Presentation: Patient with a higher-chance first-trimester combined screening result

A pregnant woman has presented for her first-trimester combined screening. An ultrasound measurement of the fetal crown-rump length (CRL), fetal nuchal translucency (NT) nuchal translucency and laboratory measurement of maternal serum PAPP-A and free beta-HCG. A statistical risk calculation is performed by clinical scientists to estimate the chance of Down syndrome (trisomy 21), or a joint chance for Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13). Screening test results show that the woman is a ‘higher-chance’ (1 in 2 to 1 in 150 risk ratio) for the conditions. She asks if there are any other tests that can be carried out.

Consider genomic testing when:

• There is a higher-chance (1 in 2 to 1 in 150 risk ratio) first-trimester combined screening result.
• Findings characteristic of a common aneuploidy are made during an ultrasound scan.

• Consult the National Genomic Test Directory. From this directory you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Refer to local and national NHS Fetal Anomaly Screening Programme (FASP) guidance regarding first-trimester screening.
• A further discussion with the screening co-ordinator or a fetal medicine midwife is usually warranted to discuss options around non-invasive prenatal testing (NIPT) or diagnostic tests as the technology can provide a more sensitive screening test for information and reproductive choice.
• If anomalies are noted on the ultrasound scan, a referral to a fetal medicine unit is usually recommended for a detailed scan and a review to determine which genomic tests are appropriate.
• Genetic referral is not routinely indicated for higher-chance first-trimester screening results. In the case of suspected anomalies, a referral to clinical genetics may be considered.
• Depending on the clinical scenario, a range of different genomic tests may be considered, as outlined below.
• Where there is an isolated higher-chance screening record:
  • R401 Common aneuploidy screening: this will process only a QF-PCR and should be requested in cases where the pregnant woman might have a diagnosis of aneuploidy (trisomy 21, 18 or 13).
• Where there are concerns regarding an atypical phenotype, the following may be considered:
  • R22 Fetus with a likely chromosomal abnormality. This will process both genome-wide common aneuploidy testing and chromosomal microarray.
• Where there are multiple or complex anomalies and/or above testing is non-diagnostic, (rapid) fetal exome sequencing may be considered:
  • R21 Fetal anomalies with a likely genetic cause: fetal exome sequencing: Referral to clinical genetics and/or multi-disciplinary discussion is required.
• NIPT is offered as part of an evaluative roll-out and is currently not part of the test directory. Contact your local screening midwife or fetal medicine team for information and support on testing.
• For whole genome sequencing (WGS)-based tests, you will need to:
  • complete an NHS GMS test order form with details of the proband and parents. Include details of the phenotype (refer to human phenotype ontology (HPO) terms and the clinical summary) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support).
  • complete an NHS GMS record of discussion (ROD) form for each person being tested. Note that, if you are undertaking trio testing of an affected child and their parents, you will need three of these forms (see How to complete a record of discussion form for support).
• For tests that do not include WGS, you will need to:
  • complete a test order form and consent (ROD) form, available from your local Genomic Laboratory Hub (GLH); and
  • include details of the phenotype (refer to HPO terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
• For all these tests, DNA can be extracted using amniocentesis, chorionic villus sample or cordocentesis (fetal blood sample). For many of the tests (particularly WGS and exome sequencing), parental samples are also needed.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• Gov.uk: Screening for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome
• NHS England: National Genomic Test Directory
• Royal College of Obstetricians and Gynaecologists: Amniocentesis and Chorionic Villus Sampling (Green-top Guideline No. 8)

References:

• Bilardo CM, Chaoui R, Hyett JA and others, ‘ISUOG Practice Guidelines (updated): performance of 11–14-week ultrasound scan‘. Ultrasound in Obstetrics and Gynecology 2023. DOI: 10.1002/uog.26106

For patients

• Antenatal Results and Choices
• Down’s Syndrome Association
• Gov.uk: Your choices after a higher-chance screening result
• NHS: Screening tests in pregnancy
• Positive about Down syndrome
• SOFT UK