NIPT Screening Flashcards
1
Q
where is down syndrome most prevalent?
A
It is more prevalent in babies of women greater than 40 years or very young women.
2
Q
what are the three types of down’s syndrome called?
A
- trisomy 21 - translocation - mosaic
3
Q
what is trisomy 21?
A
- Most common type of down syndrome
- People with trisomy 21 have a whole extra 21 chromosome in every well of their body, so they have 47 chromosomes instead of 46.
- Mild - moderate learning disabilities and may have more associate health conditions.
- This is a random event which is not influenced by any parental action.
4
Q
what is down’s syndrome translocation?
A
- This Down’s syndrome is due to an extra part which is translocated or joined to another chromosome in the cell.
- 1/3 babies, this extra chromosome by inherited from one of the parents. Parental age is not a factor.
- They do not differ from those with trisomy 21.
- They have 46 chromosomes however one chromosome is large becasye it carried the extra 21.
5
Q
what is mosaic down’s syndrome?
A
- This type of Down’s syndrome occurs when an extra chromosome 21 appears in only some of the cells.
- Depending on the proportion of cells affected, the degree to which the person is affected may sometimes but not always, be lessened.
6
Q
what are the associated health conditions with down’s syndrome?
A
- Cardiac (congenital heart disease)
- Low muscle tone
- Digestion/gut
- Hearing and vision
- Thyroid (hypothyroidism)
- Recurrent cough and infections
- Weight issues
- More likely to have autism spectrum disorder (ASD)
- More likely to have Attention deficit hyperactivity disorder (ADHD)
More likely to have Dementia from an early age
7
Q
what are the physical characteristics of down’s syndrome?
A
- Up-slanting palpebral fissures
- Epicanthic folds
- Brachycephaly
- Flat occiput
- Protruding tongue
- Hypotonia
- Board hands
- Palm of hand with only one crease
8
Q
what is up slanting palpebral fissures?
A
Up-slanting palpebral fissures - open of the eyelids slanting down
9
Q
what is the epicanthic folds?
A
skin fold of the upper eye covering the corner of the eye
10
Q
what is brachycephaly?
A
the back of the head becomes flattened, causing the head to widen, and occasionally the forehead bulges out.
11
Q
what is protruding tongue?
A
large in portion to other structures of the mouth
12
Q
what is hypotonia?
A
decreased muscle tone
13
Q
what does it mean for living with down’s syndrome?
A
- Immediate response to the idea of having a baby with down’s - health conditions can be treated and managed as they would for any child.
- Preferred language - think carefully and avoid using negative assumptions as in I’m sorry etc
- Living with down’s syndrome - they have a lot of potential. They can live healthy and fulfilling lives as part of their families community.
14
Q
what is edward’s syndrome?
A
- A life limiting condition, 7 in 10 pregnancies diagnosed with this syndrome will end at 12 weeks in miscarriage. Although chance in miscarriage or still birth with decrease with gestation.
15
Q
what are the three types of edward’s syndrome?
A
- Three types of Edward’s syndrome - trisomy 18 - translocation - mosaic
16
Q
what is trisomy 18?
A
- Most common
- Other forms of Edward’s will have less effect upon baby but can by identified by screening
- It is 3 copies of chromosome 18. this extra chromosome in cells severely disrupts normal development.
- This usually happens during the formation of either the egg or sperm.
- Babies born with T18, around 5 in 10 will live longer than on week. And around 1 in 10 live longer than 5 years.
17
Q
what is translocation? edwards syndrome
A
- Sometimes the extra number 18 chromosome, or part of it, is attached to another chromosome in the egg or sperm.
- There may be a rearrangement of part or all of one chromosome, called translocation.
The child be less affected in these cases. - Babies who do not have full form of the condition (translocation or mosaic forms) may have longer life expectancy and need less medical attention.
- There may be a rearrangement of part or all of one chromosome, called translocation.
18
Q
is trisomy 18 inherited translocation?
A
- This is the only form of T18 that may be inherited by a parent. As some parents may have balanced translocation, meaning the 18 chromosome is attached to another chromosome but this isn’t affecting their health.
19
Q
what is mosaic? edwards syndrome
A
- Can be less severe form of Edward’s syndrome, as only some of the cells have the extra copy of chromosome 18.
- How affected depends on the number and type of cells that have the extra chromosome.
- Some babies may only be mildly affected other may be severely.
Babies who do not have full form of the condition (translocation or mosaic forms) may have longer life expectancy and need less medical attention.
20
Q
what are the characteristics of edwards syndrome?
A
- They are extremely likely to have a wide range of health issues involving nearly every organ system.
- 9 in 10 babies will have heart issues.
- Most babies will have difficulties with breathing (apnoea) and feeding issues.
- Around half will have hearing loss and issues with their muscles and joints
- More likely to get infections and require on going medical care.
- Life-limiting, around 13% chance of living past first birthday. If they survive to one, there is a 80% chance of living to 5 and beyond.
- Rare chance of living to adulthood.
Their development will be slower and require ongoing assistance.
21
Q
what are the physical characteristics of edwards syndrome?
A
- Low set and malformed ears
- Small mouth and jaw
- Prominent occiput
- Ptosis - drooping of the upper eyelid
- Wide epicanthic folds
- Clenched hand and overlapping fingers
22
Q
what is ptosis?
A
drooping of the upper eyelid
23
Q
what is patau’s syndrome?
A
- Life limiting conditions and miscarriage or still births are common in these pregnancies.
24
Q
what are the three types of patau’s syndrome?
A
- trisomy 13, translocation, mosaic
25
what is trisomy 13?
- Most cases result from having 3 copies of chromosome 14 in each sell instead of the usual 2.
- The extra genetic material disrupts of course of development, causing the characteristics of trisomy 13.
- 4 in 10 will live longer than 6 months
- 1 in 10 will live longer than 5 years
26
what is translocation? patau's syndrome?
- T13 can also occur when part of chromosome 13 becomes attached (translocated) to another chromosome during the formation of reproductive cells or very early in fetal development.
- Translocated T13 have 2 normal copies of chromosome 13, plus an extra copy of chromosome 13 attached to another chromosome.
- In rare cases only part of chromosome 13 is present in 3 copies.
- The physical signs and symptoms in these cases may be different than those found in full T13.
27
is translocation for patau's syndrome inherited?
- This is the only form of T13 which may be inherited from parents. As some parents may have balanced translocation, meaning the 13 chromosome is attached to another chromosome but this isn't affecting their health.
28
what is mosaic? patau's syndrome
- Small percentage of people with T13 have an extra copy of chromosome 13 in some cells.
- This condition is called mosaic T13.
- The severity depends on the type and number of cells with the extra chromosomes.
- The physical features are often milder than those with full T13.
- Babies who do not have full form of the condition (partial or mosaic forms) may have longer life expectancy.
29
what are the characteristics of patau's syndrome?
- 11% chance of living past first birthday.
- If they live longer than a year, 9% chance of living to 5 and beyond.
- This includes those who have mosaicism or partial trisomy.
- May be born with wide range of health conditions, some of which may be serious.
- Will need care and support throughout life.
- Will have delayed development, forebrain defects, intellectual disabilities and structural anomalies.
- 8 in 10 babies will have heart issues
- 6 in 10 will have brain abnormalities
- 5 in 10 will have serious problems with their eyes
- They also may need medical assistance breathing and eating
30
what are the cardiac and central nervous system defects involved with patau's syndrome?
- Holoprosencephaly
- Ventriculomegaly
- microcephaly
- Posterior fossa and malformations
- Postaxial polydactyly
- Echogenic kidneys
31
what is holoprosencephaly?
a condition that occurs in the first two or three weeks of pregnancy and results in abnormal development of the brain
32
what is ventriculomegaly?
a condition in which the ventricles appear larger than normal on a prenatal ultrasound.
33
what is microcephaly?
small head
34
what is posterior fossa and malformations?
special group of central nervous system anomalies that present during infancy with hypotonia, developmental delay, microcephaly, or hydrocephalus.
35
what is postaxial polydactyly?
an extra digit or a part of digit on the ulnar or fibular side of hand or foot.
36
what is echogenic kidneys?
kidneys that appear bright on ultrasound imaging, a finding that indicates a possible kidney condition
37
what are the physical characteristics of patau's syndrome?
- Small triangular head and jaw
- Bilateral cleft lip and palate
- Sloping forehead
- Malformed ears
- Microphthalmia - a birth defect in which one or both eyes did not develop fully, so they are small.
- Abnormal extremities - defects in the legs and/or arms
38
what is the first line in screening (combined screening test?
First line screening is the first step in the overall screening for
- Down's syndrome
- Edward's syndrome
- Patau's syndrome
39
what is the purpose of the 1st trimester combined test and when is it offered?
Identified women with a singleton and twin pregnancies who have higher chance of having a baby or babies with these syndromes.
Offered between 11+2 - 14+1 gestation
40
what can women choose in relation to 1st trimester screening?
- No screening
- Down's syndrome screening only
- Edward's and Patau's screening only
- All three screening
41
who is eligible for 1st trimester screening?
The women is offered an ultrasound where the crown, rump and length (CRL) is measured and this is then used to calculated gestation.
Women with a CRL between 45.0mm - 84.0 mm equated to 11+2 to 14+1 are eligible from the test.
We also give special consideration to women with single demised twin or vanished twin/ these women are still eligible for the screening if the gestational sac is empty, as this does not affect the maternal biochemistry.
42
what is the first trimester screening test?
- Consists of a scan to obtained nuchal translucency (NT) (measurement of bit of baby's neck) of the fetus and blood test
- Blood test measure 2 biochemical markers free B-human chorionic gonadotrophin (free b-hCg) and pregnancy associated plasma protein A (PAPP-A).
- The NT and bloods will be used to calculate chance of the three syndromes.
- Obtaining the NT measurement depends on position of baby. If it is not possible then the second trimester screening is offered between 14-18 weeks.
- In twin pregnancies there will be a NT measurement for each fetus
The blood samples should be sent the same day as the NT measurement is taken.
43
how are the first trimester screening results calculated?
- The results of the NT and blood test will be converted to multiples of the median (MoM) and correct for co-variables to calculate chance.
- Co-variables include - woman's age (or age of donor egg), BMI, smoking status, ethnicity.
- Detection rate of approximately 86% in singleton pregnancies.
44
what does it mean if the first trimester screening results come back with a higher chance?
- Results are considered high chance if one of the conditions in 1 in 150 or greater
- If there is a high chance results, this does not mean the baby definitely has one the conditions.
- They should be invited to discuss the results within the next three working days.
45
what does it mean if the first trimester results come back low chance?
- If they receive a low chance, we can consider this to be very accurate.
- This does not rule out the baby having one of these conditions, it is unlikely.
- Overall 10#5 of babies with Down's syndrome will not be detected by screening
46
what is the 2nd trimester quadruple test?
- Women under 20 weeks (18 in tayside?) who have not been able to have 1st trimester screening should be offered 2nd trimester. This tests for Down's syndrome only.
- This test is offered for both singleton and twins between 14+2 and 20+0.
- Detection rate is approximately 75% in singleton pregnancies.
- The results are calculated the same way as 1st trimester.
47
what is the second trimester screening test?
Consists of a blood sample measuring four serum markers
- Alpha-fetoprotein (AFP)
- Total human chorionic gonadotrophin (HCG)
- Unconjugated eostriol (UE3)
- Inhibin-A (inhibin)
48
what is monozygotic (screening)?
- When one fertilised egg splits into two separate embryos.
- They almost have perfectly matched DNA.
- 30% twins are monozygotic
49
what are the dizygotic (screening)?
- This happens when two zygotes (eggs) have been released and then fertilised by two sperm
- Approx 70% are dizygotic
50
what are the chances dizygotic twin in having down's syndrome?
The chance of a dizygotic twin having Down's is higher than that from a singleton pregnancy.
51
what are the chances of monozygotic twins having downs syndrome?
The chance of a monozygotic twin having Down's is lower than that from a singleton pregnancy due to a higher fetal loss rate among affected pregnancies.
52
what is important when providing informed consent when talking about screening?
- Be mindful of disability equality
- Respect values and beliefs
- Non judgement and support
- Provide team and information to make decisions
- Consider holistic health
53
what is NIPT?
Non-invasive prenatal testing NIPT
This test is performed if women want it after receiving a high chance result.
54
what happens during pregnancy in relation to fetal DNA?
During pregnancy the placenta sheds fetal DNA into maternal blood stream.
55
what deos NIPT detect?
- The NIPT detects DNA fragments from the placenta in a sample of blood we take from pregnant women.
- Most of the DNA fragments are from the pregnant women but some are from the placenta. These fragments are called free fetal DNA (cffDNA or cfDNA)
56
what is cffDNA or cfDNA?
These fragments are called free fetal DNA (cffDNA or cfDNA)
57
when is cffDNa detectable?
cffDNA is detectable from around 7 weeks of pregnancy and the amount rises as pregnancy continues
58
when is the earliest NIPT can be done?
NIPT can be performed as early as 10 weeks.
59
what is the role of the NIPT?
- By measuring the placental cffDNA in the maternal bloodstream NIPT can produce there is a high chance of the three syndromes.
- cffDNA is suitable for pregnancy specific testing as it remains in the maternal circulation for only a few hours after completion of the pregnancy.
- Note that the NIPT is different to 1st trimester which analyses the mother's own hormones.
- NIPT analyses DNA form the placenta in the mothers blood.
60
why NIPT is used?
- NIPT identifies women with a higher chance
- Can provide more accurate prediction from the combined test and the quadruple test alone, reducing the need for invasive procedure and it is non-invasive.
NIPT is not diagnostic and not 100% accurate.
61
what will the NIPT identify?
- 97% of Down's syndrome
- 93% of Edward's syndrome
95% of Patau's syndrome
62
What does it mean if a woman with a higher chance in the first line screening result and then has a higher chance NIPT result?
- 91/100 with a high result NIPT will have a baby with Down's
- 84/100 with a high result NIPT will have a baby with Edward's
87/100 with a high result NIPT will have a baby with Patau's
63
what can results of twins NIPT result mean?
Results from identical twins can be as accurate as a singleton. However, may be less accurate in non-identical as there is two placentas releasing their own DNA.
64
NIPT tests the cffDNA from the placenta. The fetal DNA might be different from the placenta this can be due to?
- Confined placental mosaicism
- Maternal malignancy
- Maternal chromosomal anomalies
- Vanished or demised twin
65
what is confined placental mosaicism?
in which a chromosomal anomaly (usually trisomy)is restricted to the placenta. It occurs in about 2% of viable pregnancies.
66
what is maternal amlignancy?
DNA sequencing may detect abnormal cells lines secreted by a tumour in women who currently have or have recently had cancer.
67
what is maternal chromosomal anmalies?
during pregnancy, the mother's bloodstream contains a mix of cfDNA that comes from her cells and cells from the placenta. If she has a maternal chromosome anomaly this may confuse the results.
68
hat is vanished or demised twin?
refers to the spontaneous loss of embryo or fetus during the first trimester of a twin or multiple pregnancy.
69
What does it mean if a woman with a higher chance first line screening result then has a low chance of NIPT result?
- 1 in 1054 with a low NIPT result will have a baby with down's
- 1 in 930 with low NIPT will have a baby with Edwards
- 1 in 4265 with low NIPT result will have a baby Patau's
70
Who is eligible for NIPT?
Almost all pregnancy women who receive a higher chance result from the 1st trimester or 2nd trimester screening,
71
in terms of eligibility for NIPT, what are the special considerations?
These include women who have received
- Stem cell therapy - as long as it is her own stem cells and not donors
- IVF
- Egg donor
Consult the designated genetic laboratory undertaking NIPT testing if there are women in these situations.
72
who is not eligible for NIPT?
- Women who have received a transplant - all forms of transplant including bone marrow
- Women who currently or have recently had cancer - DNA sequencing may detect abnormal maternal cells lines secreted by a tumour.
- Women who have a chromosomal or genetic anomaly - dependant on type of chromosomal or genetic anomaly. Contact lab for advice.
- Women with Down's syndrome - will affect the results
- Women who have had a blood transfusion within the last four months - women who have received whole blood, FFP or plasma only, not including platelet transfusions.
73
NIPT tests for what?
- The couple should be advised that the lab will only be able to test and report all 3 conditions regardless or previous screening options.
74
what happens if the NIPT is high chance?
- High chance for NIPT is not diagnostic and further testing will be required to diagnose.
- She can choose no further testing.
- Or have a CVS/Amniocentesis to confirm the result. Invasive testing which is diagnostic.
- Offer anomaly scan
Offer further support
75
what happens if the NIPT is low chance?
- It is unlikely the baby has one of the conditions
- It does not mean there is not chance just that the chance is lower.
- Offer anomaly scan.
76
what happens if the NIPT is no result?
Means the lab has not been able to get a result.
This way be due to:
- Low fetal fraction (insufficient cffDNA in blood)
- High BMI (dilution effect)
- Early gestation (fetal fraction is lower)
- Low PAPP A/low hCg B (if baby and placental is small)
- Babies that have Edwards or Patau's (small babies and placenta)
- Technical issues in the lab
- Issues with sample admin
77
what is a false positive and why should this be?
- Incorrectly identified as having a high chance of the syndromes.
This may be a result of
- Shedding cffDNA after the demise of an affected fetus. Where the remaining fetus remains unaffected
- Chromosomal or anomaly in the pregnant woman
- Confined placental mosaicism
78
what are the false positive rates?
- Trisomy 21 - 0.08%
- Trisomy 18 - 0.20%
- Trisomy 13 - 012%
79
what is a false positive NIPT?
- Incorrectly been identified as not having a high chance of the three conditions.
- This can occur when an insufficient amount of fetal cffDNA is present in the sample, resulting in masking on fetal phenotype by maternal cfDNA.
80
what is the support available after NIPT results?
High chance make referral to:
- Fetal medicine
- Neonatologist / paediatricians
- Geneticist/g genetic counsellor
- Named midwife
- Support networks
- Obstetricians
Sign post to
- Down's syndrome scotland
- SOFT organisation for T13 and 18
ARC Antenatal results and choices
81
what does diagnostic testing involve?
CVS and Amniocentesis
Chorionic Villus sampling (CVS) and amniocentesis are invasive procedures used to obtain fetal cells or placental tissues from chromosome and genetic testing. Both chorionic villi analysis and amniotic fluid cell analysis offer the same information concerning chromosome status, enzyme levels and gene mutations.
82
what is CVS?
Performed by introducing a spinal needling percutaneously into the long axis of the placenta under ultrasound guidance. After removal of the stylet, villi are aspired into 10ml syringe then placed in tissue culture media. This requires keeping negative pressure and performing a gentle, longitudinal, back and forth movement of the needle.
83
what is amniocentesis?
A spinal needle with a stylet is introduced percutaneously into the amniotic cavity under continuous ultrasound guidance. Taking care to avoid the fetal and umbilical cord. Approx 15-20mls of amniotic fluid is aspirated.
84
what is CVS performed?
- In the first trimester of pregnancy
Usually done between 11-14 weeks but can be done up to 15 weeks.
85
when is amniocentesis performed?
- 2nd trimester of pregnancy
- Done after 15 weeks
86
what is the risks of performing diagnostic testing?
Risks of performing them
- 1 in 200 women will miscarry as the result.
- 1 in 50 for twin pregnancy
- There is evidence that a double amniocentesis has a lower risk of sampling the same fetus twice compared to double CVS. It is essential that any invasive diagnostic test on twins is performed in a unit with experience.
Maternal complications
- Transient vaginal spotting or minimal amniotic fluid leakage occur in 1& or less
- Hemorrhage
- Most serious cases sepsis
87
what can be the results of the CVS or amniocentesis?
Baby HAS NOT got any of the three syndromes
Baby HAS got any of the three syndromes
88
when do you need to offer the pregnant woman an anomaly scan when she has chosen to have no further testing following ALL of these options?
- Higher chance combined or quadruple screening result
- High chance NIPT result
- No result for NIPT
- Has not got the syndrome ( result from CVS/Amniocentesis)
- Has got the syndrome (result from CVS/Amniocentesis) where the pregnancy is continuing.
89
what are the woman's choices following diagnostic testing?
- Continue with pregnancy
- Terminate pregnancy
Provide mother with support so they can make an informed choice.
