Prenatal Screening:NHS Fetal Anomaly Screening Programme Flashcards
Screening
During pregnancy and in the first 8 weeks of life, we offer screening for over 32 different conditions within the 6 Antenatal and newborn screening programmes:
1. Infectious Disease Screening Programme [Screens for Hep B, HIV, Syphilis]
2. Blood- Sickle Cell and Thalassemia Screening Programme
3. Fetal Anomaly Screening Programme [discussing in depth today]
5. Newborn Bloodspot Screening [Screen for cystic fibrosis, sickle cell disease, congenital hypothyroidism and 6 inherited metabolic disorders]
7. Newborn Hearing Screening Programme
8. Newborn and Infant Physical Examination Programme [screens for conditions of the heart, eyes, hip and, in boys, undescended testes]
This pictorial timeline, aimed at parents, explains what current tests are offered at what gestations/ age of newborn life. The link at the bottom of the slide takes you to a link to watch a video explaining these conditions.
Fetal Anoirmally Screening Tests
- 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
Early pregnancy scan. The early pregnancy scan:
Why scan at 10-14 weeks ?
1.First thing we look at is Viability; Condition of the baby. 2 - 3 % of women attending for scan will have miscarried.
2. Accurate dating; we check the length and size of the baby to estimate the accurate due date.
NICE guidance: advise use scan of dates instead of of Last period dates to estimate due date.
- crucial for screening tests for trisomies. A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two
- reduces need for postdates induction of labour. so we need accurate dates so that we don’t induce people early. induction is painful and expensive.
3. Detect multiple pregnancy; determine chorionicity.
With twins we will check the chorionicity which is the main determinant of fetal outcome in twin pregnancy.
On the left image = monochorionic twins = insertion of intertwin membrane into placental mass. These require closer surveillance. monochorionic are identical twin as they are from the same sperm and egg.
On the right = dichorionic twins, note the lambda sign where the placental mass extends between the intertwin membrane. dichorionic originate from different sperm and egg.
4. Diagnosis of major structural anomalies
- spina bifida
- anencephaly
- exomphalos & gastroschisis
- bladder outflow obstruction
5. Screening for chromosomal conditions:
Down’s syndrome -Trisomy 21
Edward’s syndrome- Trisomy 18
Patau’s syndrome –Trisomy 13
Down’s syndrome
Trisomy 21
T21
- We have 3 copies of chromosome 21 in Down’s syndrome.
- 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
Screening test is different from diagnostic test
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.
Screening test has 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
- If you do the screening test and chose to do a diagnostic test for a definitive result, you must know that Diagnostic test carry the Risk of miscarriage.
First trimester combined screening
Called the combined test because it combines 3 different modalities to work out the risk.
1. Maternal Age
2. Nuchal Translucency Scan
3. Blood test for Markers; PAPPA, BhCG.
The combined test uses maternal age, the nuchal translucency measurement (NT) and two biochemical markers, free beta hCG and PAPP-A, together with the gestational age calculated from the crown rump length (CRL) measurement, to calculate the chance of the pregnancy being affected by T21 or T18/T13. The optimal time to perform the combined test is between 11+2 weeks to 14+1 weeks of gestation, which corresponds to a CRL of 45.0 mm to 84.0 mm.
Maternal age related risk for chromosomal abnormalities
From the age of 35, the chance of a woman developing the Down’s Edward’s Patau’s syndromes start to rise.
Nuchal Translucency [NT] Scan
The Nuchal fluid is a bubble of fluid on the back of the baby’s neck. in babies with certain conditions, there will be more of the fluid than average. The bigger the measurement of the fluid, the more likely the problem.
Nuchal Translucency is increased in over 80% of cases of T21.
Crown rump length (CRL) is the length of the embryo or fetus from the top of its head to bottom of torso. It is the most accurate estimation of gestational age in early pregnancy, because there is little biological variability at that time.
-we can only take the Nuchal fluid measurement when the CRL is between 45- 84mm [equates to 11+2 to 14+1 weeks]
- If the baby is over 84mm, we can’t measure the Nuchal fluid.
Combined screening:
Maternal serum biochemical markers
- free ß-hCG
- PAPP-A (Pregnancy associated plasma protein-A)
(The black line is the frequency of what you might see in a baby with a normal chromosome compared to what you might see in a baby with Trisomy in red).
-In a fetus with down’s, you will see a higher than average level of ß-hCG in conjunction with a lower than normal levels of 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 BHCG in conjunction with lower levels of PAPPA. In T13/18 both markers tend to be significantly lower than average.
-In babies with Trisomy 18, you will be much lower levels in both ß-hCG and PAPP-A.
Maternal /fetal influencing factors for combined screening; Other things we need to take into account
-Maternal age (the older the woman, the more likely for the baby to have down’s syndrome)
-Gestational age (we can only record the Nuchal Translucency whilst the baby is within a certain measurement)
-Ethnicity (the blood markers are naturally different in people with people with different ethnic backgrounds).
-Smoking (if a woman smokes during pregnancy, it can influence the markers in her blood).however, we don’t know whether this is dose related.
-IVF (the process of IVF can influence some blood markers if the egg was frozen i.e 2 yrs prior, if the egg was donated, check the age of the real egg donor i.e their age might be younger and it might decrease their risk)
-Multiple pregnancy
-Weight (bigger you are, bigger blood volume, less concentration of certain chemicals in taller women than shorter women with lower blood volume).
-Diabetes
-Past history of a chromosome abnormality (Although Trisomy is not genetically inherited, when one has had a baby with it, there is a chance of having another one with the condition).
-Fetal sex
-Analytical Imprecision
*for Down’s Edward’s Patau’s syndromes are not inherited. It happens sporadically. you can still get it whether or not someone has had it in your family.
Combined screening result process
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
Terminology: we never use the term high risk or screen positive - or low risk / screen negative
We always refer to results as high chance or low chance
Pregnancy screening time line
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
Second trimester maternal serum screening: quadruple test.
14+2 to 20+0 weeks: available to late bookers only
- Only screens for Trisomy 21 (Down’s syndrome)
- Blood test only [Nuchal Translucency cannot be used after 14+2 weeks]
Uses gestational age, maternal age, smoking, weight, ethnicity and
-Its called the quadruple test because we are looking for 4 markers int he maternal blood and in the case of down’s syndrome what we tend to see is;
Maternal serum markers:
- reduced levels of UE3 unconjugated estriol – placental hormone
- Reduced AFP alpha fetoprotein – protein from fetus
- Increased Inhibin A placental hormone
- BHCG beta human chorionic gonadotrophin- placental hormone
Quad test: Detection rates
The Quad test is more less specific to individual babies in twin pregnancies because its a blood test.
- in Monochorionic its fine because they have the same genetic composition but in Dichorionic twins with different genetic information, this is a problem because we might miss the diagnosis of Down syndrome in one of the twin babies.
- 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
Higher chance of T13/18/21 on combined or quad screening test ? What next?
Explain result – reframe the chance: 1 in 50 = 2%] - this is a high cut off. (the high chance cut off is 1 in 150).
Balanced information about the condition
Three main options:
1- Do nothing - continue the pregnancy without having further tests
2- Diagnostic invasive testing [CVS / Amnio] (risk of miscarriage)
3- NIPT (non-invasive prenatal testing)- Not routinely available on the NHS right now. it’s going to be implemented on the NHS from June 2021 in women with a high chance result.
[Available privately, planned implementation on NHS in June 2021]
Prenatal diagnosis / Diagnostic invasive test
- You can either have a Chorionic Villus Sampling (CVS) from the placenta at 11+ weeks
- or You can do Amniocentesis 15+ weeks to term
*both test involves an ultrasound scan which guides the insertion of a needle through the abdomen into the womb, in the case of CVS, we take a small piece of the placenta, in the case of Amniocentesis , we take a small amount of amniotic fluid. in both cases we have some of the cells in those samples that will have the same genetic makeup of the baby so we can analyse the cells to tell you whether the baby has Down’s or Patau’s syndromes.
-Around 0.5 -1% risk of miscarriage
[higher in twins]
-We can diagnose Downs syndrome [or other chromosome conditions] in an unborn baby using a procedure called amniocentesis or CVS.
However these procedures carry risk of miscarriage– So the pregnant woman or person has to make a very difficult decision – Is it worth risking miscarriage to find out if their baby has a chromosome condition? And remember - most foetuses lost to miscarriage caused by CVS or amnio will have the USUAL number of chromosomes.
Therefore we have a challenge in fetal medicine – to try and predict the chance or likelihood of an unborn baby having a chromosome condition.
And this is where screening tests come in – we use screening tests to assess the likelihood of the unborn baby having a trisomy. Then the parents can use this risk assessment to decide if it is worth risking miscarriage from amnio or CVS in order to get a definitive diagnosis.
Third option for prenatal diagnoses test is NIPT: Non-invasive prenatal testing Screening for aneuploidy
- Its a blood test from mum, we are analysing some of the DNA that’s come from the fetus. specifically, it comes from the placenta and its presence in the maternal blood from 5wks. Originates from placenta – trophoblast. The placenta is constantly regenerating and growing quickly and so releases lots of CFF DNA into maternal circulation.
- Its called Cell free fetal DNA [cff DNA] in maternal blood from 5 weeks
- Its Pregnancy specific
- within 30 minutes of delivering the pregnancy either after birth or if a woman miscarries, there won’t be any detection of Cell free fetal DNA .
- We Test for the Cell free fetal DNA in maternal blood from 10 weeks
- Aneuploidy: Screening for T21 sensitivity and specificity over 99%. Aneuploidy is the presence of an abnormal number of chromosomes in a cell,
Marketed as Harmony, SAFE, Panorama, NIFTY test.
-not offered to all women due to cost.
extra note;
Present from 5 weeks onwards but level not high enough to test until 10 weeks.
10% of cell free DNA in maternal blood is from the baby and so the remaining 90% is from the mother. Therefore when testing maternal blood for CFFDNA you are testing both the maternal and fetal DNA.
Fetal DNA is shorter than maternal DNA
CFF DNA is cleared from the maternal blood within 30 minutes of delivery. Therefore CFF DNA is pregnancy specific.
If a Y chromosome is detected it must be from the baby!
CFF DNA is from the placenta so still have risk of placentally confined mosaicism. May also detect a maternal mosaicism or maternal chromosome rearrangement or maternal malignancy.
CFF DNA is from the placenta so still have risk of placentally confined mosaicism. May also detect a maternal mosaicism or maternal chromosome rearrangement or maternal malignancy.
Current use in NHS:
Fetal Rh D typing [11 weeks]
Fetal sexing [from 7 weeks] – 99.5% accurate – for sex linked disorders only
Some monogenic disorders
Combined screen vs NIPT
Results either:
> 99% chance baby has Downs
[should be confirmed by invasive test if considering terminatin]
< 1 in 10,000 chance baby has Downs
18+0 to 20+6 week fetal anomaly ultrasound scan
Specifies screening for 11 conditions where:
- the baby may benefit from treatment before or after birth (in utero surgery might be needed).
- 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
