What are the guidelines for Down syndrome screening in pregnant women?

Guidelines for Down Syndrome Screening in Pregnant Women

All pregnant women should be offered screening for Down syndrome regardless of maternal age, with options including first-trimester, second-trimester, or integrated screening protocols. 1

Screening Options and Performance

First-Trimester Screening (11-13 weeks)

• Includes:
  • Nuchal translucency (NT) measurement
  • Maternal serum PAPP-A (pregnancy-associated plasma protein A)
  • Free β-hCG or total hCG
  • Maternal age risk assessment
• Performance: Detection rate of approximately 83% at a 5% false-positive rate 1

Second-Trimester Screening (15-22 weeks)

• Triple Test:
  • Alpha-fetoprotein (AFP)
  • hCG
  • Unconjugated estriol (uE3)
  • Detection rate: 69% at a 5% false-positive rate 2
• Quadruple Test:
  • AFP, hCG, uE3, plus inhibin A
  • Detection rate: 76% at a 5% false-positive rate 2

Integrated/Sequential Screening (Both Trimesters)

• Full Integrated Test (includes NT):

  • First trimester: NT, PAPP-A
  • Second trimester: AFP, hCG, uE3, inhibin A
  • Detection rate: 92% at a 5% false-positive rate
  • Or 85-90% detection with 1-2% false-positive rate using a 1:100 risk cutoff 1

• Serum Integrated Test (no NT):

  • First trimester: PAPP-A
  • Second trimester: AFP, hCG, uE3, inhibin A

• Sequential Screening:

  • First-trimester results reported
  • High-risk patients (e.g., >1:25 or 1:50) offered early diagnostic testing
  • Remaining patients proceed to second-trimester screening
  • Combined results reported 1

Risk Assessment and Reporting

Risk Calculation

• Patient-specific risk is calculated using:
  • Maternal age
  • Gestational age (preferably confirmed by ultrasound)
  • Serum marker levels (converted to MoM - multiples of the median)
  • NT measurement (when applicable)
  • Other factors: maternal weight, ethnicity, diabetes status, multiple pregnancy 1

Screen-Positive Definition

• Typically defined as risk ≥1:200 or 1:270
• Risk cutoff may vary by laboratory and screening protocol 1

Report Requirements

Reports must include:

• Patient identifiers and demographics
• Test information and specimen details
• Measurements in both mass units and MoM values
• Clear interpretation (screen positive/negative)
• Patient-specific risk estimate
• Risk cutoff used 1

Follow-up Recommendations

For Screen-Positive Results

1. Prompt Communication: Results should be communicated within one working day 1
2. Genetic Counseling: Especially important with family history of Down syndrome 1
3. Diagnostic Testing Options:
   • Chorionic villus sampling (CVS): 10-13 weeks gestation
   • Amniocentesis: Beginning at 15 weeks gestation 1

Special Considerations

• Twin Pregnancies: Require specialized risk calculation
• Family History: May warrant genetic counseling regardless of screening results
• Reclassification Risk: Caution when reclassifying screen-positive results to negative based on revised dating 1

Important Caveats

1. Screening vs. Diagnostic Testing: Screening provides risk assessment but not diagnosis; only amniocentesis or CVS can provide definitive diagnosis 1

2. False Positives/Negatives: All screening methods have inherent limitations; the most common outcome of a screen-positive result is still an unaffected pregnancy 1

3. Age-Based Considerations: While advanced maternal age (≥35 years) historically was the sole criterion for offering diagnostic testing, current guidelines recommend screening for all women regardless of age 1, 3

4. Patient Autonomy: Studies show that patient decisions about testing are strongly influenced by maternal age, with women ≥35 more likely to choose diagnostic testing regardless of screening results 4

5. Additional Conditions: Down syndrome screening may also detect other chromosomal abnormalities such as Trisomy 18 and Trisomy 13 1