Prenatal screening/diagnosis

Question 1

Birth defect risk

Answer 1

3-5% risk of birth defects or developmental delay apparent by 1 year of age

Question 2

Prenatal screening test parameters

Answer 2

suggested: >75% detection rate with no more than 5% false positive for Down syndrome

Question 3

Screening options

Answer 3

FTS
Quad
SIPS
IPS

Question 4

IPS

Answer 4

SIPS + nuchal translucency

Question 5

Canadian recommendations for prenatal screening tests

Answer 5

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

Question 6

Maternal serum based screening

Answer 6

measurement of different hormones/proteins that are increased/decrease with trisomy 21, 18, or open NTD

Question 7

Nuchal translucency ultrasound

Answer 7

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

Question 8

Detailed US examination timing

Answer 8

18-20 wks

Question 9

Non-invasive prenatal testin

Answer 9

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

Question 10

Prenatal diagnostic tests

Answer 10

Detailed “level II” US examination
Amniocentesis
CVS
Fetal blood sampling - not performed often due to high risk

Question 11

Indications for invasive prenatal diagnosis

Answer 11

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

Question 12

Fetal echocardiography

Answer 12

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

Question 13

Ultrasound timing

Answer 13

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

Question 14

Amniocentesis technique

Answer 14

aspiration of fluid from amniotic cavity with fine gauge needle
done with ultrasound guidance

Question 15

Amniocentesis tests

Answer 15

cytogenetic/biochemica/DNA testing
test for AFP - open NTD, abdominal wall defects
acetylcholinesterase levels if indicated (open NTD)

Question 16

Amniocentesis timing

Answer 16

> 15 w
chromosomes require 2-3 w
RAD 2-3 days (13, 18, 21 and sex chromosomes)

Question 17

Maternal complications of amniocentesis

Answer 17

spotting
amniotic fluid leakage
usually self-limited

Question 18

Risks of amniocentesis

Answer 18

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)

Question 19

CVS technique

Answer 19

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

Question 20

CVS timing

Answer 20

10-13 wks

Question 21

CVS testing

Answer 21

cannot be used to evaluate neural tube defects

Question 22

CVS complications

Answer 22

40%: mild, self-limited vaginal bleeding
+1% spontaneous loss
possible increased risk of limb abnormalities in 1/1000-2000 cases (greater if done

Question 23

Fetal blood sampling

Answer 23

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%

Question 24

Rapid aneuploidy diagnosis

Answer 24

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