Guidelines

Screening Pathways

There are 2 main screening pathways:

• Combined test and/or quadruple test – for trisomy 21, 18, 13
• 20-week anomaly scan – for 11 physical conditions
  • Offered 18⁺⁰ – 20⁺⁶ weeks

Trisomy 21, 18, 13 Screening Pathway

Approach

• First, perform screening tests (these test simply gives a result of higher or lower chance)
• If the screening test result is higher chance → 2nd line tests 

 

Screening test

Test of choice: the combined test, performed between 10-14 weeks

2nd line: quadruple test performed between 14-20 weeks. Indications:

• Women attend antenatal care after 14 weeks 
• If not eligible for combined test or unable to measure NT (see below for more details)

If combined test and/or quadruple test gives a result of higher chance → proceed to definitive testing (prenatal diagnosis)
 

Combined Test Component and Interpretation

The combined test can screen for trisomy 21, 18, 13 (Down's, Edward's, Patau's syndrome)

The combined test involves assessing:

• Maternal age
• Biochemical marker – free β-hCG and PAPP-A
• Nuchal translucency

Result trend that is suggestive of Down's syndrome:

• ↑ b-HCG
• ↓ PAPP-A
• ↑ Nuchal translucency (≥3.5 mm)

Quadruple Test Component and Interpretation

Note that the quadruple test only assesses the chance of the baby having trisomy 21 (Down's syndrome).

The quadruple test involves assessing 4 biochemical markers:

• β-hCG
• Inhibin-A
• AFP
• Unconjugated oestriol 

Results that are suggestive of Down's syndrome

• ↑ b-HCG
• ↑ Inhibin-A
• ↓ AFP
• ↓ Unconjugated oestriol 

Eligibility Criteria For Combined and Quadruple Test 

Disclaimer: eligibility criteria for combined test and quadruple test have been omitted above due to their advanced level of knowledge which may create confusion.

Eligibility criteria for combined test:

• CRL 45 – 84 mm
  • If CRL <45 mm → recall for a further US
  • If CRL >84 mm → calculate gestational age using HC and offer quadruple test if criteria met

Eligibility criteria for quadruple test:

• NT measurement cannot be obtained
• CRL​​​​​​​ >84 mm
• HC 101 – 172 mm
  • If HC >172 mm → offer 20 week screening scan (anomaly scan)

2nd Line Tests –  NIPT or Confirmatory Test

For those with a higher chance result (from the screening test), offer the women a choice of:

• NIPT, or
• Confirmatory tests – chorionic villus sampling or amniocentesis

 

NIPT (Non-Invasive Prenatal Testing)

Timing: ≤ 21⁺⁶ weeks (first sample)

Involves a maternal blood test to analyse cffDNA that circulates in the maternal circulation.

NIPT results are reported as lower chance / higher chance:

• If higher chance → offer the option of no further testing or prenatal diagnosis (confirmatory tests)

 
 

Prenatal Diagnosis (Confirmatory Test – Chorionic Villus Sampling / Amniocentesis)

These are the only confirmatory tests for prenatal diagnosis of trisomies 21, 18, 13.

Chorionic villus sampling:

• Timing: 11-14 weeks 
• Description: ultrasound-guided transabdominal / transcervical procedure to obtain a sample of placental tissue for chromosomal or genetic analysis

Amniocentesis:

• Timing: 15-20 weeks
• Description: ultrasound-guided extraction of amniotic fluid for chromosomal or genetic analysis 

 

NHS England: One in 200 women who have a CVS or amniocentesis will miscarry.

20-week Anomaly Screening Pathway

The 20-week screening scan is also known as the anomaly scan:

• Timing: 18⁺⁰ – 20⁺⁶ weeks 
• Description: ultrasound scan to screen for 11 physical conditions

If the scan detected / raised suspicion of physical conditions:

• Refer, and
• Offer confirmatory testing (chorionic villus sampling or amniocentesis), and
• Discuss options of continuing pregnancy vs terminating pregnancy 

 

11 Physical Conditions

• Trisomy 18 and 13 (Edward's and Patau's syndrome)
• 2 neural tube defects (anencephaly and spina bifida)
• 3 GI defect (cleft lip, gastroschisis, exomphalos)
• Congenital diaphragmatic hernia
• Congenital heart disease
• Bilateral renal agenesis
• Severe skeletal dysplasia

References

Original Guideline

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