Prenatal Screening · 15-20 weeks
Quad Screen — Second-Trimester Blood Test
Blood test at 15-20 weeks pregnant that screens for Down syndrome (T21), Edwards (T18), and open neural tube defects (spina bifida, anencephaly). Four markers: AFP + hCG + estriol + inhibin A. Used when first-trimester combined screen was missed.
Last reviewed 2 June 2026
Quad screen (15-20 weeks)
AFP · β-hCG · uE3 · Inhibin A — pattern recognition
MoM
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Enter AFP, β-hCG and uE3 (Inhibin A optional) in MoM.
Educational tool only — not a diagnosis. The quad screen is a pattern-recognition tool; full risk calculation uses Bayesian modelling against maternal age. NIPT (cfDNA) is now first-line in many settings for aneuploidy screening — higher sensitivity, much lower false-positive rate.
What does this mean?
The quad screen looks at four maternal serum analytes at 15–20 weeks and recognises patterns of trisomy 21, trisomy 18, and open neural- tube defects. Classic T21 signature: AFP ↓, β-hCG ↑, uE3 ↓, inhibin A ↑. Classic T18 signature: AFP, β-hCG and uE3 all low, inhibin A normal. AFP ≥ 2.5 MoM with accurate dating flags an open NTD (anencephaly, open spina bifida) — the fetal anomaly scan / fetal MRI then localises it. Detection rate for T21: ~80 % at 5 % false-positive (lower than the first-trimester combined screen and far lower than NIPT). The quad is still useful when patients book late and miss the 11–13+6 NT window, when NIPT failed, or as part of integrated/sequential screening. A “screen positive” result triggers genetic counselling and discussion of diagnostic testing (amnio) or NIPT.
What is the quad screen?
Blood test at 15-20 weeks that screens for:
- Trisomy 21 (Down syndrome).
- Trisomy 18 (Edwards).
- Open neural tube defects (spina bifida, anencephaly).
Four markers: AFP (alpha-fetoprotein), β-hCG, uE3 (estriol), inhibin A. Detection rate for T21: ~77-81% at 5-7% false-positive.
When?
15+0 to 20+0 weeks (most accurate 16-18 weeks). NHS offers if FTCS not done in time. Results in 1-2 weeks.
Why quad screen instead of NIPT?
- FTCS missed (late booking).
- NIPT not available / affordable.
- NIPT failed (recurrent “no call”).
- Quad screen tests AFP for OPEN NEURAL TUBE DEFECTS — NIPT does NOT.
- NHS-funded.
What does AFP mean?
Alpha-fetoprotein — protein made by baby’s liver. Crosses placenta into mum’s blood. Interpreted relative to gestational age (MoM = Multiples of the Median).
- High AFP (>2.5 MoM): neural tube defect, abdominal wall defect, twins, wrong dates.
- Low AFP (<0.4 MoM): T21, T18.
How accurate?
- T21: ~77-81% detection (vs ~85-90% combined, >99% NIPT).
- T18: ~80%.
- Neural tube defects: ~75-90%.
Positive needs confirmation. ~3-5% positive predictive value for T21 — 95-97% of positive quads have unaffected babies.
What it does NOT test for
- Structural abnormalities (heart, cleft).
- Most genetic conditions (cystic fibrosis, sickle cell).
- Microdeletions.
- Sex chromosome conditions.
- Autism, ADHD, learning disabilities.
If positive
- Detailed ultrasound (anomaly scan).
- NIPT for chromosomal refinement.
- Amniocentesis for definitive diagnosis if still concerns.
Support: ARC, DSA, SOFT. Take time.
High AFP — what next
Investigate for:
- Neural tube defect (detailed anomaly scan).
- Abdominal wall defect.
- Wrong dates (confirm gestational age).
- Twins.
- Placental issues.
Confirm with 20-week anomaly scan.
Different scenarios — quad screen
Scenario 1: Late booker at 16 weeks
FTCS missed. Quad screen offered. If low risk + normal anomaly scan, reassuring.
Scenario 2: High AFP, otherwise normal markers
Detailed anomaly scan. Could be neural tube defect; could be wrong dates; could be twins; could be normal variant.
Scenario 3: High risk for T21 on quad
NIPT next, then CVS or amniocentesis if positive. Counselling.
Scenario 4: Confirmed open neural tube defect
Detailed scan; fetal medicine specialist; MRI sometimes; paediatric counselling; fetal surgery option in select cases (MOMS trial). Support: Shine UK.
Scenario 5: Declining quad screen
Valid choice. Anomaly scan at 20 weeks still essential for structural assessment.
Care guidance — quad screen
- 15-20 weeks — most accurate 16-18.
- Bloods only — no ultrasound part.
- Tests AFP for NTD — NIPT doesn’t.
- Less accurate than FTCS or NIPT for chromosomes.
- Optional — informed choice.
- 20-week anomaly scan still essential.
- Positive: confirm with NIPT or diagnostic.
- Support: ARC, DSA, SOFT, Shine, Sands.
Sources
- NHS Fetal Anomaly Screening Programme (FASP).
- ACOG Practice Bulletin 226 (2020). Screening for fetal chromosomal abnormalities.
- RCOG / BMFMS. Joint position on antenatal screening.
- NICE NG201. Antenatal care.
- Shine UK. Spina bifida support.
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Frequently asked questions
What is the quad screen?
A SECOND-TRIMESTER (15-20 weeks) blood test that screens for: TRISOMY 21 (Down syndrome), TRISOMY 18 (Edwards), and OPEN NEURAL TUBE DEFECTS (spina bifida, anencephaly). Four blood markers: AFP (alpha-fetoprotein), β-hCG (pregnancy hormone), uE3 (unconjugated estriol), and INHIBIN A. Each compared to median for gestational age (MoM = Multiples of the Median). Detection rate for T21: ~77-81% at 5-7% false-positive rate. WIDELY USED when first-trimester screening (FTCS) wasn't done — late bookers, missed FTCS window, or as triple screen alternative.
When is quad screening done?
BETWEEN 15+0 AND 20+0 WEEKS — most accurate at 16-18 weeks. EARLIER than 15 weeks: not enough data; LATER than 20 weeks: too late for some decision-making. NHS UK: quad screen offered if FTCS not done in time (booking after 14 weeks). PRIVATELY: 15-20 weeks. SCHEDULE: blood test, results in 1-2 weeks. CAN BE done same time as 20-week anomaly scan for combined risk + structural information.
Why have a quad screen instead of NIPT?
REASONS: (1) FTCS missed (late booking, late attendance); (2) NIPT not available / affordable; (3) NIPT failed (recurrent 'no call'); (4) Quad screen tests for OPEN NEURAL TUBE DEFECTS (AFP) — which NIPT does NOT; (5) NHS funded; (6) Cheaper than private NIPT. NIPT is more accurate for chromosomes (>99% vs ~77% for T21). For neural tube defects, AFP from quad screen or detailed anomaly scan are still important — NIPT misses these.
What does AFP mean?
ALPHA-FETOPROTEIN — a protein made by baby's liver. Crosses placenta into mum's blood. LEVELS RISE through pregnancy. INTERPRETED relative to gestational age (MoM). HIGH AFP (>2.5 MoM) associated with: (1) OPEN NEURAL TUBE DEFECTS (spina bifida, anencephaly); (2) ABDOMINAL WALL defects (gastroschisis, omphalocele); (3) TWINS; (4) WRONG DATES (baby further along than thought); (5) RECENT BLEEDING. LOW AFP associated with: T21, T18. ACCURATE FROM 15 WEEKS. UK USED dried blood spot (heel-prick equivalent for mum) historically; now venous sample.
How accurate is the quad screen?
FOR T21: ~77-81% detection rate at 5-7% false-positive rate. LESS ACCURATE than first-trimester combined (85-90%) or NIPT (>99%). FOR T18: ~80%. FOR OPEN NEURAL TUBE DEFECTS: ~75-90% (high AFP). FALSE POSITIVES common (5-7%) — many 'positive' results turn out NEGATIVE on confirmatory testing. POSITIVE NEEDS confirmation: NIPT or amniocentesis. NEGATIVE reasonably reassuring but not 100%.
What if my quad screen is positive?
MEANS risk ≥1 in 150 for T21 OR ≥1 in 100 for T18 OR raised AFP. NEXT STEPS: (1) DETAILED ULTRASOUND (anomaly scan) to assess structures; (2) NIPT (more accurate for chromosomes); (3) AMNIOCENTESIS for definitive diagnosis if still concerns. POSITIVE PREDICTIVE VALUE for T21 ~3-5% — meaning 95-97% of 'positive' quad screens have unaffected babies. SUPPORT: ARC (UK), SOFT for T18, DSA for Down's syndrome. TAKE TIME — no rush to decide.
What does the quad screen NOT test for?
MANY conditions. NOT tested: (1) STRUCTURAL abnormalities (heart defects, cleft palate — anomaly scan handles); (2) MOST GENETIC conditions (single-gene like CF, sickle); (3) MICRODELETIONS (DiGeorge etc); (4) CHROMOSOMAL conditions OTHER than T21/T18 (T13 less reliably); (5) SEX CHROMOSOME conditions. ALSO: doesn't test for autism, ADHD, learning disabilities — no test predicts these. 20-WEEK ANOMALY SCAN + NIPT add complementary information.
What if AFP is high?
INVESTIGATE FOR: (1) NEURAL TUBE DEFECT — detailed anomaly scan; spina bifida (open) visible on ultrasound; anencephaly even more obvious; (2) ABDOMINAL WALL defect — gastroschisis, omphalocele; (3) WRONG DATES — confirm gestational age (sometimes baby further along); (4) TWINS — confirms; (5) PLACENTAL issues — increased risk PE, growth restriction, preterm birth. CONFIRM with 20-week anomaly scan. AMNIOCENTESIS RARELY needed for AFP alone — usually scan resolves. IF NEURAL TUBE DEFECT confirmed: counselling, options discussed.
What if AFP is low?
LOW AFP (<0.4 MoM) associated with T21, T18. RISK CALCULATION combines with other markers. Many causes of low AFP are non-genetic — recheck dates, ensure not too early. If confirmed low + other markers concerning: NIPT or diagnostic test. ISOLATED low AFP in low-risk pregnancy usually not concerning by itself.
Can quad screen detect twins?
YES — AFP very high (twice normal) suggests twins. CONFIRMED on ultrasound. INTERPRETATION of risk in confirmed twins different — calculations done with twin-specific software. ACCURACY lower in twins. PRIVATE NIPT for twins available; NHS not routinely. DETAILED scanning more important in twins than singletons.
I'm a late booker — should I have quad screen or NIPT?
BOTH possible. NIPT MORE ACCURATE for chromosomes. Quad screen has AFP for neural tube defects. IDEAL: have both — NIPT for chromosomal accuracy + anomaly scan with AFP for structural. PRIVATELY: NIPT 10 weeks + anomaly scan 20 weeks works well. NHS: quad screen if FTCS missed; NIPT only if high-risk on quad. EITHER WAY: 20-WEEK anomaly scan essential.
Will my insurance / NHS cover quad screen?
UK NHS: YES, if FTCS missed. Free. PRIVATE UK: £100-200. US: usually covered by insurance for prenatal care. CANADA: included in prenatal care. AUSTRALIA: Medicare-funded. INDIA / ASIA: variable. CHECK with provider. CHEAPER than full private NIPT package — for some, quad screen is the practical screening option.
What's the next step after results?
(1) LOW RISK: standard antenatal care, 20-week anomaly scan, routine monitoring. (2) HIGH RISK FOR T21 / T18: NIPT or amniocentesis offered; genetic counselling. (3) HIGH AFP: detailed anomaly scan to assess for neural tube defects + abdominal wall + dates; sometimes amniocentesis. (4) LOW AFP: detailed scan + may consider NIPT. (5) MULTIPLE MARKERS abnormal: more rigorous workup; specialist input. SUPPORT: ARC, DSA, SOFT, Sands (for bereavement). GENETIC COUNSELLOR available throughout.
Can I refuse quad screen?
YES — optional. SCREENING is parent's choice. Some decline because: (1) wouldn't change decisions; (2) prefer not to know risk numbers; (3) personal/religious beliefs; (4) anxiety about waiting. Can STILL HAVE 20-week anomaly scan (structural) — that's separate and assesses major abnormalities. INFORMED choice essential.
What if I'm carrying a baby with confirmed neural tube defect?
DIFFICULT diagnosis. NEXT STEPS: (1) DETAILED ultrasound to assess severity; (2) FETAL MEDICINE specialist referral; (3) MRI in some cases for additional information; (4) COUNSELLING with paediatric neurosurgery + paediatric medicine teams; (5) CONSIDERATIONS: open vs closed spina bifida; level (lumbar more severe than sacral); associated hydrocephalus; FETAL SURGERY in highly selected cases (MOMS trial); termination options if requested. SUPPORT: Shine UK (spina bifida charity), SOFT, ARC. TIME TO DECIDE without pressure.
How does this relate to other calculators on BumpBites?
Companion: /calculators/first-trimester-screen for combined 11-14 wk screening; /calculators/nipt-cfdna for follow-up; /calculators/pregnancy-week for gestation timing; /calculators/aspirin-pe-prevention; /calculators/twin-probability; /calculators/baby-size-by-week; /calculators/fetal-weight.