Genetic Screening

Question 1

Components of the first trimester screen? Detection rate for Downs?

Answer 1

NT, PAPP-A, free or total HCG

82-87%

Question 2

Most common aneuploidy in products of conception?

Answer 2

Trisomy 16 (non-viable)

Question 3

Most frequent monosomy?

Answer 3

Turner’s (Monosomy X)

Question 4

Most common autosmal aneuploidy in LIVE born infants?

Answer 4

Trisomy 21

Question 5

When can you perform a NT?

Answer 5

10w0d - 13w6d

Question 6

What is defined as an enlarged NT?

Answer 6

> /= 3.0 mm

Question 7

With an enlarged NT what is the likelihood of fetal aneuploidy?

Answer 7

50%

Question 8

What structures produce AFP?

Answer 8

Glycoprotein secreted by the yolk sac and liver of the fetus

Question 9

What is the detection rate for open neural tube defects with an elevated maternal serum AFP

Answer 9

65-80%

Question 10

Is msAFP elevated in CLOSED neural tube defects?

Answer 10

Nope!

Question 11

At what gestation does the neural tube close?

Answer 11

4 weeks

Question 12

What other conditions (besides open NTD) are associated with elevated AFP?

Answer 12

• Multiple Gestation
• Fetal abdominal wall defects
• Fetal nephrosis
• Fetal demise
• Placenta conditions that increase risk of adverse outcomes later on in pregnancy

Question 13

When can you perform cell free DNA testing?

Answer 13

9-10 weeks gestation (until term)

Question 14

What factors affect the quantity of fetal fraction in cf DNA?

Answer 14

Gestational Age
Maternal BMI
Med exposure
Maternal race
Aneuploidy status
Fetal or maternal mosaicism
Single or multiple gestation

Question 15

Which screening test in the most sensitive and specific for the common fetal aneuploidies?

Answer 15

cfDNA

> 98-99%

Question 16

What GA is CVS testing performed?

Answer 16

10w0d-14w0d

Question 17

Risk of materno-fetal hemorrhage with CVS testing?

Answer 17

14%

Question 18

What GA is amniocentesis performed?

Answer 18

15w-20w

Question 19

Risk of materno-fetal hemorrhage with amnio?

Answer 19

2-6%

Give Rhogam!

< 12 wks = 50-120 mcg
> 12 wks = 300 mcg dose

Question 20

GA for First Trimester Screen + components

Answer 20

10-13w6d

NT, PAPP-A, B-Hcg

Question 21

GA for Quad Screen + components

Answer 21

15w-22w6d

AFP, BHcg, Estradiol, Inhibin A

Question 22

Describe integrated screening

Answer 22

“Integrated Screening”: NT + PAPP-A @ 10-13w THEN Quad Screen 15-22w

“Serum Integrated” - same, however no NT US

Question 23

What is the difference between between Stepwise Sequential and Contingent Screening?

Answer 23

In both first trimester screen is obtained

Stepwise Sequential: low risk does QUAD screen

Contingent: low risk does NO ADDITIONAL tesing

Question 24

Components of Stepwise Sequential Screening? GA?

Answer 24

First tri screen: NT, PAPP-A, Hcg (10w-13w6d)

Low risk: THEN QUAD (AFP, Bhcg, Estradiol, Inhibin A) 15-22w

High Risk: Diagnostic vs cfDNA

Question 25

Components of Contingent Screening? GA?

Answer 25

First Tri Screen: NT, PAPP-A, Hcg (10-13w6d) Low Risk: No testing Medium: QUAD (15-22w) High: Diagnostic vs cfDNA

Question 26

Risk fo Downs Syndrome w/ maternal age > 40

Answer 26

1:51

Question 27

When a cystic hygroma is identified in the first trimester, what percentage of fetuses are aneuploid?

Answer 27

50%

Question 28

US Findings: - Thickened Nuchal Fold - Echogenic Cardiac foci - Echogenic bowel - Short humerus - Absent nasal bone

Answer 28

Down's Syndrome

Question 29

In the second trimester- what is the most sensitive and specific finding for Down Syndrome?

Answer 29

Thickened nuchal fold

Question 30

Soft markers on US for Downs Syndrome in SECOND trimester?

Answer 30

``` Echogenic Cardiac Foci Pyelectasis Echogenic bowel Thickened nuchal fold Mild ventriculomegaly Choroid plexus cysts Shortened femur length ```

Question 31

What anomalies are associated with an increased NT (> 3 mm)

Answer 31

Aneuploidy Congenital heart defects Abdominal wall defects Diaphragmatic hernies

Question 32

What percentage of fetuses with increased NT measurement (> 3 mm) will have aneuploidy?

Answer 32

50%

Question 33

At what gestational age is NT measurement MOST sensitive in screening for aneuploidy?

Answer 33

13 weeks

Question 34

Quad Screen Results for Down Syndrome?

Answer 34

PAPP-A = low B-hcg = high Estradiol = low Inhibin A= high DOWN (low) unless they are HI (hcG, Inhibin A)

Question 35

Findings of “lemon sign” and “banana sign” on ultrasound are most consistent with which of the following congenital anomalies

Answer 35

Open neural tube defect

Question 36

Tell me about cell free fetal DNA testing

Answer 36

Noninvasive prenatal testing that using cell free fetal DNA from the plasma of the pregnant woman Detection rate for Trisomy 13/18/21 is > 98% for each Very low false positive rates < 0.5% Most sensitive and specific screening test for common aneuploidies **only screening test that can tell you gender and sex chromosome aneuploidies

Question 37

Amniocentesis vs CVS

Answer 37

CVS earlier (10-12 wks), can't measure AFP, tissue specimen, inappropriate for diagnosis of NTD Amniocentesis (after 15 wks), can measure AFP, samples individual cells, appropriate for NTD detection

Question 38

How is Fragile X syndrome inherited? Mutation on what gene?

Answer 38

X linked recessive FMR1 gene Tri-nucleotide CGG repeats < 45 repeat unaffected Intermediate 45 - 54 repeats Pre-mutation 55-200 repeats Full mutation > 200 repeats

Question 39

Occurrence risk of NTD?

Answer 39

*multi factorial (environmental and genetics) *having family members with condition increases risk General population 0.3% (400 mcg folate/day) With one affected child 2-4% (4 g folate/day) With two affected children 10% Start 1-3 months prior to conception

Question 40

'folate resistant' NTD? Folate will NOT prevent them, increased dose not necessary

Answer 40

Valproic acid in first trimester High fetal glucose levels First trimester fever or prolonged elevated maternal temperature (sauna use) Obesity

Question 41

Is there anytime where an omphalocele would be considered "normal"

Answer 41

YES! Between 9-11 wks gestation (with herniation of the hind gut in normal development)