Prenatal diagnosis

Question 1

What factors determine a high risk pregnancy?

Answer 1

1. Family history of genetic disease
2. Maternal illness
3. History of abnormal pregnancy

Question 2

What is the main contributing factor to neural tube defects?

Answer 2

Folic acid deficiency

Question 3

How are open neural tube defects detected?

Answer 3

1. Ultrasound
2. Elevated levels of α-fetoprotein in maternal serum

Question 4

How are chromosome defects detected?

Answer 4

1. Aneuploidy (loss/gain of whole chromosome): Cytogenetics (e.g. karyotyping [analysis under microscope])
2. Translocations:
   - Large: Cytogenetics
   - Small: Microarray

Question 5

What causes Down’s syndrome?

Answer 5

Trisomy 21

Question 6

What are the symptoms of Down’s syndrome?

Answer 6

1. Intellectual impairment
2. Craniofacial abnormalities (e.g. flat nasal bridge, slanting palpebral fissure…)
3. Single palm crease
4. Cardiac defects

Question 7

What causes Edward syndrome?

Answer 7

Trisomy 18

Question 8

What are the symptoms of Edward syndrome?

Answer 8

1. Intellectual impairment
2. Craniofacial abnormalities (e.g. micrognathia)
3. Clenched overlapping fingers
4. Prominent heels
5. Rocker-bottom feet
6. Cardiac defects

Question 9

What causes Patau syndrome?

Answer 9

Trisomy 13

Question 10

What are the symptoms of Patau syndrome?

Answer 10

1. Intellectual impairment
2. Craniofacial abnromalities (e.g. cleft palate, cleft lip, holoprosencephaly)
3. Renal abnormalities
4. Cardiac defects

Question 11

What are the types of aneuploidies?

Answer 11

1. Down’s syndrome - Trisomy 21
2. Edward syndrome - Trisomy 18
3. Patau syndrome - Trisomy 13
4. Turner syndrome - XO
5. Kleinfelter’s syndrome - XXY

Question 12

What are the purposes of the “Early pregnancy scan”, or ‘booking scan’?

Answer 12

1. Determination of gestational age:
   - Foetal crown rump length (length from top of head to buttock)
   - Bi-parietal diameter (diameter of head in coronal plane)
2. Viability assessment
3. Number of foetuses (multiple pregnancy)
4. Detection of severe congenital abnormalities

Question 13

What type of scan is the early pregnancy scan?

Answer 13

Ultrasound scan

Question 14

When is the early pregnancy scan performed?

Answer 14

Before 15 weeks

Question 15

What is nuchal translucency thickness?

Answer 15

Thickness of collection of fluids behind neck of foetus

Question 16

What can increased nuchal translucency thickness be an indicator for?

Answer 16

1. Down’s syndrome
2. Congenital heart defects
3. Venous congestion in head and neck due to constriction of foetal body
4. Abnormalities in lymphatics system
5. Neuromuscular disorders leading to impaired foetal movements
6. Foetal anaemia/hyoproteinaemia
7. Congenital infections due to anaemia/cardiac defects

Question 17

What is the purpose of the foetal anomaly scan?

Answer 17

Confirm absence of foetal anomalies or to identify present anomalies. These include anomalies that are:

1. Not compatible with life
2. Associated with high risk of mortality/morbidity
3. Conditions that may be treated pre-natally
4. Conditions that need to be treated post-natally

Question 18

When does anencephaly become visible?

Answer 18

10-14 weeks

Question 19

When does spina bifida become visible?

Answer 19

16-22 weeks

Question 20

What are the indirect markers for neural tube defects?

Answer 20

1. Lemon sign (transverse plane): Indentation of frontal bone resulting in lemon shape of skull.
2. Banana sign (transverse plane): Tight wrapping of cerebellum around brainstem results in banana-like appearance.

Question 21

Where is α-fetoprotein produced and how does it enter maternal circulation?

Answer 21

Production:

1. Liver
2. Yolk sac

Entry into circulation:

1. Directly across placenta
2. Indirectly from amniotic fluid via uterine decidua

Question 22

How is α-fetoprotein levels measured?

Answer 22

Immunoassay (e.g. ELISA)

Question 23

What is the importance of gestational age in prenatal diagnosis?

Answer 23

Levels of different serum markers differ throughout gestation and so accurate estimate of gestational age needed to interpret data.

Question 24

What is measured in the Triple test?

Answer 24

1. α-fetoprotein (AFP)
2. Unconjugated estriol (μE3)
3. Human chorionic gonadotrophin (hCG)

Question 25

What are the invasive prenatal diagnosis techniques?

Answer 25

1. Chorionic villous sampling 2. Amniocentesis 3. Foetal blood sampling 4. Foetoscopy - Foetal skin biopsy

Question 26

What are the non-invasive prenatal diagnosis techniques?

Answer 26

1. Ultrasound 2. Free foetal DNA in maternal blood

Question 27

What is chorionic villous sampling (CVS) and what are the associated risks?

Answer 27

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

Question 28

What is amniocentesis and what are the associated risks?

Answer 28

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

Question 29

What are the advantages and disadvantages of CVS?

Answer 29

Advantages: Early diagnosis (no cell culturing) Disadvantages: - High risk of miscarriage - Use of extraembryonic tissue and so less representitive (due to placental mosaicism)

Question 30

What are the advantages and disadvantages of amniocentesis?

Answer 30

Advantages: - Foetal material so is more representitive - Lower risk of miscarriage Disadvantages: Later diagnosis due to need for cell culturing

Question 31

What is foetoscopy?

Answer 31

Passing endoscope into amnion transabdominally under ultrasound guidance to visualise foetus

Question 32

What is cell-free foetal DNA (cffDNA)?

Answer 32

- Fragmented foetal DNA present in maternal blood - Derived from placental trophoblasts - Detectable 4-5 weeks after gestation

Question 33

What techniques utilise cffDNA?

Answer 33

- 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.

Question 34

When can cffDNA not be used for diagnosis?

Answer 34

- 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.