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.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests. 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 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 multi-disciplinary discussion is required.
• • Where a specific genetic condition is considered likely or there is a relevant family history, further guided genomic testing my be recommended.
• 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 Genomic Medicine Service record of discussion form for each person being tested (for example, 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); and
• • submit parental samples alongside the child’s sample (this is called trio testing). If this is not possible, for example because the child is 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;
• • 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; and
• • bear in mind that 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 and require an amniocentesis or chorionic villus sample or fetal blood sample in an EDTA tube (purple-topped tube).
• 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 South and Central Genomics: Rapid prenatal exome sequencing (R21) inclusion criteria (PDF, 2 pages)
• Royal College of Obstetricians and Gynaecologists: Small-for-gestational-age fetus, investigation and management (Green-top Guideline no. 31)

For patients

• Royal College of Obstetricians and Gynaecologists: Having a small baby