i) the partner or husband may not be the biological father
ii) that the mother may not be the biological mother (i.e. pregnancy resulting from a donor egg)
iii) the biological father and mother of the fetus are descendents of the same ancestors (e.g. cousins)
4. FISH for certain genetic mutations. This may be indicated if there is a family history of a known autosomal recessive (e.g. thalassaemia, cystic fibrosis) or X-linked recessive genetic disorder (e.g. haemophilia), or when there is a strong suspicion of a particular genetic disorder based on abnormalities detected on ultrasound scan.