How many pregnancies are affected by neural tube defects? How can these be prevented?
1/500, can prevent with folate supplements
Why is reproductive testing utilised?
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
What types of prenatal testing are available?
SCREENING TESTS: all pregnant women, non-invasive to foetus
DIAGNOSTIC TESTS: for women at increased risk, invasive to foetus
What is the purpose of prenatal screening?
Identifies a subset of women from the general population that are at an increased risk of having a baby with a birth defect
Are prenatal screening tests definitive?
No - need to follow up with diagnostic tests
Which prenatal screening tests are used in Victoria? What does each detect?
1st trimester combined screening: T21, T28
2nd trimester combined screening: T21, T18, NTD
What is involved in first trimester combined screening?
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)
What is nuchal translucency?
Fluid behind back of baby's neck
Normal, but abnormal for it to be very thick
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?
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%
What is involved in 2nd trimester screening?
Blood taken at 14-20 weeks
Measures PAPP-A, bHCG, inhbin-A and a-fetoprotein
How is a risk calculated after second trimester screening?
What are the risk cut-offs?
What is the detection rate for T21 and NTDs?
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%
What sort of testing can be carried out before pregnancy?
Genetic carrier screening
What are the options after an increased risk is detected in first or second trimester screening?
Foetal anomaly US with/or CVS or amniocentesis
Which women are offered CVS and amniocentesis?
Increased risk screening result
Advanced maternal age
Which tests can be carried out on the cells collected via CVS or amniocentesis?
Chorionic villus sampling
From 11 weeks gestation
Sample placental tissue
From 15-16 weeks
Sample amniotic fluid containing sloughed off foetal cells
Describe the risk of miscarriage associated with CVS and amniocentesis?
CVS: 1% above background risk
Amniocentesis: 0.5% above background risk
Describe the FISH technique?
Fluorescent probes on chromosomes in non-dividing cells
Count number of chromosomes
How is a karyotype obtained?
Cells grown for 2 weeks
Arrested in metaphase
Then chromosomes released to form karyotype
What types of rearrangements can occur between chromosomes?
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
Describe how Down syndrome can be inherited due to an unbalanced translocation?
What can be detected using microarrays?
DNA sequences and/or gene expression
Number of chromosomes
What are chromosomal microarrays used for?
Probes along entire genome
Detect copy number variations (deletions and microdeletions)
First tier test for developmental delay, intellectual diasbility, autism
Briefly describe how a chromosomal microarray is performed and interpreted?
Probes along genome
Loom to see if there are equivalent amounts of DNA between patient and sample
Which chromosomal abnormality is not detected by chromosomal microarrays?
When should prenatal molecular karyotyping be performed?
Foetal abnormality detected on US
Nuchal translucency > 3.5mm
Karyotype identifies a complex change
Family member has a microdeletion syndrome
What is NIPT/S?
Non-invasive prenatal testing/screening
Samples cell free foetal DNA/RNA in maternal blood
When can NIPT/S be performed?
10 weeks gestation
How is NIPT/S performed?
Using massively parallel sequencing
Is NIPT/S a screening or diagnostic test?
Very high sensitivity and specificity for trisomy 21
Still recommend that positive result is followed up with CVS or amniocentesis
What is the disadvantage to NIPT/S?