Principles of Screening and Ante-natal Screening Flashcards
1
Q
What are features of screening?
A
- Applied to a large population with a low incidence of disease
- Aims to identify a subset of individuals at higher risk of disease
- Does not diagnose
2
Q
What are types of Screening?
A
Population screening - large scale screening of whole population group
- Newborn blood spot screening
- Newborn hearing screening
- Antenatal screening
Selective screening - Pre-selected high risk groups in the population
- Diabetic retinopathy screening
- AAA screening-men only!
Surveillance - Long term observation of individuals or populations
- Screening for HCC over time in individuals with cirrhosis.
- Earlier breast screening for patients with BRCA2 mutation.
Case Finding or “opportunistic” screening - The patient initiates the contact to seek medical help and the opportunity is used to screen for other conditions
- HIV
- Hepatitis
- Health checks- “diabetes screens”, “CHD screens
3
Q
Wht is the WHO criteria for a good screening test?
A
The Condition
- The condition screened for should be an important one
- There should be an acceptable treatment for patients with the disease
- Should be a recognised latent or early symptomatic stage
The Test
- There should be a suitable test or examination which has few false positives –specifity - and few false negatives – sensitivity
- The test or examination should be acceptable to the population
- The facilities for diagnosis and treatment should be available
The Cost
- The cost, including diagnosis and subsequent treatment, should be economically balanced in relation to expenditure on medical care as a whole
Other Considerations
- Prevalence must be known
- Screening test must be simple, safe and scaleable
- Diagnostic procedure following a positive screening results should be ethically acceptable to patients and public
4
Q
What are ethical issues of screening?
A
- Offered to the “well population”
- Initiated by the health professional NOT the patient
- Screening creates patients out of people
5
Q
What must informed consent provide to patients before screening?
A
- The disorder being screened for
- Its clinical impact
- The performance of the screening test.
- Implications of a positive result
- Subsequent diagnostic procedure
- Future treatment options
6
Q
What is Sensitivity, specificity and prevelance?
A
- Prevalence: How common the disease is in the overall population
- Sensitivity: How good the test is at detecting the disease
- Specificity: How good the test is at not detecting normal individuals as having the disease
7
Q
What is positive and negative predictive value?
A
- Positive Predictive Value: The proportion of positive tests that are true positives
- Negative Predictive Value: The proportion of negative results that are true negatives
8
Q
What are considerations made before picking a “cut-off” value?
A
Consequences of Missing a Case
- How serious is the illness or condition?
- Would it be thought beneficial even if only a small percentage were detected?
- What are the consequences economically / socially?
- What would be publicly acceptable?
- Cost
Consequences of Classifying an unaffected person as Positive
- Anxiety
- Unnecessary procedures
- What are the dangers of these procedures and are they justified?
- What would be publicly acceptable?
- Cost
9
Q
What is Antenatal Screening?
A
- During pregnancy women are offered a series of screening tests for their fetal-maternal health
- Women should be counselled and consent to the individual screening tests
10
Q
What are types of Antenatal Screening?
A
- Infectious Disease in Pregnancy (IDPS)
- Sickle cell and alpha thalassaemia screening (SCT)
- Foetal anomaly screening programme (FASP)
11
Q
What is involved in Infectious Disease screening?
A
Measure with consent:
- HIV
- Hepatitis B
- Syphillis
Failure to identify these puts the mother and baby at risk.
12
Q
What happens if an infectious disease is confirmed by screening and an alternative method?
A
Referral to specialist care for the woman to be monitored throughout pregnancy
- Hep B - Post-natal vaccination
- Syphillis - Antenatal vaccination
- HIV - Partner testing, Advice from specialist midwife, Drugs, Birth plan, Feeding advice and Partner and baby testing
13
Q
How is Sickle cell and alpha thalassaemia screening (SCT) conducted?
A
Antenatal and Neonatal programme
- Women should be screened as early as possible in pregnancy
- Both are disorders of haemoglobin morphology, and can be life-threatening
- Screened by HPLC analysis for haemoglobinopathy
- If variant identified, partner screening may be offered
14
Q
What is done if Sickle cell and alpha thalassaemia screening (SCT) is positive?
A
- Diagnostic testing, amniocentesis or fetal blood sampling.
- Most women referred to specialist care
- If condition severe some women may terminate the pregnancy
- Advice about how to live with the condition, and available treatments
15
Q
Which conditions are screened in foetal anomaly screenings?
A
- Down’s Syndrome (T21)
- Edwards’ Syndrome (T18)
- Patau’s Syndrome (T13)
16
Q
What are features of Down’s Syndrome?
A
- Extra copy of chromosome 21
- Typical facial features: Slanted eyes, flat nasal bridge, protruberant tongue
- Small stature
- 1 in 700-1000 live births
17
Q
What are clinical features of Down’s Syndrome?
A
- Hypotonia, delayed development, severe learning difficulties
- Congenital heart defects
- Duodenal atresia
- Recurrent Respiratory Infections
- Hearing and visual impairment
- Hypothyroidism
- Early onset Alzheimers
- Penetrance is highly variable, and some Down’s affected individuals lead long fulfilling lives.
18
Q
What is Edwards Syndrome?
A
- Extra copy of Chromosome 18 (3 in 10,000 births)
- Most babies die before or at birth (70%)
- Following birth one-year survival is 13.5%*
- 5-year survival is 12.5%* of the 13.5%
- Medical interventions can prolong life
19
Q
What is the clinical features of Edwards Syndrome?
A
- Small head with prominent back of head
- Low set ears
- Small jaw often cleft palate
- Fists clenched with overlapping fingers
- Club foot or rocker-bottom feet
- Severe learning disabilities
- Developmental delay
- 90% will have congenital heart defect
- Epilepsy is also common
20
Q
What is Patau’s syndrome?
A
- Extra copy of Chromosome 13
- Affects 2 in 10,000 births
- Approx 50% babies die before or at birth
- Following birth one-year survival is 11.5%*
- 5-year survival is 9.5%* of the 11.5%
- Medical interventions can prolong life
21
Q
What are clinical features of Patau Syndrome?
A
- Small head and eyes
- Significant facial dysmorphisms i.e. no eyes, single eye
- Cleft palate
- Extra digits
- Significant developmental delay and learning disabilities
- 80% with have heart condition
- Kidney defect
- Exomphalos
22
Q
What is Mosaicism is chromosomal defects?
A
- Most trisomies are complete i.e. A full extra copy of the chromosome is present in every cell
- This is because they are derived from the division of the maternal (almost always) gamete cells (egg cells)
- The extra chromosome is carried through into all the cells of the developing child
- However in some individuals a trisomy can occur in the developing embryo in some of the cell lines
- This means that some cells are normal and some have a trisomy- this is mosaicism
- Often the individual will display traits of the condition but to a lesser extent (not always)
- Estimates 2 in 100 T21 cases are mosaic
23
Q
What are some choices given to women of the screening programme?
A
- Decline screening
- Have screening for Down’s syndrome only
- Have screening for Edwards’/Patau’s syndromes only
- Have screening for all 3 conditions
24
Q
How is featal anomaly screening conducted in the first trmester?
A
The woman is given a chance for Down’s and a combined chance for Edwards’ and Patau’s available 10-14+1 weeks of pregnancy
- Measure free –BHCG & PAPP-A (pregnancy associated plasma protein A). Done on AutoDelfia/Delfia Xpress
- Measure NT nuchal translucency measurement on scan (only able to do so between 11+2-14+1weeks).
25
How is featl anomaly screening conducted in the 2nd trimester?
In the second trimester only Down’s syndrome can be screened for by a blood test. The test for Edwards’ and Patau’s is the 18-20 week foetal anomaly scan. Quadruples test
* Measures AFP, free BHCG, uE3, Inhibin A
* Taken 14+2-20 weeks of pregnancy. 15-16 weeks is optimal
* Available for late bookers
* No Edwards’ and Patau’s chance available
26
What is Pregnancy associated plasma protein (PAPP-A)?
* **Trimester:** First
* **Description:** Produced by the placenta. Involved in the regulation of feto-placental growth
* **Changes in normal pregnancy:** Blood concentration increases with gestational age
27
What is Free-beta human chorionic gonadotrophin (BhCG)?
* **Trimester:** First and second
* **Description:** Produced by the placenta. Important for the development of the early fetal-placental unit
* **Changes in Normal Pregnancy:** Blood concentration increases in the early weeks of pregnancy, then begin to fall after 10 weeks gestation
28
What are characteristics of Alpha-feto Protein (AFP) as a marker fetal anomaly screening?
* **Trimester:** Second
* **Description:** Produced by the fetal yolk sac and liver, but does not appear to be required for normal fetal development
* **Changes in normal pregnancy:** Blood concentration increases with gestational age
29
What are characteristics of Inhibin-A as a marker in fetal anomaly screening?
* **Trimester:** Second
* **Description:** Produced by the ovary and placenta. Acts at pituitary to prevent ovulation during pregnancy.
* **Changes in Normal Pregnancy:** Blood concentrations remain stable throughout the second trimester.
30
What are characteristics of Unconjugated oestriol as a marker in fetal anomaly screening?
* **Trimester:** Second
* **Description:** Steroid hormone, synthesised by fetal adrenals, liver and placenta. The major estrogen of pregnancy
* **Changes in normal pregancy:** Blood concentrations tend to increase with gestational age
31
How is the Down's Chance calculated?
* Women are classed as higher chance if their risk is 1 in 150 or higher.
* Women at higher chance are offered an invasive diagnostic procedure (amniocentesis or chorionic villus sampling) and karyotyping which will give a DIAGNOSTIC result
* A low chance result does not mean that a pregnancy will be unaffected.
32
What is the Multiples of Median?
* Marker levels change throughout gestation.
* Need to assess what is “normal” for a particular day of gestation.
* Work out the median for each day of gestation
* Calculate MoM = multiple of the median
* Must know the gestational age of the pregnancy on the day of the blood sample. MoM is a indicator of how far away from the median a particular value is and once calculated is independent of gestation
33
What is the equation for the MoM?
**MoM** = **Marker conc in woman** / **Median marker conc for that day of gestation**
34
How is the chance calculation made?
* Likelihood ratios are calculated for every marker and combined with the age risk.
* Each woman has a prior age chance as chance of trisomy is higher in older women
35
How are Higher Chance calculations resported?
* Higher chance results 1:150 or higher are telephoned and emailed to Midwife
* Electronic reporting
* Midwife will contact woman and counsel regarding options
* Woman will be offered invasive diagnostic procedure
36
What is an amniocentesis?
* Most common invasive procedure
* Only viable from 15 weeks of pregnancy
* Involves collection of amniotic fluid from amniotic sac under US guidance
* Amniotic fluid contains fetal cells which can be karyotyped at Cytogenetics
* Procedure-related loss around 1%
37
What is Chorionic Villus Sampling?
* Is used from 10 weeks gestation
* Is offered to women high risk from first trimester screening.
* Is more uncomfortable for the woman but can provide an early diagnostic result.
* Procedure related loss is 1%
* Overall pregnancy loss is 2-3% due to background risk at this gestation.
38
What are factors that affect risk calculations ?
1. **Gestation******
* Accurate gestation is essential and has large bearing on risk
* Scan measurements must be provided CRL/HC + NT if appropriate
2. **Weight**********
* Larger women have bigger blood volume which dilutes blood markers and vice versa
* Laboratory correct for this so accurate weight at time of sampling is essential
3. **Ethnicity**
* PAPP-A in 60% higher in Afro–Caribbean’s, lab corrects for this
* Different ethnic groups have different levels of markers
4. **Smoking**
* Smoking affects the levels of some markers (reason not known)
* Inhibin is 50% higher in smokers and PAPPA 20% lower in smokers. Lab corrects for this.
5. **IVF**
* Age of egg important, not age of woman, so need to know if egg/embryo frozen, or donated, need to know age of donor
* HCG is slightly higher in IVF pregnancies, correct for this
6. **IDDM**
* AFP is slightly lower in Type 1 (reason not known) and PAPPA lower in Type 2 not on insulin
* Lab corrects for this.
39
What are sample requirements for risk calculations?
* Minimum 5 ml blood sample in gel tube
* Sample should be spun and separated ideally within 24 hours.
* K-EDTA tubes must not be sent, K-EDTA chelates the Europium from the Delfia assays!
40
What is dectection rate and screen postivie rate in fetal anomaly screening?
**Detection Rate (sensitivity)**
* The proportion of screened Down’s/Edwards/Patau’s pregnancies that were identified as “higher chance” by the screening programme
**Screen Positive rate**
* The proportion of all screened pregnancies that are given a higher chacne result
41
How is Quaity control conducted in Fetal Anomaly screening?
* Internal QC, 3 levels beginning, end of plate and spread through the plate
* External QA- NEQAS every month
* Weekly monitoring of screen positive rate and median MoMs
* Monthly monitoring of gestation plots
42
What is DQASS?
* Run by fetal anomaly screening programme
* Labs send 6 monthly anonymised data to DQASS and feedback performance on how well median equations are being controlled by labs
* Also feedback to sonographers regarding NT performance
