Prenatal testing (25) Flashcards
1
Q
What are the aims of the 12 week scan?
A
- date the pregnancy accurately
- diagnose multiple pregnancy
- diagnose major foetal abnormalities
- diagnose early miscarriage
- assess risk of Down syndrome and other chromosomal abnormalities: takes into account maternal age, blood hormone levels, nuchal translucency thickness, nasal bone, blood flow through foetal heart
2
Q
What is Nuchal Translucency (NT)?
A
thickness of fluid at back of foetal neck
> 3mm can indicate:
- chromosomal abnormalities (e.g. Downs, Patau, Turners)
- birth defects (cardiac, pulmonary, renal)
- skeletal dysplasias
3
Q
When is prenatal testing arranged?
A
- following abnormal findings at nuchal scan/ mid trimester scan
- following increased risk of Downs syndrome
- if previous pregnancy affected w/ a condition e.g. CF
- if parent/s is a carrier of chromosomal translocation or genetic condition
- family history of genetic condition
4
Q
What are the aims of prenatal testing?
A
- inform and prepare parents
- allow in utero treatment
- manage remainder of pregnancy
- be prepared for complications at/ after birth
- allow termination of affected foetus
5
Q
What are the 3 types of prenatal test?
A
- Scanning- ultrasound/MRI
- Non-invasive- maternal blood test, cell-free foetal DNA
- Invasive- chorionic villus sampling, amniocentesis
6
Q
How does Cell-free petal DNA testing work?
A
- non-invasive prenatal diagnosis, so no needle
- works by analysing DNA fragments present in maternal plasma during during pregnancy–> most DNA comes from mother, but 10-20% comes from placenta, so representative of unborn baby
- cffDNA first detectable from 4-5wks, but inaccurate until 9 wks
7
Q
When is Non-invasive prenatal diagnosis (NIPD) used?
A
- maternal blood test at 9wk
- free testing for those at risk: achondroplasia, thanatrophoric dysplasia and apert syndrome
- offered when X-linked condition in family e.g. DMD–> test for sex by looking for SRY gene- if boy, do prenatal test
8
Q
When is NIPD offered privately via NHS?
A
- for autosomal dominant single gene disorders inherited from father or de novo in previous child
- for recessive conditions where both parents carry altered genes–> if no paternal alteration has been inherited, baby will not have condition (bc won’t be homozygous and we can’t distinguish between mother+baby), but if there is paternal alteration, do invasive test
9
Q
What are the testing options for a woman who has >1 in 150 risk of Down’s syndrome?
A
- Harmony or Serendipity test
- offered privately or via research studies
- blood sample looks at dosage of chromosomes 13, 18 and 21
- non-invasive, not diagnostic, but v. accurate
10
Q
What are the limitations of NIPD and NIPT?
A
- multiple pregnancies: not possible to distinguish between twin/triplet DNA
- relative proportion of cffDNA in women w/ high BMI is lower, so testing happens later on
- although it is just a blood test, it has the same implications of an invasive test (but people may not take it as seriously)
- an invasive test may still be required to confirm an abnormal result
11
Q
What are the types of invasive tests?
A
- Chorionic villus sampling at 12 wks (CVS): transabdominal or transvaginal sample of chorionic villi in placenta (same DNA as foetus)
- or amniocentesis at 15wks: lower risk of miscarriage, takes sample of amniotic fluid that contains foetal cells
- offered if there is a ‘known risk’
- uses ultrasound guidance
12
Q
What test are done with the DNA sample from invasive tests?
A
- test for genetic disorder in question
- karyotype if chromosomal abnormality in family (results in 2 wks)
- QF-PCR to look for trisomy 13, 18 and 21 (results in 24-48hrs)
13
Q
What is a CGH array and when is it used?
A
- used if there are concerns on 20 wk scan e.g. heart condition, brain abnormality
- looks for small and large imbalances in chromosomes (picks up microdeletions and duplications)
- if something found on array, test parents to see if either is a carrier (helps w/ interpretation)
- variability of phenotypes makes decision complicated due to uncertainty of penetrance of some abnormalities
14
Q
What is a trio exome sequencing test and when is it used?
A
- if fetus in previous pregnancy had significant abnormalities e.g. heart, brain, skeletal, developmental delay, dysmorphic features
(N.B. exome= coding region of genome) - take DNA from foetus and parents
- good 40%+ pickup
15
Q
What are the reproductive options if there is a known risk of having a baby with abnormalities?
A
- conceive naturally, no prenatal testing (don’t want to know)
- conceive naturally, have prenatal testing
- egg/ sperm donors
- adoption
- choose not to have children
- Pre- implantation genetic diagnosis (PGD)
