Prenatal Genetic Testing

Question 1

Screening v Diagnosis

Answer 1

Screening-
-low cost, low risk of procedure itself, for low risk patients, if positive still need confirmatory test

Diagnosis-
-for patients w/ inc risk, may be more expensive, higher risk of procedure itself, pos test considered definitive

Question 2

DS Screens (4)

Answer 2

1- Maternal serum screening/QUAD- AFP, hCG, unconjugated estriol and inhibin-A
2- First Trimester Screening- PAPP-A and hCG
3- Ultrasound -meas nuchal translucency
4- NIPT (non-invasive prenatal test) - find free cell DNA in mom’s blood then count # segments of chromosomes to detect aneuploidy

Question 3

Integrated screening

Answer 3

POWERFUL; combine 1st and 2nd trimester tests + ultrasound

-must be done as single coordinated test

Question 4

DS Screen Patterns

Answer 4

QUAD- low AFP and unconjugated estriol/ high hCG and inhibinA

1 Trimester- high hCG and low PAPP-A

Question 5

Trisomy 18 (Edwards) Screen Patterns

Answer 5

QUAD- low in all 4 proteins

1st Trimester- low PAPP-A and low hCG

Question 6

Timing of Screens

Answer 6

1st trimester blood draw and ultrasound @ 11-13 wks

QUAD @ 15-20 wks

NIPT-free DNA @ 10-20 wks

Question 7

Timing of Diagnostic Tests

Answer 7

CVS @10-12 wks

Amniocentesis @ 16-20 wks

Cordocentesis @ 18-20 wks so cord large enough

Question 8

Amniocentesis

Answer 8

-Test cells from amniotic fluid for chromosome analysis and conc of AFP AND acetylcholinesterase (for neural tube defects)

Question 9

Amniocentesis results

Answer 9

Karyotype (takes 2 wks)

FISH (takes 2 days) - use probe of chromosome 13, 18,21

Question 10

CVS

Answer 10

Chorionic Villus Sampling

-get cells from villus area of chorion w/ syringe then look at chromosome analysis, biochem and molecular diagnostics

Question 11

Cordocentesis

Answer 11

AKA fetal blood sample

Draw blood from umbilical cord

Higher risk than others (1%)

May be used if infectious disease in baby

Question 12

Pre-Implantation Genetic Screening

Answer 12

• For IVF…screen IVF cells and do not implant those w/ genetic abnormality
• Remove single cell from pre-implantation embryo and test w/ PCR or fish analysis
• Limits: PCR may fail, sperm contamination, cost, low pregnancy rates w/ IVF to begin with, allele dropout, limited availability

Question 13

Indications for Amniocentesis v CVS

Answer 13

Both-

• maternal age > or = 35 at due date
• previous kid w/ trisomy
• parent has structural chromosomal abnormality
• family hx of diagnosable genetic disorder
• if positive 1st trimester or QUAD screen
• Positive cfDNA
• Ultrasound findings associated w/ genetic disorder while pregnant

Just amnio- (NOT CVS)
-previous child/patient/spouse w/ neural tube defect

Question 14

Advantages, Risk and Limits of CVS

Answer 14

Adv- early diagnosis (safer abortion), less attached b/c no ultrasound, quicker results (in past), patient privacy

Risk- similar risk of spontaneous abortion as amnio; LOW

Limits- CANNOT test for neural tube defects, should be performed at very experienced center