Prenatal Diagnosis

Question 1

Basic principles of prenatal diagnosis

Answer 1

1. Screen the general pop for common disorders
2. Offer screening to at risk groups for clustered disorders
3. Offer screening for families with known disorders.

Question 2

What are the components of screening?

Answer 2

1. Clinical history
2. Pedigree analysis
3. Diagnostic serum tests in parents
4. Invasive testing of the fetus
5. Options counseling

Question 3

What general disorder is Tay Sachs? Specific defect? Inheritance pattern? Buzz words?

Answer 3

1. Lysosomal storage disease
2. Hexosaminidase A - accumulated GM2 ganglioside
3. AR
4. Cherry-red spot on macula

Question 4

Ultrasound indications

Answer 4

NIH & ACOG:

1. Fetal presentation (breech or normal)
2. Suspected multiple gestation
3. Fetal death
4. Oligohydramnios
5. Abnormal AFP

Others:

1. Fetal anatomy
2. Placenta location
3. Uterine / Pelvic anatomy

Question 5

Estimating Gestational Age

Answer 5

First trimester:
1. Crown-rump length (as spine lengthens, this gets less reliable)

2nd and 3rd trimester:

1. Biparietal diameter
2. Abdominal circumference
3. Femur length

Earlier the US, the more accurate the dating
1st trimester: 7 days
2nd trimester: 7-14 days
3rd trimester: 14-21 days

Question 6

How do you screen for trisomies and NTDs?

Answer 6

1. Serum analytes:
   - AFP, Unconjugated estriol, HCG, INhibin A
2. Ultrasound
   - Nuchal translucency

Question 7

Where is AFP made?

Answer 7

AFP - fetal albumin, made in the fetal liver

Question 8

What is AFP?

Answer 8

Fetal albumin

Question 9

Why do maternal defects and chromosomal abnormalities increase with maternal age?

Answer 9

Longer time in prophase.

Down syndrome is about 1/2 of chromosomal abnormalities

Question 10

How old is advanced maternal age?

Answer 10

> 35 y/o

elderly gravida

Question 11

Why is 35 y/o a special age?

Answer 11

The chance of finding an abnormality is equal to the chance of losing a normal baby from invasive testing.

Question 12

When in the time of pregnancy do you use mom’s risk for chromosomal abnormalities

Answer 12

End of gestation

Question 13

Chorionic Villus Sampling

Answer 13

• Detects genetic, metabolic & DNA abnormalities
• Sample from developing placenta
• Completed at 10-12 weeks
• Does NOT detect NTD
• Earlier than amniocentesis

Question 14

What are the benefits of cell free fetal DNA testing?

Answer 14

1. Non-invasive with no miscarriage risk
2. High sensitivity and specificity
3. Available early in gestation
4. Good for patients at increased risk for aneuploidy

Question 15

What is a limitation with cell free DNA testing?

Answer 15

This is screening, NOT diagnostic.
You cannot differentiate between mom and baby’s DNA… you can only tell that there is an overrepresentation of a chromosome.