Prenatal Screening

Question 1

What is screening?

Answer 1

Screening identifies apparently healthy people who may be at increased risk of a disease or condition, enabling earlier treatment or informed decisions.

Question 2

Fetal anomaly screening programme

Answer 2

Question 3

Fetal Anomoly Screening Programme

• … pregnancy scan
• Screening for …’s …’s …’s syndromes
  
  • First trimester … test
  • Second trimester … test
• ..+.. – ..+.. weeks fetal anomaly scan

Answer 3

• Early pregnancy scan
• Screening for Down’s Edward’s Patau’s syndromes
  
  • First trimester combined test
  • Second trimester quad test
• 18+0 – 20+6 weeks fetal anomaly scan

Question 4

The early pregnancy scan:
Why scan at 10-14 weeks ?

• V…
  
  • …-… % of women attending for scan will have miscarried
• Accurate …
  
  • NICE guidance: advise use scan of … in lieu of LMP dates
    
    • • crucial for screening tests for …
    • reduces need for post dates … of labour
• Detect … pregnancy
  
  • determine c…
• Diagnosis of major … anomalies
  
  • s.. b…
  • an…
  • ex… & gastro…
  • … outflow obstruction
• Screening for chromosomal conditions:
  
  • Down’s syndrome -Trisomy …
  • Edward’s syndrome- Trisomy …
  • Patau’s syndrome –Trisomy …

Answer 4

• Viability
  
  • 2 - 3 % of women attending for scan will have miscarried
• Accurate dating
  
  • NICE guidance: advise use scan of dates in lieu of LMP dates
    
    • • crucial for screening tests for trisomies
    • reduces need for post dates induction of labour
• Detect multiple pregnancy
  
  • determine chorionicity
• Diagnosis of major structural anomalies
  
  • spina bifida
  • anencephaly
  • exomphalos & gastroschisis
  • bladder outflow obstruction
• Screening for chromosomal conditions:
  
  • Down’s syndrome -Trisomy 21
  • Edward’s syndrome- Trisomy 18
  • Patau’s syndrome –Trisomy 13

Question 5

Screening for chromosomal conditions:

• What 3 ? What Trisomy?

Answer 5

• Down’s syndrome -Trisomy 21
• Edward’s syndrome- Trisomy 18
• Patau’s syndrome –Trisomy 13

Question 6

Screening for Down’s Edward’s Patau’s syndromes

• First trimester … test
• Second trimester … test

Answer 6

• First trimester combined test
• Second trimester quad test

Question 7

Down’s syndrome - Trisomy …

• Schematic view of full ….
• Usually we have … pairs of autosomes and two sex chromosomes making a total of … chromosomes.
• People with Downs syndrome have an extra copy of chromosome …
• People with Edwards syndrome have an extra copy of chromosome …
• People with Pataus syndrome have an extra copy of chromosome …

Answer 7

Down’s syndrome - Trisomy 21

• Schematic view of full karyotype.
• Usually we have 22 pairs of autosomes and two sex chromosomes making a total of 46 chromosomes.
• People with Downs syndrome have an extra copy of chromosome 21.
• People with Edwards syndrome have an extra copy of chromosome 18
• People with Pataus syndrome have an extra copy of chromosome 13

Question 8

People with Pataus syndrome have an extra copy of chromosome …

Answer 8

People with Pataus syndrome have an extra copy of chromosome 13

Question 9

People with Edwards syndrome have an extra copy of chromosome …

Answer 9

People with Edwards syndrome have an extra copy of chromosome 18

Question 10

People with Downs syndrome have an extra copy of chromosome …

Answer 10

People with Downs syndrome have an extra copy of chromosome 21.

Question 11

Screening Tests vs Diagnostic Tests

• Screening Tests
  
  • identify individuals at ‘high’ or ‘low’ chance of having a baby with the condition screened for
  • A low chance result does … trisomy in the baby.
  • A high chance result does not indicate that the baby is
• …
  
  • Risk of miscarriage?
  • Diagnostic Tests
    
    • give … information on the fetal chromosomes by confirming the presence of an extra chromosome or absence of a chromosome
    • Risk of miscarriage?

Answer 11

• Screening Tests…
  
  • …identify individuals at ‘high’ or ‘low’ chance of having a baby with the condition screened for
  • A low chance result does not exclude trisomy in the baby.
  • A high chance result does not indicate that the baby is definitely affected.
  • No risk of miscarriage
• Diagnostic Tests…
  
  • …give definitive information on the fetal chromosomes by confirming the presence of an extra chromosome or absence of a chromosome
  • Risk of miscarriage

Question 12

Pregnancy Screening Timeline

Answer 12

Question 13

First trimester combined screening

• 3 Modalities:
  
  • Maternal …
  • Nuchal … Scan
  • Blood Test for markers - P… and B…

Answer 13

• 3 Modalities:
  
  • Maternal Age
  • Nuchal Translucency Scan
  • Blood Test for markers - PAPPA and BhCG

Question 14

The chance of having a baby with a trisomy increases with …

Answer 14

The chance of having a baby with a trisomy increases with maternal age.

Question 15

Nuchal Translucency [NT] Scan

• Can only take measurement when CRL 45- 84mm [equates to 11+2 to 14+1 weeks]
  
  • CRL = crown rump length
• NT is increased in over …% of cases of T21.
• …% of T18
• …% Turners

Answer 15

• CRL 45- 84mm [equates to 11+2 to 14+1 weeks]
• CRL = crown rump length
• NT is increased in over 80% of cases of T21.
• 75% of T18
• 87% Turners

Question 16

What are the two maternal serum biochemical markers in combined screening?

Answer 16

free B-hCG and PAPP-A

Question 17

Combined screening:
Maternal serum biochemical markers

• free ß-… & P…-A
• Measure the concentration of the markers in the maternal blood stream. In a pregnancy where the fetus has Downs you tend to see a … levels of … in conjunction with … levels of ….
• In T13/18 both markers tend to be significantly … than average.

Answer 17

• free ß-hCG PAPP-A
• Measure the concentration of the markers in the maternal blood stream. In a pregnancy where the fetus has Downs you tend to see a higher levels of … in conjunction with lower levels of ….
• In T13/18 both markers tend to be significantly lower than average.

Question 18

Maternal /fetal influencing factors for combined screening

• … age
• … age
• E…
• S…
• I…
• … pregnancy
• W..
• D…
• Past history of … abnormality
• … sex
• Analytical …

Answer 18

• Maternal age
• Gestational age
• Ethnicity - afro caribbean inc PAPPA by up to 60%
• Smoking - inc BHG by 20% and reduces PAPPA by up t 15%
• IVF
• Multiple pregnancy
• Weight - 3kg error = 5% error in risk calculation
• Diabetes
• Past history of chromosome abnormality
• Fetal sex
• Analytical Imprecision

Question 19

Combined screening result process

• National cut off for high / low chance = 1 in …
• Higher chance? Phoned within … working days – offer further tests
• Lower chance? Letter within … weeks

Answer 19

• National cut off for high / low chance = 1 in 150
• Higher chance? Phoned within 3 working days – offer further tests
• Lower chance? Letter within 2 weeks

Question 20

National Standards – Performance thresholds for combined screening

Answer 20

Question 21

Pregnancy Screening

• We can only offer combined test up to …+… weeks.
• For women booking late, or found to be over 14+1 weeks on scan we have another option – the … test

Answer 21

• We can only offer combined test up to 14+1 weeks.
• For women booking late, or found to be over 14+1 weeks on scan we have another option – the quadruple test

Question 22

Combined screening result process

• High chance result anything from 1 in … to 1 in …
• Low chance result 1 in … or lower

Answer 22

• High chance result anything from 1 in 2 to 1 in 150
• Low chance result 1 in 151 or lower
  *

Question 23

Detection rate of combined screening test:

• T21 - …%
• T13/18 - …%

Answer 23

• T21 - 85% (Down’s)
• T13/18 - 80% (Edwards/Patau’s)

Question 24

Second trimester maternal serum screening: quadruple test

• …+… to …+0 weeks: available to late bookers only
• Only screens for Trisomy …
• Blood test only [… cannot be used after …+… weeks]
• Uses gestational age, maternal age, smoking, weight, ethnicity and …

Answer 24

• 14+2 to 20+0 weeks: available to late bookers only
• Only screens for Trisomy 21
• Blood test only [NT cannot be used after 14+2 weeks]
• Uses gestational age, maternal age, smoking, weight, ethnicity and … maternal serum markers

Question 25

* NT – nuchal translucency * The NT scan is not used after ... weeks,

Answer 25

* NT – nuchal translucency * The NT scan is not used after **14** weeks,

Question 26

The quad test is a blood test measuring **...** markers in the blood.

Answer 26

The quad test is a blood test measuring **4** markers in the blood.

Question 27

_Second trimester maternal serum screening: quadruple test - Markers_ * UE3 unconjugated estriol – ... hormone * AFP alpha fetoprotein – ... from ... * ... A placental hormone * ... beta human chorionic gonadotrophin- placental hormone

Answer 27

* UE3 unconjugated estriol – **placental** hormone * AFP alpha fetoprotein – **protein** from **fetus** * **Inhibin** A placental hormone * **BHCG** beta human chorionic gonadotrophin- placental hormone

Question 28

_Quad test : Detection rates_ * DR is similar to singleton pregnancy but the SPR doubles. * T 21 - DR is ...%, Screen positive rate is ...%

Answer 28

* DR is similar to singleton pregnancy but the SPR doubles. * T 21 - DR is **80**%, Screen positive rate is **2.5-3.5**%

Question 29

_Quad test : Detection rates : Twins_ * Monochorionic twins: * DR ...% SPR ..% * Dichorionic twins: * DR ...-...% SPR ...%

Answer 29

* Monochorionic twins: * **DR 80% SPR 3%** * Dichorionic twins: * **DR 40-50% SPR 3%** * *The combined test is the preferred screening test for twins.* * *Whilst the DR Monochorionic twins is similar to a singleton pregnancy, it is much lower for Dichorionic twins.* * *Thus overall the quad test is less useful for dichorionic twins* * *Therefore women with twin pregnancies require careful counselling about screening tests*

Question 30

* The ... test is the preferred screening test for twins. * Whilst the DR Monochorionic twins is similar to a singleton pregnancy, it is much lower for ... twins. * Thus overall the ... test is less useful for dichorionic twins * Therefore women with twin pregnancies require ... .... about screening tests

Answer 30

* The **combined** test is the preferred screening test for twins. * Whilst the DR Monochorionic twins is similar to a singleton pregnancy, it is much lower for **Dichorionic** twins. * Thus overall the **quad** test is less useful for dichorionic twins * Therefore women with twin pregnancies require **careful counselling** about screening tests

Question 31

_Higher chance of T13/18/21 on combined or quad screening test ? What next?_ * Explain result – ... the chance: 1 in 50 = 2% * Balanced information about the condition * Three main options: * 1-Do nothing - ... the pregnancy without having further tests​ * 2-Diagnostic ... testing [CVS / Amnio] * 3-NIPT – non invasive ... testing * [Available ..., planned implementation on NHS in June 2021]

Answer 31

* Explain result – reframe the chance: 1 in 50 = **2**%] * Balanced information about the condition * Three main options: * 1-Do nothing - **continue** the pregnancy without having further tests​ * 2-Diagnostic **invasive** testing [CVS / Amnio] * 3-NIPT – non invasive **prenatal** testing * [Available **privately**, planned implementation on NHS in June 2021]

Question 32

_Prenatal diagnosis / Diagnostic invasive test_ * Chorionic Villus Sampling CVS ...+ weeks * Amniocentesis ...+ weeks to term * Around ...-...% risk of miscarriage * [higher in ...]

Answer 32

* Chorionic Villus Sampling CVS **11**+ weeks * Amniocentesis **15**+ weeks to term * Around **0.5 -1**% risk of miscarriage * [higher in **twins**]

Question 33

_NIPT: Non-invasive prenatal testing Screening for aneuploidy_ * Cell free fetal DNA [cff DNA] in maternal blood from ... weeks * Pregnancy specific * Test maternal blood from ... weeks * Aneuploidy: Screening for T... sensitivity and specificity over 99% * Marketed as Harmony, SAFE, Panorama, NIFTY test

Answer 33

* Cell free fetal DNA [cff DNA] in maternal blood from **5** weeks * Pregnancy specific * Test maternal blood from **10** weeks * Aneuploidy: Screening for **T21** sensitivity and specificity over 99% * Marketed as Harmony, SAFE, Panorama, NIFTY test

Question 34

Combined Screen Test / NIPT

Answer 34

* Results either: * \> 99% chance baby has Downs * [should be confirmed by invasive test if considering terminatin] * * \< 1 in 10,000 chance baby has Downs

Question 35

_NIPT Advantages_ * ... detection rates, ... screen positive rates * Reduction in invasive diagnostic testing [... effective] hence reduction in ... caused by invasive testing [CVS/amniocentesis] * A further option for women

Answer 35

* **High** detection rates, **low** screen positive rates * Reduction in invasive diagnostic testing [**cost** effective] hence reduction in **miscarriage** caused by invasive testing [CVS/amniocentesis] * A further option for women

Question 36

_NIPT Disadvantages_ * Screening test: Not ... [...] * Confirm screen positive results with ... test * Not suitable for ... * NHS – planned implementation as a 3 year evaluative roll out commencing June 2021 * Likely to be offered to anyone with ... chance result on first or second trimester screening with ... or ... pregnancy

Answer 36

* Screening test: Not **diagnostic** **[false positives / false negatives**] * Confirm screen positive results with **invasive** test * Not suitable for **everyone** * NHS – planned implementation as a **3** year evaluative roll out commencing June 2021 * Likely to be offered to anyone with **high** chance result on first or second trimester screening with **singleton** or **twin** pregnancy

Question 37

_18+0 to 20+6 week fetal anomaly ultrasound scan_ * Specifies screening for ... conditions where: * the baby may benefit from ... before or after birth * birth is advisable in an ... hospital/ centre and/or to ... treatment after the baby is born * the baby may ... shortly after birth

Answer 37

* Specifies screening for **11** conditions where: * the baby may benefit from **treatment** before or after birth * birth is advisable in an **appropriate** hospital/ centre and/or to **optimise** treatment after the baby is born * the baby may **die** shortly after birth

Question 38

_11conditions screened at mid trimester scan_

Answer 38

Question 39

_11 conditions screened at mid trimester scan are:_

Answer 39

* Anencephaly - DR is 98% * Open spina bifida DR is 90% * Cleft lip DR is 75% * Diaphragmatic hernia DR is 60% * Gastroschisis DR is 98% * Exomphalos DR is 80% * Serious cardiac anomalies includes the following: DR is 50% * Transposition of the Great Arteries (TGA) * Atrioventricular Septal Defect (AVSD) * Tetralogy of Fallot (TOF) * Hypoplastic Left Heart Syndrome (HLHS) * Bilateral renal agenesis DR is 84% * Lethal skeletal dysplasia DR is 60% * Edwards’ syndrome (Trisomy 18) DR is 95%\*\* * Patau’s syndrome (Trisomy 13) DR is 95%\*\* \*\*Detections rates will be reviewed once sufficient data is received following implementation of screening as part of the combined screening strategy

Question 40

NCARDRS - What is this?

Answer 40

**National Congenital Abnormality and rare Disease registration Service**

Question 41

_Trisomy 21:_ * Associated with some level of learning disability – ...% in mainstream primary school. Cannot predict ... pre-birth. * Some health conditions are more ... * Typical life expectancy is ...+

Answer 41

* Associated with some level of learning disability – **80**% in mainstream primary school. Cannot predict **severity** pre-birth. * Some health conditions are more **common** * Typical life expectancy is **60**+

Question 42

_Trisomy 21: Parents Understanding_ * Most parents report ... experience [Bertrand 2017] * ...% felt outlook on life more positive * Over ...% expressed love for their child * ...% regretted having their child * ...% of people with Down’s say they enjoy their life [Skotko et al 2011]

Answer 42

* Most parents report **positive** experience [Bertrand 2017] * **79**% felt outlook on life more positive * Over **99**% expressed love for their child * **7**% regretted having their child * **99**% of people with Down’s say they enjoy their life [Skotko et al 2011]

Question 43

_Condition diagnosed - E.g. Trisomy 21_ * Options * Continue * Continue and ... * Termination [medical / surgical] [Trisomy 21: ...%] * Support * Termination under Grounds ... * There is a substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously ...

Answer 43

* Options * Continue * Continue and **adoption** * Termination [medical / surgical] [Trisomy 21: **90**%] * Support * Termination under Grounds **E** * There is a substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously **handicapped**

Question 44

* To put termination for fetal anomaly into context – in 2018 there were over 200,000 abortions in England and Wales, of which around ...% were under Ground E

Answer 44

* To put termination for fetal anomaly into context – in 2018 there were over 200,000 abortions in England and Wales, of which around **2**% were under Ground E

Question 45

_Condition diagnosed - such as Trisomy 21_ * Additional Support * Antenatal Screening Co-Ordinator / midwife * National support groups: * Antenatal Results and Choices [ARC], * Downs syndrome association [DSA] * Soft U.K. [Tri 13 and 18], Unique, Contact-A- Family * Meet other parents [Specialist Health Visitor / local groups] * Obstetric / neonatal / paediatric /surgical teams * Genetic counselling

Answer 45

* Additional Support * Antenatal Screening Co-Ordinator / midwife * National support groups: * Antenatal Results and Choices [ARC], * Downs syndrome association [DSA] * Soft U.K. [Tri 13 and 18], Unique, Contact-A- Family * Meet other parents [Specialist Health Visitor / local groups] * Obstetric / neonatal / paediatric /surgical teams * Genetic counselling

Question 46

_Pre–screening test information: what should we be discussing?_ * Prior to entering a screening programme * Tests are ... * What are we screening for? * What the test will ... * ... of tests * ... results – higher / lower chance * Options if ... chance result * Options if a condition is ... * Contact for further information

Answer 46

* Prior to entering a screening programme * Tests are **optional** * What are we screening for? * What the test **will not tell you** * **Timing** of tests * **Communicating** results – higher / lower chance * Options if **higher** chance result * Options if a condition is **diagnosed** * Contact for further information

Question 47

_National patient information leaflets: Screening tests for you and your baby_

Answer 47

National screening leaflets are available – these are all digital now. Take time to look at the leaflet – there is also a video for parents.