Prenatal Flashcards
HOW DO SERUM SCREENS WORK?
What do they measure?
What do they screen for?
What does a +VE test mean?
Serum screens measure non-DNA based information:
- Proteins
- Hormones
Various screens may include screening for:
- Down syndrome
- Trisomy 18
- Open Neural Tube Defects
+ve is only a risk estimate (many women with increased risk will not have affected babies)
How is serum screening reported?
What is the standard value used?
MoM = Multiple of the median
Raw value
Median for the pt’s gestational age
- Varies with gestational age, assay, and population tested
- 1.0 MoM used as standard
What the origin of tested analytes?
Fetal origin
- AFP (made by liver, pumped out by kidneys)
- uE3 (in cholesterol synthesis pathway)- The fetal adrenal gland secretes dehydroepiandrosterone-sulfate (DHEAS), which is converted to E3 in the placenta and diffuses into the maternal circulation.
Placental Origin
PAPP-A,
hCG,
DIA,
ITA
Typical Patterns of Ist trimester:
Typical
PAPP-A: 1.0 MoM
bhCG: 1.0 MoM
NT 1.5mm
Down sx example
PAPP-A: 0.43 MoM -> low
bhCG: 1.98 MoM -> high
NT: 3mm. -> high
Typical Patterns of the 2nd Trimester :
Typical
AFP: 1.0 MoM
hCG: 1.0 MoM
uE3: 1.0 MoM
DIA: 1.0 MoM
Down sx
AFP: 0.74 MoM. -> low
hCG: 2.06 MoM -> high
uE3: 0.75 MoM -> low
DIA: 1.77 MoM -> high
What important intake should we check before reporting the results to the pt in addition to the analytes values?
INFO that can IMPACT RISK ESTIMATE:
Key information
1- Age
2- Gestational age (second-trimester screens)
3- Race
4- Diabetic status
5- # fetuses
6- Weight
7- Prior history DS, NTD, T18
8- Analyte values
9- Review NT results
Different Factors and Calculating Serum Screen
Factors with major weight
Factors with less weight
Factors with most weight in algorithm:
1- A priori risk (maternal age)
2- Specific analyte values
- How far from median is each one
- MUST be compared against same week in gestation reference point to be accurate
3- Ultrasound NT measurement if first trimester screen
Factors that influence, but less so
1- Ethnicity
2- Weight
3- Diabetic status
What is the importance of Gestational Age?
How do analytes levels change through 2nd Trimester?
AFP
uE3
hCG
Inhibin
A- Check gestational age
- # 1 reason for abnormal results if no prior scan
- Ask patient how due date was determined
- FIRST TRIMESTER SCREENING INCLUDES GESTATIONAL AGE SO WILL NOT CHANGE
B- Medians for analytes vary throughout pregnancy
Second-trimester screening
- AFP increases by ~15%/wk
- uE3 increases by ~25%/wk
How do other factors affect interpretation?
- Ethnicity, give an example? Which ethnicity has higher average values of AFP? what cut-off measure do labs apply to them?
- Maternal Weight, how do analytes behave? are the cut-off levels adjusted according to weight?
- Pregestational Diabetes - how do different analytes behave in diabetes? are cut-off levels are adjusted?
- Mode of Conception (Natural vs IVF), how do analytes behave in IVF? are the cut-off levels adjusted?
A- Ethnicity
- Higher MSAFP average value for African Americans
- Some labs use a 2.8 cut-off, others adjust
B- Maternal Weight
- Diffusion versus concentration based on mother’s blood volume
- Decreased in heavier women, increased in lighter women
- All MoMs adjusted
C- Pregestational Diabetes
- AFP, uE3, and DIA values to be lower in diabetic pregnancies
- Most labs tend to use lower cut-off (ex. AFP cut-off of 2.0 MoM)
- Also have a higher background risk of ONTD if diabetic
D- Mode of Conception (Natural vs IVF)
- hCG levels tend to be higher while uE3 levels are lower
- Generally not adjusted for in calculation
What to do when you have incorrect screens?
When to recalculate? When not to recalculate?
When to repeat? When not to repeat?
A- Recalculate
- Wrong dates (more than 10 days difference)
- except Do NOT recalculate for dates if positive for T18
- Wrong demographic and pregnancy information
B- Repeat
- Do not repeat screens that have an NT measurement
- Do not repeat a Down syndrome screen (unless original test uninterpretable)
- Do not repeat a T18 screen (no exceptions!)
- CAN REPEAT a +VE ONTD screen with a borderline value
What is regression to the mean?
In statistics, regression toward (or to) the mean is the phenomenon that if a variable is extreme on its first measurement, it will tend to be closer to the average on its second measurement
And if it is extreme on its second measurement, it will tend to have been closer to the average on its first.
Timeline of screening options
cfDNA
FTS
NT
Anatomy scan
CVS
Amnio
cfDNA -> by or > week 10
FTS -> 10- 13w6d
Quad -> 15-20w.6d
NT U/S screen -> 11- 14 ws
Anatomy scan -> 16-22 ws
CVS. -> 11- 14 ws
Amnio -> 16-22 ws
First Trimester
- NIPT by 10th week
- OTHER
- FTS
FTS
GA
Analytes -> source, function
11w-13w6d*
- analytes –> 10w0d-13w6d;
- NT –> 11w0d-13w6d
PAPP-A
- Glycoprotein produced by the placenta
- Thought to be involved in local proliferative processes (ex. wound healing and bone remodeling)
Only useful in first trimester
βhCG
- Dimeric (α and β subunits) glycoprotein produced by the fertilized ovum and then the placenta
- Rises early in pregnancy, peaks by 10th wk, then decreases
- β Subunit more accurate than whole molecule
NT
- Measurement by ultrasound
- 11w0d to 13w6d, CRL 45-84 mm
- By certified provider for accuracy
- Over 3.0 mm automatic problem, otherwise used in FTS equation
Abnormal FTS
Detection rate for DS and Tri 18
Stepwise Sequential
1st trimester
PAPPA + bhCG
NT
- If <1 in 50 risk DS –>
2nd-trimester analytes: hCG, uE3, DIA
- < 1in 270 risk
Screen Negative
- If > 1/270 risk -> Screen Positive. -> Genetic Counseling offer further screening and diagnostic options
- If > 1 in 50 risk DS
Screen positive
Contingent
1st trimester
PAPPA + bhCG
NT
- If <1 in 300
Screen Negative
- If a Borderline risk -> (between 1/50 and 1/300)
2nd-trimester analytes: hCG, uE3, DIA, AFP ->
*if < 1in 270 risk ->
Screen Negative
- If > 1/270 risk -> Screen Positive -> Genetic Counseling, possible amnio or NIPT
- If > 1in 50 risk DS ->
Screen positive -> Genetic Counseling, possible CVS or amnio or NIPT
Second Trimester Screening
How many analytes mention each, produced by, specific to
15w0d-20w6d
AFP
- Glycoprotein produced by fetal GI tract and liver; pumped out by kidneys
- Only analyte used in Open Neural Tube Defect Screening
hCG
- Placental origin; good marker for placental function
- Falls in second trimester
uE3
- Estrogen hormone involved in cholesterol pathway
- Precursor from fetal adrenal glands
- Rises with growth of fetus
DIA
- Glycoprotein hormone produced by the ovaries and placenta
- Single best marker for DS; stable levels in second trimester
hhCG
- Hyperglycosylated hCG (hhCG ) = invasive trophoblastic antigen (ITA)
- Marked by Quest; no prospective studies showing increased efficacy
Abnormal Quad or Tetra
ONTD Screening What test do we use? When is test positive? When is it recommended to repeat the test? What is the detection rate? How the result is presented? What is the relationship between test MOM and the severity? What does it indicate?
- Significantly increased AFP levels
- 2.5 to 3.0 MoM as gray zone, may recommend repeat
- 3.0+ MoM as automatic screen positive
- Detection rates 80-90% for ONTDs
- Presented as a risk figure
- Greater MoM value, increased concern
- Indicates
– Opening somewhere or
– cause of change in concentration somewhere
INCREASED AFP
CONCENTRATION PROBLEMS
- Kidney Concerns (agenesis, cystic, oligo-hydramnios)
- Placental Bleed, Pl insuffeciency
- Multiples
Other
Wrong dates
Adverse Outcome -> IUFD
Maternal Malignancy
Normal Variation
INCREASED AFP 2
% of sensitivity for open spina bifida
% of sensitivity for anencephaly
70-85% sensitive for open spina bifida; >95% for anencephaly
Values of abnormal AFP
NTDs
Extreme AFP Elevations
What are the causes of extreme elevations?
When to suspect Congenital Finnish Nephrosis?
What is the anomaly?
How does show on U/S?
inheritance & progression
Maternal Liver Anomaly
Congenital Finnish Nephrosis
- Suspected with significantly elevated MSAFP with extremely high AFAFP (>10 MoM) and negative ACHE
- Abnormal renal tubule development with a normal appearance on ultrasound
- “Lethal” condition
Genetic testing available (AR inheritance)