Prenatal Diagnosis

Question 1

goals of prenatal diagnosis

Answer 1

• provide info to parents about testing options
• detect anaomalies/disorders
• counsel/support
• fetal therapy if available

Question 2

noninvasive screens

Answer 2

• maternal serum
• sequencing of cell-free DNA in maternal plasma
• prenatal ultrasound
• fetal MRI

Question 3

Invasive Diagnostics

Answer 3

• chorionic villus smapling CVS
• amniocentesis
• cordocentesis
• fetal biopsy
• pre-implantation genetic diagnosis PGD

Question 4

first trimester tests/screens

Answer 4

• ultrasound
• NIPT
• NT, serum screen
• CVS

Question 5

second trimester test

Answer 5

• 2nd serum
• amniocentesis
• fetal anomaly scan

Question 6

tests arent done after second trimester…

Answer 6

because a decision of whether the baby is to be kept or not needs to happen within a certain time frame (legally)

Question 7

first screening question

Answer 7

how old are you?

Question 8

indications for invasive prenatal diagnosis

Answer 8

• maternal age 35 or older at time of delivery
• major anomoly on ultrasound
• abnormal maternal serum
• positive cell free DNA
• fmaily history of single gene disorder/chromosomal
• maternal anxiety

Question 9

screening for fetal down syndrome

Answer 9

• measure placental proteins
• nunchal translucency screening
• offer invasive test

Question 10

nuchal translucency

Answer 10

• normal fluid filled space between back of fetal neck and overlying skin
• increased in fetuses with: down syndrome, turner syndrome, trisomy 18, trisomy 13, triploidy

Question 11

maternal serum screening

-what must be known

Answer 11

• measurement of proteins produced by the fetus or placenta
• calculated relative to population standards
• mom and gest age must be known as well as race, diabetes, and smoking

Question 12

benefits of CVS

• cells are what so you can do what
• preferable to…
• does not detect…

Answer 12

• done at 11 weeks, restoring privacy to reproductive decision
• mitotically active cells = rapid karyotype
• tissue obtained is preferable for DNA analysis
• mosaic trisomy detected identifying fetuses risk for uniparental disomy
• does not detect mosaicism in the fetus itself

Question 13

risk of cVS

Answer 13

• elevated risk of fetal loss
• slightly elevated risk of maternal infection
• limb malformation syndrome
• confined placental mosaicism in 1% of cases
• amniotic fluid alpha fetoprotein not assayed (not info on neural tube defects

Question 14

amniocentesis

• cell arise from
• timeline
• associated birth defects
• type of analysis used
• risk
• mosaicism

Answer 14

• cells from amniotic fluid arise from fetal mouth and urniary bladder and amnios
• prefered at 15-17 weeks
• early amniocentesis associated with fetal club foot
• FISH analysis of non-dividing cells permits rapid diagnosis of aneuploidy
• risk of miscarriage 1/200 to1/600
• mosaicism in placenta not detected

Question 15

fetal cell-free DNA

• found where
• origin
• used for

Answer 15

• surprisingly high amounts of fetal DNA circulate in the blood of pregnant women
• origin of fetal DNA is in the placenta
• in 2011 started to be used as an advanced screen for fetal aneuploidy: trisomy 13, 18, 21; screening for sex chromosome anomalies, providing info on fetal sex

Question 16

NIPT is safer for…

Answer 16

• high risk women
• less than 0.1% of trisomy 21 are missed (false neg)
• 95% of women do not have aneuploidy detected

Question 17

Limitations of NIPT

Answer 17

• finite amount of fetal DNA
• may not be detectable in overweight women as the concentration will be lower
• less reliable in twin pregnancies
• will not detect open neural tube defects such as spina bifida

Question 18

ultrasound findings in down syndrome

Answer 18

-increased sandal gap

Question 19

benefit of 2D ultrasound to 3D 4D and HD

Answer 19

• can see internal anomalies using 2D ultrasound

- higher can can see exterior changes easily

Question 20

preimplantation genetic diagnosis

Answer 20

• the process of screening the embryos for genetic abnormalities prior to transferring to the uterus
• requires the use of IVF
• may also require intrcytoplasmic sperm injections
• embryo biopsy on 3rd day
• FISH or PCR analysis of single blastomere
• comparable to success rate of natural pregnancy
• expensive 12k-18k per cycle

Question 21

clinical apps for PGD

Answer 21

• single gene diagnosis by PCR
• familial chromosome rearrangement by FISH
• fetal sex selection, only if it is at a high risk for certain genetic conditions (x-linked)

Question 22

controversial issues with PGD

Answer 22

• pre disposition for adult onset disorders
• aneuploidy screening by FISH
• sex selection
• creation of HLS matched stem cell donors