Antenatal screening Flashcards
1
Q
What options for antenatal screening exist in NZ/Australia?
A
- MSS1 / first trimester combined screening - MA & USS NT & blood test (bHCG and PAPP-A)
- MSS2 / second trimester maternal serum screening - MA & blood test (Estriol E3, AFP, inhibin, bHCG)
- NIPT - blood test for cell free fetal DNA in maternal circulation
- Monogenic carrier screening - for common recessive / x-linked conditions can be done in the private sector (e.g. cystic fibrosis, spinal muscular atrophy and fragile X syndrome)
- All women should have a FBC to screen for thalassemia and high risk ethnic groups should be considered for more detailed carrier status
2
Q
What gestation can each screening test be used?
A
MSS1/combined test - 11-13+6 weeks
MSS2/serum test - 15-20 weeks
NIPT - any time after 10 weeks
3
Q
What are the pros and cons of combined screening?
A
Pros:
- early detection from 11 wks
- sensitivity 85%; specificity 95%
- Includes PAPP-A (also helpful for predicting risk of PET and SGA)
- Includes late 1st trimester scan which can confirm chronicity, abnormal placentation, major anatomical abnormalities (incl. turners syndrome)
Cons:
- Needs to be done at a specific timeframe
- Not as sensitive of specific as NIPT, thus resulting in more anxiety and possible unnecessary invasive testing, and missing more true positive cases
- Serum screening markers can be affected by smoking, obesity and IVF conception
4
Q
What are the pros and cons of NIPT?
A
Pros:
- Most sensitive (99%) and specific (99%) screening modality
- Can be used at any time after 10 weeks
- Can detect other genetic abnormalities including X-linked and point mutations (e.g. fragile X)
Cons:
- Only available privately - causing health inequity
- In 1-6% cases unable to provide result - NB women with a ‘no call’ result are at higher risk of having a chromosomal abnormality and should be offered USS and either repeat NIPT or routine combined screening
- Obesity can affect the result
- Does not routinely involve USS which can detect other anatomical abnormalities
- May detect genetic imbalances which may have health consequences for the mother and should be included in counselling
5
Q
How does NIPT work?
A
- Capture fetal Cell free DNA in maternal blood stream which is analysed using real-time PCR (FISH can be used but less accurate)
6
Q
What is the accuracy of each screening test?
A
First trimester combined - 85%, 95%
second trimester serum - 70-75%, 93%
NIPT - 99%, 99%
7
Q
What would the maternal serum screening be for trisomy 21, 18, 13 and neural tube defects?
A
T21 - bHCG and inhibin A = high; uE3 and AFP = low
T18 - bHCG, AFP, uE3 = low
T13 - bHCG = low
Open spina bifida- AFP = high, rest normal
Anencephaly - AFP = high, rest low
8
Q
Counsel a woman on amniocentesis.
A
- Diagnostic test for chromosomal abnormalities
- Undertaken after 15 weeks (prior to this increases risk of limb defects like talipes).
- Day case procedure. Under US guidance a needle is used to remove a sample of amniotic fluid which is sent for genetic testing
- Results take around 2 weeks
- Risks: - 1/100 to 1/1000 risk if miscarriage due to procedure (i.e. above background risk)
- bleeding - infection (chorioamnionitis) 1:1000
- Amniotic fluid leak
- Rhesus isoimunisation
- Limb defects (if <15 weeks)
9
Q
Counsel a woman on CVS.
A
- It is a diagnositc test for chromosmal abnormalities
- Day case procedure. Under US guidance a needle is used to take a sample of the chorionic villi in the placenta for genetic testing. Can be done transabdoinally or transvaginally, depending on placental location.
- Undertaken after 11 weeks (prior to this increases risk of transverse limb defects), and ususally before 14 weeks.
- Full results take around 2 weeks
Risks:
- 1/100 - 1/500 risk miscarriage due to procedure (i.e. above background risk)
- bleeding
- infection (chorioamnionitis)
- Amniotic fluid leak
- Rhesus isoimunisation
- Limb defects (if <11 weeks)
10
Q
What genetic tests can be conducted on CVS or amniocentesis sample?
A
- Rapid aneuploidy tests: FISH, quantitive fluorescent PCR (results within 3 days). Looks for specific known abnormalities -for T13/T18/T21 and X/Y.
- G-banded karyotype (traditional method - number length and banding pattern of chromosomes are visually assessed by cytogenetisist)
- Chromosomal microarray / molecular karyotype - assesses microscopic DNA differences (<5-10Mb mutations) across whole genome, and compares it to a normal control genome. More detailed assessment and more sensitive than traditional G-banded karyotype, detecting 10% more significant chromosomal defects. BUT will not detect balanced chromosome rearrangements. Can also detect small mutations of uncertain clinical significance - this needs to be carefully discussed during genetic counselling. (results take 2 weeks or more)
11
Q
Who is offered amniocentesis/CVS?
A
- High risk of T21, T13 or T18 on combined screening, maternal serum screening or NIPT
- Age >35 years as carries higher risk chromosomal abnormality
- Previous child with chromosomal abnormality
- Family history of certain heritable disease incl.: CF, SMA, haemophilia
12
Q
What is reproductive carrier screening and what are the two options?
A
- Genetic screening for autosomal recessive or X-linked genetic conditions
- Paired couple screening OR sequential screening (screening the female partner first, then only screenig the male partner if she is a carrier for autosomal recessive or X-linked condition)
13
Q
If both members of a couple are found to carry an autosomal recessive condition, or the woman found to have an x-linked condition, what are their options?
A
- Having a child naturally and testing after birth to see if the child is affected.
- Conceiving naturally and having diagnostic testing during pregnancy to determine if the fetus is affected. This is usually performed with an invasive test (amniocentesis or chorionic villus sampling).
- Conceiving the pregnancy by in vitro fertilisation (IVF) and testing embryos by preimplantation genetic diagnosis (PGD). Unaffected embryos would then be selected for achieving pregnancy.
- Using donor sperm, egg or embryo from unaffected individuals.
- Adoption.
- Not having children
14
Q
What are the options for aneuploidy screening in twin pregnancies? Evaluate their performance.
A
Combined first trimester screening
- all serum markers are affected by multiple pregancy and become less accurate
- sensitivity 72-80% (can be improved by USS assesment of nasal bones)
- The serum markers and scans must be obtained within 1-2 days of each other to run the algorithm
NIPT
- Not very comprehensive data on this yet
- Evidence that 100% sensitive for detecting T21
- Higher ‘no-call’ result >5% compared with singeltons, potentially requirirng other screening
Second trimester serum screening
- can be offered but sensitivity and specificity signifcanlty reduced
15
Q
What are the options for aneuploidy screening in triplets and higher order pregnancies?
A
- serum markers are not validated
- NIPT not validated
- USS assessmeent of NT and nasal bones should be offered at 11-13 weeks
