L6 Prenatal Diagnosis Flashcards
What are the benefits of prenatal diagnosis where an abnormality is detected?
- Gives parents options (further testing, referral, termination)
- Allows clinicians to adapt their approach (altered obstetric and neonatal management)
What are some key risks of prenatal diagnosis?
- Parental anxiety
- True and false positive
- Pregnancy complications
- Pregnancy loss
What are the common forms of chromosomal abnormalities and how common are they, as a whole?
- 1 in 300 pregnancies
- 95% are Trisomy 21, 13, 18 or sex chromosome issues
List some key risk factors for chromosomal abnormalities:
- Age (e.g. Downs syndrome risk increases steeply after the mother is over 35)
- Family history of genetic abnormalities
- Chromosomal abnormality in one of prospective parents
- Previous miscarriage or stillbirth
- Previous baby with birth defect
Why is prenatal screening still important when we can do risk assessments for risk factors?
- More than 90% of structural and chromosomal foetal abnormalities are born to low-risk women
- All pregnant women are thus offered rapid screening
What factors are used to screen for genetic disease?
- Maternal age -> poor screening on its own (~30% DS cases detected)
- Biomarkers are crucial
What screening tests are used during the first trimester for CAs?
- At 11 - 14 weeks the combined test will be offered….
- Nuchal translucency (based on USS, looking for an excess of fluid at the back of baby’s neck) -> high NT also an indicator for heart defects
- High hCG levels
- Low PAPP levels
- Results are taken into context with maternal age to produce the likelihood of an affected child
What are the components of the quadruple maternal serum screen and when is it performed (CAs):
- hCG (high->DS), AFP (alpha fetoprotein; low in DS and high in neural tube defects), unconjugated estriol (low -> DS), inhibin A (high->DS)
- Performed at 15 - 20 weeks (second trimester)
What is nuchal translucency?
- Based on USS
- Looking for an excess of fluid at the back of baby’s neck
- High for GA: Higher DS risk
- High (for GA) NT also an indicator for heart defects
- Naturally increases with gestational age
List some conditions that might be indicated by raised NT with normal karyotype:
- Cardiac defects
- Diaphragmatic hernia
- Pulmonary defects
- Skeletal dysplasias
- Congenital infection
- Metabolic/haem disorders
What would be the clinical pathway following raised NT with normal karyotype?
- Various cardiac and pulmonary issues risked
- Diagnostic testing and foetal echocardiogram required at 20 weeks
- More detailed anatomy scan to be performed at 18 - 20 weeks
- Genetic counselling!
Give 2 examples of non-invasive chromosomal evaluation methods:
- Foetal cells from maternal circulation
- PGT-A
Give 3 examples of invasive chromosomal evaluation methods:
- Amniotic fluid (amniocentesis) ->usually later due to risk of damage to body structure
- Placenta (CVS) -> earlier diagnosis
- Foetal blood
When and how is chorionic villus sampling performed?
- From ~10 weeks (typically 11 - 14)
- Typically abdominal
- Transcervical and transvaginal less common
What features can be tested using samples from invasive testing methods?
- Karyotype (trisomy, monosomy, polyploidy)
- Other genetic aberrations (deletion, duplication, inversion, translocation, ring chromosome
- Infectious diseases (e.g. CMV)
- Biochemical markers (e.g. chorioamnionitis, raised IL-6)
What is ring chromosome and what can it result in?
- Very uncommon event where chromosome ends fuse, usually with loss of telomeres
- Either developmental onset or due to radiation
- Associated syndromes depend on affected chromosome but often involve marked growth delay
Outline how amniocentesis is performed:
- High resolution USS-guided removal of 20cc amniotic fluid
- Not under GA
- Skin cells present in fluid can then be used for various tests (e.g. following rapid culture or more reliable and lengthy biochemical analysis)
Outline the CVS procedure:
- Bigger needle than amnio in order to agitate villi
- GA will be used
- Chorionic villus sample taken from placenta
What methods of testing can be used on CV samples?
- Direct analysis: Examining placental trophoblasts; rapid but vulnerable to mitotic error
- Cultured analysis: Examining fibroblast-like cells of villus stroma or mesenchymal core; takes >10 days but is more accurate
Outline the complications that can arise from invasive prenatal testing:
- Pregnancy loss 1:100 - 200
- Bigger needle -> Greater risk
- Leakage of amniotic fluid -> respiratory distress syndrome
- Limb reduction
- Amnionitis
- Maternal visceral injury or bleeding
- Potential iso-immunisation
Mosaicism can affect…
- Foetus
- Placenta (placental mosaicism)
- Both
- Arises from non disjunction at various points in meiosis or later mitosis
Why might CVS be offered later than 15 weeks to older mothers?
- Increased risk of mosaicism with maternal age due to somatic mosaicism
- CVS must check both layers of placenta…
- -> Cytotrophoblast to check placenta
- -> Mesenchymal core to check foetal karyotype
What are the health implications of uniparental disomy?
- Parental imprinting (heterodisomy, isodisomy)
- Unmasking of recessive conditions in some cases of isodisomy
What chromosomes have links with adverse phenotypic imprinting effects?
- 15 (PWS/AS)
- 11 (B-W)
- 6
- 7
- 14
- Molecular UPD testing should be considered for these chromosomes
