Presentation: Second- or third-trimester intrauterine death or stillbirth

A woman in her third pregnancy attends at 25 weeks for her first scan. She has already had two healthy babies. The pregnancy was dated based on the head circumference. The team identifies polyhydramnios with a visible stomach and normal bladder. The baby is small. The woman declines any screening or genomic testing. At a follow-up scan at 28 weeks, the team identifies an IUD.

Genomic testing should be considered in the presence of:

• severe intrauterine growth restriction, especially in the absence of pre-eclampsia; and
• a structural fetal anomaly.

• Follow your local protocol for consent for post-mortem and cytogenetic testing. If the obstetrics team or pathologist deem it appropriate, a referral to clinical genetics may be completed.
• The clinical genetics team will review the National Genomic Test Directory eligibility criteria to determine which tests are available. The directory itself provides a list of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• Genomic testing will depend on the phenotype of the fetus. It can include:
  • R27 Paediatric disorders;
  • R22 Fetus with a likely chromosomal abnormality; and
  • R412 Fetal anomalies with a likely genetic cause – non-urgent (this should be considered if R27 has not been possible, for example if there is insufficient DNA for whole genome sequencing).
• Where a skeletal condition is suspected, the following tests may also be useful:
  • R24 Achondroplasia;
  • R25 Thanatophoric dysplasia;
  • R104 Skeletal dysplasia; and
  • R102 Osteogenesis imperfecta.
• Note: R27 is an amalgamation of over 10 panels of genes known to be associated with a broad range of paediatric developmental conditions. It may now be ordered directly by paediatricians, though a discussion with clinical genetics services may be beneficial.
• For tests that do not include WGS, including R22, R412, R24, R25, R104 and R102:
  • you can use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) forms; and
  • 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 tests that are undertaken using WGS, including R27, you will need to:
  • complete an NHS GMS test order form with details of the affected individual (proband) and their parents where available, including details of the phenotype (using human phenotype ontology (HPO) terms) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support in completing WGS-specific forms); and
  • complete an NHS GMS record of discussion (RoD) form for each person being tested – for example, if you are undertaking trio testing of an affected individual and their parents, you will need three RoD forms (see How to complete a RoD form for support).
• Please refer to your local GLH for details of test request forms and where to send samples.
• For DNA-based tests (the above listed tests), a cord sample is preferred (though alternative samples may come from a post-mortem). For more information, 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
• Royal College of Obstetricians & Gynaecologists: Late intrauterine fetal death and stillbirth (Green-top Guideline No. 55) (PDF, 33 pages)

References:

• Kooper AJA, Faas BHW, Feenstra I and others. ‘Best diagnostic approach for the genetic evaluation of fetuses after intrauterine death in first, second or third trimester: QF-PCR, karyotyping and/or genome-wide SNP array analysis‘. Molecular Cytogenetics 2014: volume 7, issue 1, page 6. DOI: 10.1186/1755-8166-7-6
• Liu J, Huang L, He Z and others. ‘Clinical value of genetic analysis in prenatal diagnosis of short femur‘. Molecular Genetics & Genomic Medicine 2019: volume 7 issue 11, page e978. DOI: 10.1002/mgg3.978

For patients

• Sands: Deciding about a post-mortem examination: Information for parents (PDF, 40 pages)
• Tommy’s: Stillbirth information and support