Sample · RANZCOG
Increased nuchal translucency and low PAPP-A on combined first-trimester screening
Antenatal care & screening · 4 parts · 15 marks. Decide what you would write, then compare with the rubric and model answer. In the app you write it under time and it comes back marked.
Mei, a 38-year-old woman in her second pregnancy (one previous uncomplicated vaginal birth), attends your antenatal clinic at 12+5 weeks. She had combined first-trimester screening (cFTS) two days ago. The report reads:
- Crown-rump length 62 mm, consistent with dates; single live intrauterine pregnancy
- Nuchal translucency (NT) 3.9 mm
- Pregnancy-associated plasma protein A (PAPP-A) 0.32 multiples of the median (MoM)
- Free beta human chorionic gonadotrophin (beta-hCG) 2.6 MoM
- Combined risk for trisomy 21: 1 in 18 (high chance); trisomy 18/13: 1 in 2,400 (low chance)
She and her partner are distressed and ask whether they can "just have the blood test" (non-invasive prenatal testing) instead of a needle test.
(a) Interpret this result and outline how you would counsel the couple about their request for non-invasive prenatal testing. 4 marks
Show the rubric and model answer
- High-chance cFTS result for trisomy 21 (1 in 18), driven by maternal age, increased NT, raised beta-hCG and low PAPP-A; this is a screening result, not a diagnosis (1)
- NT of 3.5 mm or more is independently significant: raised risk of other aneuploidy, pathogenic copy number variants, single-gene disorders (e.g. RASopathies such as Noonan syndrome) and structural anomalies, especially cardiac, even if karyotype is normal (1)
- NIPT (cell-free DNA) screens mainly for trisomies 21, 18, 13 and sex chromosomes; it will miss many of the conditions associated with NT of 3.5 mm or more, and a high-chance NIPT still needs diagnostic confirmation; RANZCOG advises offering diagnostic testing (not NIPT alone) when NT is 3.5 mm or more (1)
- Non-directive, supportive counselling: their choice is respected (diagnostic test, NIPT with understanding of limits, or no further testing); written information; genetic counsellor / fetal medicine referral; time to decide (1)
Interpretation
- This is a high-chance (1 in 18) combined first-trimester screening result for trisomy 21. It is a screening result, not a diagnosis: most fetuses with this risk will still have normal chromosomes.
- The increased nuchal translucency (3.9 mm, i.e. 3.5 mm or more) matters in its own right. Even with normal chromosomes it is associated with other chromosomal problems, pathogenic copy number variants, single-gene conditions (e.g. Noonan syndrome and other RASopathies) and structural anomalies, especially congenital heart disease.
- The low PAPP-A (below 0.4 MoM) separately signals placental dysfunction risk (see part d).
Counselling about NIPT
- Acknowledge their distress and that the wish to avoid a procedure is understandable.
- Explain that NIPT is an excellent screen for trisomy 21 but is still a screen, looks mainly at trisomies 21, 18, 13 and sex chromosomes, and would not detect many of the conditions linked to an NT of 3.5 mm or more. A high-chance NIPT would still need a diagnostic test; a low-chance NIPT would not reassure them about the other conditions.
- Recommend a diagnostic test with chromosomal microarray, in line with RANZCOG guidance, while respecting that the decision is theirs. If they still prefer NIPT, document that they understand its limitations and still offer detailed ultrasound.
- Non-directive approach, written information, referral to fetal medicine and a genetic counsellor, and time to decide.
(b) Outline the diagnostic tests available to Mei, including timing, the laboratory test you would request and the key risks and limitations. 4 marks
Show the rubric and model answer
- Chorionic villus sampling (CVS) from 11+0 weeks (usually 11-14 weeks), transabdominal under ultrasound guidance; result earlier, allowing earlier decisions (1)
- Amniocentesis from 15+0 weeks; avoid early amniocentesis (before 14 weeks: higher loss and talipes) (1)
- Request chromosomal microarray (with rapid aneuploidy test, e.g. QF-PCR, for chromosomes 13, 18, 21, X, Y); microarray detects additional clinically significant copy number variants missed by karyotype; consider RASopathy/exome testing if anomalies or persistent NT (1)
- Procedure-related additional miscarriage risk generally quoted as below 0.5% for both; other risks: infection, bleeding, Rh D sensitisation (give Rh D immunoglobulin if Rh D negative), culture failure; CVS limitation: confined placental mosaicism (about 1-2%) may need amniocentesis to clarify; microarray may find variants of uncertain significance (1)
Chorionic villus sampling (CVS)
- From 11+0 weeks (she can have it now), transabdominal under continuous ultrasound guidance.
- Gives an early result (rapid aneuploidy result in 1-3 days, microarray in about 1-2 weeks), allowing earlier decisions.
- Limitation: confined placental mosaicism in about 1-2% of samples, which may need amniocentesis to clarify.
Amniocentesis
- From 15+0 weeks. Early amniocentesis (before 14 weeks) is avoided because of higher loss and talipes.
- Amniocytes reflect the fetus, so mosaicism is less of a problem.
Laboratory request
- Rapid aneuploidy testing (e.g. quantitative fluorescent polymerase chain reaction, QF-PCR, for chromosomes 13, 18, 21, X and Y) plus chromosomal microarray. Microarray detects clinically significant copy number variants that a conventional karyotype misses.
- If the karyotype and microarray are normal but the NT persists or anomalies appear, discuss a RASopathy panel or exome sequencing with clinical genetics.
Risks and limitations (both procedures)
- Additional procedure-related miscarriage risk generally quoted as below 0.5%.
- Infection, bleeding, leakage of fluid (amniocentesis), culture or test failure.
- Rh D sensitisation: check blood group; give Rh D immunoglobulin if Rh D negative and not sensitised.
- Microarray may report variants of uncertain significance, which must be discussed before testing.
Mei has CVS at 13 weeks. Rapid aneuploidy testing and chromosomal microarray are both normal (46,XX equivalent, no pathogenic copy number variants).
(c) Outline your ongoing management of the pregnancy in relation to the increased nuchal translucency. 3 marks
Show the rubric and model answer
- Explain the reassuring result honestly: most babies with increased NT and normal microarray are healthy, but residual risk of structural anomaly and genetic syndromes remains (higher with larger NT) (1)
- Early detailed anatomy scan at about 16 weeks plus a detailed morphology scan at 18-22 weeks in a fetal medicine unit; look for hydrops, cardiac and other structural anomalies (1)
- Fetal echocardiography at about 18-22 weeks (congenital heart disease is the main residual risk); refer to clinical genetics for targeted testing (e.g. RASopathy panel) if anomalies, polyhydramnios or persistent nuchal oedema (1)
- Explain the result: normal chromosomes and microarray substantially reduce the risk, and most babies in this situation are healthy. However there is a residual risk (higher as NT increases) of structural anomalies, especially heart defects, and of single-gene conditions such as Noonan syndrome that microarray does not detect.
- Early detailed anatomy scan at about 16 weeks (resolution of the NT, early structural survey, signs of hydrops).
- Detailed morphology scan at 18-22 weeks in a fetal medicine unit.
- Fetal echocardiography at about 18-22 weeks.
- If any anomaly, polyhydramnios, persistent nuchal oedema or hydrops is found: referral to clinical genetics for a RASopathy panel or exome sequencing on the stored CVS sample, and paediatric (cardiology) counselling.
- If all of these are normal, reassure that the outlook is very good and return to routine care, with the placental surveillance in part (d).
(d) Outline the significance of the low PAPP-A and how you would modify her antenatal care. 4 marks
Show the rubric and model answer
- PAPP-A below 0.4 MoM (with normal chromosomes) is a marker of impaired placentation: increased risk of fetal growth restriction (FGR), pre-eclampsia, preterm birth and stillbirth (1)
- Low-dose aspirin 150 mg at night, started before 16 weeks and continued to 36 weeks, if pre-eclampsia risk is assessed as increased (e.g. first-trimester pre-eclampsia screening with mean arterial pressure, uterine artery Doppler and placental growth factor, or clinical risk factors such as age 38); consider calcium if dietary intake low (1)
- Serial growth surveillance: uterine artery Doppler at the morphology scan; serial ultrasound for fetal biometry, liquor and umbilical artery Doppler from about 28 weeks (e.g. 4-weekly, increased if concerns), rather than relying on fundal height (1)
- BP and urinalysis monitoring, education on pre-eclampsia symptoms and fetal movement awareness (Safer Baby Bundle), stop smoking if applicable, side-sleeping from 28 weeks; plan timing of birth according to growth (1)
Significance
- With normal chromosomes, a PAPP-A below 0.4 MoM is a marker of abnormal placentation. It is associated with fetal growth restriction, pre-eclampsia, preterm birth and stillbirth. It is a risk marker, not a diagnosis.
Changes to care
1. Pre-eclampsia prevention: combine with her other risks (age 38) or first-trimester pre-eclampsia screening (mean arterial pressure, uterine artery pulsatility index, placental growth factor). If increased risk, start aspirin 150 mg at night before 16 weeks and continue to 36 weeks. Ensure adequate calcium intake (supplement if dietary intake is low).
2. Growth surveillance: uterine artery Doppler at the morphology scan; serial growth ultrasound (biometry, estimated fetal weight, liquor, umbilical artery Doppler) from about 28 weeks, for example 4-weekly, more often if growth slows. Do not rely on symphysis-fundal height.
3. Blood pressure and urine protein checks at each visit; teach her the symptoms of pre-eclampsia.
4. Safer Baby Bundle messages: fetal movement awareness and prompt presentation with decreased movements, going to sleep on her side from 28 weeks, smoking cessation if relevant.
5. Plan timing of birth according to growth and Doppler findings.
Where candidates lose marks here
- Agreeing to NIPT as an equivalent alternative without explaining that it cannot assess the conditions linked to an NT of 3.5 mm or more: candidates who do not know this guideline point lose most of part (a).
- Answering the counselling part as a list of facts with no acknowledgement of the couple or of their right to choose: structure and non-directive language earn marks.
- Forgetting that the low PAPP-A is a separate placental issue once the chromosomes are normal.
- Vague growth surveillance ("monitor growth") without saying how, from when, and why fundal height is not enough.
- Spending 10 minutes on part (a): this is a 15-mark question for about 20 minutes, so allocate time by marks.
Original content written for Fellowship Ready, for exam preparation only, not clinical advice. Not affiliated with RANZCOG.