Fetal genotyping – diagnostic

Optimising antenatal care

• Clinicians can focus on women with an antigen positive fetus
• Closely monitor antigen negative women with maternal allo-antibodies against fetal red cell surface antigens Preventing Haemolytic Disease of the Fetus and New-born (HDFN)
• Mothers with an antigen negative fetus can relax and enjoy their pregnancy with minimal monitoring

Overall, it saves cost and time for those mothers who do not need:

• repeated clinic attendance
• Doppler scans
• referrals for antibody quantification and titres

• Molecular Diagnostics Service User Guide INF1135 (PDF 406KB)
• TC140 Molecular Diagnostics Terms and Condition's contract (PDF 411KB)
• Fetal Genotyping Sample Referral Form - FRM4674 (Word 113KB)
  
  • Guidance for completion of form FRM4674 (PDF 143KB) 
• Preparation of plasma to be sent to IBGRL for fetal (PDF 124KB) genotyping (INF1291)
• Filton-Molecular Diagnostics-address labels (Word document 54KB)
• Information about Blood Groups and Red Cell Antibodies in Pregnancy (INF166) 

Demand printed labels

If you would like NHSBT to consider accepting samples from your hospital / Trust which have been labelled using a demand printed labelling system, please complete the application form below.  The sample label requirements are specified on the form.

Complete the application form 

UK LABORATORIES

Turnaround times will depend on the complexity of the test required. IBGRL normally issues 85% of reports within the turnaround times stated. Quicker turnaround times are possible for urgent samples - please enquire (see details above).

Summary of 2017/22 turnaround times achieved (PDF 352KB)

A single report will be posted to the address indicated on the referral form. Reports are also available on the Sp-ICE reporting system.

Reports available to view on the Sp-ICE system in PDF format:

• Fetal genotyping from maternal plasma
• Full genotyping for common blood group antigens

If you do not currently have access to the Sp-ICE browser and wish to view these reports, please contact your local Transfusion Laboratory Manager (Sp-ICE primary contact) or e-mail ICE@nhsbt.nhs.uk for training and access

INTERNATIONAL LABORATORIES

A paper copy of results will be sent to the clinician indicated on the accompanying form. Urgent cases can be reported by E-mail.

Please see user guide INF1135 for sample acceptance criteria.

 Samples should be sent by first class mail or courier to ensure arrival, between Monday and Friday, within the specified time frame listed in the user guide. Blood samples can be sent at room temperature.

Samples which have lysed due to prolonged time in transit, or which are not in the desired anti-coagulant (See table above), will not be tested.

Please complete and return the appropriate form (See table above).

Please indicate the urgency of the investigation and the infection risk status, if known.

Information regarding the ethnic origin of the patient and partner and previous relevant clinical history is very useful for interpretation of results.

Please indicate which clinician the result should be reported (other than the referring laboratory) and where the invoice should be addressed.

Please see user guide INF1135 for sample acceptance criteria

Samples should be sent by express mail, courier or by air freight to ensure arrival, between Monday and Friday, within the specified time frame listed in the user guide.

If the time frame cannot be met, samples can be sent as aliquots of frozen plasma prepared to a protocol provided by IBGRL – see INF1291. Please contact the laboratory prior to sending frozen plasma. Frozen plasma aliquots that do not meet the sample labelling requirements listed in INF1291 will not be tested.

Samples which have lysed due to prolonged time in transit, or which are not in the desired anti-coagulant (See table above), will not be tested.

Please complete and return the appropriate form (See table above).

Please indicate the urgency of the investigation and the infection risk status, if known.

Information regarding the ethnic origin of the patient and partner and previous relevant clinical history is very useful for interpretation of results.

Please indicate which clinician the result should be reported (other than the referring laboratory) and where the invoice should be addressed.

There are now known to be several genetic causes for the RhD-negative phenotype of an individual. These causes vary according to ethnic origin. In Caucasian RhD-negative individuals the RHD gene is nearly always absent, however the majority of RhD-negative black Africans have an intact but non-functional RHD gene, termed the RHD-pseudogene. This pseudogene contains a 37 base pair insert in exon 4 and a nonsense mutation in exons 5+6, which may introduce stop codons preventing translation. Singleton et al. Blood, 95:12-18 (2000)

The non-invasive test from maternal plasma uses quantitative polymerase chain reaction (PCR) to amplify exons 4, 5, 7 + 10 of the RHD gene. Quantitative PCR is also carried out to detect the CCR5 gene to confirm the presence of DNA in the sample, although this does not distinguish between maternal and fetal DNA.

These non-invasive tests from maternal plasma use quantitative PCR to amplify the appropriate exons in the RHCE gene for typing Rhc and RhE. RhC is genotyped by targeting a sequence in intron 2 of the RHCE gene that is always associated with RhC. Kell genotyping is performed by detection of a single nucleotide polymorphism in exon 6 of the KEL gene. Quantitative PCR is also carried out to detect the CCR5 gene to confirm the presence of DNA in the sample, although this does not distinguish between maternal and fetal DNA.