Prenatal Diagnosis Flashcards
1
Q
prenatal diagnosis
A
- medical evaluation of a fetus that provides both physical and genetic information
- genetic testing has the capability to diagnose fetal disease
- prior to testing, parents should be counseled about the reasons to do the test and possible outcomes
- depending on type of test, there could be risk to mom and pregnancy
2
Q
indications for prenatal diagnosis-inherited
A
- familial chromosome anomaly
- family hx of genetic disorder for which testing is available
- familial X linked recessive disorder without testing available
- increased risk of open neural tube defect (recurrence risk of 2-5%)
- carrier of genetic disorder, ethnic risk
- consanguinity
3
Q
other indications for prenatal diagnosis
A
- US anomaly
- repeated miscarriages
- abnormal MSAFP
- anxiety
- environmental exposures
- increased risk of chromosomal abnormality
4
Q
relative freq of types of aberration in chromosomally abnormal abortuses- mothers of all ages
A
- trisomies, 16 most common aborted
- 45X
- triploid
- tetraploid
- unbalanced translocation
5
Q
spontaneous termination freq
A
- 95% of 45X conceptions
- 90% of trisomy 13 conceptions
- 80% of trisomy 18 conceptions
- 65% of trisomy 21 conceptions
6
Q
types of tests available
A
non-invasive: -examination -US invasive: -cytogenetics -biochemical -molecular studies
7
Q
invasive vs non invasive
A
- in general, non invasive is better, less risk ot fetus
- want the most specific info at least risk
- type of testing performed depends on clinical indication- and what info needs to be collected
8
Q
US
A
- verify viability
- detect multiple pregnancy
- determine gestational age
- determine the sex
- identify possible abnormalities
- may indicate that additional studies are needed
- nuchal translucency- may be associated with chromosome abnormality- 6.0 mm for Down Syndrome
- unilateral or bilateral cleft lip/ palate or both
- neural tube defects (meningomyelocele)
9
Q
maternal serum alphafetoprotein
A
- 15-20 weeks
- high, low, normal
- gestational age
- mother’s weight, race, diabetic status
- albumin like protein produced in fetal liver
- if bigger mother, more volume, less AFP might be normal
- screening test for risk assessment
- low levels-down syndrome and other chromosome anomalies
- high levels- ONTD
- hard to interpret though
10
Q
maternal serum quad test
A
- AFP low
- hCG high
- unconjugated estriol (uE3) low
- dimeric inhibin A high
- 80% combined detection for DS
- 60% for 40 years
11
Q
integrated prenatal testing
A
- 10-13 weeks gestaion
- PAPP-A (preg associated plasma protein A, when low, inc risk of DS)
- nuchal translucency
- 15-21 weeks gestatoin the Quad MSAFP testing
12
Q
non-invasive prenatal screening/testing
NIPS/NIPT
A
- newest non invasive assay
- 4 commercial companies
13
Q
cffDNA
A
- cell free fetal/placental DNA
- isolated from maternal blood at 10-22 weeks
- 10-15% of cfDNA in maternal blood is fetal origin
14
Q
technology
A
- sequencing to identify DNA fragments
- determine chromosomal source of each fragment
- statistically analyze the number of fragments per chromosome compared to expected number for mother and fetus
- then use software to evaluate data
- expected amounts of DNA per chromosome are analyzed, increase or decrease suggests aneuploidy
- screening test for risk, has to be confirmed
15
Q
NIPS accuracy
A
- DS and trisomy 18 99%, false pos of 0.2%
- trisomy 13- 72-92%, false pos 1%
- XX 98.4%
- XY 99%
- abnormals should be confirmed
- 0.5-7% failure rate- due to not enough DNA
- but is better than serum screening
16
Q
invasive testing
A
- amnio
- chorionic villus sampling
17
Q
amniocentesis
A
- 14-20 weeks, usually 16-18, can be as late as 35
- risk at 1/200
- tests possible: AFAFP, cytogenetics, metabolic assays, molecular diagnostics
- needle into amniotic cavity and fluid take
- transabd with US guidance
- removing too much fluid can lead to contractures or IUGR
18
Q
amniotic fluid AFP
A
- rises and declines
- need to know gestational age
- should confirm maternal numbers
- screening
19
Q
low AFP levels
A
- trisomy 13, 18, 21
- mosaic turner syndrome
- triploidy
- unbalanced translocations
- need karyotype to confirm
20
Q
elevated AFP
A
- open neural tube defects
- multiple preg- MSAFP, not AFAFP
- monozygotic twins, both up
- small mother can have high MSAFP
- AChE is test- only present in fluid if there is a defect in neural tube
21
Q
chorionic villus sampling
A
- 10-14 weeks
- limb reduction when done sooner than 10 weeks
- risk 1/100
- cytogenetics, molecular diagnostics, metabolic
- transabd or transvaginally
- 7% risk of vaginal bleeding, infections, hematome
- 5-30 mg tissue, no AFP can be done
- placenta instead of fetus, but should be same, if mosaic, need it in both
- both from zygote
- if problem, amnio done to confirm, since it might just be placenta
- could also have normal placenta ad sick fetus
22
Q
why choose CVS?
A
- earlier knowledge, can abort earlier if needed
- if you have known mutation, DMD carrier, translocation, older mother
23
Q
case 1
A
-estrela is 22 year old 16 weeks pregnant first child
-brother in law’s 2nd son has DS
considerations:
-patient age, weeks gestation, family history, risk of DS?
-counsel patient and discuss possibility of testing
-US to look for anomalies
-MSAFP for risk
-check to see if affected individual has chromosome abnormality
-check to see if Dad has a chromosome abnormality
-amnio and karyotype if necessary
24
Q
case 2
A
- margaret is 30 and 24 weeks pregnant
- late care seeker
- brother with fragile X
- what should be done?
- test margaret for fragile
- if negative, no need to test the fetus
- if positive- counsel about additional testing- check sex of fetus, probably only need to do further testing if male
25
genetic counseling
- subspecialty of medical genetics
- work with physicians
- provide patients with all the relevant information that has been collected
- need family history
- patient makes own decisions (non-directive)
- must have all facts and options
- easiest to make informed choices based on family history, disorder in question, inheritance patterns, recurrence risk
- options and outcomes
26
outcomes of prenatal diagnosis
- no anomalies in 98% of cases
- termination
- fetal treatment in urtero
- IVF
27
ART
- assisted repro technologies
- couples who have experienced a high number of unexplained fetal losses
- IVF-fert in petri dish- implanted
- intracytoplasmic sperm insertion- sperm injected into egg and egg implanted
- zygotes intrafallopian transfer-eggs to fallopian tube instead of uterus
- donor egg-single male or female can contract to have a biologically related child
28
polar body analysis
- if both parents are CF carriers
| - if polar body has CF gene, egg will be fine
29
preimplantation genetic diagnosis
- screening for embryos
- general assay to look for chromosomal aneuploidies
- ethical concerns for some, but others think its much better than finding out when already pregnant
- eggs are collected from mom and fertilized in vitro
- at 8 cell stage, single cell is separated and tested by FISH or molecular assay
- karyotype not an option because one cell is not likely to be in metaphase
- next gen seq replacing this
- whole genome
- next gen powers NIPS
- if aneuploidy is detected, embryo flagged and not implanted
- 3,000-5,000 dollars per screening
30
donor egg
- eggs from mother and unhealthy related donor
- nuclei removed, mothers nucleus put into donor egg
- IVF or ICSI follows to fertilize egg
- zygote without patients mito, no risk for mito disease to be passed
- tuner syndrome can carry but doesn't produce eggs- use whole donor egg
