73 Prenatal testing

Question 1

Features of screening tests offered during pregnancy?

Answer 1

• Offered to all pregnant women to assess the chance of mother or baby having a particular health problem or disability
• Simple tests (e.g. blood test, ultrasound scan or questionnaire)
• They don’t provide a definite diagnosis

Question 2

Features of diagnostic tests used during pregnancy?

Answer 2

• Follow-on tests to find out whether the baby does have a particular condition
• Offered to women who have had a ‘higher-chance’ result from screening
• E.g. chorionic villus sampling or amniocentesis (risk of miscarriage), detailed ultrasound scan

Question 3

Why carry out screening and testing?

Answer 3

1. To REASSURE parents
2. To inform and PREPARE parents for the birth of an affected infant
3. To allow in utero TREATMENT
4. To allow TERMINATION of an affected fetus
5. To provide information so that parents may choose between 2, 3 or 4: key issue here = choice

Question 4

Examples of screening and diagnostic testing?

Answer 4

1. Natural conception
   • Non-invasive screening, e.g. ultrasound, serum test
   • Invasive prenatal diagnostic (PND) testing, e.g.
   chorionic villus sampling, amniocentesis
   • NIPT, sometimes ‘NIPD
2. In vitro fertilisation
   • Preimplantation genetic diagnosis (PGD)

Question 5

Ultrasound in screening:
•  What is it?
•  When is it?
•  Why is it?
•  Ethical issues arising?

Answer 5

•  What is it?
– Uses sound waves; painless; no risk
•  When is it?
–  Dating scan: 12 weeks (8 – 14)
–  Anomaly scan: 20
weeks (18 – 20 weeks + 6 days)
•  Why is it?
– Anomaly: physical abnormalities e.g. spina bifida
•  Ethical issues arising
–  Everyone is offered anomaly scan, not everyone chooses to take it

Question 6

What is Down’s syndrome?

Answer 6

• Trisomy 21
• Commonest cause of identifiable learning disability
• Usually due to non- disjunction at chromosome 21 at meiosis
• 50 % will have a congenital abnormality
• 80% profound or severe intellectual impairment
• Natural prevalence 1:600 live births but incidence now 6:10,000

Question 7

Down's Syndrome screen:
•  What is it?
•  When is it?
•  Why is it?
•  Ethical issues arising

Answer 7

• What is it?
– Combination of ultrasound + serum test
• When is it?
– 10 – 13 (+6) weeks
• Why is it?
– Measures the chance of DS; not a diagnostic test (can also detect other
trisomies - Edwards, Patau)
• Ethical issues arising
– Risk (low v high); if greater than 1:150 then option to take diagnostic test (amniocentesis or CVS)

Question 8

What are the analyse markers in blood in the serum test for Down’s Syndrome?

Answer 8

• Pregnancy associated plasma protein-A (PAPP-A)

* Free ß- human chorionic gonadotrophin (free ß-hCG)

Question 9

What does ultrasound in Down’s Syndrome screen look for?

Answer 9

Nuchal translucency (NT)

Question 10

How good is the ‘combined’ screening test for DS?

Answer 10

• False positives
– Test indicates DS, but fetus not affected – 2.2%
• False negatives (related to “detection rate”)
– Test does not indicated DS, but fetus affected – 16%
• Combined test: FN 16%, FP 2.2%
• Recommended screening test

Question 11

How is the quadruple test used during DS screening?

Answer 11

• Used if women presents later (14 weeks 2 days +)
• Blood test: alpha-fetoprotein (AFP); total human chorionic gonadotrophin (hCG); unconjugated oestriol; inhibin-A
• FN: 20% FP: 3.5%

Question 12

Name screening tests

Answer 12

1. Ultrasound

2. Down’s Syndrome screen/ Quadruple test

Question 13

Name diagnostic tests

Answer 13

1. Amniocentesis

2. Chorionic villus sampling

Question 14

Amniocentesis:
•  What is it?
•  When is it?
•  Why is it?
•  Ethical issues arising

Answer 14

• What is it?
– Needle inserted through the abdomen and into amniotic fluid
• When is it?
– 15+ weeks (15 – 18)
• Why is it?
– For karotyping if screening tests suggest aneuiploidy
– DNA anaylsis if parents carrier of an identifiable gene
– Enzyme assays for inborn errors of metabolism
– Diagnosis of foetal infections
• Ethical issues arising
– 0.5-1% risk of miscarriage (also, delay in getting results); infection, injury

Question 15

How good is amniocentesis?

Answer 15

• False-positive rate of 0.1-0.6%

* False-negative rate of 0.6%

Question 16

Chorionic villus sampling:
• What is it?
• When is it?
• Why is it?
• Ethical issues arising

Answer 16

• What is it?
– Fine needle inserted through abdomen and into uterus; or through
cervix, and small piece of developing placenta removed
• When is it?
– 11 weeks (11-14 weeks)
• Why is it?
– Tests for inherited disorders (cystic fibrosis, sickle cell, thalassemias, muscular dystrophy) and chromosomal disorders ; (sex) – allows you to test earlier in pregnancy
• Ethical issues arising
– 1% risk of miscarriage (also, delay in getting results); infection; heavy
bleeding

Question 17

How good is chorionic villus sampling?

Answer 17

• False-positive rate of 1-2%

* False-negative rate of 2%

Question 18

Examples of diseases for which DNA tests are available

Answer 18

• Cystic fibrosis
• Phenylketonuria
• Tay-Sachs
• Duchenne Muscular dystrophy
• Huntington’s disease
• Inherited breast + ovarian cancers

Question 19

What is prenatal genetic diagnosis used for?

Answer 19

• If the baby is found to be affected, people can prepare for the birth of a child with a genetic disorder or to terminate the pregnancy
• Prevent the birth of a child with a disability

Question 20

What are the disadvantages of prenatal genetic testing?

Answer 20

• Costly
• Inconvenient
• Risk of miscarriage
• Sample can only be used for a couple of tests

Question 21

What is Non-invasive prenatal genetic testing (NIPT)

Answer 21

• Cell-free foetal DNA (DNA from placenta, v similar to DNA from foetus)
• Early use: 9— 10 weeks:
– Risk of chromosomal abnormalities with more accuracy than other
non-invasive methods (invasive still required for definitive result)
– Definitive diagnosis of some conditions (e.g. cystic fibrosis, achrondroplasia)
– Can determine gender

Question 22

Where the 4 principles of medical ethics?

Answer 22

• Autonomy
• Non-maleficence
• Beneficence
• Justice

Question 23

Preimplantation genetic diagnosis:
• Offered to?
• Process?

Answer 23

• Offered to couples who are at risk of passing on a genetic disorder
• Involves removing 1 cell from the early embryo (4-8 cell embryo)
• PGD is not common and it’s expensive (but – cheaper in the long run?)

Question 24

What disorders are acceptable (HFE Act 2008) for preimplantation genetic diagnosis?

Answer 24

• A disorder that may affect capacity for live birth
• Risk of child being born with or developing a serious disability (genetic, chromosomal, mitochondrial)
• If gender-related disorder, can use to select gender

Question 25

Code of practice guidance to definition of "serious" illness?

Answer 25

``` • Take into consideration the views of those seeking treatment • Likely degree of suffering • Availability of effective treatment • Speed of degeneration • Extent of intellectual impairment • Social support available • Family circumstances ```

Question 26

What is Huntington's Disease?

Answer 26

* Inherited, late onset, degenerative condition * Manifests ~ 30-50 yrs * 50/50 chance of inheriting it from affected parent * Non sex linked dominant inheritance pattern

Question 27

What are the 2 issues in testing for Huntington's Disease?

Answer 27

1. Prenatal genetic testing for HD – If seek testing, understand that they will terminate if test positive – Why? Testing is only available to adults, and not all at risk choose to take it; prenatal testing means that the parents know something about the child’s future that the child has not elected to know 2. PGD for HD – Thus select an embryo that does not carry the inherited HD gene

Question 28

What is PGD?

Answer 28

Pre-implantation genetic diagnosis is a treatment which involves checking the genes or chromosomes of your embryos for a specific genetic condition

Question 29

What is the case for preference FOR disabled embryo's?

Answer 29

* The case of Tomato Lichy and Paula Garfield | * (note: they did not want to positively select but it opened the debate)

Question 30

What are saviour siblings

Answer 30

• Create an embryo (using PGD) that will be a tissue match (“tissue typing”) for an existing child who has a condition that requires e.g. bone marrow transplant

Question 31

Legal approval of saviour siblings?

Answer 31

* Initially (2001): this was approved for removal of cord blood cells (source of stem cells) AND the embyro had to be at risk of inheriting the same disorder * But in 2004 both of these conditions were removed, hence bone marrow transplant now possible (although solid organ donation is prohibited)

Question 32

Examples of saviour siblings

Answer 32

• Hashmi family (2002) – Beta-thalassaemia, inherited – UK (HFEA) granted permission • Whittaker family (2002) – Diamond Blackfan anaemia, not inherited – UK (HFEA) refused; US granted • Fletcher family (2004) – Diamond Blackfan anaemia, not inherited – UK (HFEA) granted approval

Question 33

Are saviour siblings ethical?

Answer 33

• Is the saviour sibling being “used” as a means (to help the other child) rather than an end in themselves (just for being them)? • What is the psychological effect on the saviour sibling (and the existing child) and their resultant relationship? – But then, what of the impact of bereavement on a family?