Presentation: Pregnant woman with a previous pregnancy or baby diagnosed with full trisomy 21, 18 or 13

A pregnant woman is referred to an appropriately trained midwife (or genetic counsellor), having disclosed that her first pregnancy was terminated following a diagnosis of Patau syndrome (trisomy 13). This was diagnosed via a chorionic villus sample following a higher-chance first-trimester combined screening result and non-invasive prenatal testing (NIPT). She wants to discuss the chance of recurrence in this pregnancy and wishes to explore what prenatal options are available.

• The R445 testing pathway is offered to all women with a history of a pregnancy or child diagnosed with full trisomy 21, 18 or 13. This is because having this history is associated with an increased chance of recurrence in a future pregnancy (a priori chance of about 1% or the chance related to maternal age, whichever is the greatest).
• R445 is not to be offered, and referral to clinical genetics should be considered instead, if:
  • a previous pregnancy was a trisomy involving chromosomes other than chromosome 21, 18 or 13;
  • a previous pregnancy was not a full trisomy – for instance, it involved mosaicism, translocation or partial trisomy of chromosome 21, 18 or 13; or
  • one of the parents has a Robertsonian translocation or a balanced translocation involving chromosome 21, 18 or 13.
• R445 should not be offered where the current pregnancy was conceived using a donor egg, unless the egg for this pregnancy is from the same egg donor used in a previous pregnancy diagnosed with trisomy 21, 18 or 13.
• In addition, the standard exclusion criteria for NIPT apply (see section 1.2 of the guidance).
• Eligibility and exclusion criteria may change over time. Always refer to the latest version of the test directory to confirm eligibility criteria prior to offering a test. Discuss with your local NIPT laboratory or clinical genetics team if there is any uncertainty about eligibility.

• Consult the National Genomic Test Directory. From here 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 Genomic testing in the devolved nations.
• For information about the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Confirm that the eligibility criteria for R445 are met prior to offering the testing pathway.
• • Prior to offering R445, it is recommended that the report from the previous affected pregnancy is reviewed to confirm full trisomy of chromosome 21, 18 or 13. However, the test can still be offered even if the previous report is unavailable. In such cases, it should be explained to the woman that the test is being performed on the basis that the previous pregnancy was a full trisomy 21, 18 or 13 and not another chromosomal anomaly, as these will not be detectable by NIPT.
• • Note that R445 replaces the combined first-trimester screening test (or quadruple screening test) on the NHS Fetal Anomaly Screening Programme (FASP) for affected women. Therefore, women eligible for the R445 pathway should not be offered a combined or quadruple screening test on the NHS FASP.
• Where the eligibility criteria for R445 are met, the pregnant woman should be offered the following three options:
• • no testing for trisomy 21, 18 or 13;
• • prenatal diagnosis (via chorionic villus sampling or amniocentesis); or
• • screening via R445 Common aneuploidy testing – NIPT.
• Where the woman opts to proceed directly for prenatal diagnosis via invasive testing, rather than R445, arrange for an amniocentesis or chorionic villus sample according to local guidelines.
• Where the woman opts for R445, arrange an early dating scan to confirm gestation prior to taking a blood sample. The blood sample can be taken from 10⁺⁰ to 21⁺⁶ weeks’ gestation (inclusive) for both singleton and twin pregnancies. Refer to local NIPT laboratory guidance on sampling procedures – including correct bottles, sample volume, form completion, sample storage and transport to laboratory.
• If anomalies are noted at the time of the dating scan, R445 should not be undertaken. A referral to a fetal medicine unit is usually recommended for further detailed scanning and a review to determine appropriate testing options.
• 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) form.
• 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

• Birmingham Women’s and Children’s NHS Foundation Trust: Prenatal-reproductive genomic testing
• Central and South NHS Genomic Medicine Service Alliance: Offering non-invasive prenatal testing (NIPT) for pregnant women (Video, 5 minutes 24 seconds)
• Gov.uk Guidance: Down’s syndrome, Edwards’ syndrome and Patau’s syndrome screening pathway
• Gov.uk Guidance: Screening for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome
• Gov.uk Guidance: Screening for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome: NIPT
• NHS England: National Genomic Test Directory
• St George’s University Hospitals NHS Foundation Trust: Non-Invasive Prenatal Testing (NIPT) – The SAFE Test
• The Doctors Laboratory: NIPT via the National Genomics Test Directory

References:

• Navaratnam K and Alfirevic Z on behalf of the Royal College of Obstetricians and Gynaecologists. ‘Amniocentesis and chorionic villus sampling: Green-top Guideline no. 8‘. The British Journal of Obstetrics and Gynaecology 2022: volume 129, issue 1, pages e1–e15. DOI: 10.1111/1471-0528.16821

For patients

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