Prenatal Diagnosis

Question 1

What does prenatal dx allow clients?

Answer 1

timely treatment of condition (before or after birth)

decision-making about continuing pregnancy

prenatal and neonatal management

time to plan and prepare psychologically, socially, etc

Question 2

Who should be offered prenatal dx? in common practice?

Answer 2

everyone

fetal anomalies on US
abn screening result
previous child with genetic condition
AMA
FHx of genetic condition of ONTD

Question 3

What does CVS sample? When is it completed?

Answer 3

chorionic villi

should be representative of fetus

10-14wks GA

Question 4

What type of studies can be used with CVS?

Answer 4

cyto, molecular, biochemical

Question 5

What types of CVS can be done? Patient decision?

Answer 5

transcervical, transabdominal

no

Question 6

What are the risks associated with CVS?

Answer 6

1/100-1/200 (new studies say closer to 1/500)

Question 7

What types of results can be seen in CVS? accuracy?

Answer 7

1%: mosaic
1% maternal cell contamination

99% detection of chromosomal adn

Question 8

Limitations of CVS?

Answer 8

No ONTD info -> MS_AFP only @ 16-18wk and anat scan at 18-20wks
pt cannot choose method
mosaic results require follow up

Question 9

What % of mosaic results in CVS are true mosaicism? What’s the other percentage make up?

Answer 9

10-20%

80-90% confined placental mosaicism

Question 10

What are the outcomes of CPM? What chromosomes have higher rate of CPM? Follow up for CPM?

Answer 10

generally good
possible increased risk of fetal growth restriction

trisomy 13, monosomy X, rare autosomal trisomies

amnio

Question 11

What cells are present in amniotic fluid that can be used?

Answer 11

skin and fetal urogenital tract

Question 12

What types of studies can be done from amniotic samples?

Answer 12

cells -> cyto, molecular, and/or biochemical

fluid -> AF-AFP, AChE and/or biochem

Question 13

When is amnio done?

Answer 13

16-20wks ideally

15wks-delivery (amnion and chorion must be fused)

Question 14

What are some other indications for amnio?

Answer 14

fetal lung maturity
dx of infection/other conditions
treatment/therapy (amnio drainage/reduction)

Question 15

What are the risks associated with amnio?

Answer 15

complications leading to pregnancy loss/preterm labor -> 1/200-1/400 (most recently maybe 1/500-1/1000)

Question 16

How accurate is amnio?

Answer 16

99.5% DR for chromosome abn

98% of ONTDs by AFP
- High AFP -> AChE analyzed -> >99% DR for ONTD

Question 17

Caveats to amnio?

Answer 17

procedure can be difficult/impossible if:

• anterior placenta
• mulitple pregnancy
• maternal obesity (more painful)
• low amniotic fluid (oligohydramnios)

Question 18

What types of anticipatory guidance is given to those with invasive prenatal testing?

Answer 18

complications:

• fever or chills not related to cold/flu
• heavy, rhythmic contractions lasting 2-3 hrs or more
• fluid leakage from vagina
• bleeding from vagina (spotting is common after transcervical CVS)

Question 19

What is PUBS? When is it completed? Accuracy?

Answer 19

AKA cordocentesis -> samples fetal blood from umbilical vein under US

roughly 20wks

99.9% DR for chromosome abn

Question 20

Why is PUBS done? Uses?

Answer 20

detect and treat blood conditions

fetal hematologic status
fetal blood transfusion/delvier meds
congenital infection eval
rapid karyotype
follow-up mosaicism (not often)

Question 21

Risks with PUBS?

Answer 21

2-5% risk of miscarraige (dependent on provider)
- fetal bleeding from puncture
- cord hematoma
- fetal bradycardia
- infection
-fetal-maternal bleeding
pregnancy loss

Question 22

What test does ACOG be recommended for any pt undergoing invasive testing?

Answer 22

CMA

Question 23

What types of FISH exist? Probes?

Answer 23

Interphase (count) and Metaphase (identify)

chromosome specific probes
locus specific

Question 24

When would you use interphase FISH? Caveats?

Answer 24

rapid identification of common aneuploidy (same chromo as NIPT)

cannot detect structural abn or numerical abn of other chromosomes

usually ordered with karyotype and/or array to get early results

Question 25

Limitations of Interphase FISH?

Answer 25

maternal cells are not distinguished

considered a screen (an not considered dx)

Question 26

Why would you use Metaphase FISH?

Answer 26

identify location of particular DNA seq (often for specific fetal microdeletion)

Question 27

Caveats of Metaphase FISH?

Answer 27

Longer TAT than interphase, require cultured samples

Question 28

What are karyotypes used for?

Answer 28

identify aneuploidy, structural rearragements and chromosomal abn >5-10Mb

Question 29

Caveats to karyotype?

Answer 29

cell culture req (longer TAT)

low resolution

Question 30

When would you use a CMA?

Answer 30

detect clincally sig chromosome CNV too small to be seen on karyotype

Question 31

Caveats for CMA?

Answer 31

not useful for single gene (incidental dx may arise)
cannot deetct balanced translocations
cannot detect triploidy
may detect consanguinity (ROH)
can report VUS

Question 32

Benefits of CMA?

Answer 32

can be performed on culture or uncultured cells
prenatal CMA interpreted diff than ped or adult CMA
detected 1.7% of variants in fetus with normal US and karyotype, 6% of fetuses w US abn and normal karyotype

Question 33

What should we consider when ordering prenatal dx?

Answer 33

utility (what does it provide for the pt)
how pregnant is the pt?
what is TAT and how would this limit their options?
client values, priorities, and needs
limitations