Presentation: Patient with a higher-chance non-invasive prenatal test (NIPT) result

A couple have opted to have non-invasive prenatal testing (NIPT) following a combined screening result that gave an increased chance (1 in 20) of Down syndrome (trisomy 21). The couple have just been given the results of that NIPT, which show a higher chance of trisomy 21. This is in keeping with their combined screening results.

• All women who have a higher-chance NIPT result should be offered the option of diagnostic genomic testing.
• If the first NIPT sample gives no result, or the sample is rejected, the pregnant woman should be offered either a further NIPT sample or diagnostic genomic testing.
• If the second sample also fails to give a result, the patient should be given the option of diagnostic genomic testing.

• Refer to local guidance regarding higher-chance NIPT discussion and fetal medicine referral.
• Referral to clinical genetics is not routinely indicated for a higher-chance NIPT result. A review by the fetal medicine team will determine whether genomic testing is appropriate, and referral to clinical genetics can be considered in certain circumstances.
• The relevant team will refer to the National Genomic Test Directory to determine which tests are appropriate, depending on the clinical scenario.
• • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• If there is an isolated higher-chance NIPT result in a fetus that appears otherwise structurally normal for that gestation:
• • R401 Common aneuploidy testing – prenatal: Genome-wide common aneuploidy testing (QF-PCR).
• If there are structural anomalies present in addition to a higher-chance NIPT result, further testing may be relevant:
• • R22 Fetus with a likely chromosomal abnormality. This will process both:
• • • R22.1 Genome-wide common aneuploidy testing; and
• • • R22.2 Genome-wise microarray.
• Although it is unlikely to be required in this scenario, if there are multiple or complex anomalies fetal exome sequencing may be considered following discussion with tertiary fetal medicine and clinical genetics teams:
• • R21 Fetal anomalies with a likely genetic cause: Rapid fetal exome sequencing.
• None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion, or RoD) form.
• Parental samples may be needed for interpretation of the proband’s result. Parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed.
• For R21 Fetal anomalies with a likely genetic cause, you will need to:
• • ensure that the required multidisciplinary discussions have taken place, including fetal medicine, clinical genetics and the regional specialist R21 laboratory, and that there is an agreement that R21 can be offered;
• • inform your local laboratory of the plan for R21 testing, so that they can arrange the necessary exports to the specialist R21 laboratories in a timely fashion;
• • fill in the R21-specific test order form;
• • take informed consent for both parents, documented on R21-specific RoD forms;
• • send blood samples for both parents to the local laboratory (if only one parent is available, let the lab know – testing can still proceed, but there will be a small reduction in diagnostic yield); and
• • arrange and send a chorionic villus sample or amniocentesis sample for the fetus.
• Note that, in Scotland, referral to clinical genetics is required for consideration of rapid prenatal exome testing.
• All of the above tests are DNA based and require an amniocentesis or chorionic villus sample, or a fetal blood sample in an EDTA (typically purple-topped) tube. For more information about different sample types, see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• 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

• NHS England: National Genomic Test Directory
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: National Genomic Test Directory Clinical Indication R21 Rapid prenatal exome sequencing test request (PDF, two pages)
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: Record of discussion regarding prenatal exome sequencing (PDF, two pages)

For patients

• Antenatal Results & Choices: Non-invasive prenatal testing (NIPT) (also known as cfDNA screening)
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: Information on prenatal exome sequencing for parents (PDF, two pages)
• St George’s University Hospitals NHS Foundation Trust: The SAFE test (PDF, two pages)