L13 - Prenatal screening Flashcards
What is screening
- Screening identifies apparently healthy people who may be at increased risk of a disease or condition, enabling earlier treatment or informed decisions
What is HCPS
- HCPS: scan is a medical test – need to concentrate to take precise measurements
Why scan at 10-14 weeks?
- Viability
- Accurate dating
- NICE guidance (use scan dates in lieu of LMP dates)
- Crucial for screening tests
- Reduces need for post dates induction of labour
- Detect multiple pregnancy to determine chorionicity
- Diagnosis of structural abnormality
- Screening for chromosomal conditions
Examples of structural abnormalities
- Spina bifida
- Anencephaly
- Exomphalos and gastroschisis
- bladder outflow obstruction
Examples of chromosomal conditions
- Down’s - trisomy 21
- Edward’s - trisomy 18
- Patau’s - trisomy 13
Features of downs
Chromosome 21 – lowest gene density 237
Chr 22 = 693
Chr 1 = 2610
Primary
Translocation
Mosaic
Explain to parents – extra chrom = extra genes – which cause the problems we associate with T21.
Diagnostic invasive test - downs
- Chorionic villus sampling CVS 11+ weeks
- Amniocentesis 16+ weeks
Screening tests vs diagnostic tests
- Screening tests identify individuals at ‘high’ or ‘low’ chance of having a baby with a trisomy
- Diagnostic tests give definitive information on the fetal chromosomes by confirming the presence of an extra chromosome or absence of a chromosome
When is amniocentesis carried out
- From 15 weeks
What is PAPPA
- Pappalysin-1, also known as pregnancy-associated plasma protein A, is a protein encoded by the PAPPA gene in humans
What is nuchal translucency
- Is a collection of fluid under the skin at the back of the baby’s neck
NT - Trisomy 21
- NT is increased in over 80% of cases of T21
NT - Trisomy 18
- 75% of T18
NT - Turners
- 87% Turners
Maternal serum biochemical markers
- free beta-hCG
- PAPP-A
Maternal/fetal influencing factors for combined screening
- Maternal age
- Gestational age
- Ethnicity
- Smoking
- IVF
- Multiple pregnancy
- Weight
- Diabetes
- Past history of chromosome abnormality
- Fetal sex
- Analytical imprecision
Classification for increased NT
Increased NT > 3.5 mm
What does an increased NT increase the chance of
Increased chance of:
- Chromosomal anomaly
- Cardiac anomaly
- ‘Syndromes’
NT - scans
Offer:
Karyotyping - array CGH
Fetal cardiac scan
Anomaly scan
Features of first trimester combined screening
- Maternal age + ultrasound + PAPPA BhCG
Maternal age related risk for chromosomal abnormalities
- Increase in risk of trisomy 21, trisomy 18, trisomy 13 with an increase in maternal age
- No change in risk of turner and triploidy with increase in maternal age
Features of second trimester maternal serum screening: quadruple test
- 14+2 to 20 weeks: late bookers only
- Chance of T21 only
- Gestational age, maternal age, smoking, weight, ethnicity and maternal serum markers
Examples of maternal serum markers
- UE3
- AFP
- Inhibin A
- BHCG
Changes in levels of maternal serum markers during pregnancy
- Decrease in UE3, AFP
- Increase in inhibin A, BHCG
What is NIPT
- Noninvasive prenatal testing (NIPT), sometimes called noninvasive prenatal screening (NIPS), is a method of determining the risk that the fetus will be born with certain genetic abnormalities
What does NIPT involve
- NIPT involves analysing small fragments of DNA that are circulating in a pregnant woman’s blood
Features of NIPT
- Cell free fetal DNA (cff DNA] in maternal blood from 5 weeks
- Pregnancy specific
- Test material blood from 10 weeks
- Aneuploidy - screening for T21 sensitivity and specificity over 99%
- Marketed as harmony, SAFE, panorama, NIFTY test
What is placental confined mosaicism
- Represents a discrepancy between the chromosomal makeup of the cells in the placenta and the cells in the fetus
Where is cell free fetal DNA [cff DNA] taken from
- CFF DNA is from the placenta so still have risk of placentally confined mosaicism
Current use of NIPT in the NHS
- Fetal Rh D typing [11 weeks]
- Fetal sexing [from 7 weeks] - 99.5% accurate
- Some monogenic disorders
NIPT - Absolute exclusions (due to risk of false positive results)
- Maternal malignancy
- Multiple pregnancy
- Blood transfusion within 4 months
- Organ transplant
- Vanished twin/demised twin
- Known chromosome or genetic anomaly in the mother
Who should NIPT be offered to
- To be offered to women with high chance result on screening [combined or quad] with a singleton pregnancy
NIPT - considerations if positive
- Stem cell therapy
- Egg donation
- IVF
Advantages of NIPT
- High detection rates, low screen positive rates
- Reduction in invasive diagnostic testing [cost effective]
- A further option for women
Disadvantages of NIPT
- Screening test - not diagnostic [false positive/false negatives]
- Confirm screen positive results with invasive test
Options if a condition is diagnosed
- Continue
- Continue and adoption
- Termination [medical/surgical] [Trisomy 21: 90%]
Support measures if a condition is diagnosed
- Antenatal screening co-ordinator
- National support groups
- Meet other parents
- Obstetric/neonatal/paediatric teams
- Genetic counselling
