Prenatal diagnosis Flashcards
What factors determine a high risk pregnancy?
- Family history of genetic disease
- Maternal illness
- History of abnormal pregnancy
What is the main contributing factor to neural tube defects?
Folic acid deficiency
How are open neural tube defects detected?
- Ultrasound
- Elevated levels of α-fetoprotein in maternal serum
How are chromosome defects detected?
- Aneuploidy (loss/gain of whole chromosome): Cytogenetics (e.g. karyotyping [analysis under microscope])
- Translocations:
- Large: Cytogenetics
- Small: Microarray
What causes Down’s syndrome?
Trisomy 21
What are the symptoms of Down’s syndrome?
- Intellectual impairment
- Craniofacial abnormalities (e.g. flat nasal bridge, slanting palpebral fissure…)
- Single palm crease
- Cardiac defects
What causes Edward syndrome?
Trisomy 18
What are the symptoms of Edward syndrome?
- Intellectual impairment
- Craniofacial abnormalities (e.g. micrognathia)
- Clenched overlapping fingers
- Prominent heels
- Rocker-bottom feet
- Cardiac defects
What causes Patau syndrome?
Trisomy 13
What are the symptoms of Patau syndrome?
- Intellectual impairment
- Craniofacial abnromalities (e.g. cleft palate, cleft lip, holoprosencephaly)
- Renal abnormalities
- Cardiac defects
What are the types of aneuploidies?
- Down’s syndrome - Trisomy 21
- Edward syndrome - Trisomy 18
- Patau syndrome - Trisomy 13
- Turner syndrome - XO
- Kleinfelter’s syndrome - XXY
What are the purposes of the “Early pregnancy scan”, or ‘booking scan’?
- Determination of gestational age:
- Foetal crown rump length (length from top of head to buttock)
- Bi-parietal diameter (diameter of head in coronal plane) - Viability assessment
- Number of foetuses (multiple pregnancy)
- Detection of severe congenital abnormalities
What type of scan is the early pregnancy scan?
Ultrasound scan
When is the early pregnancy scan performed?
Before 15 weeks
What is nuchal translucency thickness?
Thickness of collection of fluids behind neck of foetus
What can increased nuchal translucency thickness be an indicator for?
- Down’s syndrome
- Congenital heart defects
- Venous congestion in head and neck due to constriction of foetal body
- Abnormalities in lymphatics system
- Neuromuscular disorders leading to impaired foetal movements
- Foetal anaemia/hyoproteinaemia
- Congenital infections due to anaemia/cardiac defects
What is the purpose of the foetal anomaly scan?
Confirm absence of foetal anomalies or to identify present anomalies. These include anomalies that are:
- Not compatible with life
- Associated with high risk of mortality/morbidity
- Conditions that may be treated pre-natally
- Conditions that need to be treated post-natally
When does anencephaly become visible?
10-14 weeks
When does spina bifida become visible?
16-22 weeks
What are the indirect markers for neural tube defects?
- Lemon sign (transverse plane): Indentation of frontal bone resulting in lemon shape of skull.
- Banana sign (transverse plane): Tight wrapping of cerebellum around brainstem results in banana-like appearance.
Where is α-fetoprotein produced and how does it enter maternal circulation?
Production:
- Liver
- Yolk sac
Entry into circulation:
- Directly across placenta
- Indirectly from amniotic fluid via uterine decidua
How is α-fetoprotein levels measured?
Immunoassay (e.g. ELISA)
What is the importance of gestational age in prenatal diagnosis?
Levels of different serum markers differ throughout gestation and so accurate estimate of gestational age needed to interpret data.
What is measured in the Triple test?
- α-fetoprotein (AFP)
- Unconjugated estriol (μE3)
- Human chorionic gonadotrophin (hCG)
What are the invasive prenatal diagnosis techniques?
- Chorionic villous sampling
- Amniocentesis
- Foetal blood sampling
- Foetoscopy
- Foetal skin biopsy
What are the non-invasive prenatal diagnosis techniques?
- Ultrasound
- Free foetal DNA in maternal blood
What is chorionic villous sampling (CVS) and what are the associated risks?
Method:
- Carried out between 11-14 weeks
- Needle penetrates placenta to take sample of trophoblast cells
- Sufficient DNA for analysis without cell culturing needed
Risk: Infection & 1-2% miscarriage
What is amniocentesis and what are the associated risks?
Method:
- Carried out between 15-20 weeks
- Needle passed into amnion transabdominally under ultrasound guidance
- Fluid sample removed
- Foetal cells need at least 2 weeks to culture
Risk: Infection & 0.5% miscarriage
What are the advantages and disadvantages of CVS?
Advantages: Early diagnosis (no cell culturing)
Disadvantages:
- High risk of miscarriage
- Use of extraembryonic tissue and so less representitive (due to placental mosaicism)
What are the advantages and disadvantages of amniocentesis?
Advantages:
- Foetal material so is more representitive
- Lower risk of miscarriage
Disadvantages: Later diagnosis due to need for cell culturing
What is foetoscopy?
Passing endoscope into amnion transabdominally under ultrasound guidance to visualise foetus
What is cell-free foetal DNA (cffDNA)?
- Fragmented foetal DNA present in maternal blood
- Derived from placental trophoblasts
- Detectable 4-5 weeks after gestation
What techniques utilise cffDNA?
- Non-invasive prenatal diagnosis (NIPD): Use of cffDNA to confirm diagnosis of disease (e.g. single gene disorders).
- Non-invasive prenatal testing (NIPT): Use of cffDNA to test for possibility of disease followed by invasive technique to confirm diagnosis.
When can cffDNA not be used for diagnosis?
- Aneuploidy: Since in tact chromosomes are needed.
- Single-gene defects: If mother is a carrier for disease being tested for, since the gene will be present in maternal blood.
