Prenatal testing

Question 1

How many pregnancies are affected by neural tube defects? How can these be prevented?

Answer 1

1/500, can prevent with folate supplements

Question 2

Why is reproductive testing utilised?

Answer 2

Offers reproductive choices

Provides risk information to couples who may otherwise not choose to begin a pregnancy

Choice of termination of affected foetus

Allows couples to prepare for affected baby

Helps medical team to prepare for delivery, management and care of affected baby

Provides reassurance when result is normal

Question 3

What types of prenatal testing are available?

Answer 3

SCREENING TESTS: all pregnant women, non-invasive to foetus

DIAGNOSTIC TESTS: for women at increased risk, invasive to foetus

Question 4

What is the purpose of prenatal screening?

Answer 4

Identifies a subset of women from the general population that are at an increased risk of having a baby with a birth defect

Question 5

Are prenatal screening tests definitive?

Answer 5

No - need to follow up with diagnostic tests

Question 6

Which prenatal screening tests are used in Victoria? What does each detect?

Answer 6

1st trimester combined screening: T21, T28

2nd trimester combined screening: T21, T18, NTD

Question 7

What is involved in first trimester combined screening?

Answer 7

Blood at 9 weeks - 13 weeks and 6 days
Measure PAPP-A and bHCG

Us at 11 weeks and 3 days - 13 weeks and 6 days
Measure nuchal translucency and crown rump length (dating)

Question 8

What is nuchal translucency?

Answer 8

Fluid behind back of baby’s neck

Normal, but abnormal for it to be very thick

Question 9

How is a risk calculated after 1st trimester combined screening?

What are the cut-offs?

What is the detection rate for T21 wuth this testing?

Answer 9

Combine results of blood analysis, US and other factors (e.g. maternal age)

T21: 1 in 300
T18: 1 in 175

T21 detection rate is 93%

Question 10

What is involved in 2nd trimester screening?

Answer 10

Blood taken at 14-20 weeks
Measures PAPP-A, bHCG, inhbin-A and a-fetoprotein

Question 11

How is a risk calculated after second trimester screening?

What are the risk cut-offs?

What is the detection rate for T21 and NTDs?

Answer 11

Result of blood tests plus other risk factors (e.g. maternal age)

T21: 1 in 250
T18: 1 in 200
NTD: _> _2.0 MoM

Detection rate for T21 is 85%, NTDs in 93%

Question 12

What sort of testing can be carried out before pregnancy?

Answer 12

Genetic carrier screening

Question 13

What are the options after an increased risk is detected in first or second trimester screening?

Answer 13

No action

OR

Foetal anomaly US with/or CVS or amniocentesis

Question 14

Which women are offered CVS and amniocentesis?

Answer 14

Increased risk screening result

Advanced maternal age

Known carriers

Question 15

Which tests can be carried out on the cells collected via CVS or amniocentesis?

Answer 15

FISH/PCR

Karyotype

Question 16

Describe CVS?

Answer 16

Chorionic villus sampling

From 11 weeks gestation

Sample placental tissue

Question 17

Describe amniocentesis?

Answer 17

From 15-16 weeks

Sample amniotic fluid containing sloughed off foetal cells

Question 18

Describe the risk of miscarriage associated with CVS and amniocentesis?

Answer 18

CVS: 1% above background risk

Amniocentesis: 0.5% above background risk

Question 19

Describe the FISH technique?

Answer 19

Fluorescent probes on chromosomes in non-dividing cells

Count number of chromosomes

Question 20

How is a karyotype obtained?

Answer 20

Cells grown for 2 weeks
Arrested in metaphase
Then chromosomes released to form karyotype

Question 21

What types of rearrangements can occur between chromosomes?

Answer 21

Reciprocal translocation: part of one chromosome attaches to another (balanced)

Robertsonian translocation: translocation between two acrocentric chromosomes (13, 14, 15, 21, 22)

Unbalanced translocation: extra copy of chromosome attaches to another chromosome

Question 22

Describe how Down syndrome can be inherited due to an unbalanced translocation?

Answer 22

Question 23

What can be detected using microarrays?

Answer 23

DNA sequences and/or gene expression

SNPs

CNVs

Number of chromosomes

Question 24

What are chromosomal microarrays used for?

Answer 24

Probes along entire genome

Detect copy number variations (deletions and microdeletions)

First tier test for developmental delay, intellectual diasbility, autism

Question 25

Briefly describe how a chromosomal microarray is performed and interpreted?

Answer 25

Probes along genome

Loom to see if there are equivalent amounts of DNA between patient and sample

Question 26

Which chromosomal abnormality is not detected by chromosomal microarrays?

Answer 26

Balanced translocations

Question 27

When should prenatal molecular karyotyping be performed?

Answer 27

Foetal abnormality detected on US

Nuchal translucency > 3.5mm

Karyotype identifies a complex change

Family member has a microdeletion syndrome

Question 28

What is NIPT/S?

Answer 28

Non-invasive prenatal testing/screening

Samples cell free foetal DNA/RNA in maternal blood

Question 29

When can NIPT/S be performed?

Answer 29

10 weeks gestation

Question 30

How is NIPT/S performed?

Answer 30

Using massively parallel sequencing

Question 31

Is NIPT/S a screening or diagnostic test?

Answer 31

Very high sensitivity and specificity for trisomy 21

Still recommend that positive result is followed up with CVS or amniocentesis

Question 32

What is the disadvantage to NIPT/S?

Answer 32

Cost