Presentation: Fetus that is small for gestational age

A woman attends her 28-week community midwife appointment and is found to have a symphysis fundal height below the 10th centile on her customised growth chart. She is referred to secondary care for a fetal growth scan, during which it is confirmed that the fetus is on the first centile based on fetal biometry.

Genomic testing should be considered if:

• there is significant intrauterine growth restriction – particularly if there is no evidence of placental insufficiency or other suspected explanation (note that there may be co-existing placental insufficiency with a genomic cause for small fetal size);
• there are additional fetal anomalies on ultrasound scan;
• early pregnancy aneuploidy screening gave a higher-chance result; and/or
• there is a family history of a genetic condition.

If the fetus has short long bones, rather than generalised reduced growth, please see Pregnancy with suspicion of a skeletal dysplasia.

• 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.
• Refer to local guidance regarding fetal medicine referral, as further review in a fetal medicine unit is usually warranted.
  • The fetal medicine review will determine whether genomic testing is appropriate, and referral to clinical genetics will be considered.
  • The fetal medicine team will decide which testing is most suitable and/or discuss the case with a multidisciplinary team, depending on the specific clinical scenario and the parents’ wishes.
  • Routine referral to clinical genetics is not routinely indicated.
• Depending on the clinical scenario, a range of different genomic tests 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.
  • R21 Fetal anomalies with a likely genetic cause: fetal exome sequencing can be considered under the following circumstances:
    • all measurements < third percentile (including abdominal circumference and head circumference), with a confirmed early ultrasound estimated date of delivery scan; and
    • no evidence of placental insufficiency, including normal fetal and maternal dopplers;
    • no history of previous fetal growth restriction or stillbirth;
    • normal PAPP-A (if measured); and
    • no maternal history of systemic lupus erythematosus or similar.
  • Referral to clinical genetics and/or multidisciplinary discussion is required for R21.
• Where a specific genetic condition is considered likely or there is a relevant family history, specific genomic testing my be recommended.
• 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.
• 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, 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 record of discussion 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 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 England and NHS Improvement: Guidance document: Rapid exome sequencing service for fetal anomalies testing (PDF, 19 pages)
• 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)
• NHS South and Central Genomics: Rapid prenatal exome sequencing (R21) inclusion criteria (PDF, 2 pages)
• Royal College of Obstetricians & Gynaecologists: Small-for-gestational-age fetus and a growth restricted fetus, investigation and care (Green-top Guideline no. 31)

For patients

• Antenatal Results & Choices
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: Information on prenatal exome sequencing for parents (PDF, two pages)
• Royal College of Obstetricians & Gynaecologists: Having a small baby