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

A woman has attended her appointment for combined first-trimester screening. A nuchal translucency measurement was taken, along with a blood sample for biomarkers (bhCG and PAPP-A). Following the appointment, the measurements were used, along with the woman’s age, to calculate the chance of this baby having certain chromosome conditions. The patient has been informed that she has a high-chance result for aneuploidy and would like to know what further tests can be carried out.

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

• Refer to local and national 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.
• 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.
• The clinical genetics team will review the NHS England National Genomic Test Directory eligibility criteria, which identifies the tests for which patients are eligible. The directory itself provides a list of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• 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 in which you think your patient might have a diagnosis of aneuploidy (trisomy 13, 18 or 21) based on the risk calculation.
  • 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, 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.
        • A record of discussion form 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 all these tests, an amniocentesis or chorionic villus sample or fetal blood sample (in an EDTA tube) is required. For many of the tests (particularly whole genome and exome sequencing), parental samples are also needed or are helpful. Please refer to your local Genomic Laboratory Hub for details of test request forms and where to send samples.
• 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

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