20.05.08 Maternal Serum Screening and Down Syndrome screening methods Flashcards
What is the UK national Screening committee’s definition of screening
- The process of identifying apparently healthy people who may be at increased risk of a disease or condition.
- They can then be offered information, further tests and appropriate treatment to reduce their risk and/or any complications from the disease or condition.
What is the NHS Fetal Anomaly Screening Programme (FASP)
-Offered to all pregnant women, to assess risk of Trisomy 21 and a number of fetal anomalies.
How was Downs syndrome risk originally based
- Advanced maternal age used to identify increased risk of Downs syndrome in pregnancy.
- However, detection rate was only 30%, with 5% false positive rate.
What method is now used to identify women with increased risk of Down syndrome
Maternal serum screening, ultrasound and maternal age
What should all women be offered regarding Downs syndrome screening
- Information to help them decide if they want screening or not
- A down syndrome screening test that meets national standards
- An ultrasound scan to check for physical abnormalities in fetus.
Describe the Down syndrome screening pathway
- Undertaken from 10 to 20 weeks of pregnancy
- Couples receive counselling about procedure, possible outcomes and decisions they may face.
- Screening is nuchal translucency measurement, maternal serum testing or both.
- Screen positive if greater to or equal 1:150
- If risk is above this then offered invasive testing (AF or CVS).
- 3 day TAT
What is prevalence
Number of individuals in a population with the target condition
What is sensitivity
A screens ability to positively identify individuals who have the target condition
What is specificity
A screens ability to not detect individuals who do not have the target condition.
What is the detection rate
Proportion of affected individuals with a positive screening result
What is a screen positive rate (SPR)
Proportion of individuals who will be given a high risk result following screening.
What is a false positive rate (FPR)
Proportion of unaffected individuals with a positive screening result. Complement to specificity. i.e Specificity= 100-FPR
What is a false negative rate (FNR)
Proportion of women who are given a lower risk result but have an affected pregnancy. Complement to sensitivity.
What is nuchal translucency
- Maximum thickness of the subcutaneous translucency between the fetal skin and soft tissue overlying the cervical spine.
- Measured between 11 and 14 weeks.
- Combined with maternal age and size of baby to calculate risk.
What NT is associated with aneuploidy
- NT ≥3.5mm
- Highest to lowest prevalence= 21, 18, 13, 45,X and triploidy.
- Also linked to structural malformations or genetic syndromes.
- Diagnostic test offered
What percentage of pregnancies have NT ≥3.5mm
1%
What is maternal serum screening
Measuring the levels of serum analytes that have passed from fetus to mother’s blood
-Multiples of Median (MoM) are calculated for each serum marker
-
How is risk determined using maternal serum screening
- Multiples of Median (MoM) (serum marker concentration for a pregnant woman) is divided by the median concentration value for unaffected pregnancies of the same gestational age.
- Mother’s serum results, age, weight and gestation all used in risk calculation
Why is the median marker level used (rather than mean) for serum results
-Median is not skewed by very high or very low values.
What screening strategy is recommended
- Combined screening
- serum screening (β-hCG, PAPP-A) and NT
- Can be done at 10-14 weeks
- If screen positive result received, a woman should have rapid access to appropriate counselling.
- Looks for trisomy 13, 18 and 21
What factors affect serum screening
- Serum marker levels tend to be decreased in heavier women and increased in lighter women.
- Serum marker levels tend to be higher in Afro-Caribbean women than Caucasian.
- IVF can alter levels (β-hCG and hCG levels higher in IVF pregnancies).
- AFP and uE3 levels tend to be lower in women with insulin dependent diabetes mellitus
- Smokers have lower PAPP-A, free β-hCG and hCG levels
What kind of screening is recommended for twin pregnancies
- Quadruple screening
- AFP, β-hCG, uE3+ Inhibin A
- Done at 14-20 weeks
What risks are there for screening twin pregnancies
- Marker levels raised in twin pregnancies
- One twin could be affected and the other not
- Dichorionic twins and monochorionic twins have different serum levels
- Procedural risk for prenatal testing is higher for twins.
What else is the quadruple test used for
- Downs syndrome testing
- When NT is not available, not as accurate as combined.
What is the fetal anomaly scan
- Performed at 18-20 weeks
- Detailed ultrasound scan to detect foetal anomalies.
- Includes heart defects, cleft lip/palate, cystic hygroma, neural tube defects, polydactyly, talipes, short femur
What is the policy for reporting normal Down screening results
- Should not be referred for further assessment of chromosome abnormalities even if certain findings are seen at 18-20 fetal anomaly scan.
- Exception is if nuchal fold >6mm, echogenic bowel, small measurements (below 5th centile), ventriculomegaly
Prenatal testing following high risk screen result: CVS
- 1-2% procedural loss.
- Same genetic origin as fetus but differentiated from it by 5-6 weeks gestation
- Risk of CPM
- Performed from 10-12 weeks
Prenatal testing following high risk screen result: Amniotic fluid sampling
- Performed at 16 weeks gestation.
- Contains cells from fetal skin, urinary and respiratory tracts
- 0.5-1% procedural loss
Prenatal testing following high risk screen result: Fetal blood sampling
- Sample of blood taken from umbilical cord at 18+ weeks
- 2-2.5% procedural loss
- Usually only done if previous prenatal test failed or showed findings of mosaicism.
What is non-invasive prenatal testing
Isolation and testing of free fetal DNA (largely derived from placenta) circulating in mother’s blood. Levels are sufficient from 10 weeks gestation
What is the basis of cffDNA aneuploidy testing
- Looking for an over representation of DNA sequences from chromosomes 21, 18, 13.
- Not reliable enough to be a diagnostic test but very sensitive and specific as a screening test for trisomy 21. Not as reliable for trisomy 18 and 13.
What should happen for positive NIPT results
-Confirmed using an invasive diagnostic test such as CVS or amniocentesis.
When is NIPT testing offered
Women with a risk of greater than 1:150
Benefits of offering NIPT testing
-Reduces the need for invasive testing, thus reducing the number of miscarriages.
What could be used in the future for screening programmes
- Proteomics. To identify and characterise proteins in maternal serum from patients at high risk for trisomy 21, 18, 13.
- SELDI-TOF MS, SDS-PAGE, MALDI-TOF
What is serum marker PAPP-A
- Pregnancy associated plasma protein-A
- Levels optimum at 11 weeks.
- Decreased in trisomy 21, 18, 13 and sex chromosome abnormalities.
What is serum marker free β-hCG
- Free β human Chorionic gonadotrophin (β hCG)
- Effective in 1st and 2 trimester
- Increased in DS, decreased in +13, +18
What is serum marker AFP
- Alpha fetoprotein (AFP)
- 2nd trimester. Decreased in DS and fetal demise. Increased in some fetal abnormalities (neural tube defects, renal abnormalities)
What is serum marker uE3
- Unconjugated oestriol (uE3)
- 2nd trimester
- Decreased in +21, +13 and +18
