4.3 UK National Screening Committee (UK NSC) Antenatal Screening Programmes

UK National Screening Committee (UK NSC) Antenatal Screening Programmes

Antenatal screening in the United Kingdom is governed by the UK National Screening Committee (UK NSC) and the NHS Fetal Anomaly Screening Programme (FASP). Screening programmes are designed to systematically evaluate an asymptomatic pregnant population to identify individuals at higher chance of carrying a fetus with a chromosomal anomaly or serious structural condition.

Midwives play a critical role in facilitating informed choice. Screening is never mandatory; every woman possesses the absolute right to accept all, some, or decline all screening tests without compromising her ongoing universal midwifery care. Midwives must provide balanced, non-directive, evidence-based information regarding test accuracy, potential findings, and subsequent diagnostic and management pathways.

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Principles of Screening & Non-Directive Midwifery Communication

Under classical screening principles (Wilson and Jungner criteria, adapted for modern genomic medicine), an effective screening programme requires a recognizable latent stage, an acceptable, safe, validated screening test, and an agreed diagnostic and management pathway. Midwives must communicate the distinction between a screening test (which estimates statistical probability or chance without providing a definitive answer) and a diagnostic test (which provides a definitive chromosomal or genetic diagnosis via invasive tissue sampling).

When counselling women, midwives must use non-stigmatizing language, articulating results as "lower chance" (e.g. less than 1 in 150) or "higher chance" (e.g. 1 in 150 or greater, such as 1 in 50), rather than misleading terms like "positive", "negative", "normal", or "abnormal".

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The First-Trimester Combined Screening Test

The combined test is the primary first-line screening modality offered to all pregnant women in the UK for three specific chromosomal trisomies:

1. Trisomy 21 (Down's syndrome)
2. Trisomy 18 (Edwards' syndrome)
3. Trisomy 13 (Patau's syndrome)

Gestational Eligibility & Crown-Rump Length (CRL)

The combined test must be performed within a strict clinical window:

• Gestational Window: 11+2 to 14+1 weeks' gestation.
• Ultrasonic Parameter: Fetal Crown-Rump Length (CRL) must measure between 45.0 mm and 84.0 mm.

If the fetal CRL is <45.0 mm, the woman must be re-booked for an ultrasound once the fetus reaches 11+2 weeks. If the CRL is >84.0 mm (gestation beyond 14+1 weeks), the nuchal translucency measurement is no longer valid, and the woman is offered the second-trimester quadruple test for Down's syndrome.

Dual Components of the Combined Test

The combined test integrates an ultrasound measurement with maternal serum biochemical analytes:

1. Ultrasound Nuchal Translucency (NT):

   • An ultrasound measurement of the maximum subcutaneous fluid collection behind the fetal cervical spine.
   • Must be measured by a validated, accredited practitioner adhering to strict Down's Syndrome Quality Assurance Support Service (DQASS) standards (fetal mid-sagittal view, neutral neck position, magnification showing only head and upper thorax, distinguishing amniotic membrane from fetal skin).
   • Increased NT reflects lymphatic congestion, fetal heart failure, abnormal extracellular matrix composition, or thoracic compression.

2. Maternal Serum Biochemistry:

   • Pregnancy-Associated Plasma Protein-A (PAPP-A): A high molecular weight metalloproteinase synthesized by the placental syncytiotrophoblast that cleaves insulin-like growth factor binding proteins (IGFBPs), releasing free IGF essential for placental trophoblast invasion.
   • Free beta-human chorionic gonadotropin (free β-hCG): Glycoprotein hormone subunit produced by placental trophoblast cells.

Biochemical & Ultrasound Profiles across Trisomies

Analyte concentrations are converted into Multiples of the Median (MoM), adjusted for gestational age, maternal weight, smoking, ethnicity, diabetes, and assisted reproduction:

• Trisomy 21 (Down's syndrome):
  • Nuchal Translucency (NT): Increased (≥2.0 MoM or >3.5 mm)
  • Free β-hCG: Significantly Elevated (median ≈ 2.0 MoM)
  • PAPP-A: Decreased (median ≈ 0.5 MoM)
• Trisomies 18 (Edwards') and 13 (Patau's):
  • Nuchal Translucency (NT): Markedly Increased
  • Free β-hCG: Severely Depressed (median <0.2–0.3 MoM)
  • PAPP-A: Severely Depressed (median <0.2–0.3 MoM)

Under national algorithms, the combined test achieves a detection rate of approximately 85% to 90% for a false-positive rate of 2.5% to 3%.

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Clinical Significance of Isolated Low PAPP-A

Beyond aneuploidy risk calculation, maternal serum PAPP-A serves as an essential biomarker of early placentation and trophoblast invasion.

Inadequate trophoblastic PAPP-A production impairs early spiral artery remodelling, significantly elevating the risk of subsequent obstetric complications:

• Fetal Growth Restriction (FGR) and Small-for-Gestational-Age (SGA)
• Pre-eclampsia and gestational hypertension
• Placental Abruption
• Spontaneous Preterm Birth (<37 weeks)
• Intrauterine Fetal Demise (Stillbirth)

Management Pathway for Low PAPP-A (Saving Babies' Lives v3)

When a first-trimester screening report shows low PAPP-A, even if the aneuploidy result is "lower chance", the woman is placed on the high-risk fetal growth restriction pathway. The midwife's role is to recognise this, explain it and refer appropriately:

1. Aspirin Prophylaxis: Consider aspirin 150 mg at night, started before 16 weeks, as appropriate. For this indication aspirin must be prescribed by a doctor or other prescriber; it is not a midwives exemption medicine.
2. Uterine Artery Doppler: Arrange uterine artery Doppler assessment between 18+0 and 23+6 weeks.
3. Serial Growth Scans: If the uterine artery Doppler is normal, arrange serial ultrasound growth scans from 32 weeks, every 2 to 4 weeks until birth. If it is abnormal, start serial scans from 28 weeks. If it is abnormal and the estimated fetal weight or abdominal circumference is below the 10th centile, discuss with fetal medicine.

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The Second-Trimester Quadruple Test

When a pregnant woman books late (gestation beyond 14+1 weeks / CRL >84.0 mm), or when technical factors (such as high maternal BMI or unfavorable fetal position) preclude valid measurement of nuchal translucency, the quadruple test is offered.

Parameters of the Quadruple Test

• Gestational Window: 14+2 to 20+0 weeks' gestation (ideally between 15 and 18 weeks).
• Target Condition: The quadruple test screens exclusively for Trisomy 21 (Down's syndrome). It does not provide screening for Trisomy 18 or Trisomy 13.
• Serum Analytes Measured:
  1. Alpha-fetoprotein (AFP): Synthesized by the fetal yolk sac and liver; decreased in Trisomy 21 (median ≈ 0.7 MoM).
  2. Unconjugated Oestriol (uE3): Synthesized by fetoplacental unit; decreased in Trisomy 21 (median ≈ 0.7 MoM).
  3. Total human chorionic gonadotropin (total hCG): Elevated in Trisomy 21 (median ≈ 2.0 MoM).
  4. Inhibin-A: Glycoprotein hormone secreted by the placenta; elevated in Trisomy 21 (median ≈ 1.8 MoM).

The quadruple test achieves a Down's syndrome detection rate of approximately 80% with a 3.5% false-positive rate.

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The UK NSC Screen-Positive Cut-Off & The Reflexive NIPT Pathway

The UK NSC establishes a standardized national cut-off to differentiate screening results:

• Screen-Positive / Higher-Chance Threshold: A calculated chance of 1 in 150 or greater at term (e.g. 1 in 80, 1 in 20). Numerical chances smaller than 1 in 150 (e.g. 1 in 500, 1 in 2,000) are classified as lower chance.
• Communication Window: Women with a higher-chance result must be contacted by a specialist screening midwife within 3 working days to arrange dedicated face-to-face counselling.

Non-Invasive Prenatal Testing (NIPT)

In 2021, the NHS rolled out Non-Invasive Prenatal Testing (NIPT) as an evaluative, secondary screening option within the FASP pathway for women receiving a higher-chance result (≥1 in 150) from the combined or quadruple test.

• Biological Mechanism: Analysis of cell-free fetal DNA (cffDNA) circulating in maternal venous plasma. cffDNA originates from apoptotic placental trophoblast cells (syncytiotrophoblast) and comprises approximately 4% to 10% of total maternal cell-free DNA from 10 weeks' gestation.
• Diagnostic Accuracy: Highly sensitive and specific (>99% sensitivity for Down's syndrome; >95% for Edwards' and Patau's) with an exceptionally low false-positive rate (<0.1%).
• Important Limitation: NIPT remains an advanced screening test, not a diagnostic test. Discordant results can occur due to confined placental mosaicism (CPM) (where chromosomal abnormalities are confined to the placenta while the fetus is euploid, or vice versa), maternal copy number variations, or a "vanishing twin". Therefore, termination of pregnancy must never be undertaken based on an NIPT result alone without confirmation via invasive diagnostic testing.

Triad of Informed Choices Following a Higher-Chance Result

A woman receiving a higher-chance screening result (≥1 in 150) has three distinct options:

1. No Further Testing: Decline additional screening or diagnostic tests and continue routine antenatal care.
2. Secondary Screening via NIPT: Undergo NHS-funded NIPT blood sampling to obtain a highly refined risk estimate before deciding on invasive testing.
3. Immediate Invasive Diagnostic Testing: Proceed directly to Chorionic Villus Sampling (CVS) or Amniocentesis to achieve a definitive genetic diagnosis.

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Invasive Diagnostic Testing: CVS vs. Amniocentesis

When a definitive genetic karyotype is required, invasive diagnostic testing is performed under continuous real-time ultrasound guidance by a fetal medicine specialist.

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The 20-Week Mid-Pregnancy Anomaly Scan

Offered between 18+0 and 20+6 weeks' gestation, the mid-pregnancy detailed ultrasound anomaly scan assesses structural fetal anatomy.

Under FASP guidelines, the anomaly scan specifically surveys for 11 core structural conditions:

1. Anencephaly (absence of cranial vault and cerebral hemispheres; lethal)
2. Open Spina Bifida (neural tube defect; "lemon" cranial sign and "banana" cerebellum)
3. Cleft Lip (with or without cleft palate)
4. Diaphragmatic Hernia (abdominal viscera herniating into thoracic cavity)
5. Gastroschisis (paraumbilical full-thickness anterior abdominal wall defect, bowel floating free in amniotic fluid)
6. Exomphalos / Omphalocele (midline anterior abdominal wall defect, viscera herniated into protective peritoneal sac)
7. Serious Congenital Heart Anomalies (evaluated via 5-chamber views: 4 chambers, left ventricular outflow tract, right ventricular outflow tract, 3 vessels and trachea [3VT] view)
8. Bilateral Renal Agenesis (absence of both kidneys, severe anhydramnios, pulmonary hypoplasia; lethal)
9. Lethal Skeletal Dysplasia (severe micromelia, narrow bell-shaped thorax)
10. Trisomy 18 (Edwards' syndrome)
11. Trisomy 13 (Patau's syndrome)

The scan also documents placental location. If the lower placental edge lies within 20 mm of the internal cervical os or overlaps the os, a low-lying placenta or placenta praevia is suspected, mandating a follow-up transvaginal ultrasound at 32 to 36 weeks' gestation.