L13 - Prenatal screening

Question 1

What is screening

Answer 1

• Screening identifies apparently healthy people who may be at increased risk of a disease or condition, enabling earlier treatment or informed decisions

Question 2

What is HCPS

Answer 2

• HCPS: scan is a medical test – need to concentrate to take precise measurements

Question 3

Why scan at 10-14 weeks?

Answer 3

• 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

Question 4

Examples of structural abnormalities

Answer 4

• Spina bifida
• Anencephaly
• Exomphalos and gastroschisis
• bladder outflow obstruction

Question 5

Examples of chromosomal conditions

Answer 5

• Down’s - trisomy 21
• Edward’s - trisomy 18
• Patau’s - trisomy 13

Question 6

Features of downs

Answer 6

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.

Question 7

Diagnostic invasive test - downs

Answer 7

• Chorionic villus sampling CVS 11+ weeks

- Amniocentesis 16+ weeks

Question 8

Screening tests vs diagnostic tests

Answer 8

• 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

Question 9

When is amniocentesis carried out

Answer 9

• From 15 weeks

Question 10

What is PAPPA

Answer 10

• Pappalysin-1, also known as pregnancy-associated plasma protein A, is a protein encoded by the PAPPA gene in humans

Question 11

What is nuchal translucency

Answer 11

• Is a collection of fluid under the skin at the back of the baby’s neck

Question 12

NT - Trisomy 21

Answer 12

• NT is increased in over 80% of cases of T21

Question 13

NT - Trisomy 18

Answer 13

• 75% of T18

Question 14

NT - Turners

Answer 14

• 87% Turners

Question 15

Maternal serum biochemical markers

Answer 15

• free beta-hCG

- PAPP-A

Question 16

Maternal/fetal influencing factors for combined screening

Answer 16

• Maternal age
• Gestational age
• Ethnicity
• Smoking
• IVF
• Multiple pregnancy
• Weight
• Diabetes
• Past history of chromosome abnormality
• Fetal sex
• Analytical imprecision

Question 17

Classification for increased NT

Answer 17

Increased NT > 3.5 mm

Question 18

What does an increased NT increase the chance of

Answer 18

Increased chance of:

• Chromosomal anomaly
• Cardiac anomaly
• ‘Syndromes’

Question 19

NT - scans

Answer 19

Offer:
Karyotyping - array CGH
Fetal cardiac scan
Anomaly scan

Question 20

Features of first trimester combined screening

Answer 20

• Maternal age + ultrasound + PAPPA BhCG

Question 21

Maternal age related risk for chromosomal abnormalities

Answer 21

• 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

Question 22

Features of second trimester maternal serum screening: quadruple test

Answer 22

• 14+2 to 20 weeks: late bookers only
• Chance of T21 only
• Gestational age, maternal age, smoking, weight, ethnicity and maternal serum markers

Question 23

Examples of maternal serum markers

Answer 23

• UE3
• AFP
• Inhibin A
• BHCG

Question 24

Changes in levels of maternal serum markers during pregnancy

Answer 24

• Decrease in UE3, AFP

- Increase in inhibin A, BHCG

Question 25

What is NIPT

Answer 25

• 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

Question 26

What does NIPT involve

Answer 26

• NIPT involves analysing small fragments of DNA that are circulating in a pregnant woman’s blood

Question 27

Features of NIPT

Answer 27

• 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

Question 28

What is placental confined mosaicism

Answer 28

• Represents a discrepancy between the chromosomal makeup of the cells in the placenta and the cells in the fetus

Question 29

Where is cell free fetal DNA [cff DNA] taken from

Answer 29

• CFF DNA is from the placenta so still have risk of placentally confined mosaicism

Question 30

Current use of NIPT in the NHS

Answer 30

• Fetal Rh D typing [11 weeks]
• Fetal sexing [from 7 weeks] - 99.5% accurate
• Some monogenic disorders

Question 31

NIPT - Absolute exclusions (due to risk of false positive results)

Answer 31

• Maternal malignancy
• Multiple pregnancy
• Blood transfusion within 4 months
• Organ transplant
• Vanished twin/demised twin
• Known chromosome or genetic anomaly in the mother

Question 32

Who should NIPT be offered to

Answer 32

• To be offered to women with high chance result on screening [combined or quad] with a singleton pregnancy

Question 33

NIPT - considerations if positive

Answer 33

• Stem cell therapy
• Egg donation
• IVF

Question 34

Advantages of NIPT

Answer 34

• High detection rates, low screen positive rates
• Reduction in invasive diagnostic testing [cost effective]
• A further option for women

Question 35

Disadvantages of NIPT

Answer 35

• Screening test - not diagnostic [false positive/false negatives]
• Confirm screen positive results with invasive test

Question 36

Options if a condition is diagnosed

Answer 36

• Continue
• Continue and adoption
• Termination [medical/surgical] [Trisomy 21: 90%]

Question 37

Support measures if a condition is diagnosed

Answer 37

• Antenatal screening co-ordinator
• National support groups
• Meet other parents
• Obstetric/neonatal/paediatric teams
• Genetic counselling