Prenatal testing (25) Flashcards
What are the aims of the 12 week scan?
- 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
What is Nuchal Translucency (NT)?
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
When is prenatal testing arranged?
- 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
What are the aims of prenatal testing?
- inform and prepare parents
- allow in utero treatment
- manage remainder of pregnancy
- be prepared for complications at/ after birth
- allow termination of affected foetus
What are the 3 types of prenatal test?
- Scanning- ultrasound/MRI
- Non-invasive- maternal blood test, cell-free foetal DNA
- Invasive- chorionic villus sampling, amniocentesis
How does Cell-free petal DNA testing work?
- 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
When is Non-invasive prenatal diagnosis (NIPD) used?
- 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
When is NIPD offered privately via NHS?
- 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
What are the testing options for a woman who has >1 in 150 risk of Down’s syndrome?
- 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
What are the limitations of NIPD and NIPT?
- 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
What are the types of invasive tests?
- 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
What test are done with the DNA sample from invasive tests?
- 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)
What is a CGH array and when is it used?
- 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
What is a trio exome sequencing test and when is it used?
- 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
What are the reproductive options if there is a known risk of having a baby with abnormalities?
- 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)
What is PGD and when is it used?
- pre-implanation genetic diagnosis
- uses IVF w/ additional step to genetically test embryo before it is implanted
- useful for people who do not want termination of pregnancy (TOP)
- select healthy embryos
- for many genetic disorders e.g. DMD, Huntington’s, CF
What is the function of maternal serum screening?
tests maternal serum markers in the blood to detect increased risk of foetal trisomy 21, trisomy 18 and/or neural tube defects
What are the benefits of NIPD and NIPT?
- number of invasive tests reduced
- no inc. risk of miscarriage
- less expertise required to perform blood test than invasive test
- can offer it earlier than invasive tests, so get result earlier
What are the eligibility criteria for PGD?
- female partner under 39
- female partner BMI of 19-30
- both partners non-smokers
- couple live together in stable relationship
- no living unaffected children from relationship
- known risk of having a child affected by a serious genetic condition (at least 10%)
- female partner has hormone levels that suggest response to treatment
- an accurate genetic test is available
- no welfare concerns for unborn child
- licence required from HFEA for each genetic condition on list
- eligible couples are funded for 3 rounds of PGD by NHS
What is the role of a GC in prenatal testing?
- arrange and explain CVS, amniocentesis, PGD, cffDNA
- 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
