73 Prenatal testing Flashcards
Features of screening tests offered during pregnancy?
- 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
Features of diagnostic tests used during pregnancy?
- 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
Why carry out screening and testing?
- To REASSURE parents
- To inform and PREPARE parents for the birth of an affected infant
- To allow in utero TREATMENT
- To allow TERMINATION of an affected fetus
- To provide information so that parents may choose between 2, 3 or 4: key issue here = choice
Examples of screening and diagnostic testing?
- Natural conception
• Non-invasive screening, e.g. ultrasound, serum test
• Invasive prenatal diagnostic (PND) testing, e.g.
chorionic villus sampling, amniocentesis
• NIPT, sometimes ‘NIPD - In vitro fertilisation
• Preimplantation genetic diagnosis (PGD)
Ultrasound in screening: • What is it? • When is it? • Why is it? • Ethical issues arising?
• 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
What is Down’s syndrome?
- 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
Down's Syndrome screen: • What is it? • When is it? • Why is it? • Ethical issues arising
• 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)
What are the analyse markers in blood in the serum test for Down’s Syndrome?
- Pregnancy associated plasma protein-A (PAPP-A)
* Free ß- human chorionic gonadotrophin (free ß-hCG)
What does ultrasound in Down’s Syndrome screen look for?
Nuchal translucency (NT)
How good is the ‘combined’ screening test for DS?
• 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
How is the quadruple test used during DS screening?
- 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%
Name screening tests
- Ultrasound
2. Down’s Syndrome screen/ Quadruple test
Name diagnostic tests
- Amniocentesis
2. Chorionic villus sampling
Amniocentesis: • What is it? • When is it? • Why is it? • Ethical issues arising
• 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
How good is amniocentesis?
- False-positive rate of 0.1-0.6%
* False-negative rate of 0.6%
Chorionic villus sampling: • What is it? • When is it? • Why is it? • Ethical issues arising
• 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
How good is chorionic villus sampling?
- False-positive rate of 1-2%
* False-negative rate of 2%
Examples of diseases for which DNA tests are available
- Cystic fibrosis
- Phenylketonuria
- Tay-Sachs
- Duchenne Muscular dystrophy
- Huntington’s disease
- Inherited breast + ovarian cancers
What is prenatal genetic diagnosis used for?
- 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
What are the disadvantages of prenatal genetic testing?
- Costly
- Inconvenient
- Risk of miscarriage
- Sample can only be used for a couple of tests
What is Non-invasive prenatal genetic testing (NIPT)
• 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
Where the 4 principles of medical ethics?
- Autonomy
- Non-maleficence
- Beneficence
- Justice
Preimplantation genetic diagnosis:
• Offered to?
• Process?
- 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?)
What disorders are acceptable (HFE Act 2008) for preimplantation genetic diagnosis?
- 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
Code of practice guidance to definition of “serious” illness?
• 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
What is Huntington’s Disease?
- Inherited, late onset, degenerative condition
- Manifests ~ 30-50 yrs
- 50/50 chance of inheriting it from affected parent
- Non sex linked dominant inheritance pattern
What are the 2 issues in testing for Huntington’s Disease?
- 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 - PGD for HD
– Thus select an embryo that does not carry the inherited HD gene
What is PGD?
Pre-implantation genetic diagnosis is a treatment which involves checking the genes or chromosomes of your embryos for a specific genetic condition
What is the case for preference FOR disabled embryo’s?
- The case of Tomato Lichy and Paula Garfield
* (note: they did not want to positively select but it opened the debate)
What are saviour siblings
• 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
Legal approval of saviour siblings?
- 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)
Examples of saviour siblings
• 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
Are saviour siblings ethical?
• 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?
