Genetic Testing (pregnancy) Flashcards
What are the testing steps in a normal pregnancy?
Positive pregnancy test
Book into antenatal care
Nuchal scan - 10-14 weeks gestation. Different tests, eg. Nuchal translucency, combined test. Hormone levels tested, nuchal fold (back of neck of baby) is tested. Also risk figure for downs is also calculated (higher than 1/150 is high)
Mid trimester anomaly scan - all women offered one at 11-14 and 20-22 weeks
What are the aims of the 12 week scan?
To date the pregnancy accurately
Diagnose multiple pregnancy
Diagnose major foetal abnormalities
Diagnose early miscarriage
Assess the risk of Down syndrome and other chromosomal abnormalities
What is the nuchal translucency?
Done at 10-14 weeks
The thickness of fluid at the back of the foetal neck
Less than 3mm is normal, anything higher can indicate: chromosomal abnormalities (downs, patau, turners) Boeth defects (cardiac abnormalities, pulmonary defects, renal and abdominal wall defects) Skeletal dysplasia
Screening, not diagnostic
When is prenatal testing arranged?
Following abnormal findings at nuchal or mid trimester scan
Following results of combined test which give an increased risk of downs
If previous pregnancy affected with a condition
If parents carrier of chromosome rearrangement or genetic condition
FH or genetic condition
What are the aims of prenatal testing?
To inform and prepare parents for the north of an affected baby
To allow in utero treatment
Manage the remainder of the pregnancy
Be prepared for complications after birth
Allow the termination of an affected foetus
What is cell free foetal DNA (cffDNA)?
Non invasive prenatal diagnosis (NIPD) works by analysing the DNA fragments present in the maternal plasma during pregnancy
Most of this DNA comes from the mother (cell free DNA)
10-20% of it comes from the placenta, which is representative of the unborn baby (cell free foetal DNA)
cffDNA is first detectable from about 4-5 weeks gestation but cannot be accirately detected till around 9 weeks.
What is the NIPD?
Non invasive prenatal diagnosis
Done at 9 weeks
Can test for some genetic diseases, such as achondroplasia, thanatophoric dysplasia and apert syndrome
Can also be used for sexing. It is offered when there is an X linked condition in the family (eg. Duchenne muscular dystrophy). The test detects the SRY gene on the Y chromosome
How is cffDNA testing used to test for aneuploidy?
Tests for T13, T18 and T21
It identifies 92% with triaonomy 13, 97% woth trisonomy 18 and 99% with trisonomy 21
Offered privately or through research studies
Not diagnostic. Just a test so NIPT
What are the limitation of NIPD and NIPT?
Multiple pregnancies - not possible to tell which foetus the DNA comes from
The relative proportion of cffDNA is reduced in women with a high BMA as they have more of their own cf DNA
Although it’s just a blood test, women must still consider the magnitude of the results
An invasive test may still be required to confirm an abnormal result
What are the benefits of NIPD and NIPT?
The number of invasive tests carried out is likely to reduce
No increased risk of miscariage
Less expertise is required to carry out the test
Can be offered earlier than invasive tests so gives earlier results
When are invasive tests offered?
If there is a known risk of a disease
What are the two invasive tests?
Chorionic Villus Sampling (CVS) - tests a small bit of tissue from the placent
Amniocentesis - tests the fluid around the developing baby
Molecular, cytogenic and biochemical tests are carried out with both
They are done on an outpatient basis
Both involve ultrasound guidance
What is a CVS?
Chorionic villus sample
11-14 weeks
1-2% of miscarriage
Trans abdominal or transvaginal
Takes sample of chorionic villi - part of developing placenta - same DNA as baby
Gives an earlier result than an amino. Important for decisions around termination of pregnancy
What is an amniocentesis?
Takes place at 15-16 weeks
Takes sample of amniotic fluid which contains foetal cells
Up to 1% risk of miscarriage
Small risk of infection and Rh sensitisation
What tests are done to the DNA sample from an amino or CVS?
Test for the genetic disorder in question
Test for the karyotype if there’s a chromosomal abnormality in the family - takes 2 weeks
QF-PCR for all. Looks for t13,18 and 21 and maybe sex chromosomes - results in 24-48 hours
What is a CGH array?
Done if there are concerns on the 20 weeks scan
Looks for small/large imbalances in chromosomes ( picks up microdeletions and duplications)
If something is found the parents are tested to see if either is a carrier. This can help to determine phenotype
What is trio exome testing?
Very new. Only made available in October 2020
Can try to explain why a baby has developmental defects but doesn’t necessarily always give results
Exome is the coding region of the genome. DNA is taken from foetus/baby and parents
What are the reproductive options when there is a known reproductive risk?
Conceive naturally with no prenatal testing
Conceive naturally with prenatal testing
Use an egg and/or sperm donor
Adoption
Choose not to have children
Pre implanatation genetic diagnosis (PGD)
What is egg or sperm donation?
In the name
No longer anonymous. Children have a right to contact the donor when they are 18. This has led to a decrease in donors
Best to go through a licensed UK fertility center. But can get a private donor or go abroad
What happens in adoption?
- Registration and checks
Registering interest with agency. Medical and criminal checks, three written references. Usually takes around 2 months
- Assessment and approval
Home visits by social worker. Report taken to adoption panel. Panel review about suitability to adopt. Takes around 4 months
What is pre implantation genetic diagnosis?
PGD
Uses IVF with ana additional step to genetically test the embryo before implantation
Used particularly by people who do not want termination of pregnancy
What is the process of PGD?
Stimulation of the ovaries
Egg collection
Insemination (sperm injected into egg (ICSI))
Fertilisation
Embryo biopsy at blastocyst stage
Embryo testing
Embryo transfer
Pregnancy test
What is the eligibility criteria for PGD?
Female is under 39 and must have a normal BMI
Both parents non smokers
Living together in a stable relationship
No living unaffected children from the relationship
Known risk of children having a serious genetic condition
Female must have hormone levels suggesting she will respond to treatment
What is the role of a genetic counsellor in prenatal testing?
Arrange and explain CVS, amniocentesis, PGD, cffDNA
Facilitate decision making
Give results
See patients in clinic following diagnosis in utero
Arrange termination if necessary
Discuss recurrence risks and plans for future pregnancies
