Prenatal Screening Flashcards
What are some differences between prenatal screening & diagnostic testing
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
What are prenatal screening options
MSS, carrier screening, cfDNA, routine blood work, US, MRI, fetal echo
Where is AFP made, how can it be detected, & what is it associated with
Fetal liver & yolk sac, detected in MSS or amniocentesis, high levels are associated with neural tube defects & abdominal wall defects
What trimester is AFP measured in
Second trimester
What is the cutoff for at risk AFP levels
Greater or equal than 2.5 is high risk for NTDS
What factors can affect AFP
Incorrect dating, twins, increased maternal weight, ethnicity, diabetes, other birth defects
When is a first trimester screen offered, what does it screen for, and what does it measure
10-13.6 weeks, trisomy 21,18,13, nuchal translucency, crown rump length, nasal bone, PAPP-A, bHCG,
What is the cutoff value for nuchal translucency, & what are the associated risks
Greater than 3 mm, trisomy 21, trisomy 18, Turner syndrome, noonan syndrome, congenital heart defects
When is second trimester screening offered, what does it measure, & what does it screen for
15-21.6 weeks, bHCG, AFP, uE3, IA, trisomy 21, 18, neural tube defects & abdominal wall defects
What factors can affect second trimester screening
Gestational age, maternal diabetes, multiples, family history of Down syndrome or NTDS, correct age & weight
What is uE3 associated with
Smith Lemli opitz, x linked icthyosis
What screening results would indicate trisomy 21 in the first & second trimesters
First: high NT, low PAPPA high BhCG
Second: low AFP, high BhCG, low uE3, high iA
What is the screening results would indicate trisomy 18 in the first & second trimester
First: high NT, low PAPPA, low bHCG
Second: low AFP, low BhCG,, low uE3, low iA
What is the serum marker patter for trisomy 13
Low bHCG, low PAPP-A
What should be done next when a prenatal screen is abnormal
Targeted US, confirm gestational age, offer diagnostic testing
When can can NIPT be offered
As early at nine weeks for some labs, screening after 12 weeks most helpful
What can NIPT screen for
Trisomy 18, 22, 13, sex chromosome aneuploidies, some micro deletions, some companies do single gene
Where does fetal DNA come from
Placental cells undergoing apoptosis
What kind of maternal results can NIPT give
Sex chromosome aneuploidy, 22q, somatic cell variation, maternal malignancy
What are the two methods for NIPT
Counting method - massive parallel shotgun sequencing or targeted sequencing, or SNP (Natera only)
How does the counting method work
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
What are benefits of the counting method for NIPT
Targeted is less expensive, faster results than SNP, less reliant on fetal fraction
What are downsides of the counting method
Can’t differentiate between fetal & maternal DNA
How does the SNP based method for NIPT work
Targeted sequencing of SNPS, selected based on reference genome, sequence data analyzed for allelic measurement, put through bioinformatics
What are benefits of the SNP based method
Can differentiate between maternal & fetal dna, can screen for triploidy & vanishing twins, can provide separate fetal sexes in twin pregnancies
What are downsides of the SNP based method
More reliant on fetal fraction, can take longer for results
What are possible result types for NIPT
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
What characteristics would indicate someone is not a candidate for NIPT
auto immune conditions - can cause fetal dna to degrade, cancer, very high BMI
