12.) Methods For Prenatal Diagnosis Of The Fetus, Methods For Prenatal Diagnosis

Question 1

What are the two main categories of prenatal diagnostic methods?

Answer 1

1. Invasive methods
2. Non-invasive methods

Question 2

What are the common invasive prenatal diagnostic methods?

Answer 2

1. Chorionic Villus Sampling (CVS)
2. Amniocentesis
3. Cordocentesis (Percutaneous Umbilical Blood Sampling - PUBS)
4. Fetal Biopsy

Question 3

What are the common non-invasive prenatal diagnostic methods?

Answer 3

1. MRI
2. Maternal blood tests
   • Cell-free fetal DNA (cfDNA)
   • Biochemical markers (e.g., triple test, quadruple test)

3.) Ultrasound

Question 4

What genetic testing can be done with fetal DNA or tissue?

Answer 4

1. Karyotyping – for chromosomal abnormalities.
2. FISH (Fluorescence In Situ Hybridization) – to detect specific chromosomal abnormalities.
3. CMA (Chromosomal Microarray Analysis) – for microdeletions/duplications.

Question 5

What are the key indications for prenatal diagnostic testing?

Answer 5

1. Advanced maternal age (>35 years)
2. Pregnancy with twins
3. History of chromosomal abnormalities in previous pregnancies
4. Recurrent miscarriage
5. Neural tube defects (e.g., spina bifida)
6. Parental carriers of genetic disorders (e.g., cystic fibrosis, thalassemia)

Question 6

At what gestational age is Chorionic Villus Sampling (CVS) typically performed, and what are its advantages?

Answer 6

• Gestational age: 10–13 weeks (first trimester).
• Advantages:
  
  • Earlier detection in the first trimester.
  • Quick results.
  • Good source of DNA for testing.

0.5-1% risk

Question 7

What are the indications for performing Chorionic Villus Sampling (CVS)?

Answer 7

1. Karyotyping if first-trimester screening suggests high risk for aneuploidy (e.g., Down syndrome).
2. DNA analysis for genetic mutations (e.g., cystic fibrosis, thalassemia).
3. Risk of miscarriage: Very low but present.
4. Risk of bloodborne infections: Slightly increased (e.g., HIV, hepatitis B).

Question 8

At what gestational age is Amniocentesis typically performed, and what is its purpose?

Answer 8

• Gestational age: From 15 weeks onwards (second trimester).
• Purpose:
  
  • Collect amniotic fluid containing fetal cells for genetic testing.

Risk 0.25-0.5%

• Indications: Karyotyping, DNA analysis, enzyme assays, fetal infections (e.g., CMV, toxoplasmosis).

Question 9

What is Cordocentesis (Percutaneous Umbilical Blood Sampling - PUBS) and when is it used?

Answer 9

• Performed after 20 weeks’ gestation.
• Purpose:
  
  • Obtain fetal blood for hematological analysis (e.g., hematocrit, Rh status).
  • Cytogenetic and DNA analysis.
  • Can provide rapid results (18-24 hours) for fetal karyotyping.
  • Declining in use due to advances like FISH.

Risk 1%

Question 10

What are the non-invasive biochemical tests used in prenatal diagnosis?

Answer 10

1. Triple Test (16–18 weeks):
   
   • Alpha-fetoprotein (AFP), hCG, Unconjugated estriol.
   • Low AFP, high hCG, high estriol: Risk for Down syndrome.
   • Low AFP, low estriol, low hCG: Risk for Trisomy 18 (Edwards syndrome).
   • High AFP: Associated with neural tube defects (e.g., spina bifida).
2. Quadruple Test (95% detection rate):
   
   • AFP, hCG, Unconjugated estriol, Inhibin A.
   • High Inhibin A: Risk for Trisomy 21 (Down syndrome).
   • Unchanged Inhibin A: Risk for Trisomy 18 (Edwards syndrome).

Question 11

What is the significance of Plasma Protein A (PAP-A) in prenatal testing?

Answer 11

• PAP-A is used as a screening marker for Down syndrome, especially in women over 35 years old.
• It helps improve the accuracy of the triple test.

PAPP-A = Pregnancy associated plasma protein-A

Question 12

What prenatal conditions can be detected using Ultrasound?

Answer 12

• Neural tube defects (e.g., spina bifida)
• Serious heart defects
• Kidney problems
• Absence of a limb
• Other structural abnormalities

Question 13

What is the primary advantage of Non-Invasive Prenatal Testing (NIPT) using cell-free fetal DNA?

Answer 13

• Highly accurate for detecting aneuploidies like Down syndrome.
• No risk to the fetus as it only requires a blood sample from the mother.
• Can be performed as early as 10 weeks’ gestation.

Question 14

What is the main difference between Karyotyping and FISH (Fluorescence in situ hybridization)?

Answer 14

• Karyotyping: Provides a full chromosomal analysis to detect aneuploidy, translocations, and deletions.
• FISH: Used for detecting specific chromosomal abnormalities, such as Down syndrome, using fluorescent probes for targeted regions.