Lecture 5- Prenatal Testing

Question 1

What happens in a normal pregnancy?

Answer 1

1) booked into antenatal care with midwife
2) Nuchal scan- 10-14 weeks
3) mid trimester anomaly scan
4) ultrasound scans at 11-14 and 20-22 weeks

Question 2

What is the purpose of the nuchal scan at 12 weeks?

Answer 2

• date the pregnancy
• multiple pregnancies
• major foetal abnormalities
• risk of miscarriage
• assess risk of Down syndrome and chromosomal abnormalities

Question 3

How do you diagnose chromosomal abnormalities around 10-14 weeks of gestation?

Answer 3

Nuchal translucency: measure fluid at back of baby’s neck

Normal = <3.5mm

Question 4

What can an increased NT indicate?

Answer 4

1) CHROMOSOMAL ABNORMALITIES
- downs, patau, Turners, Edwards
- NT + maternal age = 75% of Down’s syndrome diagnoses and 5% false positive rate
2) BIRTH DEFECTS
- cardiac anomalies, pulmonary defects, renal defects
3) SKELETAL DYSPLASIA

Question 5

During the diagnosis of Downs, a combined test is done as well as NT, what does the combined test look for?

Answer 5

High hCG levels and low PAPP-A levels

Question 6

What are the criteria for arranging prenatal testing?

Answer 6

• abnormal findings at Nuchal scan or mid- trimester scan
• after results of combined test
• if previous pregnancy was affected by DS or CF etc
• if parents are carriers of chromosomes (HD or DMD)
• FH of genetic condition

Question 7

What is the purpose of prenatal testing?

Answer 7

• to inform and prepare parents for the birth of an affected baby
• to allow in utero treatment
• manage the remainder of pregnancy
• prepare for complications post birth
• allow termination of affected foetus

Question 8

What are three different types of prenatal tests?

Answer 8

1) Non- invasive (ultrasound/ MRI)
2) Minimally invasive (maternal blood test/ cell- free foetal DNA)
3) invasive (chorionic villus sampling/ amniocentesis)

Question 9

What does the high level anomaly scan detect?

Answer 9

• hydrocephalus
• neural tube defects
• limb deformities
• heart defects
• ‘soft markers’ Nasal bone - DS

Question 10

What can maternal serum screening be used to diagnose?

Answer 10

Trisomy 21, trisomy 18 and neural tube defects

Question 11

In maternal serum screening what is investigated in the 1st trimester?

Answer 11

11-14 weeks

Look for hCG (human chorionic gonadotropin) and PAPP-A (pregnancy associated plasma protein A)

Question 12

In maternal screening during the second trimester what is investigated?

Answer 12

hCG, PAPP-A, AFP(alpha foetal protein) and uE3 (oestriol)

Question 13

What is cell free fetal DNA?

Answer 13

• DNA fragments present in maternal plasma during pregnancy
• which comes from the placenta
• And is representative of the unborn baby

Question 14

When is cffDNA detectable and when can it be used for testing?

Answer 14

• detectable from 4-5 weeks

- used for testing until around 9 weeks

Question 15

How can you determine the sex of a baby using cffDNA?

Answer 15

Look for SRY gene on Y chromosome

Question 16

When is cffDNA testing offered?

Answer 16

If there is an X-linked disease in the family and the baby is male–> prenatal testing

Question 17

What are the limitations of NIPD?

Answer 17

• multiple pregnancies, can’t tell which foetus the DNA came from
• not suitable for women of high BMI because cfDNA is mostly theirs
• Invasive test may still be required

Question 18

What are the benefits of NIPD?

Answer 18

• reduced number of invasive tests taken
• no increased risk of miscarriage
• less expertise required
• can get earlier result

Question 19

When is CVS performs?

Answer 19

11-14 weeks

Question 20

What is the risk of miscarriage for CVS?

Answer 20

1-2-% risk of miscarriage

Question 21

How is CVS performed?

Answer 21

• transabdominal or transvaginal
• take sample of chorionic villi (developing placenta)
• contains same DNA as foetus
• earlier diagnosis than amniocentesis (important for TOP)

Question 22

When is amniocentesis done?

Answer 22

From 16 weeks

Question 23

What are the risks of amniocentesis?

Answer 23

• up to 1% risk of miscarriage
• infection
• Rh sensitisation

Question 24

How is amniocentesis performed?

Answer 24

• transabdominal needle

- take sample of amniotic fluid which contains foetal cells

Question 25

What is done with the DNA samples

Answer 25

• karyotype if chromosomal abnormality

- QF-PCR (quantitative fluorescence PCR) to test for T13, T18 and T21 and sex chromosomes

Question 26

What are the different reproductive options?

Answer 26

• conceive naturally (no prenatal testing)
• conceive naturally (with prenatal testing)
• use egg/ sperm donors
• adoption
• choose not to have children
• PGD

Question 27

Where should you go to find a egg/ sperm donor?

Answer 27

A UK HEFA licensed fertility centre which conforms to strict medical, ethical and legal practices

Question 28

What are the two stages of adoption?

Answer 28

1) registration and checks (medical and criminal background)

2) assessment and home approval ( home visits, prospective adopters report, panel review)

Question 29

What is PGD?

Answer 29

IVF with an additional test of genetically testing the embryo before implantation

Question 30

Describe the process of PGD

Answer 30

1) stimulation of the ovaries
2) egg collection
3) insemination- by intracytoplasmic sperm injection
4) Fertilisation
5) Embryo biopsy- once embryo is 8 cells in size
6) Embryo testing
7) Embryo transfer
8) Pregnancy test

Question 31

What is the age criteria and weight criteria for PGD?

Answer 31

Under 39

Between 19-30 BMI

Question 32

What are some of the problems with PGD?

Answer 32

• may not be eggs to collect
• eggs may not have been fertilised
• all embryos may have been affected
• embryos might not have survived biopsy
• lengthy emotional process
• low success rates

Question 33

What is the role of genetic counselling in prenatal testing?

Answer 33

• arrange and explain the different procedures
• facilitate decision-making
• give results
• see patients in clinic following a diagnosis in utero
• arrange termination if necessary
• discuss recurrence risks and plans for future pregnancies