There are 2 main screening pathways:
- Combined test and/or quadruple test – for trisomy 21, 18, 13Trisomy 21 (Down's syndrome) Trisomy 18 (Edward's syndrome) Trisomy 13 (Patau's syndrome)
- 20-week anomaly scan – for 11 physical conditions- Trisomy 18 and 13 (Edward's and Patau's syndrome) - 2 neural tube defect (anencephaly and spina bifida) - 3 GI defect (cleft lip, gastroschisis, exomphalos) - Congenital diaphragmatic hernia - Congenital heart disease - Bilateral renal agenesis - Severe skeletal dysplasia
- 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
Step 1: Screening Tests
There are 2 main screening tests:
| Screening test | Indications |
|---|---|
| Combined test (1st line) | Most common screening test, used for most patients who follow the routine antenatal care pathway
Performed between 10-14 weeks |
| Quadruple test | Performed between 14-20 weeks
Indicated if the combined test is NOT appropriate:
|
Interpretation and subsequent actions (based on combined and/or quadruple tests):
- Lower chance → reassure and no further tests
- Higher chance
1 in 150 chance or less
→ proceed to 2nd line tests
Combined Test Component and Interpretation
The combined test can screen for trisomy 21, 18, 13 (Down, Edward, Patau syndrome)
The combined test involves assessing:
- Maternal ageThe risk only increases rapidly with age after 30 y/o - 30 y/o → 1 in 900 chance of having T21 baby - 40 y/o → 1 in 100 chance of having T21 baby For the same maternal age, the chance is T21 > T18 > T13
- Biochemical marker – free β-hCGbeta human chorionic gonadotropin and PAPP-APregnancy associated plasma protein-A
- Nuchal translucency
Trend interpretation:
| Condition | Nuchal translucency | β-hCG | PAPP-A |
|---|---|---|---|
| Down syndrome (trisomy 21)* | ↑ (≥3.5 mm) | ↑ | ↓ |
| Edwards syndrome (trisomy 18) | ↑ | ↓ | ↓ |
| Patau syndrome (trisomy 13) | ↑ | ↓ | ↓ |
*Most likely to be examined.
Quadruple Test Component and Interpretation
The NHS Fetal Anomaly Screening Programme previously only offered the quadruple test for Down syndrome.
However, a recommendation to include Edwards syndrome was approved by the government in December 2025. [Ref]
The quadruple test only assesses the chance of the baby having trisomy 21 (Down syndrome) and trisomy 21 (Edwards syndrome)
The quadruple test involves assessing 4 biochemical markers:
| Condition | β-hCG | Inhibin-A | AFP | Unconjugated oestriol |
|---|---|---|---|---|
| Down syndrome (trisomy 21) | ↑ | ↑ | ↓ | ↓ |
| Edward syndrome (trisomy 18) | ↓ | Normal | ↓ | ↓ |
Step 2: NIPT or Confirmatory Test
For those with a higher chance result (from the screening test), offer the women a choice of:
- Non-invasive prenatal testing (NIPT), or
- Confirmatory tests (invasive prenatal diagnosis)
NIPT (Non-Invasive Prenatal Testing)
| Timing | ≤ 21+6 weeks (first sample) |
| Description | Maternal blood test to analyse cffDNACell free fetal DNA (cffDNA) Derived from the placental cells and usually identical to fetal DNA. Therefore, analysis of cffDNA has very high sensitivity and specificity for chromosomal abnormalities. that circulates in the maternal circulation |
| Interpretation and subsequent actions | NIPT results are reported as lower chance or higher chance
Subsequent action:
|
NIPT is still a screening test, it is more sensitive than the combined and quadruple test, but NOT a diagnostic test.
The only diagnostic tests are chorionic villus sampling or amniocentesis for chromosomal or genetic analysis.
Confirmatory Tests (Invasive Prenatal Diagnosis)
There are 2 confirmatory tests that allow prenatal diagnosis of trisomies 21, 18 and 13:
- Chorionic villus sampling
- Amniocentesis
| Test | Gestational age* | Description |
|---|---|---|
| Chorionic villus sampling | 11-14 weeks | Ultrasound-guided transabdominal / transcervical procedure to obtain a sample of placental tissue for chromosomal or genetic analysis |
| Amniocentesis | 15-20 weeks | Ultrasound-guided extraction of amniotic fluid for chromosomal or genetic analysis |
*Gestational age at the time of referral is a key determinant in selecting the appropriate confirmatory test
NHS England: One in 200 women who have a CVSchorionic villus sampling 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
NHS Fetal Anomaly Screening Programme (FASP)
NICE Guideline Antenatal Care