Is the QUTARNERAY test a valid screening method for Down syndrome in pregnancy, and what are the recommended screening and diagnostic options?

Prenatal Screening for Down Syndrome: The "Quaternary" Test Does Not Exist

There is no recognized test called the "quaternary test" for Down syndrome screening. You may be referring to either the quadruple (quad) marker test performed in the second trimester, or the double marker test performed in the first trimester combined with nuchal translucency ultrasound.

Validated Screening Options for Down Syndrome

First-Trimester Combined Screening (11-13 Weeks)

This is the preferred early screening approach, combining maternal age, ultrasound, and two biochemical markers 1:

• Components:

  • Pregnancy-associated plasma protein-A (PAPP-A) - typically reduced in Down syndrome 2
  • Free β-hCG - typically elevated in Down syndrome 2
  • Nuchal translucency (NT) ultrasound measurement 1
  • Maternal age 1

• Performance: Detects 83-86% of Down syndrome cases at a 5% false-positive rate 2

• Optimal timing: 12 weeks gestation when combined with NT ultrasound 2

• Biochemical marker nuances: Free β-hCG yields 2-3% higher detection at 11-12 weeks, while intact hCG shows modest 1-2% advantage at 13 weeks 1, 2

Second-Trimester Quadruple (Quad) Marker Test (15-20 Weeks)

This four-marker panel is the standard second-trimester screening option 2:

• Components:

  • Alpha-fetoprotein (AFP) 2
  • Human chorionic gonadotropin (hCG) 2
  • Unconjugated estriol (uE3) 2
  • Inhibin-A 2

• Performance: Detects approximately 75-80% of Down syndrome cases 2

• Optimal timing: 16-18 weeks gestation 2, 3

Critical Distinction: Screening vs. Diagnosis

All maternal serum marker tests and ultrasound measurements are screening tests only—they are NOT diagnostic 1. The distinction is crucial:

• Screening tests identify pregnancies at sufficient risk to warrant genetic counseling and offer of diagnostic testing 1

• Definitive diagnosis requires karyotyping of fetal cells obtained by:

  • Chorionic villus sampling (CVS) at 10-13 weeks 1, 4
  • Amniocentesis at ≥15 weeks 1, 4

Risk Thresholds and Interpretation

• Screen-positive threshold: Calculated risk ≥1:250 (or 1:300) for trisomy 21 2

• Screen-positive management: Prompt notification (within one working day), genetic counseling, and offer of CVS or amniocentesis 1

• Screen-negative interpretation: Provides reassurance but does not eliminate residual risk 2

Cell-Free DNA (NIPS): Superior Alternative

Cell-free DNA testing achieves >99% detection with <1% false-positive rate 2:

• Positive predictive value of 50-95% for trisomy 21 (compared to 3.6% for traditional combined screening) 2
• Requires only 1-2 invasive procedures per confirmed case (versus 28 for traditional screening) 2
• More costly but dramatically superior performance 2

Essential Adjustments and Pitfalls to Avoid

Risk calculations must be adjusted for 1, 2, 3:

• Maternal weight (AFP inversely related to weight) 3
• Maternal race 1, 3
• Insulin-dependent diabetes 3
• Twin pregnancies (require specialized algorithms; singleton cutoffs are invalid) 1, 2

Common technical errors 1, 2, 3:

• Failing to use ultrasound dating (crown-rump length) instead of last menstrual period 1
• Not reinterpreting results when gestational age is revised by ≥2 weeks 1, 3
• Using singleton cutoffs for twin pregnancies 1, 3
• Inadequate gestational age precision (use weeks and days, not rounded weeks) 3

Recommended Clinical Algorithm

1. Offer all pregnant patients screening early in pregnancy, regardless of age 2

2. For patients presenting at 11-13 weeks: Offer first-trimester combined screening (double marker + NT) 2

3. For patients presenting at 15-20 weeks: Offer second-trimester quad screen 2

4. For patients ≥35 years at delivery: Offer diagnostic testing (CVS or amniocentesis) in addition to screening 2, 5

5. If screen-positive: Genetic counseling and offer of diagnostic testing within one working day 1

6. If NT measurement is enlarged: Counsel regarding increased risk for spontaneous abortion and diverse fetal abnormalities beyond Down syndrome; arrange follow-up ultrasound and fetal echocardiography even if karyotype is normal 6