Prenatal Screening

Question 1

What are some differences between prenatal screening & diagnostic testing

Answer 1

Screening determines chance, negative is low risk but not zero, positive is increased chance, identifies patients to offer additional testing to, widely available & affordable
Dx testing provides or rules out diagnosis, negative usually rules out, positive provides diagnosis, risk associated with procedure, usually more costly

Question 2

What are prenatal screening options

Answer 2

MSS, carrier screening, cfDNA, routine blood work, US, MRI, fetal echo

Question 3

Where is AFP made, how can it be detected, & what is it associated with

Answer 3

Fetal liver & yolk sac, detected in MSS or amniocentesis, high levels are associated with neural tube defects & abdominal wall defects

Question 4

What trimester is AFP measured in

Answer 4

Second trimester

Question 5

What is the cutoff for at risk AFP levels

Answer 5

Greater or equal than 2.5 is high risk for NTDS

Question 6

What factors can affect AFP

Answer 6

Incorrect dating, twins, increased maternal weight, ethnicity, diabetes, other birth defects

Question 7

When is a first trimester screen offered, what does it screen for, and what does it measure

Answer 7

10-13.6 weeks, trisomy 21,18,13, nuchal translucency, crown rump length, nasal bone, PAPP-A, bHCG,

Question 8

What is the cutoff value for nuchal translucency, & what are the associated risks

Answer 8

Greater than 3 mm, trisomy 21, trisomy 18, Turner syndrome, noonan syndrome, congenital heart defects

Question 9

When is second trimester screening offered, what does it measure, & what does it screen for

Answer 9

15-21.6 weeks, bHCG, AFP, uE3, IA, trisomy 21, 18, neural tube defects & abdominal wall defects

Question 10

What factors can affect second trimester screening

Answer 10

Gestational age, maternal diabetes, multiples, family history of Down syndrome or NTDS, correct age & weight

Question 11

What is uE3 associated with

Answer 11

Smith Lemli opitz, x linked icthyosis

Question 12

What screening results would indicate trisomy 21 in the first & second trimesters

Answer 12

First: high NT, low PAPPA high BhCG
Second: low AFP, high BhCG, low uE3, high iA

Question 13

What is the screening results would indicate trisomy 18 in the first & second trimester

Answer 13

First: high NT, low PAPPA, low bHCG
Second: low AFP, low BhCG,, low uE3, low iA

Question 14

What is the serum marker patter for trisomy 13

Answer 14

Low bHCG, low PAPP-A

Question 15

What should be done next when a prenatal screen is abnormal

Answer 15

Targeted US, confirm gestational age, offer diagnostic testing

Question 16

When can can NIPT be offered

Answer 16

As early at nine weeks for some labs, screening after 12 weeks most helpful

Question 17

What can NIPT screen for

Answer 17

Trisomy 18, 22, 13, sex chromosome aneuploidies, some micro deletions, some companies do single gene

Question 18

Where does fetal DNA come from

Answer 18

Placental cells undergoing apoptosis

Question 19

What kind of maternal results can NIPT give

Answer 19

Sex chromosome aneuploidy, 22q, somatic cell variation, maternal malignancy

Question 20

What are the two methods for NIPT

Answer 20

Counting method - massive parallel shotgun sequencing or targeted sequencing, or SNP (Natera only)

Question 21

How does the counting method work

Answer 21

MPSS sequences entire genome, targeted amplifies regions of interest, chromosome origins determined for each fragment, then compared to reference genome, quantitative amount compared to reference to give ratio

Question 22

What are benefits of the counting method for NIPT

Answer 22

Targeted is less expensive, faster results than SNP, less reliant on fetal fraction

Question 23

What are downsides of the counting method

Answer 23

Can’t differentiate between fetal & maternal DNA

Question 24

How does the SNP based method for NIPT work

Answer 24

Targeted sequencing of SNPS, selected based on reference genome, sequence data analyzed for allelic measurement, put through bioinformatics

Question 25

What are benefits of the SNP based method

Answer 25

Can differentiate between maternal & fetal dna, can screen for triploidy & vanishing twins, can provide separate fetal sexes in twin pregnancies

Question 26

What are downsides of the SNP based method

Answer 26

More reliant on fetal fraction, can take longer for results

Question 27

What are possible result types for NIPT

Answer 27

Low risk negative screen, High risk positive screen, no results due to lab errors/failure in quality metrics/ low fetal fraction, partial results - pending microdeletions, no call on Y analysis or fetal sex result

Question 28

What characteristics would indicate someone is not a candidate for NIPT

Answer 28

auto immune conditions - can cause fetal dna to degrade, cancer, very high BMI