Diagnostic Testing to Confirm Fetal Trisomy or Chromosomal Abnormalities
For definitive confirmation of trisomy or chromosomal abnormalities in the fetus, amniocentesis or chorionic villus sampling (CVS) are the gold standard diagnostic tests, both achieving >99% detection rates for all aneuploidies. 1
Diagnostic Test Selection Algorithm
Primary Diagnostic Options
Both amniocentesis and CVS provide definitive chromosomal diagnosis with >99% detection rates, compared to 99% for cell-free DNA screening which remains only a screening test requiring diagnostic confirmation. 1
- Amniocentesis has a procedure-related loss rate of 0.2% and is typically performed at 15-18 weeks gestation 1
- CVS has a procedure-related loss rate of approximately 1% and can be performed earlier at 10-13 weeks gestation 1, 2
Timing-Based Decision Making
If the patient is in the first trimester (10-13 weeks), CVS is the appropriate choice as it allows earlier diagnosis and reduces psychological burden of waiting. 2, 3
If the patient is at 15 weeks or beyond, amniocentesis is preferred as it has a lower procedure-related loss rate (0.2% vs 1%) and avoids the risk of confined placental mosaicism. 1, 3
Critical Consideration: Type of Abnormality Suspected
When cell-free DNA screening is positive for specific chromosomes, the choice between CVS and amniocentesis should be tailored:
- For trisomy 13, monosomy X, or rare autosomal trisomies (RATs): Consider amniocentesis over CVS if first-trimester ultrasound is normal, as these have high rates of confined placental mosaicism (CPM) 4
- For chromosomes with imprinted genes (6,7,11,14,15,20): CVS should be considered first, followed by amniocentesis if abnormal, due to risk of uniparental disomy 4
- For trisomy 21 or 18: Either CVS or amniocentesis is appropriate based on gestational age, as these have lower CPM rates 2, 4
Laboratory Testing Methods
Chromosome analysis (karyotyping) on either CVS or amniotic fluid samples provides definitive diagnosis, with chromosomal microarray (CMA) available as an alternative or reflex test for detecting smaller copy-number changes. 1
If CVS demonstrates mosaicism, follow-up amniocentesis is mandatory, as CVS mosaicism cannot distinguish between confined placental mosaicism and true fetal mosaicism. 1, 5, 4
Important Caveats and Pitfalls
Never terminate a pregnancy based on positive cell-free DNA screening alone without diagnostic confirmation—the risk to euploid pregnancies from termination without testing is excessive at all positive predictive values. 6
CVS samples placental tissue, which carries a 1.0% risk of confined placental mosaicism showing chromosomal abnormalities not present in the fetus. 5, 4
For patients with advanced maternal age or genetic disorder history, diagnostic testing should be offered directly rather than screening, as it provides definitive information without the need for follow-up procedures. 1
Early amniocentesis (before 15 weeks) should be avoided when possible, as it carries a 1% risk of talipes equinovarus and higher pregnancy loss rates compared to CVS. 3, 6
Counseling Requirements
Patients must be counseled that diagnostic confirmation with CVS or amniocentesis is recommended for all abnormal cell-free DNA results, as false-positive and false-negative results occur with screening tests. 1
Women desiring definitive information about all chromosomal conditions should be offered amniocentesis or CVS directly, as cell-free DNA screening does not detect all chromosomal abnormalities—approximately 16.9% of chromosomal abnormalities detected by traditional screening would be missed by cell-free DNA alone. 1