Lecture 4.2: Prenatal Genetic Testing

Question 1

What is Screening?

Answer 1

A program applied to a whole population/ large numbers of asymptomatic, but potentially at risk individuals

Question 2

What is Testing?

Answer 2

Is applied to either symptomatic individuals to establish diagnosis, or asymptomatic individuals with a positive screening test

Question 3

Screening Target Audience

Answer 3

Foetus
Newborns
School Leavers
Adult Volunteers
Couples

Question 4

Screening offered during pregnancy

Answer 4

• Infectious diseases
• Inherited conditions
• 11 physical conditions (20 week scan)
• Down’s syndrome, Edwards’ syndrome and
Patau’s syndrome

Question 5

Screening offered for the newborn

Answer 5

• Newborn physical examination
• Newborn hearing screening
• Newborn Blood spot screening

Question 6

The NHS young person and adult programmes

Answer 6

• Eye problems in people with diabetes
• Abdominal aortic aneurysms

Question 7

Pre cancerous cell changes screening

Answer 7

• Breast
• Cervical
• Bowel

Question 8

Newborn Blood Spot: when? by whom?

Answer 8

Day 5

Carried out by a Healthcare Professional:
• Heel prick
• 4 spots on special card
• Occasionally may need to be carried out later or second test

Question 9

Newborn Blood Spot: what are they testing for? Name 5

Answer 9

Phenylketonuria (PKU)
Congenital hypothyroidism (CHT)
Sickle cell disease (SCD)
Cystic fibrosis (CF)
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD)
Homocystinuria (HCU)
Maple Syrup Urine Disease (MSUD)
Glutaric Aciduria type 1 (GA1)
Isovaleric Aciduria (IVA)

Question 10

Newborn Hearing Screening

Answer 10

The automated otoacoustic emission (AOAE) test

Quick, non invasive, a small soft-tipped earpiece is placed in baby’s ear and gentle clicking sounds are played

If results unclear offered a 2nd test. This may be repeat AOAE or another test called the automated auditory brainstem response (AABR) test

The AABR test involves placing 3 small sensors on baby’s head and neck. Soft
headphones are placed over baby’s ears and gentle clicking sounds are played

Question 11

Newborn Physical Examination

Answer 11

Offered within 72hrs of birth

Examine:
• General health (colour, tone)
• Eyes
• Heart
• Hips
• Testicles
• Back
• Hands/feet
• Palate
• Anus

Question 12

Maternal Health Screening

Answer 12

Looking for risk factors which may predispose to conditions which may impact pregnancy and baby’s health and/or maternal health

Risk assessed using information gathered from clinical history +/- examinations +/- investigations

If classified as high risk mother offered further intervention

Question 13

Maternal Health Screening: Possible Conditions Detected

Answer 13

Gestational diabetes
Preeclampsia
Mental health disorders
Blood group and Rhesus factor

Question 14

Screening for Infectious Diseases

Answer 14

Blood test

3 infectious diseases:
• Hepatitis B
• HIV
• Syphilis

Enables early treatment to prevent vertical transmission

Question 15

Screening for Inherited Diseases

Answer 15

Sickle Cell

Thalassemia

Question 16

Screening for Physical Conditions

Answer 16

20 Week Scan

Detailed look at bones, heart, brain, spinal cord, face, kidneys and abdomen

Question 17

Cleft Lip/ Palate

Answer 17

The tissue that makes up the roof of the mouth does not join together completely during pregnancy

Question 18

Diaphragmatic Hernia

Answer 18

A birth defect where there is a hole in the diaphragm

There are multiple air filled loops in the left hemi-thorax with mediastinal shift to the right and ipsilateral lung hypoplasia

Question 19

Spina Bifida

Answer 19

A condition that affects the spine

Failure of closure of the vertebral arch

Question 20

“Combined Test”

Answer 20

10-14 weeks pregnancy

Nuchal translucency (fluid at the back of the baby’s neck)

Blood test (Beta HCG, Serum pregnancy-associated plasma protein A)

Combined results of both tests calculate risk for all 3 condition (T13, T18, T21)

Question 21

“Quadruple Test”

Answer 21

14-20w

Blood test (Alpha feta protein, BHCG, Unconjugated estriol and Inhibin A)

Down’s only

Less accurate

Question 22

Outcome of Foetal Anomaly Screening

Answer 22

Higher-risk result: Offered a diagnostic test to find out for certain whether the baby has Down’s, Edwards’ or Patau’s syndrome or not

Question 23

Screening for Neural Tube Defects

Answer 23

Levels of AFP tested

However, there is overlap of AFP levels in normal pregnancies and those with neural tube defects

Question 24

What happens with high-risk individuals?

Answer 24

Genetic diagnostic tests (tests/biopsies of foetus, PCR, karyotyping)

Psychological support in prenatal screening (genetic counselling)

Question 25

Foetal DNA Screening

Answer 25

Amniotic fluid cells
Chorion villus biopsy
Foetal DNA in mother’s blood

Question 26

Amniocentesis

Answer 26

15–20 weeks of gestation

Ultrasound guidance

Cells must be recovered and may need to be cultured for 2 weeks

0.5–1.0% risk of causing miscarriage

Question 27

Chorion Villus Biopsy

Answer 27

10–13 weeks gestation

Ultrasound guidance

Trans-cervical or transabdominal

Foetal villi must be separated from maternal tissue

2% risk of causing miscarriage