Prenatal Diagnosis

Question 1

genetic screening

Answer 1

1st step in checking for prenatal abnormalities

questionnaire that considers maternal age, family history, ethnic background

NOT a full pedigree or full genetic counseling

if this is positive –> more detailed counseling or referral to geneticist is indicated

Question 2

types of genetic fetal disorders

Answer 2

chromosomal

Mendelian (AD, AR, X linked)

multifactorial

uniparental disomy

Question 3

what is the cause of 50% of 1st trimester losses in patients with no history of genetic abnormalities

Answer 3

chromosomal disorderes

commonly trisomy, monosomy, triploidy, 45X

risk of nondisjunction aneuploidy increases with maternal age
–> 1st trimester losses = 10% at 20YOA….20% at 40
overall average = 15%

Question 4

3% of couples with recurrent miscarriages have a ?

Answer 4

balanced translocation in one of the partners

chromosome analysis or microarray is useful in diagnosing these translocations in parents

Question 5

% of still borns that will have a chromosomal abnormality

Answer 5

7%

Question 6

& of live borns that will have a chromosomal abnormality

Answer 6

0.5%

not necessarily deleterious

Question 7

% of free trisomies that are due to maternal nondisjunction

Answer 7

95%

Question 8

nondisjunction in meiosis I

Answer 8

sister chromatids fail to separate

producing 2n-1 and 2n+1 gametes

these n+1 gametes can go on to produce free trisomies (Down Syndrome, etc)

Question 9

2 options for prenatal screening

Answer 9

blood test

US for structural abnormalities

Question 10

common blood test for prenatal screening

Answer 10

maternal serum alpha fetoprotein

Question 11

NT defects display what kind of inheritance

Answer 11

polygenic, multifactorial

usually interaction between predisposing genes and environmental factors

can also be associated with chromosomal or Mendelian disorders

can be screened for with maternal serum alpha fetoprotein

Question 12

maternal serum alpha fetoprotein

Answer 12

= fetal albumin that leaks into amniotic fluid then the fetus has a neural tube defect

higher levels in amniotic fluid increases alpha fetoprotein in maternal serum

downside to test = lots of false positives, but still a reasonable test

usefule to diagnose neural tube defects or defects covered only by a thin membrane …. basically needs to be sufficient permeability to allow alpha fetoprotein to leak out of the fetus

can also be used to diagnose anencephaly and gastroschisis

Question 13

Spina bifida occulta

Answer 13

can just be a dimple or tuft that indicates a deeper spinal issue

Question 14

meningocele

Answer 14

consists of a CSF containing cyst that herniates outside the spinal column

Question 15

myelomeningocele

Answer 15

meningocele that contains spinal cord elements

Question 16

NT defects are associated with what other defects

Answer 16

hydrocephalus or microcephaly

Question 17

folic acid therapy for pregnant women

Answer 17

400ug of folic acid starting 1 month prior to pregnancy

atleast through the 1st trimester (NT closes at 6 menstrual weeks/23 days)

water soluble and excreted in urine so taking large doses is not dangerous

Question 18

Quadruple screen

what 4 maternal serum metabolites

Answer 18

AFT

estriols

bHGC

Inhibin A

Question 19

biggest reason a MSAFP false positive?

Answer 19

incorrect gestational age

because the lab uses reference values based on gestational age

Question 20

when are MSAFP values predictive?

Answer 20

15-20 gestational weeks

Question 21

another way MSAFP can have a false positive

Answer 21

placenta separates from the wall and fetal blood leaks into amniotic fluid

AFP increases without NTD

Question 22

what does an amniocentesis test for?

Answer 22

o test for acetylcholinesterase (a neural system enzyme that degrades ACh in the synaptic cleft)

Question 23

decision tree after elevated MSAFP blood test

Answer 23

1. US for NTD
   (+) –> NTD diagnosis
   (-) –> amniocentesis
2. amniocentesis
   (-) –> false positive or non-NTD cause
   (+) –> NTD diagnosis

Question 24

Quad screen results for

Down Syndrome

Answer 24

AFP = down

Estriols = down

bHCG = up

Inhibin A = up

Question 25

Quad screen results for

Trisomy 18

Answer 25

AFP = down

Estriols = down

bHCG = down

Inhibin A = unchanged

all values are low because baby is tiny

Question 26

Quad screen results for

open NTD

Answer 26

AFP = up

Estriols = N/A

bHCG = N/A

Inhibin A = N/A

Question 27

if a test has a 1.3% positive predictive value…what does that mean

Answer 27

if quad screen gives a positive, only 1.3% actually have the disorder

Question 28

if a test has a 70-80% detection sensitivity

Answer 28

it finds 70-80% of positive cases out of 100%

it is possible to raise this, but false positive rate would be higher (trade-off)

Question 29

under what conditions would you have to obtain a fetal sample

Answer 29

screening test is positive

theres is a family history

advanced maternal age with preference to skip the screening

Question 30

fetal sample obtaining techniques

Answer 30

1. chorionic villus sampling (less common)
2. amniocentesis (most common)
3. fetal blood sampling (not used anymore)

Question 31

chorionic villus sampling

Answer 31

earlier than 15 weeks

take tiny bits of placenta

done through vaginal catheter (most common) or abdominal needle

contraindications = cervical infections

Question 32

amniocentesis technique

Answer 32

done AFTER 15 weeks

US guided 22 gauge needle takes a 20cc sample of amniotic fluid

lab will centrifuge –> the pellet is fetal skin or urinary tract cells

cells are grown and karyotyped or specific molecular DNA testing is done

contraindications = anhydraminos because of Potters syndrome or other causes….certain infections (maternal HIV+)

Question 33

ultrasound screening

Answer 33

used for structural abnormalities
- especially duodenal atresia (double bubble) with Down Syndrome

mostly 2nd trimester abnormalities

Question 34

1st trimester screening

Answer 34

combination of US and blood tests

US = nuchal translucency

• fluid level under the skin at the neck
• if large = turner, Trisomy 21 (most likely), 18, 13, or complex CHD

blood = PAPP A and B hCG

Question 35

Fetal DNA in maternal blood

Answer 35

fairly new test in past 5 years

as placenta remodels and grows….releases fDNA in maternal blood

Trisomy = disproportionately increased fragments of the trisomy chromosome

screening not diagnositic

more expensive than quad test and not extensively studied in low risk

indications of use = AMA, abnormal US, abnormal biochemical screen, close relative with trisomy 18

low false positive:

• vanishing twin with trisomy degenerates before US
• maternal mosaicism
• maternal cancer has abnormal karyotype that gives of cell free DNA

Question 36

1st trimester US

Answer 36

anencephaly, omphalocele, major structural abornmalities

***note: herniation and rotation of midgut outside the gut…not to be mistaken for a omphacele

Question 37

preimplantation diagnosis

Answer 37

basis = family history of Tay Sachs, doesn’t agree with abortion but doesn’t want a child with Tay Sachs

woman undergoes in vitro fertilization (in this case, not because of a fertility issue)

one of the blastomeres is removed and nuclear DNA is analyzed

non-affected ones can be implanted and affects ones in Louisiana are frozen

Question 38

3D ultrasound

Answer 38

birth defect that OB wants to get a better look at (cleft palate, etc)

medial geneticists disagree with this being used outside of this setting