Presentation: Pregnancy in which the mother is diagnosed with, or is a known carrier of, a haemoglobinopathy disease

A pregnant woman attends an antenatal clinic. She is concerned because results from the sickle cell screening test she consented to (as part of her recent antenatal booking appointment) have shown that she is a carrier of an atypical haemoglobin or variant.

• If a pregnant woman is found to have, or be a carrier of, sickle cell disease or thalassaemia, or has had an inconclusive screening result, the biological father should be offered screening.
  • Testing may be a haematological screen (with a blood film) or a genomic test.
  • Often, assessing for sickle cell carrier status does not require genomic testing because it is possible to diagnose via haematological investigations.
• If both parents are carriers of genetic variants that cause a significant haemoglobinopathy, prenatal testing should be considered.
• If the biological father is not available for testing, prenatal testing should still be offered for at-risk pregnancies, along with counselling about test limitations.
• If a pregnant women is clinically affected with a haemoglobinopathy (rather than being a carrier), she will likely require specialist input in the management of her pregnancy. Discussion with obstetrics, maternal medicine and/or haematology services is key.

• Collect a detailed family, medical and clinical history from the couple.
  • In addition to the full blood count and haemoglobinopathy screening sample, you should submit a family origin questionnaire to the laboratory that includes information about the family origins of both the pregnant woman and the biological father. This enables clinical scientists to interpret results.
• Comprehensive guidelines have been published around when to refer for molecular testing (see the sickle cell and thalassaemia antenatal laboratory handbook). This process is designed to identify couples at risk of severe haemoglobinopathies so that prenatal diagnosis can be performed in a timely fashion.
• Follow local protocols to determine appropriate onward referral.
• The relevant team will refer to 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 options depend on the specific variant(s), but may include the below.
  • Carrier screening for the pregnant woman and the biological father:
    • R361 Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing. This test is for individuals who are likely to have or carry a clinically significant haemoglobinopathy (other than sickle cell disease) based on initial protein testing.
  • Diagnostic testing should be used in individuals who are likely to be affected with a haemoglobinopathy
    • R93 Sickle cell, thalassaemia and other haemoglobinopathies test.
      • R361 and R93 require blood to be collected in an EDTA (typically purple-topped) tube. Refer to your local Genomic Laboratory Hub for details of test request forms and where to send samples.
  • Prenatal invasive testing may be offered in pregnancies with known familial disease-causing variant(s). Referral to a fetal medicine unit is required.
  • Pre-implantation genetic testing may be available if the woman presents pre-conceptually. Referral via clinical genetics is required.
• A completed record of discussion form, or an alternative local consent form, will be required by the laboratory to process the sample.
• 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

• Gov.uk Guidance: Referral of antenatal samples for molecular analysis
• Gov.uk Guidance: SCT screening: Handbook for antenatal laboratories
• Gov.uk Guidance: Sickle cell and thalassaemia screening programme: Standards
• NICE: Antenatal care guidelines
• NICE: Sickle cell disease scenario: Screening
• NHS England: National Genomic Test Directory

References:

• Oteng‐Ntim E, Pavord S, Howard R and others. ‘Management of sickle cell disease in pregnancy. A British Society for Haematology Guideline‘. British Journal of Haematology (2021): volume 194, issue 6, pages 980–995. DOI: 10.1111/bjh.17671

For patients

• Gov.uk Guidance: Sickle cell and thalassaemia
• Gov.uk Guidance: Sickle cell and thalassaemia screening: Information for fathers
• NHS England: Maternal medicine networks: Service specification
• NHS Health A to Z: Screening for sickle cell and thalassaemia
• Sickle Cell Society
• UK Thalassaemia Society