Prenatal Testing

Question 1

Prenatal Screening

Answer 1

Focuses on finding problems among a large population with affordable and non-invasive methods. Examples are Down Syndrome, Bloodborne virus and Ultrasound Scan

Question 2

Prenatal Diagnosis

Answer 2

Focuses on pursuing additional detailed information once a particular problem has been found, and can sometimes be more invasive. Examples are Amniocentesis and Chorionic Villus Sampling.

Question 3

Why do we do prenatal testing?

Answer 3

• To enable the timely medical or surgical treatment of a condition before or after birth.
• To give the parents the chance to terminate the pregnancy with the diagnosed condition.
• To give parents the chance to prepare psychologically, socially, financially, and medically for a baby with a health problem or disability, or for the likelihood of a stillbirth.
• To organise appropriate foetal surveillance.

Question 4

Screening in Pregnancy UK

Answer 4

• Offered to all women to assess if either woman or baby have particular health issue or disability.
• Simple tests - Ultrasound, blood test, questionnaire.
• Not diagnostic, there is a follow on diagnostic test.

Question 5

Blood tests in Pregnancy Screening

Answer 5

• FBC
• Blood group and Rhesus state
• Haemoglobinopathies - thalasaemia and sickle cell
• Infectious diseases
• Chromosomal disorders - e.g. trisomies (21, 18, 13)

Question 6

Screening for Haemoglobinopathies

Answer 6

• Inherited altered haemoglobin gene disorders, usually autosomal recessive.
• High risk - family origins from Africa, the Carribean, the Mediterranean, South East Asia, the Middle East and Far East. Can be found in all ethnic groups but is less common.
• If the woman is a carrier then partner testing will be offered. If partner is positive, genetic counselling will be offered.
• The screening involves an Amniocentesis or Chorionic Villus Sample to see if the foetus is affected. And Blood Spot Screening Test which will be done when the baby is born.

Question 7

Screening for Trisomies

Answer 7

• Assess the chance of the baby being born with Down’s, Edwards’ or Patau’s Syndromes.
• The test is sensitive singleton or twin pregnancies, not for higher multiple pregnancies.
• Risk factors which affect screening tests include; smoking, ethnicity, BMI, age, assisted pregnancy (donor egg or frozen embryo).

Question 8

Down’s Syndrome

Answer 8

Commonest cause of identifiable learning disability usually due to non-disjunction at chr.21 at meiosis. 50% will have congenital abnormality, 80% profound or severe intellectual impairment. 1:1000 live births. Approx. 40,000 people in UK have Down’s Syndrome.

Question 9

Edwards’ Syndrome

Answer 9

Trisomy 18 - these babies rarely survive to adulthood, most die before or shortly after birth.

Question 10

Patau’s Syndrome

Answer 10

Trisomy 13 - not many babies survive to adulthood, many die before or shortly after birth.

Question 11

First Trimester Combined Test

Answer 11

• Optimal time for this test - 11+2 weeks to 14+1 weeks of gestation.
• Factors used for calc. - maternal age, nuchal translucency measurement, two biochemical markers (free beta hCG and PAPP-A), gestational age calculated from the crown rump length measurement.
• Result is low or high chance. 1 to 150 chance is the cut-off point.

Question 12

Nuchal Translucency

Answer 12

Measure the amount of fluid under the skin at the back of the baby’s neck.

Question 13

Detection Rates

Answer 13

• Down’s Syndrome detection rate is 84%. False positive rate is 2.2%.
• Edwards’ Syndrome detection rate is 85% and false positive rate is 0.2%

Question 14

Second Trimester Screening

Answer 14

• Quadruple Test
• The optimal time for it is between 14+2 weeks and 20 weeks.
• Factors used in this calculation are; maternal age, four biochemical markers (alpha-fetoprotein, hCG (total, intact or free beta subunit), uE3 and Inhibin-A).
• No scan in 2nd trimester screening.
• Quadruple test has a lower detection rate than the combined test. Detection rates are lower; 80% for Down’s Syndrome with a FPR of 3.5%. And 73% detection rate for Edwards Syndrome and a FPR of 0.1%.
• If risk of having a term pregnancy affected with Edwards’ Syndrome is 1 in 100 or higher an ultrasound and amniocentesis are offered.

Question 15

Getting Results from Screening

Answer 15

• Tells you if the woman has a higher or lower chance of having a baby with one of the conditions screened for.
• Woman will receive 2 results for trisomies: 1 chance of having a baby with Down’s Syndrome and a 2 combined chance of having a baby with Edwards’ or Patau’s Syndrome.
• If it shows high chance, results should be told within 3 working days of result being available. If lower chance then should be told within 2 weeks.
• Further options for women who receive high chance result are: no further tests, Non-Invasive Prenatal Testing or Diagnostic Tests.

Question 16

Non-Invasive Prenatal Testing (NIPT)

Answer 16

• Cell free DNA screening test (cfDNA), as cell free DNA is extracted and analysed from maternal blood test.
• Can be performed from 10 weeks of pregnancy.
• Most of the DNA comes from the mother but a small amount comes from the placenta.
• In 3% of cases, not enough cfDNA can be extracted to provide the results. Results are given as low or high chance.
• NIPT can be just as accurate in identical twin pregnancies but less so in non-identical twins because there would be two placentas releasing their own DNA.

Question 17

Diagnostic Tests

Answer 17

Invasive tests like Amniocentesis or Chorionic Villus Sampling. These are offered to women who have had a higher chance result from screening. Alternatively can use a detailed ultrasound scan.

Question 18

Chorionic Villus Sampling

Answer 18

• Fine needle inserted through the abdomen and into uterus, or through cervix, and small piece of developing placenta removed. Done from 11 weeks onwards. In 2%, no results will be obtained and/or risk of miscarriage. Tests for inherited disorders (cystic fibrosis, sickle cell, thalassemias, muscular dystrophy) and chromosomal disorders.
• Ethical issues include; risk of miscarriage, delay in getting results, risk of infection and heavy bleeding.
• False positive rate of 1-2%, false negative rate of 2%.

Question 19

Amniocentesis

Answer 19

• A needle is inserted through the abdomen and into the amniotic fluid. It collects some of this amniotic fluid which it then karyotypes, if the screening tests suggest aneuploidy. DNA analysis if the parents are carrier of an identifiable gene. Enzyme assays for inborn errors of metabolism: done after 15 weeks, amniotic fluid is aspirated to study foetal chromosomes. 1% risk of miscarriage.
• Risks of miskcarriage, delay in getting results, infection, injury
• False positive rate of 0.1-0.6% and false negative rate of 0.6%.

Question 20

Ultrasound Screening Scans

Answer 20

• Dating Scan - between 10-14 weeks of pregnancy (try for 12th), number of pregnancies, viability, gestational weeks, neural tube thickness and defects.
• Anomaly Scan - 18-20 weeks & 6 days (but closest to 20 weeks). Can spot physical annormalities e.g. spina bifida or placental position.
• Ethical - not everyone chooses to have this scan.

Question 21

Preimplatation Genetic Diagnosis (PGD)

Answer 21

• Offered to couples who are at risk of passing on a genetic disorder.
• It involves removing one cell from the early embryo (4-8 cell embryo).
• It is not common and is expensive (maybe cheaper in long run)
• A disorder that may affect the capacity for live birth or risk of the child being born with or developing a serious disability are seen as acceptable to run PGD in. If the disorder is gender-related, can use PGD to select gender. Conditions include: cystic fibrosis, fragile X syndrome, blood disorders (e.g. sickle cell, haemophilia and Von Willebrand Disease), Tay-Sachs Disease, and Spinal Muscular Atrophy.
• If genetic disorder is found, professional genetic counselling is usually recommended.

Question 22

Ethical issues of prenatal testing for Huntington’s Disease

Answer 22

• inherited late onset degenerative condition, mainfests between 30-50yrs old. 50/50 chance of inheriting it.
• if the baby does have the gene, they will terminate?
• knows something about the childs future that they may have not wanted to know?
• selecting a child which does not carry the gene?

Question 23

Saviour Sibling

Answer 23

A saviour baby or sibling is a child who is born to provide an organ or cell transplant to a sibling that is affected with a fatal disease, such as leukaemia, beta-thalasemmia, diamond-blackfan anaemia or Fanconi anaemia, that can best be treated by haematopoietic stem cell transplantation. The saviour sibling is conceived via in vitro fertilisation. Can be tested for genetic compatibility using preimplantation genetic diagnosis. Only zygotes compatible with the child are implanted. The zygotes are also tested to make sure they are free of the original genetic disease.

Question 24

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)

Answer 24

• CRISPRs are the hallmark of a bacterial defence system that forms the basis for CRISPR-Cas9 genome.
• CRISPR gene editing is a genetic engineering technique in molecular biology by which genomes of living organisms may be modified. The technique is considered highly significant in biotechnology and medicine as it allows for the genomes to be edited in vivo with extremely high precision, cheaply and with ease. It can be used in the creation of new medicines.
• Applications include disease models, biomedicine, treatment of infection and cancer.