Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Screening for trisomy and diagnostic testing
Obstetrics and gynaecology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending
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Time-sensitive abnormal results need prompt fetal-medicine access
Markedly increased nuchal translucency, a major ultrasound anomaly, a higher-chance or no-result NIPT, or acute pain, bleeding, fluid loss or fever after CVS or amniocentesis requires prompt specialist assessment.
Action: Contact the screening or fetal-medicine team without delaying for routine review, provide gestation and exact result, arrange diagnostic counselling or urgent post-procedure assessment, and avoid irreversible decisions based on a screening result alone.
Purpose and principles
Explain England's current trisomy screening sequence, interpret chance results accurately and support timely choice between no further testing, NIPT and invasive diagnosis.
Antenatal screening and diagnosis answer different questions. Screening combines maternal, biochemical and ultrasound information to estimate the chance that a pregnancy has trisomy 21, 18 or 13. A diagnostic test analyses placental or amniotic cells and can provide a much more definitive result for the condition tested, but it is invasive and cannot guarantee every aspect of fetal health. Offer each step with neutral language, accessible numerical information and respect for the patient's values; neither acceptance nor decline implies a preferred pregnancy outcome.
The combined test is the programme test of choice for eligible singleton and twin pregnancies. Maternal blood supplies pregnancy-associated plasma protein A and free beta-human chorionic gonadotropin, while ultrasound supplies crown-rump length and nuchal translucency; maternal age contributes to the calculation. Eligibility requires a crown-rump length from 45.0 to 84.0 mm, corresponding approximately to 11+2 through 14+1 weeks. Blood may be collected from 10 weeks, but the calculation is completed only after a valid ultrasound measurement.
Indications, selection and cautions
Combined-test eligibility
Crown-rump length from 45.0 to 84.0 mm permits the maternal-age, nuchal-translucency and two-marker calculation for all three trisomies.
Quadruple-test eligibility
Unavailable nuchal translucency or crown-rump length above 84.0 mm redirects to the second-trimester biochemical pathway within the head-size and sampling limits.
Higher-chance screening
A result between 1 in 2 and 1 in 150 reaches the programme threshold for counselling and further-test choices.
NIPT no result
The laboratory cannot issue a lower- or higher-chance result, so the patient needs active review of repeat and diagnostic options.
Discordant placental result
Placental mosaicism, vanished twin or maternal biological factors can make cell-free DNA or CVS findings differ from the fetal genotype.
Red flags requiring action
Nuchal translucency of 3.5 mm or more requires immediate referral through the local fetal-medicine pathway without waiting for the calculated combined-test chance.
A major structural anomaly or several markers may indicate a chromosomal or genetic disorder outside the standard trisomy screen and needs specialist diagnostic discussion.
A higher-chance NIPT result is not diagnostic and should be confirmed by an appropriately selected invasive test before an irreversible pregnancy decision.
Method and interpretation
01Combined trisomy screeningFirst step
Why
Estimate chance of trisomy 21, 18 and 13 using maternal age, serum markers and nuchal translucency.
Interpretation and limitations
Apply only within the validated crown-rump-length range and classify the numerical result at the 1-in-150 threshold without calling it diagnostic.
02Quadruple biochemical screening
Why
Provide a later screen when the combined test cannot be completed and head circumference and gestation remain eligible.
Interpretation and limitations
It screens for trisomy 21 and, when nationally implemented in the active laboratory pathway, trisomy 18; it does not assess trisomy 13 and performs less well than combined testing.
03Non-invasive prenatal testing
Why
Refine trisomy 21, 18 and 13 chance after a higher-chance NHS combined or quadruple result without an invasive procedure.
Interpretation and limitations
Report lower chance, higher chance or no result; because the DNA is predominantly placental, diagnostic confirmation is needed after a higher-chance result before irreversible action.
04Chorionic villus sampling
Why
Obtain placental tissue for diagnostic cytogenetic or molecular testing from the appropriate first-trimester gestation.
Interpretation and limitations
A definitive result can diagnose the tested disorder, but placental mosaicism may require amniocentesis and the procedure carries a small additional miscarriage risk.
Clinical next steps
01Initial offerMatch screening to the validated windowFirst stepThe patient chooses trisomy screening during the first or second trimester.+
1Use crown-rump length to determine combined-test eligibility, obtain valid nuchal translucency and blood markers, and refer immediately when NT is at least 3.5 mm.
2When combined testing is not possible, check head circumference and the 14+2-to-20+0 sampling window before offering the quadruple test and explain its narrower or implementation-dependent scope.
3PreferredCommunicate the numerical chance, test limitations and failsafe action in the patient's preferred format, recording separate choices for the conditions offered.
02Higher chanceOffer three legitimate next choicesThe combined or quadruple result lies between 1 in 2 and 1 in 150 at term.+
Risks, monitoring and follow-up
Use programme failsafes to confirm that every accepted combined, quadruple or NIPT sample yields a result and every higher-chance result reaches counselling.
Record crown-rump length, nuchal translucency, head circumference and sample dates so eligibility and any recalculation can be audited accurately.
Track higher-chance referrals and make prenatal diagnosis available within the national pathway timescale rather than allowing gestational options to narrow silently.
After CVS or amniocentesis, provide a direct contact route for bleeding, fluid loss, pain, fever or illness and document anti-D assessment where relevant.
Reconcile rapid and full laboratory reports, including mosaic or uncertain findings, before counselling about fetal prognosis.
Continue the 20-week screening scan and other indicated imaging because trisomy screening and diagnostic tests do not replace structural assessment.
Special situations
Ratios run opposite to intuition
A 1-in-50 result represents a higher chance than 1 in 500, so both numerator language and a natural-frequency explanation reduce misunderstanding.
NIPT samples placenta indirectly
Cell-free DNA originates mainly from trophoblast, which explains both excellent performance and occasional discordance from the fetal genotype.
A no-result test contains information
Low fetal fraction or technical failure does not confer reassurance; repeat sampling and invasive diagnosis are choices after individual review.
NT reaches beyond trisomy
Marked nuchal translucency can accompany cardiac, structural and single-gene conditions, so referral should not depend solely on the trisomy calculation.
Diagnostic scope is assay limited
A normal rapid aneuploidy result answers its target question but cannot exclude all copy-number changes, single-gene disorders or structural anomalies.
Common pitfalls
01
Calling NIPT diagnostic or recommending termination from a higher-chance NIPT without invasive confirmation.
02
Offering combined screening after crown-rump length has exceeded 84.0 mm instead of using the eligible later pathway.
03
Claiming that every current quadruple test includes trisomy 18 without confirming whether implementation is active locally.
04
Saying the quadruple test screens for trisomy 13, which lies outside that biochemical pathway.
05
Waiting for the calculated chance before referring a nuchal translucency measurement of 3.5 mm or more.
06
Performing amniocentesis before 15+0 weeks or CVS before 10+0 weeks and increasing avoidable procedure risk.
Practice
Two practice questions
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Question 1 of 2
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Obstetrics and gynaecologyOriginal SBA
Screening after the combined window
A singleton pregnancy is scanned at 14+4 weeks; crown-rump length is 91 mm, nuchal translucency was not obtained and head circumference is within the programme range. What should be offered?
Sources and review status5 sources · checked 27 Aug 2026 · clinical review pending+
Sources
Sources and review status
National guidance is shown before implementation-dependent detail. Apply principles in context and verify current guidance when a decision affects care. Source check completed 27 Aug 2026; clinical approval remains outstanding.
Nuchal translucency is a screening marker as well as part of the chance calculation. A measurement of at least 3.5 mm activates immediate local referral because it can accompany chromosomal, cardiac and other structural or genetic conditions even if the final trisomy calculation would not be higher chance. Explain that increased thickness is not itself a diagnosis. Specialist assessment may include diagnostic testing, detailed ultrasound, fetal cardiac evaluation and broader genomic discussion according to the complete phenotype.
When nuchal translucency cannot be obtained or crown-rump length exceeds 84.0 mm, the quadruple blood test is the programme alternative if head circumference is within 101.0 to 172.0 mm and sampling occurs from 14+2 to 20+0. It combines maternal age with alpha-fetoprotein, hCG or free beta-hCG, inhibin A and unconjugated oestriol. Its detection rate is lower and screen-positive rate higher than the combined test. The July 2026 handbook states it screens for trisomy 21 and for trisomy 18 when that extension is implemented; service communications must reflect the active laboratory pathway, and quadruple testing does not screen for trisomy 13.
The national chance cut-off for combined and quadruple testing is 1 in 150 at term. Results from 1 in 2 to 1 in 150 are called higher chance, while 1 in 151 or numerically lower probability is lower chance. Use both the ratio and plain-language frequency rather than saying positive or negative. A result of 1 in 100 means that about one pregnancy among one hundred with the same calculated features is expected to be affected; it does not mean the fetus is 100% affected or that ninety-nine specific fetuses are known to be unaffected.
After a higher-chance result, the patient may choose no further testing, NHS NIPT or invasive prenatal diagnosis. NIPT uses placental cell-free DNA in maternal blood and, in the FASP contingent pathway, screens for trisomy 21, 18 and 13. It has better screening performance than combined or quadruple testing but remains a screen because placental DNA may differ from fetal DNA and biological or technical factors can produce no result. A lower-chance NIPT substantially reduces risk but cannot eliminate it; higher-chance and no-result outcomes require prompt, condition-specific counselling.
Choose an invasive test with gestation, placental biology and the suspected condition in mind. CVS samples placental villi, usually at 11+0 to 13+6 weeks and never before 10+0. Amniocentesis samples amniotic fluid from 15+0 weeks. The additional miscarriage risk in a singleton pregnancy performed by a skilled operator is likely below 0.5%; risk is higher in twins and procedure counselling must be personalised. Because CVS samples placenta, confined placental mosaicism can create an uncertain or discordant result and may require later amniocentesis.
Laboratory testing is selected, not unlimited. Rapid QF-PCR commonly targets the suspected common aneuploidies, while karyotype, chromosomal microarray or a condition-specific molecular test may be offered when ultrasound, family history or initial results justify it. Before sampling, agree which questions the laboratory will answer, turnaround, possible uncertain or incidental findings and what happens if culture or analysis fails. After any result, provide trained counselling and continuing pregnancy, neonatal, palliative or termination pathways according to the patient's informed decision and gestation.
Key points
The combined test uses maternal age, nuchal translucency, pregnancy-associated plasma protein A and free beta-hCG when crown-rump length is 45.0 to 84.0 mm, approximately 11+2 to 14+1 weeks.
A combined test estimates chance of trisomy 21, trisomy 18 and trisomy 13; it is not a diagnostic fetal karyotype.
If nuchal translucency cannot be obtained or crown-rump length exceeds 84.0 mm, offer the quadruple test when head circumference is 101.0 to 172.0 mm and blood is taken from 14+2 to 20+0 weeks.
The 2026 FASP handbook describes quadruple screening for trisomy 21 and trisomy 18 when T18 implementation is active; confirm the current laboratory pathway, and do not claim that quadruple testing screens for trisomy 13.
A chance from 1 in 2 through 1 in 150 at term is higher chance; 1 in 151 or lower is lower chance. These categories are probability thresholds, not affected or unaffected diagnoses.
After a higher-chance combined or quadruple result, offer an informed choice of no further testing, NHS NIPT or invasive prenatal diagnosis.
NIPT analyses placental cell-free DNA for trisomy 21, 18 and 13 in this NHS pathway; lower chance reduces risk, while higher chance or no result needs specialist discussion and may lead to CVS or amniocentesis.
A no-result NIPT can be associated with low fetal fraction, placental dysfunction or aneuploidy and needs active counselling rather than being reported as low chance.
Persistent pain, heavy bleeding, fluid loss, fever or feeling unwell after CVS or amniocentesis requires urgent maternity or fetal-medicine contact.
A twin, vanished-twin or placental mosaicism context can complicate screening attribution and requires specialist interpretation of what the result applies to.
05Amniocentesis
Why
Obtain amniotic-fluid fetal cells for diagnostic testing from 15+0 weeks onward.
Interpretation and limitations
It provides fetal-cell analysis with a small procedure-related miscarriage risk; the assay chosen controls which chromosomal or genetic findings can be reported.
06Detailed fetal and cardiac ultrasound
Why
Assess structural associations when nuchal translucency is increased or a screening or diagnostic result raises concern.
Interpretation and limitations
Normal anatomy does not negate a diagnostic chromosome result, and an abnormal scan may justify testing beyond the three common trisomies.
1
Arrange prompt counselling that distinguishes a chance estimate from diagnosis and accounts for ultrasound findings, gestation, twin status and personal values.
2Offer no further testing, contingent NHS NIPT or direct invasive prenatal diagnosis, explaining what each option can show, timing and miscarriage implications.
3DefinitiveFor higher-chance or no-result NIPT, revisit diagnostic testing and avoid definitive fetal labels or irreversible decisions without appropriate confirmation.
03Prenatal diagnosisSelect, sample and interpret safelyThe patient chooses a diagnostic test after screening, ultrasound or inherited-risk counselling.+
1Choose CVS at an appropriate gestation or amniocentesis from 15+0 weeks based on the clinical question, placental limitations and patient preference.
2Before consent, state operator-related miscarriage risk, sampling route, laboratory test, possible mosaic or uncertain results, turnaround and post-procedure warning symptoms.
3Communicate results through the fetal-medicine or genetics pathway and provide non-directive support for all pregnancy and neonatal care choices.
CVS is usually performed from 11+0 to 13+6 weeks and not before 10+0; amniocentesis is performed from 15+0 weeks. In skilled hands, additional procedure-related miscarriage risk is likely below 0.5% in singleton pregnancy.