What is the most appropriate diagnostic test for a 12-week pregnant woman at high risk of trisomy 21 (Down syndrome) after First Trimester Screening (FTS)?

Chorionic Villus Sampling (CVS) is the Most Appropriate Diagnostic Test

For a 12-week pregnant woman with high-risk First Trimester Screening results for trisomy 21, chorionic villus sampling (CVS) is the most appropriate diagnostic test to offer, as it provides definitive chromosomal diagnosis at this gestational age and allows for earlier decision-making regarding pregnancy management. 1

Why CVS is Preferred at 12 Weeks Gestation

• CVS is specifically designed for first-trimester diagnostic testing and is typically performed between 10 weeks 0 days and 13 weeks 6 days of gestation, making it the ideal timing for this 12-week patient who desires definitive diagnostic information 1

• CVS provides definitive karyotype results with >99% detection rate for all aneuploidies, including trisomy 21, compared to screening tests 1

• The procedure allows for earlier diagnosis compared to amniocentesis (which begins at 15 weeks), reducing the psychological burden of waiting and allowing for earlier pregnancy management decisions if termination is considered 1

Why Other Options Are Inappropriate

NIPT (Non-Invasive Prenatal Testing) is NOT Diagnostic

• NIPT remains a screening test, not a diagnostic test, despite its high sensitivity (99%) and specificity for trisomy 21 1

• All positive NIPT results require diagnostic confirmation with either CVS or amniocentesis before making definitive pregnancy decisions 1

• Since this patient already has a positive screening result (high-risk FTS) and specifically wants diagnostic testing to determine if the fetus has Down syndrome, offering another screening test would be inappropriate and delay definitive diagnosis 1

Amniocentesis is Suboptimal at This Gestational Age

• Amniocentesis is generally offered beginning at 15 weeks of gestation, making it unavailable for this 12-week patient 1

• Waiting an additional 3 weeks for amniocentesis unnecessarily delays diagnosis when CVS can provide the same definitive information now 1

Morphology Ultrasound is NOT Diagnostic

• Morphology ultrasound cannot definitively diagnose or exclude trisomy 21—it can only identify structural abnormalities that may be associated with chromosomal conditions 1

• Ultrasound findings have insufficient sensitivity and specificity for chromosomal diagnosis and cannot replace karyotyping 1

Important Counseling Points About CVS

Procedure-Related Considerations

• CVS has a procedure-related pregnancy loss rate of approximately 1%, which should be discussed during counseling 1

• CVS samples placental tissue, which carries a small risk of confined placental mosaicism (CPM)—if mosaicism is detected on CVS, follow-up amniocentesis is required to determine true fetal status 1

• For suspected trisomy 21 specifically, CVS provides reliable diagnostic information, as true trisomy 21 (non-mosaic) on CVS confirms an affected fetus 1

Testing Methodology

• Chromosome analysis (karyotype) on CVS tissue is the standard diagnostic test for trisomy 21 confirmation 1

• Results are typically available within 1-2 weeks, with preliminary FISH results potentially available within 24-48 hours in some centers 2

Clinical Algorithm for This Patient

1. Offer genetic counseling immediately to discuss CVS procedure, risks, benefits, and alternatives 1

2. Schedule CVS as soon as possible (ideally within the current week while still at optimal gestational age) 1

3. Perform transabdominal CVS with chromosome analysis for definitive karyotype 1

4. If CVS confirms trisomy 21: Provide comprehensive counseling about Down syndrome, pregnancy options, and if continuing pregnancy, arrange appropriate prenatal and postnatal care 3

5. If CVS shows normal karyotype: Reassure patient but explain residual risk is not zero, and continue routine prenatal care 1

6. If CVS shows mosaicism: Perform follow-up amniocentesis at 15+ weeks to clarify true fetal chromosomal status 1

Common Pitfall to Avoid

Do not offer NIPT as the next step after positive First Trimester Screening when the patient explicitly desires diagnostic testing. This creates an unnecessary intermediate screening step that delays definitive diagnosis and may lead to confusion, as NIPT would still require diagnostic confirmation if positive 1. The patient has already screened positive and wants definitive information—proceed directly to diagnostic testing with CVS 1.