Maternal Serum Screen (MSS) Flashcards
How does a screening test differ from a diagnostic test?
It’s a risk assessment, the result you get is a likelihood not a certainty. The screening procedure itself does not diagnose any illness. If a patient tests positive then they will get referred to do diagnostic tests.
What is the purpose of screening tests?
To identify individuals from an apparently healthy group that are sufficiently at risk of a specific disorder to justify a subsequent diagnostic test or procedure. Usually the screen is less invasive and can be followed by a more invasive diagnostic test.
What is meant by the sensitivity of a test?
It is the ability of a test to assign an individual with the disease as positive
A highly sensitive test means that are ____ false negative results, and thus _____ cases of disease are missed
Few, fewer
What is meant by the specificity of a test?
The ability of a test to assign an individual who does not have the disease as negative
A highly specific test means that there are ______ false positive results
Few
What types of diseases are screened for?
Severe or of high incidence
Well-defined with known prevalence
Has a substantial public health burden
May not be an effective remedy for the disorder
What are the requirements for screening tests?
They should be simple, safe, and stable
They should be cost-effective
They should have follow-up diagnostic procedures in place
Should be available to most of the population
The degree of overlap with unaffected populations is small and the cut-off point is defined
The distribution of test values in the affected population is known
Why are screening test cut off values a limitation of screening tests?
Because of the possibility of false negatives and false positives
What are screening test cut off values?
It is a point (value) used to determine negative and positive values of the test
What does a false negative mean for a screening test?
That below the cut-off value there will be members of the affected population that will get a negative screen result
What does a false positive mean for a screening test?
That above the cut-off value there will be members of the unaffected population who will get a positive screen result
What happens when we change a cut-off for a screening test?
An increased cut-off means a decreased false positive rate but also a lower detection rate. A decreased cut-off means an increased detection rate but also a higher false positive rate.
How does fetal circulation work?
Umbilical arteries deliver deoxygenated blood from the fetus to the placenta, and umbilical veins deliver oxygen rich blood from the placenta to the fetal heart
What is the test called that is used to determine the likelihood that a fetus might have trisomy 21 or 18?
Pre-natal screening
What are 3 kinds of pre-natal screens?
Enhanced first trimester screening (eFTS), maternal serum screening (MSS), and non-invasive prenatal testing (NIPT)
What is Newborn Screening Ontario (NSO)?
A screening program that uses newborn blood spot samples to test for groups of diseases
Which groups of diseases does NSO screen for?
Metabolic
Endocrine
Severe Combined Immune Deficiency
Spinal Muscular Atrophy
Critical Congenital Heart Disease
What are the different testing methodologies used by NSO?
Tandem Mass Spectrometry (flow-injection and LC-MSMS)
Immunoassay
Enzymatic assays
HPLC
DNA testing
What is it called when all or part of the neural tube fails to close completely during fetal development?
Neural Tube Defect
What are the 2 types of Neural Tube Defects (NTDs)?
Open defect
Closed defect
Which type of NTD is most common?
Open defect
What differentiates the 2 types of NTDs?
A closed defect is covered by bone and skin and causes less impairment than an open defect not covered by anything
What types of disorders are spina bifida and anencephaly?
Open NTDs
What is the name of the condition in which a newborn is born with a failure of their spinal cord to close?
Spina bifida
What is it called when a newborn is born with a failure of the skull to close, leaving neural tissue exposed?
Anencephaly
What are 4 key symptoms of spina bifida?
Paralysis of lower limbs
Loss of motor control of bladder and bowels
Hydrocephalus (water on brain)
Variable mental disabilities
What type of spina bifida is it when the spinal cord is involved and protrudes from a hole in the bone of the spine?
Myelomeningocele
What type of spina bifida is it when the spinal cord does not leave the protective bone tube?
Meningocele
In open NTDs, where are increased AFP levels detected?
In both the amniotic fluid and maternal serum
What is the first marker used for MSS?
Alpha-fetoprotein (AFP)
How is AFP made by the fetus?
Initially by the fetal yolk sac and then later by the fetal hepatocytes
When do AFP levels peak in the fetus?
At 10-13 weeks gestation and then decline until term
When do AFP levels peak in the maternal serum?
At 28-32 weeks gestation and then decline until term
Why do we need to know gestation age for MSS?
The reference intervals for the markers are based on gestation age
With what units are MSS markers reported in?
Multiples of the Median (MoM)
Why are the units of MoM used for MSS markers?
They correlate to the risk of NTDs and are more reliable and allow for inter-laboratory variation/comparisons
What condition is indicated when there are increased AFP MoM levels above the cut-off?
an NTD
What follow-up testing is done for a positive MSAFP screen result?
Level 2 ultrasound to assess the brain and spinal cord, and if that is positive, the next test is an amniocentesis to get amniotic fluid to test for AFP and AChE (acetylcholinesterase)
What is the significance of AChE levels in an NTD investigation?
This enzyme is specific to the CNS and is detectable when nerve tissue or CSF is exposed to amniotic fluid (as would occur with open NTDs)
What are the key symptoms of Down Syndrome?
Mental retardation
Low muscle tone
Congenital heart defects
Flat facial profile
Large protruding tongue
Which condition is associated with decreased maternal serum AFP levels (<0.5 MoM)?
Down Syndrome
What is the problem with using AFP levels to detect Down Syndrome?
There’s too much overlap with the levels of unaffected fetuses
What confirmation test is used to diagnose Down Syndrome?
Karyotyping
Can do amniocentesis, chorionic villus sampling, or percutaneous umbilical cord blood sampling for a sample to test
What does a CVS sample contain?
Fetal cells from chorion which is placental tissue derived from the fetal side of the placenta
How is a PUBS sample obtained?
A needle guided by ultrasound through the abdomen and uterine wall to the umbilical cord, where it samples a small amount of fetal blood
Which 3 markers are measured in a Triple Marker Screen?
AFP, hCG, and uE3
In which trimester is a Triple Marker Screen done?
Second
Which condition is associated with increased levels of hCG and decreased levels of unconjugated estriol (uE3)?
Down Syndrome
Which conditions does the Triple Marker Screen look for?
NTDs and Down Syndrome
Is the Triple Marker Screen offered to only some pregnant women?
No, it is offered to all pregnant women regardless of age
An hCG MoM of 2.5 or higher is associated with which condition?
Down Syndrome
Is hCG alone a good marker for Down Syndrome?
No, when used alone it only catches 40% of cases
Can hCG be used as a marker for NTDs?
No
When does a fetus start to make uE3?
Early in the second trimester and levels rise progressively throughout gestation
Which conditions are predicted when there are decreased levels of uE3 in the maternal serum?
Down Syndrome and NTDs
Why must lab requisitions for maternal screens include patient variables such as maternal weight, gestation age, if she’s carrying multiples, etc?
To assess risk for the conditions being screened for
What does the final lab report of a maternal screen contain?
MoM of each marker measured
Interpretation of the findings as a negative or positive screen (usually determined by the LIS)
Which marker is added in the new Quad maternal screen?
Dimeric Inhibin A (DIA)
What is the name of the glycoprotein hormones secreted by the ovaries in non-pregnant women, and by the placenta?
Inhibins
What do inhibins suppress in non-pregnant women?
The secretion of FSH
Is the function of inhibins in pregnant women known?
No
In which conditions are there increased inhibin levels?
NTDs and Down Syndrome
Why is adding an additional marker in the Quad Screen beneficial?
It helps increase detection rate and decrease false positives
When is the first trimester screening (FTS) performed?
11-14 weeks gestation
What is measured in an FTS?
free-beta subunit hCG (increased in DS)
pregnancy associated plasma protein A (PAPP-A) (decreased in DS)
fetal ultrasound for nuchal translucency (increased in DS and other birth defects)
What are the 3 advantages of FTS?
Assess DS risk earlier
Can confirm abnormal results with CVS and perform karyotyping
Allows for a safer and earlier termination of pregnancy
What are the 2 disadvantages of FTS?
Does not detect NTDs
You still need to draw blood in the second trimester for triple or quad markers
What is included in integrated prenatal screening (IPS)?
1st trimester markers (11-13 weeks)
Ultrasound for NT (11-13 weeks)
2nd trimester quad screen markers (15-20 weeks)
What is the main benefit of IPS?
It offers the highest screening performance for DS (85-95% detection rate)
What condition is trisomy 18?
Edwards syndrome
What are the main issues with Edwards syndrome fetuses and babies?
95% of these pregnancies result in miscarriage or stillbirth and 95% of live births result in death by year 1 of life. Also, any surviving babies have severe intellectual disability and multiple congenital anomalies.
What is NT level of Edwards syndrome?
Increased
What are the AFP, hCG, uE3, DIA, and PAPP-A levels in Edwards syndrome?
All decreased
What are the detection rates for DS in the cell free (cf)-DNA test?
98-99%
