Prenatal screening/diagnosis Flashcards
Birth defect risk
3-5% risk of birth defects or developmental delay apparent by 1 year of age
Prenatal screening test parameters
suggested: >75% detection rate with no more than 5% false positive for Down syndrome
Screening options
FTS
Quad
SIPS
IPS
IPS
SIPS + nuchal translucency
Canadian recommendations for prenatal screening tests
all pregnant women should be offered option of a prenatal screening test for most common clinically significant fetal aneuploidies (e.g. 18, 21 trisomies) in addition to a second trimester US fo dating, assessment of fetal anatomy and detection of multiples
Maternal serum based screening
measurement of different hormones/proteins that are increased/decrease with trisomy 21, 18, or open NTD
Nuchal translucency ultrasound
sonographic appearance of a fluid collection under skin behind fetal neck in 1st trimester
NT thickness increased with chromosomal abnormalities, cardiac defects and many genetic syndromes
Done between 11-13 w 6 d gestation at certified US sites
Detailed US examination timing
18-20 wks
Non-invasive prenatal testin
new option, not covered by MSp atm
uses cell-free fetal DNA to determine if a pregnancy is at high/low risk for trisomies 21, 18, 13 and sex chromosome aneuploidy
Very high DR, very low false positive rate
failure rate 2-4% in samples
High risk result –> followup with amniocentesis
Usually offered after 9-10 w
Prenatal diagnostic tests
Detailed “level II” US examination
Amniocentesis
CVS
Fetal blood sampling - not performed often due to high risk
Indications for invasive prenatal diagnosis
1) fetus at increased risk for a chromosomal abnormality
- maternal age >40, or >35 in twin pregnancy
- prenatal genetic screening result above cutoff, positive NIPT result
- >35 with NT >3.0 mm, or 4
- Fam Hx of previous stillbirth/livebirth with chromosomal abnormality, mother/partner known to carry a chromosomal abnormality, fetus at risk for a genetic disorder with identifiable chromosomal abnormality, mother carrier of X-linked recessive disorder, abnormal fetal ultrasound with soft markers/identified anomaly associated with a chormosomal abnormality
2) fetus increased risk for a genetic disease identifiable by molecular/biochem testing
- previously affeted child
- mother/partner with dominant condition
- mother known carrier of X-linked condition
- mother and partner both known carriers of recessive condition
Fetal echocardiography
aid visualization of cardiac structures/outflow tracts in US
performed when cardiac anomaly is suspected on detailed US or if increased a priori risk for a congenital heart defect
Doppler to visualize vascular flow - placental function, fetal cardiac abnormalities
Ultrasound timing
Screening: 17-22 w gestation for fetal physiological variations (soft markers) used in conjunction with other screening tests - SIPS/IPS/QUAD to determine if diagnostic testing should be offered to patient
Amniocentesis technique
aspiration of fluid from amniotic cavity with fine gauge needle
done with ultrasound guidance
Amniocentesis tests
cytogenetic/biochemica/DNA testing
test for AFP - open NTD, abdominal wall defects
acetylcholinesterase levels if indicated (open NTD)
Amniocentesis timing
> 15 w
chromosomes require 2-3 w
RAD 2-3 days (13, 18, 21 and sex chromosomes)
Maternal complications of amniocentesis
spotting
amniotic fluid leakage
usually self-limited
Risks of amniocentesis
safer than CVS, can be done up to day of delivery
increased risk of spontaneous loss by 0.5-1% + background
early AC associated with risk for club foot (only do >15 wk)
CVS technique
aspiration of small piece of chorion from developing placenta
sample taken from tissue where placenta is growing into uterine wall
done through vagina (trans-cervical) or through abdominal wall (transabdominal) - both with US guidance
Cells may be analyzed directly/cultured for chromosomal, biochemical or DNA analysis
chromosomes require 2-3 wk
CVS timing
10-13 wks
CVS testing
cannot be used to evaluate neural tube defects
CVS complications
40%: mild, self-limited vaginal bleeding
+1% spontaneous loss
possible increased risk of limb abnormalities in 1/1000-2000 cases (greater if done
Fetal blood sampling
rarely performed
limited to clinical situations where lower risk diagnostic procedures does not provide adequate or sufficiently timely diagnostic information
obtaining blood from vein in umbilical cord near placental insertion
done >17 wks
Fetal loss rate ~2%
Rapid aneuploidy diagnosis
for trisomy 13, 18, 21, sex chromosome
2-3 days
DR for those conditions approach 100%, considered diagnostic
will not detect low level mosaicism or other chromosomal abnormalities
If RAD is normal in cases at increase risk for trisomy 21, 13, 18 or sex chromosome aneuploidy, risk for other chromosome anomalies is not increased above background
