5 Prenatal Testing Flashcards
Q: What are the normal stages of a pregnancy? (4)
A: 1. Positive pregnancy test - does not have to be confirmed at the GP
- Booked into antenatal care - see midwife
- Nuchal Scan - 10-14 weeks - different tests dependent on the NHS trust
- A Mid-Trimester anomaly scan (around 20 weeks)
Q: What is the main method for prenatal diagnosis of foetal abnormalites? Offered?
A: Ultrasound examination
All pregnant women should be offered routine ultrasound scans at:
- 11-14 weeks
- 20-22 weeks
Q: What occurs during a normal mid-trimester scan?
A: -measure long bones
- measure head diameter
- do more detailed scans if indicated by family history/defects in previous pregnancy
Q: What are the aims of the 12 week scan? (5)
A: (nuchal scan)
- Date pregnancy
- detect Multiple Pregnancies
- detect Major Foetal Abnormalities
- diagnose Early Miscarriage (no foetal heartbeat)
- Assess risks of Down Syndrome and other chromosomal abnormalities
Q: How do you assess the risks of Down Syndrome and other chromosomal abnormalities? (6)
A: -looking at Nuchal Translucency
-taking into account: maternal age, hormone levels, nasal bone, blood flow through the foetal heart and foetal abnormalities
Q: What is nuchal translucency measured? What is it? What should it be? What can it suggest? (3)
A: -10-14 weeks
- Measure of the fluid at the back of the baby’s neck.
- usually below 3.5mm // Increased >3mm can indicate:
- Chromosome Abnormalities - e.g. Down’s, Patau, Turner, Edwards
- Birth Defects: Cardiac Anomalies, Pulmonary Defects (e.g. diaphragmatic hernia), Renal Defects, Abdominal Wall Defects
- Skeletal Dysplasia (if long bones aren’t in proportion -> do followups to check if it rectifies or not)
*Q: When is prenatal testing arranged? (5) -indications for referral to genetics services for prenatal genetic testing.
A: -Following abnormal findings at nuchal or mid-trimester scan.
- Following results of combined test which give an increased risk of Down Syndrome.
- If previous pregnancy affected with a condition e.g. Down Syndrome, Cystic Fibrosis (midwife would refer about this)
- If the parent(s) is a carrier of chromosome rearrangement or genetic condition e.g. Duchenne Muscular Dystrophy, Huntingdon’s Disease
- Family History of genetic condition
Q: What are the aims of prenatal testing? (5)
A: -inform and prepare parents for the birth of an effected child.
- In utero treatment could be offered (for some cardiac abnormalities)
- Aids management of the rest of the pregnancy (extra tests)
- Allows parents to prepare for complications at or after birth.
- To allow TERMINATION of an affected foetus
*Q: What are the 3 types of prenatal tests? Include 2 examples for each.
A: -Non-Invasive (Ultrasound/MRI which is v detailed)
- Minimally Invasive (Maternal Blood Test/Cell-Free Foetal DNA)
- Invasive = go through abdominal cavity -> v accurate (Chorionic Villus Sampling (CVS)/Amniocentesis)
*Q: What are the 3 ultrasound scans during a pregnancy?
A: (Non-Invasive Prenatal Tests)
- Early/dating scan
- Nuchal Translucency and nasal bone
- High level/anomaly scan
Q: When is the early/dating scan taken? What does it show?
A: from 5 weeks but best from 9 weeks
- confirms pregnancy
- see if it’s ectopic
- or multiple
Q: When is the high level and anomaly scan usually taken? What can it indicate? (4)
A: around 20 weeks
- can be diagnostic - showing cleft lip, limb deformity or cardiac problem
- It can also show soft markers for other problems
Q: What’s an example of a soft marker? What can this indicate?
A: nasal bone
presence or absence can indicate Down Syndrome
*Q: What can foetal MRIs show? (3) When is it taken?
A: -how heart and brain are developing
- what’s happening in abdomen
- can indicate CF (or other disorders using soft markers)
20+ weeks
Q: What can a foetal cardiac scan show? When are they taken?
A: -cardiac problems (looks at bloodflow, heart formation, valve function)
-only done if the other scans indicate potential problem
*Q: Name 2 minimally invasive prenatal tests. What makes them minimall invasive?
A: -Maternal Serum Screening
-cell free foetal DNA
These tests involve blood tests for the mum so there is no risk to the foetus.
*Q: What does maternal serum screening involve? What does it detect? Result?
A: -tests maternal serum markers in the blood
-detects increased risk of trisomy 21, trisomy 18 and/or neural tube defects
If these tests find that the woman is at high risk of some genetic diseases, she will be offered more invasive prenatal tests
*Q: What are the 4 types of maternal serum screening?
A: 1st Trimester - 11-14 weeks - done alongside the NT measurement (looks for the presence of hCG (human chorionic gonadotrophin) and PAPP A (pregnancy associated plasma protein A)).
2nd Trimester - 16-20 weeks - done if they are booked in later in pregnancy - looks for hCG and PAPP A and AFP (alpha foetal protein) and uE3 (oestriol).
Nuchal Translucency Measurement - 11-14 weeks
Private - combined 1st and 2nd Trimester Screening available
*Q: What is cffDNA? What does a cffDNA test involve? When is a cffDNA test offered? How can trisomy 21 be indicated?
A: cfDNA are short DNA fragments and cfDNA in maternal blood comes from both mother and foetus (comes from placenta and is representative of foetal DNA)
- non invasive prenatal diagnosis works by analysing the DNA fragments present in the maternal plasma during pregnancy
- currently offered when there is an X-linked condition in the family eg DMD
- in trisomy 21 the amount of cfDNA for chromosome 21 is higher than in normal pregancy
*Q: When cffDNA first detectable? Accurate?
A: from 4-5 weeks but is more accurately detected around 9 weeks (usually taken 6-7)
*Q: What can cffDNA testing reveal apart from trisomy 21? (3) Cost?
A: -achondroplasia
-thanatophoric dysplasia
-apert syndrome
testing is free on the NHS for ^
Q: What are the stages to test for DMD?
A: test detects SRY gene on Y chromosome-> enabling us to determine if male or female foetus
if male-> go to prenatal test
if female-> don’t as can only be a carrier
Q: Which NIPTs are offered privately on the NHS?
A: -autosomal dominant single gene disorders inherited from the father or arise de novo eg. NF1 (neurofibromatosis type 1)
*Q: Who offers cffDNA testing for aneuploidy? Currently test for? (3)
A: private (Harmony) or via research studies
-T13, T18 (97), T21 (99)
92% identified with 13, not that accurate-> room for error
*Q: Provide 2 examples of research involved in NIPD?
A: -translation of non-invasive prenatal diagnosis (NIPD) for duchenne and becker muscular dystrophy into a clinical setting
-evaluating early NIPD based on cffDNA and RNA in maternal plasma
*Q: What are the limitations of NIPD and NIPT? (4)
A: Multiple Pregnancies - cannot tell which foetus the DNA is from - only useful if the twins are identical.
High BMI - relative proportions of cffDNA is reduced in women with a high BMI as they have more of their own cell-free DNA.
Ethical Issues - women may not think about the implications of the testing and what results it may give.
An invasive test may still be needed to comfirm
*Q: What are the benefits of NIPD and NIPT? (4)
A: Reduced number of invasive tests - due to identification of sex
No risk of miscarriage
Less expertise required to perform a blood test
NIPD and NIPT can be offered earlier than invasive tests - results come earlier
*Q: When are invasive tests offered? 2 examples. Risk?
A: when there is a KNOWN RISK shown by other prenatal testing and if there is a known genetic condition in the family that the baby is at risk of.
- Chorionic Villus Sampling (CVS)
- Amniocentesis
of miscarriage
*Q: When is Chorionic Villus Sampling (CVS) taken? Risk of miscarriage? Method? Compared to amniocentesis?
A: 11-14 weeks
- 1-2%
- Transabdominal or Transvaginal : take sample of Chorionic Villus - part of the developing placenta - has the same DNA as the foetus
- Gives an earlier result than amniocentesis - important for patients deciding on termination of pregnancy
*Q: When is Amniocentesis done? Risk of miscarriage? Method? Other risks? (2) Compared to Chorionic Villus Sampling?
A: -16+ weeks
- Up to 1%
- Takes sample of amniotic fluid which contains foetal cells
- infection, Rh sensitisation
- done later
*Q: What type of test is done with the DNA sample from CVS or Amniocentesis? (2) What does it depend on? Timing?
A: 1. Karyotype - done if there is a chromosomal abnormality in the family / previous pregnancy-> Results in 2 weeks (dependent upon the cells growing)
- QF-PCR (Quantitative Fluorescence PCR) where all prenatal samples have a QF-PCR test
- Test for T13, T18 and T21 (and sex chromosomes if sex chromosome disorder is suspected)
- Results: 24-48 hours
- Type of test done depends on the genetic disorder that they are looking for.
- The timing of the test also depends on the genetic disorder.
*Q: If there is a known reproductive risk, the options for having children include what?
A: -Conceive naturally - no prenatal testing
- Conceive naturally - have prenatal testing
- Egg and/or Sperm Donors
- Adoption
- Choose not to have children
- Pre-implantaion Genetic Diagnosis (PGD)
*Q: Anonymity of egg and sperm donation? Done through? (3)
A: -No longer anonymous - children conceived have the right to contact the donor when they are 18.
- Done through UK HFEA licenced fertility centre - conform to strict medical, ethical and legal standards
- Can find donor privately
- Some couples may consider going abroad
*Q: What are the 2 stages of adoption before a search for a child begins? Include time for first each.
A: Registration and Checks
- Registering interest with adoption agency
- Medical and Criminal background checks - three written references
- 2 months roughly
Assessment and Approval
- Home visits by social workers
- Prospective Adopters Report is made - taken to adoption panel
- Panel review the report and make decision about the couple’s suitability to adopt
- 4 months roughly
*Q: What does Pre-implantation Genetic Diagnosis use and involve? Mainly used by? Where is it available? (2)
A: Uses IVF but with an extra step - genetically test the embryo before implantation (when there’s 8 cells)
PGD is mainly used by people who aren’t comfortable with terminating the pregnancy
UCH and Guy’s hospital (v expensive)
*Q: Describe the process of PGD? (8)
A: 1. Stimulation of the ovaries (to produce more eggs)
- Eggs are collected (as many as you can)
- Insemination - either by IVF (sperm and egg placed together in a culture dish) or ICSI (Intra-Cytoplasmic Sperm Injection - injection of a single sperm into each egg).
- Fertilisation
- Embryo Biopsy - once embryo gets to about 8 cells in size, a cell is removed by embryo biopsy.
- Embryo Testing
- Embryo Transfer - embryos that don’t have the genetic condition or are carriers are considered for embryo transfer (maximum 2 are transferred)
- Pregnancy Test
Q: When is ICSI (Intra-Cytoplasmic Sperm Injection) used?
A: for conditions caused by a single gene to reduce the amount of non-embryo DNA (inc sperm DNA) which could make the risk of a wrong diagnosis higer
*Q: What is the eligibility criteria for PGD? (6) Licence? Funding?
A: -Female partner is under 40
- Female partner has BMI between 19 and 30
- Both partners are non-smokers
- No living unaffected children from the relationship
- Known risk of having a child affected by a serious genetic condition
- no welfare concerns for unborn child
- A licence is required from the HFEA for each genetic condition or indication
- Eligible couples are usually funded for three rounds of PGD
*Q: Name 5 genetic disorders that patients usually use PGD for.
A: -translocation errors
- HD
- DMD (only implant female embryos where mutation in family is unknown)
- CF
- BRCA1/2 (cancer predisposition gene)
*Q: What are the problems with PGD? (2) Success rate?
A: -Emotional and Physical implications
- Lengthy process
- Success Rates: 30% per cycle, 40% per embryo transfer
*Q: What’s the role of genetic counselling (GC) in prenatal testing? (6)
A: -Arrange and explain the different prenatal tests
- Facilitate decision-making
- Give results
- See patients in clinic following a diagnosis in utero
- Arrange termination if necessary
- Discuss recurrence risks and plans for future pregnancies (liase with midwife)
*Q: What should be considered when facilitating decision making? (8)
A: -Previous experience
- Family situation
- Religion
- Personal beliefs
- Psychosocial situation
- Balancing miscarriage risk with genetic risk
- Dealing with indecision
- Couples do not always agree
