Presentation: Patient with a previous history of stillbirth

A woman books her pregnancy at eight weeks’ gestation. She had a previous intrauterine death (IUD) at 35 weeks’ gestation. All appropriate fetal loss tests were completed following the birth. At the time of the birth and afterwards, she was advised that it was “just one of those things” and was never given a reason. She has wondered ever since whether there was a genetic cause.

• Many stillbirths cannot be attributed to any cause. The most common identifiable cause of stillbirth is disorders of placental function, often manifesting as poor fetal growth.
• Up to 1 in 4 (25%) of all stillbirths have a genetic cause. This is more likely when fetal structural anomalies are identified.
• Genomic testing should be offered where:
  • Prenatal or postnatal fetal structural anomalies are identified.
  • There is a family history of a genetic condition.

• 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 the patient for consultant-led care via local pathways.
• Referral to clinical genetics services for clinical review where there is no clear cause for the previous pregnancy loss.
• Genetic testing of previous pregnancies may be considered where the history suggests that this is appropriate and tissues or samples are available. If management of an ongoing pregnancy would be altered by a genetic diagnosis, these processes can often be expedited.
• If there is evidence of fetal anomaly in the current pregnancy, the following testing may be considered:
  • R22 Fetus with a likely chromosomal abnormality. This will process both:
    • R22.1 Genome-wide common aneuploidy testing; and
    • R22.2 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.
• For tests that are undertaken using whole genome sequencing (WGS), 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 or 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 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).
  • parental samples should be submitted alongside the child’s sample. This is called trio testing. If this is not possible, such as when testing a child in care or a parent is unavailable for testing, the child may be tested as a singleton.
• For tests that do not include WGS, you will need to:
  • complete a test order form and consent (record of discussion) form, available from your local Genomic Laboratory Hub (GLH).
  • include details of the phenotype in the test order form (refer to HPO terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
  • 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.
• All of the above tests are DNA based, an EDTA sample (purple-topped tube) is required.
• 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
• Royal College of Obstetricians and Gynaecologists: Late intrauterine fetal death and stillbirth (Green-top Guidelines No.55)

For patients

• Antenatal Results and Choices: Another pregnancy
• Royal College of Obstetricians and Gynaecologists: When your baby dies before birth: Patient information
• Sands
• Tommy’s: Pregnant after a stillbirth