Guidance

Counselling and referral for prenatal diagnosis (PND)

Updated 6 July 2018

1. Introduction

This guidance is for healthcare professionals who provide counselling and referral for prenatal diagnosis (PND) to couples and women at risk of having a baby with sickle cell disease or thalassaemia major.

Couples or women at risk are defined as:

• both biological parents being either a carrier of a significant haemoglobin variant or affected by sickle cell disease or thalassaemia
• the woman is a carrier of a significant haemoglobin gene variant or affected by sickle cell disease or thalassaemia and the screening status of the biological father is unknown

If it is not possible to test the baby’s biological father in every pregnancy and a previous result is being used then this fact must be recorded in the woman’s notes for the current pregnancy.

The previous result must be from a laboratory accredited by the UK Accreditation Service (UKAS), previously Clinical Pathology Accreditation (CPA). It must be consistent, unequivocal, well documented, and interpreted and reported within the testing algorithms of the laboratory handbook.

All maternity units should provide a publically available and advertised direct dial number or email address, or both, for the use of women or couples, GPs and midwives. There must be a clear pathway, with a named individual or team responsible at each step to:

• provide direct access to counselling and PND for known at risk couples and known carrier women
• check screening results
• offer testing to the baby’s biological father
• identify women and couples at risk of having a baby with sickle cell disease or thalassaemia major in their current pregnancy
• counsel women and couples and refer for PND
• obtain the fetal sample and dispatch to the molecular laboratory along with parental venous blood samples
• follow-up after PND

See Appendix 6 for a flowchart outlining the pathway.

1.1 Carrier women and at risk couples

Carrier women with no paternal result available, and known carrier couples, who are at risk of having a baby with a major haemoglobin disorder must be:

• offered an urgent face to face counselling appointment to explain their carrier status (see Appendix 5 for sample counselling form)
• given information about the condition that may affect their baby
• made aware that in pregnancies that result from egg or sperm donation, the genes inherited by the baby are those of the biological donor
• provided with an explanatory leaflet^{[footnote 1]} before or after the counselling session
• given information regarding the options for the pregnancy
• given contact details for the relevant condition of UK patient societies the Sickle Cell Society or the UK Thalassaemia Society
• made aware that the decision to have a diagnostic test is an informed choice by the woman or couple
• offered an appointment for PND
• made aware of the intrinsic miscarriage risk associated with PND whether the baby is affected or not ^{[footnote 2]}

1.2 Women and couples who present as known carriers

Women and couples with carrier status known before the current pregnancy must be fast-tracked and immediately offered a counselling appointment to discuss their options as soon as they present in pregnancy. Confirmatory carrier screening must still be offered to the couple. To avoid delay in access to PND, this should occur at the same time as the referral.

If the baby’s biological father is unavailable for screening in this pregnancy, then the woman should still be counselled and offered PND without a paternal screening result. There should be a risk assessment based on the ethnicity of the baby’s father to determine the risk of him being a carrier.

2. Referral for prenatal diagnosis

If there is any doubt about the parental genotypes, or the need for further parental testing prior to fetal sampling, contact the relevant molecular haemoglobinopathy laboratory for advice.

There are 4 haemoglobinopathy DNA laboratories in England which offer analysis of PND samples for sickle cell disease and thalassaemia disorders^{[footnote 3] [footnote 4]}. Each laboratory has its own specified PND request form. A fully completed form must accompany the fetal and parental samples.

See laboratory contacts details at the bottom of this section for links to PND request forms.

In addition to demographic information for both parents, the details on the PND referral form must include:

• maternal and paternal (if available) haemoglobinopathy results
• gestational age of the fetus including estimated date of delivery (EDD) by last menstrual period (LMP)
• the following maternal antenatal screening booking blood results (where feasible but should not delay the referral):
  • full blood count
  • hepatitis B status
  • HIV status
  • blood group and rhesus factor
• whether the woman or couple consent to PND for any other condition, such as fetal anomaly

2.1 Parental samples

A parental blood sample (10 ml EDTA from each parent), must be sent to the DNA laboratory with the fetal sample, whether or not the woman or couple has had a previous PND.

If a paternal sample is unavailable, a maternal blood sample should still be sent to confirm the maternal genotype and to exclude maternal contamination of the fetal sample.

If the paternal genotype is known (because the father has been tested before) but the father is unavailable or declines testing, then a copy of his laboratory result should be sent to the PND laboratory so the fetal risk can be assessed. The result should be from a laboratory accredited by UKAS, and be consistent, unequivocal and well documented.

If the paternal genotype is unknown and the father is unavailable or declines testing, PND can still be carried out but this makes diagnosis of conditions more complex. If extended testing is required, this could delay the turnaround time of the fetal diagnosis. If the ethnic origin of the father is known, this should be included on the PND referral form.

2.2 Sickle cell disease

Fetal diagnosis of a haemoglobin disorder in the case of sickle cell disease is generally a straightforward process. It is usually achieved without the need for molecular confirmation of parental carrier status.

2.3 Thalassaemia conditions

In thalassaemia conditions, it is possible to inherit one of a large range of genetic mutations. If a couple have not had PND before, you should send parental bloods for molecular confirmation of carrier status prior to fetal sampling. This will assist with a quicker fetal diagnosis result. If the couple has had PND before, or molecular confirmation, details of the previous PND should be included on the referral form.

3. Declining prenatal diagnosis

If PND is declined, the healthcare professional who has counselled the couple and recorded their decision must inform:

• the couple of the process for screening their baby after birth and how they will obtain the result
• the maternity department screening coordinator or equivalent
• the woman’s GP
• the newborn screening laboratory of the at risk couple (see Appendix 7 for an example of a pregnancy alert form)
• the couple of contact details for UK patient societies for the relevant condition
• parents that they can reconsider their decision at a later date

4. Prenatal diagnosis procedure

Local arrangements must be in place to obtain an urgent fetal sample for prenatal diagnosis. The diagnostic approach^{[footnote 2] [footnote 5]} usually depends on the gestational age of the fetus. The sample will be obtained by one of the following methods:

• chorionic villus sampling (CVS) undertaken from 11 weeks of pregnancy
• amniocentesis performed from 15 to 16 weeks of pregnancy
• fetal blood sampling

The molecular haemoglobinopathy laboratory must be contacted before dispatching the sample, so that it expects a prenatal diagnosis sample for analysis and can follow up samples that do not arrive.

5. Prenatal diagnosis follow-up

5.1 Reporting

PND results assume the stated family relationships are true. Any inaccuracies, such as non-paternity, can lead to a misdiagnosis of the fetal condition.

Results must be:

• issued within 3 working days following receipt of the sample in the DNA laboratory
• sent to the named healthcare professional via a secure, confidential method (a copy of the report may also be sent by first class post)
• communicated to the woman or couple within 5 working days of the PND test

In special circumstances, the final result may be delayed beyond 3 working days, for example if there:

• is no paternal sample or genotype
• are complicated genetics
• is an inadequate sample
• is maternal contamination of the sample
• are multiple pregnancies

5.2 Results

The pathway for giving the woman or couple the results should be agreed during the counselling session prior to the procedure.

Clinicians must ensure there are processes in place for all the PND results, including fetal karyotyping, to be communicated to the parents, ideally at the same time.

The report will show one of the following results: not affected, carrier or affected.

If the baby is not affected, or is a carrier, then:

• no further appointments or follow-up is required during pregnancy and the pregnancy should continue as normal
• a record of the results and the baby’s due date should be kept by the maternity or specialist counselling service for review after the baby’s birth
• the relevant newborn blood spot screening laboratory should be informed of the PND result (a sample notification form is in Appendix 7)
• parental screening and PND results should be included on the newborn blood spot card^{[footnote 6]}

If the baby is affected with a major haemoglobin disorder and the woman or couple choose not to have a termination of pregnancy, then the responsible healthcare professional must:

• offer the woman or couple an opportunity for a face to face discussion about the results
• offer the parents a paediatric consultation to discuss the implications for their baby
• offer counselling
• offer the couple contact details for the relevant condition of UK patient societies the Sickle Cell Society or the UK Thalassaemia Society
• communicate information about the PND results to all healthcare professionals involved in the ongoing pregnancy
• notify the newborn screening laboratory of the PND result and the fact that the couple are continuing with the pregnancy (see sample notification form in Appendix 7)
• ensure that arrangements are made for parental screening and PND results to be included on the newborn blood spot card

If the baby is affected with a major haemoglobin disorder and the woman or couple choose to terminate the pregnancy, an opportunity for a face to face discussion with the relevant healthcare professional(s) must be provided to:

• confirm the decision to proceed with a termination of pregnancy
• explain the termination procedure, and what happens afterwards

The PND results and subsequent parental decision must be recorded in the maternity and counselling records and communicated to all relevant healthcare professionals involved in the screening pathway.

Termination of pregnancy should be organised and provided within 5 days of making the decision^{[footnote 7]}.

A qualified healthcare professional should offer ongoing counselling support.

5.3 Termination of pregnancy

Arrangements for termination of pregnancy should be organised locally by the trust that makes the referral for PND.

5.4 Pre-implantation genetic diagnosis

Pre-implantation genetic diagnosis (PGD) enables people with a specific inherited condition in their family to avoid passing it on to their children. PGD involves checking the genes of embryos created through IVF for specific genetic conditions, avoiding the need for invasive prenatal diagnostic procedures and possible termination of an affected pregnancy.

The process to establish pregnancy is identical to that used for infertility treatment with the genetic status of embryos pre-determined in vitro using assisted reproductive technology.

Further information is available from Genetic Alliance UK and NHS.UK.

5.5 Data collection

The NHS Sickle Cell and Thalassaemia Screening Programme collects and publishes annual data on all PNDs performed throughout England^{[footnote 8]}.

Screening midwives or specialist counselling services are required to complete a pregnancy outcome form (Appendix 8) for each PND. They must then return the information to the relevant haemoglobinopathy DNA laboratory, so that a record of the pregnancy outcome can be completed.

The National Congenital Anomaly and Rare Disorders Registration Service (NCARDRS)^{[footnote 9]} collects screening results and outcomes for the NHS SCT Screening Programme on pregnant women who have opted for PND. Data is collected from the PND laboratories.

NCARDRS has permission to collect patient-identifiable data without the need for individual informed consent (CAG ref: CAG 10-02(d)/2015). Women can opt out of the register at any time.

The main aim is evaluate the screening programme. To achieve this, the screening co-ordinator or specialist nurse at the maternity unit providing antenatal care must return the pregnancy outcome form to the PND laboratory.

6. Laboratory contact details

John Radcliffe Hospital Oxford

Molecular Haematology
Level 4
John Radcliffe Hospital
Headington
Oxford
OX3 9DU

Email hbopathy.screening@nhs.net; molhaem@ouh.nhs.uk; oxford.molecularhaem@nhs.net

Contact form http://www.oxford-tran...

Telephone 01865 572 769

Telephone 01865 572 826

Fax 01865 572 775

King’s College Hospital

C/O Central Specimen Reception
Blood Sciences Laboratories
Ground Floor Bessemer Wing
King's College Hospital
Denmark Hill
London
SE5 9RS

Email kch-tr.PND@nhs.net

Contact form http://www.viapath.co....

Telephone 020 3299 4337

Laboratory telephone 020 3299 9000 ext. 2265

Fax 020 3299 1035

University College London Hospitals NHS Foundation Trust

Haemoglobinopathy Genetics Centre
Molecular Genetics Laboratory
307 Euston Road
London
NW1 3AD

Email haemoglobinopathygenetics@nhs.net

Contact form https://www.uclh.nhs.u...

Telephone 020 344 79458

Fax 020 344 79864

Central Manchester University Hospitals NHS Foundation Trust

Directorate of Laboratory Medicine
Molecular Diagnostics Centre
Top floor, CADET and MDC Building
Oxford Road
Manchester
M13 9WL

Contact form http://www.cmft.nhs.uk...

Telephone 0161 276 5990

Telephone 0161 276 4809

Fax 0161 276 5989

PND referral form http://www.cmft.nhs.uk/info-for-health-professionals/laboratorymedicine/haematology/haemoglobinopathy

1. NHS Sickle Cell & Thalassaemia Screening Programme (2017) Information for couples at risk of having a baby with sickle cell disease and Information for couples at risk of having a baby with thalassaemia major ↩

2. Public Health England (2017) CVS and amniocentesis diagnostic tests: description in brief ↩ ↩²

3. UK Genetics Testing Network ↩

4. NHS Sickle Cell & Thalassaemia Screening Programme (2017) Handbook for Antenatal and DNA Laboratories 4th edition ↩

5. Royal College of Obstetricians & Gynaecologists (2010) Amniocentesis and Chorionic Villus Sampling (Green-top Guideline No.8) ↩

6. Newborn Bloodspot Screening Programme (2016) Guidelines for newborn blood spot sampling ↩

7. UK Thalassaemia Society (2016) Thalassaemia Standards ↩

8. NHS Sickle Cell & Thalassaemia Screening Programme (2017) Data report, trends and performance analysis ↩

9. National Congenital Anomaly and Rare Disease Registration Service ↩