Down’s, Edwards’ and Pataus syndromes screening protocol (CG481)

Approval and Authorisation

Approval Group Job Title, Chair of Committee Date Maternity Clinical Governance Chair, Maternity Clinical 4th June 2021 Committee Governance Committee

Change History Version Date Author, job title Reason 8.0 Mar 2018 Jo Young, AN screening Reviewed and updated to reflect coordinator current practice 8.1 February J Young, AN screening Live change to update reporting 2019 coordinator body to PHE FASP and adjust working practices in line with this change. 8.2 August J Young, AN screening Live change following PHE Audit 2019 coordinator July 2019 Pg 6 – 5.5 The Combined Test gestation period in which NT scan can take place updated to read 11+2 and 14+1 weeks 9.0 March 2020 J Young, AN screening Reviewed, changes throughout to coordinator reflect current practice pg 5 – 16 and introduction of new MATSOP039 and update of consent form 10.0 May 2021 S Lindsay-Birch, ANNB Live change to reflect process post Screening Specialist MW Go Live and introduction of NIPT from 1/6/21 ...... This protocol should be read in conjunction with the following: • Antenatal Screening protocol (CG474) • MAT-SOP-039 NT daily failsafe (WBCH only)

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 1 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

Contents 1.0 Purpose ...... Error! Bookmark not defined. 2.0 Scope ...... 3 3.0 Roles and Responsibilities ...... 3 4.0 Definitions ...... 4 5.0 Content ...... 5 5.1 The offer of screening ...... 5 5.2 Written information for Women ...... 5 5.3 Booking the scan appointment ...... 6 5.4 Late Bookers ...... 6 5.5 The Combined Test...... 6 5.6 NT greater than or equal to 3.5mm ...... 6 5.7 Bloods - Reading ...... 7 5.8 Bloods - Newbury ...... 7 5.9 Multiple ...... 8 5.10 The Quadruple Test ...... 8 5.11 Test Results ...... 8 5.12 Non-Invasive (NIPT) ...... 9 5.11.1 Eligibility - Inclusions ...... 9 5.11.2 Eligibility - Exclusions ...... 10 5.11.3 Eligibility Uncertain criteria ...... 10 5.13 Failsafe’s ...... 11 5.14 Test Results: Low PAPP-A ...... 12 5.15 NIPT results ...... 12 5.15.1 Managing NIPT results ...... 13 5.15.2 Giving results to women ...... 13 5.16 Prenatal diagnosis (PND) ...... 14 5.17 Education and training ...... 14 5.18 Audit and QA Requirements ...... 14 5.19 Unexpected Down’s, Edwards’ or Patau’s Live Births following Low Chance Screening ...... 15 5.20 Suspected Screening Incidents ...... 15 6.0 Local Contacts ...... 16 7.0 Consultation ...... 16 8.0 Dissemination/Circulation ...... 16 9.0 References ...... 17 10.0 Auditable standards: ...... 17 11.0 Implementation ...... 17 12.0 Training ...... 17

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 2 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

1.0 Purpose Public Health England (PHE) Fetal Anomaly Screening Programme (FASP) recommends that all women booking for antenatal care before 20 weeks’ gestation should be offered screening for Down’s, Edwards and Pataus syndromes. All Trusts work to the standards.

2.0 Scope To outline the procedures and working practices for Down’s, Edward’s and Patau’s syndrome screening, ensuring that the following aims are achieved: 1. To offer screening and diagnosis to all women booked before 20 weeks of pregnancy and attending for antenatal care within the booked cohort of the Royal Berkshire NHS Foundation Trust Maternity Services 2. To provide adequate high quality information on the screening process to support each woman to make an informed decision on whether to accept or decline the offer of screening. 3. To provide adequate information and support to enable the woman and her partner to make a decision on the outcome of the pregnancy. 4. For women with a confirmed diagnosis or in the event of positive NIPT following additional testing as a result of screening, who choose to continue the pregnancy, provide optimal management of the pregnancy, birth and newborn period. 5. For women with a confirmed diagnosis following additional testing as a result of screening who opt for termination of pregnancy to provide the optimal care and support including signposting to bereavement counseling

3.0 Roles and Responsibilities 3.1 Trust Antenatal and Newborn Screening Committee The Trust Antenatal and Newborn Screening Committee will: • Ensure that PHE FASP standards are implemented locally • Monitor compliance with Key Performance Indicators (KPIs) • Ensure audits against standards are completed. Facilitate and advise on all local policies, protocols and guidelines to be implemented into practice

3.2 Antenatal and Newborn Screening Co-ordinators The screening co-ordinators will: • Ensure local policies, protocols and guidelines for antenatal and newborn screening are in place • Ensure that failsafe systems are in place to ensure robust service provision. • Ensure that training on antenatal and newborn screening is available for all appropriate staff Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 3 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

• Ensure quarterly Screening KPIs are reported in a timely manner • Produce an annual report

3.3 Matrons The Matron for community and midwifery led services and the Matron for Hospital Service will: • Ensure that all midwifery staff have access to training on antenatal and newborn screening • Ensure that all local policies, protocols and guidelines are implemented into practice • Ensure that remedial actions are taken when KPIs fall below the expected standards

3.4 Individual Staff Members Staff will • Ensure their knowledge and skills on antenatal and newborn screening are regularly updated • Ensure that they provide all women with information to enable informed choice on screening • Ensure that individual practice is in line with local policies, protocols and guidelines.

4.0 Definitions 4.1 : the method of obtaining a sample of amniotic fluid for cytogenetic analysis of the 4.2 Chorionic Villus Sampling (CVS): the method of obtaining a small placental biopsy for cytogenetic analysis of the fetus 4.3 National Congenital Anomaly and Rare Disease Register Service (NCARDRS). This is a national database. Its purpose is to identify clusters of birth defects, help research, and monitor detection of fetal abnormalities through Ultra Sound Scan and Diagnostic and Screening tests. 4.4 Cytogenetics: the laboratory process whereby a diagnosis of chromosomal normality or abnormality can be made 4.5 Downs syndrome: the commonest cause of learning disability in children. Can be associated with other problems such as cardiac anomalies and hypothyroidism. Caused by having an extra copy of chromosome 21, also known as 21 4.6 DQASS: The Downs syndrome screening Quality Assurance Support Service. All laboratories and ultrasound departments involved in Downs’s syndrome screening have to submit data to DQASS at least every 6 months

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 4 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

4.7 Nuchal Translucency (NT): the fluid filled space at the back of the fetal neck visible on ultrasound scan. An increased NT measurement is associated with Downs’s syndrome and cardiac anomalies in the fetus 4.8 Serum/ Biochemical Screening: using the levels of certain biochemical markers in the mother’s blood to determine a chance of Downs’s syndrome in the fetus 4.9 Prenatal Diagnosis: the use of amniocentesis, CVS and detailed ultrasound scans to determine specific problems in the fetus

5.0 Content

5.1 The offer of screening All women attending for antenatal care before 20 weeks’ gestation will be offered antenatal screening for Down’s, Edward’s and Pataus syndromes. Screening is offered in 2 forms depending on gestation and technical ability to obtain certain images and measurements during USS examination. Combined Screen- 11+2 to 14+1 gestation (or Crown Rump Length of 45mm- 84mm) and NT measurement, with accompanying blood serum of Beta hCG and PAPP-A. This test offers screening for Downs, Edwards and Pataus Syndromes Quadruple test- From 14+1to 20+0 gestation (or Head Circumference of 101 to 170mm) a blood serum of Beta hCG, AFP and uE3 and Inhibin A. This test offers screening for Downs Syndrome. The offer of screening and the decision to accept or decline should be recorded in on EPR and on the designated consent form. The woman may choose: 1. To have screening for all 3 conditions 2. To have screening for Down’s syndrome only 3. To have screening for Edward’s and Pataus syndromes only 4. To decline all screening

5.2 Written information for Women Screening should be preceded by the provision of written information or information on how to access the information electronically via Gov.uk or the Mother and Baby App. At the initial contact with the GP surgery the woman should be given the PHE “Screening Tests for You and Your Baby” booklet. Where English is not the woman’s first language arrangements should be made to obtain a version in her first language, from the Gov.uk website: https://www.gov.uk/government/publications/screening-tests-for-you-and- your-baby-description-in-brief.

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 5 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

When the woman attends for her first scan the Sonographer will refer to the consent form in Appendix A, confirm choices and scan accordingly and on completing that scan file in the hospital notes.

5.3 Booking the scan appointment All women are offered an ultrasound scan with the option of screening for Downs Edwards or Pataus syndrome (dependent on gestation). Information regarding the screening options is given in PHE booklet Screening Tests for You and Your Baby, either how to access electronically or a written format. Women self-refer their pregnancy via the bookings line 0118 322 8964. A booking appointment is made on EPR for the relevant Community Midwife. Women phone 0118 322 7425 to book their nuchal scan following their booking appointment.

5.4 Late Bookers All women who book with their community midwife at or after 13 weeks will be fast-tracked for a scan to provide optimum opportunity for screening. The community midwife will phone the maternity ultrasound department on 0118 322 7279 and obtain an appointment for a scan within 5 days of the request. If the community midwife thinks the woman will be over 20 weeks in 5 days from booking, she should take blood for the Quad test at the booking appointment and inform the screening midwife. The bloods should be brought to the antenatal clinic and then sent to the Oxford University Hospital Screening Laboratory in the usual way. The screening midwife will update the Laboratory with the scan information via Lifecycle when it is available.

5.5 The Combined Test The NT scan can be performed between approximately 11+2 and 14+1 gestation (Crown-Rump Length (CRL) of 45-84mm), the scan and bloods are performed on the same day. It is the recommended test for women with multiple . The completed consent form for screening is filed in the woman’s hospital notes On completion of the NT measurement the Sonographer will enter the scan data onto the purple request form and send the woman directly to Antenatal Clinic for her bloods. The remainder of the form is completed by the blood taker in the antenatal clinic. It is the blood takers responsibility to ensure that all fields are completed correctly.

5.6 NT greater than or equal to 3.5mm All women with a fetal NT of ≥3.5mm are referred to one of the Screening Coordinator Midwives where possible. The SCO will discuss options for further testing with the woman and her partner and supply written information on the tests available. The couple may choose to have a Chorionic Villus Sampling (CVS) as soon as possible, or they may decide to wait for the

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 6 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

chance calculation first. If the woman chooses to complete the Combined Test and wait for the result, the SCO will contact the Oxford Screening Laboratory to expedite this result. If the woman chooses to have a CVS this will be booked onto EPR by the Screening Midwife. As an NT measurement ≥3.5mm is an abnormality the woman will be offered an appointment to see a Fetal Medicine Doctor within 2 working days. This will either be booked by the Sonographer or the SCO. A NT of greater than 3.5mm will be measured even if the woman has declined screening

5.7 Bloods - Reading The antenatal clinic (ANC) staff will scan the consent form onto EPR and document on the screening sticker (placed on both copies of the scan report) that information has been given and consent obtained. The scan report is scanned onto EPR. The bloods are batched together and labeled “Urgent samples for the Screening Lab at the John Radcliffe Hospital” and delivered to pathology by 13.00 hrs. The Maternity Care Assistants (MCAs) in the antenatal clinic will obtain a list from Viewpoint of the NT scans performed up to that point and cross reference these with the bloods done. See Standard Operating Procedure MAT-SOP-024 Failsafe process of arrival of Trisomy blood samples to OUH. The checking process also detects missing information which will be updated prior to sending; however, bloods should never be delayed to obtain information. If any woman who has not attended for her bloods the SCO will be alerted by one of the MCAs and the SCO will delegate contacting the woman or contact the woman to advise her to attend ANC as soon as possible to complete the test. Any samples taken after 13.00 are sent in another batch following final attendance to ANC of the clinic day. These are refrigerated in biochemistry at the RBH and sent on to Oxford University Hospital Screening Laboratory the following day.

5.8 Bloods - Newbury The woman is seen immediately after her scan by one of the community MCAs for her blood test. All bloods are batched together as above, and must be on the 11.30 specimen transport to Reading, in order to reach the Oxford University Hospital Screening Laboratory, the same day. The sonographer will print a list of NT USS performed from Viewpoint software and the MCA will complete the failsafe form process, following MAT-SOP-039, Any women attending Newbury in whom the fetal NT measures >3.5mm will be notified to the SCO by the Sonographer responsible. The SCO will then contact the woman by phone to discuss her options as outlined above. The Screening MCA cross-references between Viewpoint and Lifecycle software that all women who have attended Newbury for NT scans have had their bloods received by the Laboratory.

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 7 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

5.9 Multiple Pregnancy The Combined NT scan and bloods is the recommended test for women with twin pregnancies. However, there are important considerations when counseling women pregnant with twins and the SCO can be contacted for further counseling. When the scan shows an empty second pregnancy sac, the Combined Test can still be performed. If the scan shows a second sac containing non-viable fetus (“vanished twin”) the Laboratory will be unable to interpret the biochemistry. For this reason, the Sonographer will complete the scan information and send the card to the screening midwife. She will complete all other necessary fields and send the card without bloods to the Oxford screening Laboratory for them to calculate the chance on NT alone and send out a letter to the woman. The same processes are followed for triplet and higher order multiple pregnancies. All pregnancies of triplet or higher order will have a chance calculated on NT alone, following information and support offered by Fetal Medicine Unit and the screening midwife. Whilst a Combined Test is the test of choice for twin pregnancies, a Quadruple Test can be offered in the absence of a nuchal translucency measurement; be this due to advanced gestation or technically being unable to provide a nuchal translucency measurement.

5.10 The Quadruple Test This is a blood test which can be taken between 14+1 weeks and 20 weeks’ gestation (HC 101-170mm). This is available for women, who book too late for the 1st trimester test, or in whom it has not been possible to obtain measurement of the NT. The Quadruple Test screens for Downs Syndrome alone. There are appointment slots for the bloods to be taken in the antenatal clinic. Women who are too late for the Combined Test at the time of their first scan can be sent directly to the antenatal clinic for their bloods (minimum HC of 101 mm) Women who are not yet 14+1 weeks will have an appointment booked to come back to the antenatal clinic at RBH or WBCH for their bloods at the appropriate gestation. This appointment will be booked by the reception staff in the USS department. Women who fail to attend for their bloods will be contacted by one of the Screening Team and counseled regarding their choices to take up screening, if screening is desired then a second appointment is offered. If the woman declines, then the screening choice is documented in EPR

5.11 Test Results

All women should receive the result of their test within two weeks of the date of the blood test. All women are informed when the blood is taken to contact their named midwife if they haven’t received a result within 2 weeks.

Low chance results (>1:150 for both tests) are notified directly to the woman by first class post from the Oxford screening laboratory. These results are also sent to the SCO in batches and entered onto the woman’s record on EPR by the antenatal clinic MCAs prior to being forwarded to the GP surgery. It is the responsibility of the community midwife to document in the woman’s

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 8 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

record on EPR at the next appointment that a result has been received by the woman. In the absence of the woman receiving a letter through the post the Community Midwife can find the result on EPR in the first instance. The Community Midwife will then contact the Oxford University Hospital Screening Laboratory on 01865 220488 to request a second copy of the result to be sent, checking the demographics directly with the woman at the time of phoning.

High chance results (1 in 2 to 1 in 150 for either test) are notified electronically via Lifecycle to the SCO who contacts the women by telephone. All women with high chance results are offered telephone consultation or a face to face appointment within 3 working days to discuss options with the Screening Midwife, and referred in a timely manner for NIPT or prenatal diagnosis should they so wish. A pack of information is emailed to the woman including written information on the result, CVS and/or amniocentesis as appropriate, Non-Invasive Prenatal Testing (NIPT), support groups and the appropriate syndrome.

A copy of the result is scanned into the woman’s EPR record and Community Midwife is emailed a copy of the result. The Community Midwife will forward the result to the GP for the woman’s surgery records

5.12 Non-Invasive Prenatal Testing (NIPT) PHE Screening recommends the offer of NIPT screening for T21, T18 and T13, following a higher chance result from the combined or quadruple test in singleton and twin pregnancies. As part of the NHS FASP care pathway NIPT screens for T21, T18 and T13 and will not screen for other chromosomal conditions or assess the baby’s sex. For women choosing to have NIPT, the options would be: • T21, T18 and T13 • T21 only • T18 and T13 only NIPT screening will report individual chance results for T21, T18 and T13. During the discussion with the SCO, women should be informed that the laboratory may keep NIPT screening samples for quality assurance (for example, validation) and testing development purposes for up to 5 years. The healthcare professional should inform the laboratory if a woman does not want her sample to be kept for these purposes. These discussions (including the decision on the retention of samples) must be recorded in the woman’s maternity notes.

5.11.1 Eligibility - Inclusions As part of the NHS FASP evaluative rollout, NIPT can be offered and performed: Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 9 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

• when a woman receives a higher chance result for T21 or a joint higher chance result for T18 and T13 from the combined test • when a woman receives a higher chance result for T21 from the quadruple test • in both singleton and twin pregnancies • up to 21 weeks and 6 days (21+6) of pregnancy Women with in-vitro fertilisation (IVF) or donor egg pregnancies are eligible for the offer of NIPT. The relevant details must be recorded accurately on the NIPT screening request form.

5.11.2 Eligibility - Exclusions As part of the NHS FASP evaluative rollout, NIPT cannot be offered and performed: • when a woman receives a lower chance result for T21, T18 or T13 from the combined or quadruple test • in higher multiple pregnancies (triplets or more) • after 21+6 weeks of pregnancy Also, NIPT cannot be offered and performed as part of the NHS FASP pathway when a pregnant woman has: • cancer, unless in remission, as NIPT may detect cell free DNA (cfDNA) in the maternal blood which is released by a cancerous tumour • received a blood transfusion in the previous 4 months, as studies show that donor DNA in blood transfusion recipients lasts for several months, sometimes longer • had bone marrow or organ transplant, as donor DNA will be present • immunotherapy in the current pregnancy, excluding intravenous immunoglobulin (IVIg) treatment • had stem cell therapy, as this will depend on whether she has received her own stem cells or stem cells from a donor (certain methods of NIPT are not suitable for stem cell transplants) • a vanished twin pregnancy (an empty second pregnancy sac or a second pregnancy sac containing a non-viable fetus), as there is evidence to suggest that the can continue to shed cell free fetal DNA (cffDNA) even after the baby has died • Down’s syndrome or a balanced translocation or mosaicism of T21, T18 or T13

5.11.3 Eligibility Uncertain criteria To confirm eligibility for NIPT screening, contact the laboratory before taking a NIPT sample when the woman has any other chromosomal condition other than T21, T18 or T13. This is because it may affect the analysis of NIPT.

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 10 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

(Screening for Downs Syndrome, Edward’s Syndrome and Pataus Syndrome: NIPT gov.uk May 2021). All women with an increased chance result and no further testing will be offered to have their 20-week scan performed by the Fetal Medicine Team. This appointment will be booked by the screening midwife. The SCO puts a flag alert on EPR highlighting the high chance screening result “declined further testing” and the need for a paed check at delivery. Women who undertake NIPT and the result shows High Chance for Downs, Edwards or Pataus whom express the wish to terminate their pregnancy will be advised to have a diagnostic test. If the woman wishes to continue her pregnancy following High Chance NIPT discussion will take place of diagnostic testing benefits and disadvantages. Women will also be offered contact to local relevant support groups.

5.13 Failsafe’s The Maternity Care Assistants (MCA) in antenatal clinic will cross-reference NTs against bloods performed daily (this check is performed at the end of the morning clinic and afternoon clinic, and women with outstanding blood tests will be contacted by phone. The printed cross reference list accompanies the blood samples to Pathology reception to cross check all samples have reached the pathology reception. This list is agreed and signed by the staff, then a copy is sent with the bloods and a copy filed in the SCOs office. At all NT USS performed at WBCH the sonographer will print a list for the MCA’s to confirm the bloods samples have been taken. This list is copied, 1 copy in with the bloods samples and another copy is scanned and emailed to the SCO at [email protected]. 2 working days later the lists are checked to see all samples have reached OUH Screening Laboratory by cross referencing samples on Lifecycle. See MAT-SOP-024 Failsafe process of arrival of Trisomy blood samples to OUH. Once a week the Screening MCA will run 3 queries from Viewpoint to obtain • A list of women who have declined screening at their first scan. She will then enter this information onto EPR. system • A list of women in whom it has not been possible to measure the nuchal fold. The MCA will cross-reference these women against EPR and the daily bloods sent lists. This is to ensure that all these women have either had a Quadruple test performed or have an appointment to return to the clinic for a Quadruple test • A list of women who were too late for the nuchal fold to be measured. The same process is then followed as for the “failed” nuchals, see above Any women who don’t have appointments will have these booked by the Screening MCA and in the first instance contacted by telephone and if unable to contact the woman a letter is sent. Any women who do not attend for their

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 11 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

Quadruple test appointments will be followed up by the Screening Midwife by phone and appropriate action taken All women will have the results of all their antenatal booking bloods, including 1st trimester screening for Down’s, Edwards’ and Patau’s syndromes, recorded in their hand-held notes at the 16 week visit to the Community Midwife. The community midwife will revisit the subject of screening for Downs, Edwards and Pataus syndromes in order to ensure the woman has understood the process, and has a valid result. Any woman with no result at this stage will be offered a Quadruple test, and the SCO informed. Missing results are considered a screening incident. Every Monday the Screening Midwife receives a weekly list of all women booked in the preceding week from informatics to the generic screening email ([email protected]) the list has patient identifiers, hospital booked at, gestation and accepted or declined screening. The list is checked that appointments for combined screening have been requested and made for all women accepting screening booked below 20/40. If no appointment has been made the SCO will investigate the reason why and offer an appointment as indicated. On the day of the booked scan appointment checks will be made to ensure attendance/screen/rebook as indicated. This check is performed daily on the running lists. Standard Operating Procedure MAT-SOP-026 Failsafe Process for ensuring women accepting screening for TRI 13/18/21 complete screening pathway

5.13.1 NIPT failsafe: The SCO will check the NIPT portal daily to ensure samples sent have arrived at the lab. SCO will check for any samples which have missing information to be updated.

5.14 Test Results: Low PAPP-A The Screening midwife will run a monthly check via Lifecycle of women with a low PAPP-A level (<0.4 MOM) from their first trimester screening. She will refer all these women to be booked under Consultant care. These women will then have extra growth scans performed in the 3rd trimester. See PAPP-A guideline (GL1008).

5.15 NIPT results NIPT results are reported as either lower chance or higher chance. A numerical value is not reported. NIPT results must only be reported according to the woman’s choice on the conditions screened for. For example, a lower or higher chance result at term for: • T21, T18 and T13 • T21 only • T18 and T13 only Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 12 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

NIPT screening will report individual chance results for T18 and T13. This is unlike the combined test which reports a joint chance result for these conditions. For example, when a woman chooses NIPT screening for T18 and T13 she will receive both: • a lower or higher chance result for T18 • a lower or higher chance result for T13 In twin pregnancies, the higher chance result report should state that one or both babies may have the condition screened for. Women should expect their NIPT results around 2 weeks from sample collection.

5.15.1 Managing NIPT results Women receiving a higher chance or ‘no result’ NIPT result should attend an appointment with the SCO in ≤ 3 working days of maternity services receiving the result (FASP NIPT-S04. This appointment should be face to face or virtual, depending on the woman’s choice, and discuss the option of: • no further testing • having PND, which should be completed in ≤ 3 working days of the woman receiving the NIPT result (FASP NIPT-S05)

5.15.2 Giving results to women The result should be given by a healthcare professional with knowledge of NIPT and the NHS FASP pathway. Healthcare professionals should provide clear and accurate documentation in line with local guidelines - Pre Natal Invasive Testing: Amniocentesis and Chorionic Villus Sampling (GL1097) Both CVS and amniocentesis are performed in-house without referral to a tertiary centre. CVS is performed between 11 and 14 weeks’ gestation, and amniocentesis from 15 completed weeks by scan. In accordance with regional guidelines, samples are tested by PCR only for Trisomy’s 13, 18 and 21, with further testing of all chromosomes by karyotyping / CGH array only in cases of high NT>/=3.5mm or in case of structural abnormalities. Rates of multiple insertion, bloody tap, failed samples and following invasive testing for each operator are audited annually by the Screening Coordinator as per RCOG guidelines. Results from cytogenetic tests are emailed from the Cytogenetics Laboratory to the SCO, to the generic fetal medicine email [email protected] . The SCO then relays them to the patient the same day on an agreed contact number, and files them in the hospital notes. Women receiving a positive diagnosis following this testing are offered a next working day appointment by the SCO to a member of the Fetal Medicine Team. Care is then as per Fetal Anomaly guideline GL838.

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 13 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

Women requesting invasive prenatal diagnosis at booking are referred to the Screening Midwives. This allows these women to have a consultation with a suitably trained professional in a timely manner regarding their choices for screening and diagnosis.

5.16 Prenatal diagnosis (PND) Information on PND can be found in the NHS FASP handbook and chorionic villus sampling (CVS) or amniocentesis parent information. PND results should be reported in ≤ 3 calendar days of sample receipt (FASP NIPT-S06).

5.17 Education and training NHS FASP recommends all healthcare professionals who are involved in the offer of screening for T21, T18 and T13 in England, complete the ‘NIPT – evaluative rollout’ e-learning resource. This resource includes: • a full version, which should be completed by healthcare professionals who have not completed the old NIPT cascade training • a short summary and update version, which should be completed by healthcare professionals who completed the old NIPT cascade training All newly employed healthcare professionals involved in the screening process will have training in the Trusts Down’s, Edward’s and Pataus syndrome screening programme as part of their induction programme. All healthcare professionals directly involved in the screening process will undertake an annual update session on Down’s, Edward’s and Pataus syndrome screening. All education and training provided is audited annually, where appropriate utilising tools and media provided by the PHE FASP. A record of attendance of training will be maintained by the Screening Co- coordinator. The local coordinator will disseminate regional and national information via e- mail to relevant healthcare professionals.

5.18 Audit and QA Requirements The Thames Valley Antenatal & Newborn Screening Group is responsible for establishing appropriate links with the laboratory and ultrasound service providers to establish mechanisms for collection and reporting of data, in line with national standards for Down’s Edwards and Pataus syndrome screening. The RBH Antenatal and Newborn Screening Group meets quarterly as a minimum to review all relevant local and national standards for screening and to ensure ongoing audit of standards. This group reports to the Maternity Clinical Governance Committee.

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 14 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

The Screening Support Sonographer (SSS) will monitor the NT and CRL measurements of the Sonographers and review practice and reports provided at least 6 monthly by the Downs syndrome screening Quality Assurance Support Service (DQASS). They will liaise directly with the ultrasound department Lead for this purpose. Data on all women receiving high chance results is available via Lifecycle. Data on women tested is supplied by the Laboratory. Quarterly reports from the Laboratory Lead comparing performance to standards are submitted to DQASS at least 6 monthly. The SCO is responsible for collecting, checking and submitting data quarterly for all Key Performance Indicators for Screening to the PHE Quality Assurance, PHE Commissioners and PHE screening. See MAT-SOP-003 KPI data submission to PHE Provision of appropriate information for inclusion in National Congenital Anomaly and Rare Disease Register and (NCARDRS) is collated by the Screening Co-coordinator Notification forms for NCARDRS will be completed and returned as contemporaneously as possible The SCO is responsible for producing an annual report on screening services. This will be shared with the RBH Trust Board, PHE commissioners, PHE Quality Assurance.

5.19 Unexpected Down’s, Edwards’ or Patau’s Live Births following Low Chance Screening In the event of affected babies being born to women who had received low chance results from Downs’s screening program, the following measures will be instigated: • SCO informs the SSS and Fetal Medicine Doctors whom review images and enters outcome onto Viewpoint • SCO informs Lead Biochemist at Screening Laboratory • The case is discussed and minuted in the ANNBSG quarterly meeting.

5.20 Suspected Screening Incidents Suspected safety or serious incidents within the screening program will be notified by the Screening Midwives to the QA team and the screening and immunization team at PHE via the Screening incident assessment Form (SIAF). She will then act as guided by the QA Team. Managing Safety incidents in NHS Screening Programmes Guidance and the Screening Incident Assessment form (SIAF) can be obtained at: https://www.gov.uk/topic/population-screening-programmes/screening-quality- assurance

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 15 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

6.0 Local Contacts Amy Wood (0118 322 8507) Antenatal Screening Co-coordinators Sarah Lindsay-Birch (0118 322 7292) Public Health Lead for Screening and Nisha Jayatilleke Immunisations (07860 177988 ) Surabhi Bisht Lead Obstetrician (0118 322 8910) Dr Ann Gordon Lead Paediatrician (0118 322 7439) Tracy Oliver / Suruchi Arora Obstetric Ultrasound Lead (0118 322 7279) Hayley Clarke Trust Bereavement Midwife/Link (0118 322 8394) Laboratory Provider Lead Biochemist Oxford Screening Ian Smith Laboratory, John Radcliffe Hospital, (01865 220488) Oxford Regional Cytogenetics Department Director, Carolyn Campbell Churchill Hospital, Oxford (01865 226001) Regional Genetics Centre Deirdre Cilliers Consultant Churchill Hospital, Oxford (01865 226048) Kay Randall NCARDRS (01865 221716) Siobhan O’Callaghan Senior QA Manager (07976 770296)

7.0 Consultation This protocol was written in consultation with personnel from the following departments: Screening Coordinators, Fetal Medicine and Maternity Ultrasound, Pathology and Oxford Screening Laboratory.

8.0 Dissemination/Circulation This protocol will be available electronically on the departmental website, and is available to community midwives and GPs via the website. The Maternity Information Officer will be responsible for archiving old versions of this document. This protocol can be translated on request. Please contact The Patient Information Manager on 0118 322 8706. Disseminated by the Maternity Clinical Governance Committee.

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 16 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

9.0 References 9.1 PHE NHS Fetal Anomaly Screening Programme Handbook Valid from August 2018 9.2 NHS Screening Programmes: Fetal Anomaly Screening Programme Standards (Updated 12 April 2021) 9.3 NHS Screening Programmes: Fetal Anomaly Screening Programme Handbook for ultrasound practitioners April 2015 (Updated October 2019) 9.4 NHS Fetal Anomaly Screening Programme Down’s syndrome, Edwards’ syndrome and Patau’s syndrome screening Handbook for Laboratories Valid from August 2018 (Updated Sept 2019 9.5 PHE Antenatal and Newborn screening KPIs for 2018 to 2019: definitions March 2018. 9.6 PHE Downs, Edwards and Patau’s syndromes screening: checks and audits to improve quality and reduce risks (July 2018) 9.7 Amniocentesis and Chorionic Villus Sampling Royal College of Obstetricians and Gynaecologists Green Top Guideline no 8 9.8 Managing Safety Incidents in NHS Screening Programmes Guidance. October 2015 Public Health England (updated Jan 2018) 9.9 Screening for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome: non-invasive prenatal testing (NIPT) https://www.gov.uk/government/publications/screening-for-downs-syndrome- edwards-syndrome-and-pataus-syndrome-non-invasive-prenatal-testing-nipt 9.10 Fetal anomaly screening: care pathways https://www.gov.uk/government/publications/fetal-anomaly-screening-care- pathways

10.0 Auditable standards: Audits will be performed following audit recommendations for PHE FASP Downs, Edwards and Patau’s syndromes screening: checks and audits to improve quality and reduce risks. These audits will be registered with the RBH QI & Audit Midwife and auctioned as recommended by PHE.

11.0 Implementation Matrons and Managers will be responsible for communicating the standards and information on the requirements of this protocol to staff and ensuring implementation in the clinical areas.

12.0 Training Training required to fulfil this protocol will be provided in accordance with the National Screening Committee requirements which are incorporated within the

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 17 of 19 Maternity guidelines – Downs, Edwards & Pataus syndromes screening protocol (CG481) June 2021

Maternity Training Needs Analysis. This information can be accessed via the Maternity pages on the Trust intranet.

Author: S Lindsay-Birch Date: June 2021 Job Title: ANNB Screening Specialist MW Review Date: June 2023 Policy Lead: Group Director Urgent Care Version: V10.0 Location: Policy hub/ Clinical/ Maternity/ Antenatal/ CG481 This document is valid only on date last printed Page 18 of 19 Maternity guidelines - Downs Syndrome screening protocol (CG481)

Appendix A – Consent form for chromosome abnormalities screening

This document is valid only on date last printed Page 19 of 19