Presentation: Pregnancy where previous pregnancy or child diagnosed with 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 (CVS) following a higher-chance first-trimester combined screening 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 group of women are offered this test because a past history of a pregnancy or child with full trisomy 21, 18 or 13 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 instead be considered, where:
  • 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: mosaicism, translocation or partial trisomy of chromosome 21, 18 or 13; or
  • one of the parents has a Robertsonian translocation or 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 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 our dedicated Knowledge Hub resource.
• For information on the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Confirm 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/ quadruple screening test on the NHS Fetal Anomaly Screening Programme (NHS FASP) for this group of women. Therefore, women eligible for the R445 pathway should not be offered a combined or quadruple screening test on the NHS FASP.
• Where eligibility criteria for R445 is met, pregnant women should be offered the following three options:
  • No testing for trisomy 21, 18 or 13.
  • Pre-natal diagnosis (CVS or amniocentesis).
  • Screening via R445 Common aneuploidy testing – NIPT: For trisomy 21, 18 or 13.
• Where the woman opts to proceed directly for prenatal diagnosis via invasive testing, rather than R445, refer for an amniocentesis or chorionic villus sample as according to local guidelines.
• Where the women 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 procedure to include using correct bottles, sample volume, form completion, sample storage and transport to laboratory.
• If anomalies are noted at the time of the dating scan, then R445 should not be taken. A referral to a fetal medicine unit is usually recommended for further detailed scanning and a review to determine appropriate testing options.
• 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

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 2021: issue 9, pages e1–e15. DOI: 10.1111/1471-0528.16821

For patients

• Antenatal Results and Choices
• Down’s Syndrome Association
• Gov.uk guidance: Your choices after a higher-chance screening result
• NHS: Screening tests in pregnancy
• Positive about Down syndrome
• SOFT UK (Support Organisation for Trisomy 13/18)