Term
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Definition
| The proportion of unaffected individuals with a negative result |
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Term
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Definition
| The proportion of affected individuals with a positive results |
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Term
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Definition
| The percentage of people that get positive results -- both true and false! |
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Term
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Definition
The “multiple of the population median” value. This is a score that allows us to compare our patient’s value to their population (race, ethnicity, gestational age, weight) reference median value, which is written as 1.
Therefore, a MoM of 2 is twice the median value. |
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Term
| Second Trimester Screening |
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Definition
(AKA the Quad or Tetra screen)
Originally introduced to screen for AFP for neural tube defects -- expanded when it was realized AFP was low for Down Syndrome pregnancies. Detects Down syndrome and spina bifuda 80% of the time, trisomy 18 60% of the time. However, 5% will have a positive screen -- most of these pregnancies are healthy.
Done around 15-22 weeks. Looks at AFP, hCG, DIA, and uE3.
This test gives a patient specific risk, basically the positive predictive value. |
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Term
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Definition
Alpha-fetoprotein. Synthesized by the yolk sack, GI tract, and liver of the fetus (considered of fetal origin). Elevated if a neural tube defect, low for down syndrome.
A markedly elevated value is over 2.5 MoM
Used on quad screen. |
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Term
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Definition
Human chorionic gonadotropin. Synthesized by the early placenta (used in pregnancy tests, placental in origin).
The most sensitive marker for DS in the quad screen (though PAPP-A is more sensitive than it in the first trimester screen).
Used on quad screen and the first trimester screen. |
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Term
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Definition
Unconjugated estriol. Both placental and fetal (adrenal glands and liver) in origin. Steadily increases throughout pregnancy.
Very low levels occur with Smith-Lemli-Opitz syndrome (a cholesterol metabolism problem) and X-linked ichthyosis (a steroid sulfatase deficiency, causes dry itchy skin and dirty brown necks).
Used on quad screen. |
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Term
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Definition
Inhibin A. Primarily placental origin.
Used on quad screen. |
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Term
| What is the quad screen screening pattern that should make you suspect Down syndrome? |
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Definition
Low AFP
High Inhibin A (DIA)
High hCG (human gonadotropin)
Low uE3 (unconjugated estriol)
Remember, HIGH. The HcG and the Inhibin are High. Everything else is low. |
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Term
| What is the quad screen screening pattern that should make you suspect trisomy 18? |
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Definition
Unusual AFP (high or low)
Low hCG
Low uE3
Generally all three are low. AFP might be high because they have a chance of neural tube defects. |
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Term
| What is the quad screen screening pattern that should make you suspect neural tube defects? |
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Definition
High AFP. Open spina bifida is usually 4 MoM, anencephaly is 7.
However, abnormal results can happen because of a gestational age being older than thought, maternal weight, renal abnormalities, bleeding, multiple gestation, anencephaly, skin defects, etc -- so many reasons. Also stillbirth or fetal growth restriction. |
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Term
| When should you repeat a quad screen? |
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Definition
Do not repeat for Down Syndrome results unless the gestational age was estimated 10 to 14 days too early. Do not repeat for trisomy 18 results unless the gestational age was 4 weeks off (the pattern is more unique and pregnancies measure small anyway).
The gestational age is critical to this sample. However, waiting longer will make it look more normal, so rerunning doesn’t say much unless it’s very off.
Repeat for AFP. Means of normal and abnormal are very different (and become more different) so it shouldn’t matter. |
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Term
| If someone has a positive quad screen for Down syndrome, what else could it be? |
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Definition
It could be Down syndrome, but the gestational age might also be wrong -- if the gestational age was too early, it might cause this.
It can also mean other chromosome abnormalities like mosaic trisomies, XXX, XXY, or Turner’s syndrome. |
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Term
| First Trimester Screening |
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Definition
Also called the “combined screen.” Done between 11-13 weeks.
Looks at PAPP-A, hCG, and sometimes AFP or Inhibin. The nuchal translucency is also measured. All of this information (plus demographics) is used to give risk estimates for Down syndrome (85% detection rate) and trisomy 13/18 (90%) detection rate. 1/20 will have a positive screen (though most are fine). |
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Term
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Definition
| An enlarged (usually septated) nuchal translucency. Can either disappear or progress to hydrops and fetal death. Occasionally persists to birth. |
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Term
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Definition
A first trimester measurement (between 10 and 14 weeks). It is a accumulation of fluid on the back of the fetus’s neck. Used in risk assessment.
Usually greater than 3 mm or 95th percentile is high risk.
Associated with chromosomal abnormalities, other abnormalities, fetal death, heart defects, and developmental delay. |
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Term
| Nuchal thickness (aka Nuchal fold) |
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Definition
| A second trimester measurement (between 14 and 21 weeks). A measure of the excess skin or soft tissue on the back of the fetal neck. If thicker than 5 to 6 mm considered a marker for Down Syndrome. |
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Term
| When should you use nuchal translucency to screen for Down syndrome? |
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Definition
Not usually -- only has a 70% detection rate, so better with hormones.
But we can’t use hormones in triplet or above pregnancies, so you use nuchal translucency instead. |
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Term
| What is the first trimester screen pattern that should make you suspect Down syndrome? |
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Definition
High hCG
Low PaPP-A
Large NT |
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Term
| What is the first trimester screen pattern that should make you suspect trisomy 13/18? |
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Definition
Low hCG
Low PAPP-A
Just like for the quad screen, everything being low makes you think of trisomies |
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Term
| What are the different first trimester/second trimester combined screens? |
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Definition
Integrated screening
Stepwise Sequential Screening
Contingent Screening |
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Term
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Definition
You take all the parts of both tests!
The nuchal translucency and PAPP-A
Then the whole quad screen
(so that’s everything but hCG in the first one so that you don’t use the same protein twice)
Detection rate is 95% (better than both first trimester and quad) but no results in the first trimester and two blood draws. |
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Term
| Stepwise Sequential Screening |
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Definition
They do the first trimester screen. If it’s abnormal, they offer a CVS.
However, if the first trimester is normal, they offer a second trimester screen and then the final risk assessment takes the first and second trimester screening results into account. |
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Term
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Definition
They do a first trimester screen. If it’s abnormal, they offer a CVS.
If there is an intermediate first trimester screening, then the second trimester screening is done and the integrated results are assessed.
If there is a normal first trimester screening, there is no second trimester screening done. |
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Term
| What step should you recommend if a fetus has a large NT but a normal karyotype? |
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Definition
Offer a microarray and Noonan syndrome testing. The microarray is to throw a wide testing net for genetic abnormalities, the Noonan syndrome because it is common enough to test for.
If nothing is found, scan again in two weeks. If nothing is found, scan again at 20 weeks. If nothing is found, there is a 5% residual risk. |
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Term
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Definition
| The amount of placental DNA in the blood (as compared to Maternal DNA). If there is not enough of a fetal fraction, NIPS can’t be done. |
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Term
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Definition
| A type of non-invasive prenatal screening. Look at the DNA fragments in the maternal plasma. Sequence them and figure out which chromosome they came from. (No need to separate maternal from fetal DNA). Figure out if the ratios are correct between chromosome. Is there too much chromosome 13, 18, or 21? |
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Term
| How does GC content affect amplification in NIPS? |
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Definition
| Chromosomes with a high GC content amplify well while those with less GC content don’t amplify as well. For NIPS we need to amplify the DNA before analyzing it, so chromosomes with less GC (like chromosome 13) are less accurate when we test for them. |
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Term
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Definition
| A NIPS strategy where only DNA from 13, 18, and 21 is amplified. These amounts are then compared to each other in order to use the counting method. This significantly reduces cost, but less coverage may reduce sensitivity or specificity (no clinical trials at this time). |
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Term
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Definition
| Good luck understanding this. A method for NIPS. Instead of the counting method, SNPS are analyzed to separate maternal and fetal DNA. Able to detect microdeletions and trisomy. |
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Term
| What are some of the biological reasons you might have a false positive NIPS? |
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Definition
Confined placental mosaicism
A vanished twin
A maternal malignancy
A maternal aneuploidy |
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Term
| What are some things that can affect fetal fraction? |
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Definition
An early gestational age
A high maternal BMI
Fetal aneuploidy (usually trisomy 13 and 18) can create a lower fetal fraction |
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