Manchester Newborn Screening Laboratory Annual Report

Transcription

1 Newborn Screening Laboratory Clinical Biochemistry Department Central Manchester University Hospitals NHS Foundation Trust Manchester Newborn Screening Laboratory Annual Report Beverly Hird Lesley Tetlow Laura Hamilton Claire Hart

2 INDEX 1 Introduction 2 2 Newborn Screening Laboratory 3 Laboratory Staffing 3 Equipment 6 Workload 7 Services Provided 8 Analysis and Reporting 10 3 Clinical Governance 11 Accreditation 11 External Quality Assessment 11 Governance Arrangements 11 Audit (National, Regional & Local) 11 Research & Development 12 Training & Education 12 4 Summary of Programme Performance 13 Standard 2: Enhanced Tracking Abilities 13 Standard 3: Timely Sample Collection 16 Standard 4: Timely Sample Dispatch 19 Standard 5: Quality of bloodspot sample 21 5 Clinical Referral Data 27 PKU Screening 27 MCADD Screening 28 CHT Screening 28 CF Screening 32 Sickle Cell Disease & Other Haemoglobinopathies Screening 38 6 Summary of Audit Work & Adherence to National Standards 42 UKNSPC Process Standards 42 Clinical Referral of PKU, MCADD & CHT Positive Cases 42 Cystic Fibrosis 43 Sickle Cell 43 Newborn Screening Incidents 44 7 Future Developments 46 Appendices 47 Appendix 1: Research & Development & Audit 47 Appendix 2: Newborn Screening Clinical Incidents Reported 2012/13 48 Appendix 3: Data by Hospital of Birth 51

3 Acknowledgements We are grateful to all staff in the Newborn Screening and Willink Laboratories for all their continuing hard work, and to our colleagues in the Haematology Department, Manchester Royal Infirmary and the Molecular Genetics Laboratory, St Mary s Hospital for their collaboration with regards to the Haemoglobinopathy and Sickle Cell Screening Programme and the Cystic Fibrosis Screening Programme respectively. We are also indebted to the Regional Newborn and Antenatal Screening Team with whom we work closely on governance and quality assurance aspects of the newborn bloodspot programme and on teaching and training of health professionals involved in delivery of the programme. 1

4 1. Introduction The report is a summary of the activities of the laboratories involved in screening of all newborns within the Greater Manchester Strategic Health Authority (SHA) and a major part of the Cumbria and Lancashire SHA. The laboratories carry out screening for Congenital Hypothyroidism (CHT), Phenylketonuria (PKU), Haemoglobinopathy and Sickle Cell disorders (SCD), Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD) and cystic fibrosis (CF). PKU and MCADD testing is carried out by the laboratory within the Willink Biochemical Genetics Unit which is a clinical unit for inherited metabolic disorders. In July 2012 a one year pilot programme for expanded screening was introduced. Five additional genetic conditions are screening for as part of this pilot Maple syrup urine disease (MSUD), Homocystinuria (Hcys), Glutaric aciduria type 1 (GA1), Isovaleric acidaemia (IVA) and Long chain hydroxyl-coa dehydrogenase deficiency (LCHADD). Testing for all five conditions is performed by the Willink Laboratory. Testing for CHT, CF and SCD is carried out within the Newborn Screening and Paediatric Specialist Endocrine Laboratory which is a section of the Clinical Biochemistry Department within the Directorate of Laboratory Medicine (Clinical and Scientific Services Division). Initial clinical investigations for PKU and MCADD, and follow up and treatment are carried out within the Willink Unit and initial clinical investigation of CHT screen positives is usually carried out by the Paediatric Endocrinology Department of the children s hospital. However, babies that are still in hospital at the time of the positive CHT result are usually investigated within the corresponding hospital. Clinical follow up of SCD positive patients is carried out by the Consultant Paediatric Haematologists at Royal Manchester Children s Hospital (RMCH). Clinical follow up of positive CF cases is usually carried out within the CF centre now located at RMCH (previously located at Booth Hall Children s Hospital), however, there are a few hospitals within the region that carry out their own clinical follow up in collaboration with the regional CF centre (shared care centres). 2

5 2. Laboratory Staffing April 2012 CMFT Director of Newborn Screening Lesley Tetlow BSc MSc DipCB FRCPath, Consultant Paediatric Biochemist Newborn Screening/ Specialist Endocrine Laboratory Clinical Scientists Mandy Pickersgill BSc MSc PhD FRCPath, Higher Principal Biochemist & Clinical Lead for Newborn Screening (1.0 WTE) Beverly Hird BSc MSc DipRCPath, Principal Biochemist (rotational post) (0.8 WTE)* Fiona Ivison BSc MSc PhD FRCPath, Principal Biochemist (rotational post) (1.0 WTE)* * Period of rotation - 12 months. In 2012 there were a number of changes to the Clinical Scientist staffing in newborn screening: Beverly Hird replaced Mandy Pickersgill as Clinical Lead in September Fiona Ivison moved to a post in specialist biochemistry. Claire Manfredonia and Helen Jopling were appointed as rotational Senior Biochemists in October 2012, replacing the previous rotational Principal Grade posts. Biomedical Scientists Laura Hamilton BSc MSc FIBMS CSci Chief Biomedical Scientist (1.0 WTE) Bernadette McQuade BSc FIBMS Senior Biomedical Scientist (1.0 WTE) Anne Walsh BSc FIBMS Senior Biomedical Scientist (1.0 WTE) Medical Laboratory Assistants Gayle Mobey (0.8 WTE) Anne Butler (0.6 WTE) Dawn Mechan (0.8 WTE) Anne Butler left in August 2012 and was replaced by Selina Keaveney in January the post was increased to 1.0 WTE. Secretarial/Clerical Lorraine Staton Screening Administrator (0.85 WTE) Mo Adamopoulos Clerical assistant/data entry clerk (0.5 WTE) Neera Jones Clerical assistant/data entry clerk (0.8 WTE) Mo Adamopoulos left in February

6 Willink Biochemical Genetics Laboratory Clinical Scientists Claire Hart, Consultant Clinical Scientist, Head of Service for Willink Biochemical Genetics (1.0 WTE) Teresa Hoi-Yee Wu, Principal Clinical Scientist, Head of Metabolites and Newborn Screening section (1.0 WTE) Alistair Horman, Principal Clinical Scientist, Deputy Head of Metabolites and Newborn Screening section (1.0 WTE) (Teresa Wu replaced Jackie Till as Head of the Metabolites and Screening Section during 2012, and the post was increased from 0.5 WTE to 1.0 WTE). Technical Staff in Metabolites and Newborn screening section with rotational duties in screening James Cooper, Senior Medical Technical Officer (1.0 WTE) Graeme Smith, Senior Medical Technical Officer (1.0 WTE) Liz Smith, Senior MLA (0.8 WTE) Milly Cretney, Senior MLA (0.6 WTE) Julie Workman, MLA (1.0 WTE) Stephen Dent, MLA (1.0 WTE) The staffing complement and structure of the screening laboratories at the end of the financial year (March 2013) is depicted in the following organisational chart. 4

7 NEWBORN SCREENING/ SPECIALIST ENDOCRINE LABORATORY* CHT, Sickle Cell and CF Screening Newborn Screening Staffing Structure CMFT DIRECTOR OF NEWBORN SCREENING Lesley Tetlow WILLINK LABORATORY** PKU and MCADD Screening PRINCIPAL CLINICAL SCIENTIST (0.8) Beverly Hird CONSULTANT CLINICAL SCIENTIST Claire Hart SENIOR CLINICAL SCIENTIST (ROTATIONAL) Claire Manfredonia/ Helen Jopling CHIEF BIOMEDICAL SCIENTIST Laura Hamilton SENIOR BIOMEDICAL SCIENTISTS (2) Anne Walsh Bernadette McQuade SCREENING ADMINISTRATOR (0.85) Lorraine Staton PRINCIPAL CLINICAL SCIENTIST Alistair Horman PRINCIPAL CLINICAL SCIENTIST Teresa Wu SENIOR CLINICAL SCIENTIST Pam Grundy SENIOR MEDICAL TECHNOLOGISTS (2) James Cooper / Graeme Smith MEDICAL LABORATORY ASSISTANTS (2.6) Gayle Mobey Dawn Mechan Selina Keaveney BASIC GRADE BIOMEDICAL SCIENTIST (ROTATIONAL) CLERICAL ASSISTANTS (1.3) Neera Jones Vacant post MLA / SENIOR MLA (3.4) Liz Smith Milly Cretney Julie Workman Stephen Dent *All scientific staff cover both newborn screening and specialist endocrine services. The duties of medical laboratory assistants and clerical staff are predominantly screening related. **All Willink staff have other functions in addition to NBS within the Willink laboratory (diagnostic + screening) as a whole. Collectively screening activities account for ~20% of the WTE of this group of staff. 5

8 Equipment 2 x AutoDELFIA immunoassay analysers (Perkin Elmer) used for the analysis of TSH and IRT in bloodspots for the purposes of newborn screening and also for bloodspot 17-hydroxyprogesterone analysis for monitoring patients with CAH. 2 x BioRad Variant NBS HPLC system for SCD screening Semi-automated DELFIA system (Perkin Elmer) used for non-screening assays (LH/FSH, and 17-α-hydroxyprogesterone). Microtitre plate washer and reader for manual ELISA assays for Insulin and C-peptide Siemens Immulite XPi. This analyser is situated within the automated biochemistry laboratory which is a separate location from the Newborn Screening Laboratory and is used for routine less specialised paediatric endocrine tests (Growth Hormone and IGF-I). Perkin Elmer Multipuncher for punching dried bloodspot samples prior to analysis. Specimen Gate laboratory screening IT system (Perkin Elmer ) 3 x Waters LC-MS/MS instruments (collectively used to provide both screening and diagnostic services by Willink laboratory). 6

9 Workload A total of samples were received in the laboratory which included first samples, 4288 repeat samples and 1346 pre-transfusion day 0 samples from within the two SHAs covered by the service (Greater Manchester and Cumbria and North Lancs). The laboratory also analysed 399 samples (313 first samples, 30 pre-transfusion day 0 samples and 56 repeats) taken on babies that were resident in other areas of the country but were in-patients in hospitals within our catchment area. The laboratory was notified of 64 declines for screening on a first sample, all of which were declined for all 5 tests. In addition in the first 3 quarters of the expanded newborn screening pilot project (which started on 17 th July 2012) there were 37 declines solely for the expanded testing (the standard 5 tests were carried out as usual). The majority of the declines were in the initial few months of the project, totalling 18, 13 and 6 in Q1, Q2, and Q3 respectively. Decline levels have remained in single figures since. 7

10 Services Provided Newborn Screening/ Specialist Endocrine Laboratory Newborn Screening Newborn Screening for Congenital Hypothyroidism (CHT), Cystic Fibrosis (CF) and sickle cell and haemoglobinopathy disorders for all babies born within Greater Manchester and South Cumbria and North Lancs. Reporting of newborn screening results for CHT, CF, SCD, PKU and MCADD, including follow up of repeat tests, queries and missing information. Clinical referral to RMCH department of Paediatric Endocrinology and subsequent laboratory investigation for positive CHT cases. Clinical referral of babies with haemoglobinopathy disorders to the department of haematology, RMCH and referral of babies with carrier status for counselling or any further investigation. Clinical referral of babies with a positive CF test to the regional CF centre at Royal Manchester Children s Hospital. Punching of bloodspot samples for an anonymised HIV survey. Long term storage of bloodspot samples. Cards received within the last 5 years are stored on site within the Newborn Screening Laboratory and older cards are shipped out to CELLNASS for archiving. Specialist Endocrinology Provision of a regional laboratory service for 17-α-hydroxyprogesterone in serum and in bloodspot samples for investigation and monitoring of Congenital Adrenal Hyperplasia. Provision of a paediatric immunoassay laboratory service to the Trust. Provision of an analytical and interpretative service for insulin and C-peptide for other hospitals within the region and as part of NORCHI, the North West component of the two-centre national service for babies and infants with congenital hyperinsulinaemia. 8

11 Willink Biochemical Genetics Laboratory The Willink laboratory is located on the 6 th floor of St Mary s Hospital, together with the Newborn Screening Laboratory but managerially resides within the Genetics Directorate (St Mary s Division) and is organisationally part of the Genomic Diagnostics Laboratory. The analytical service for PKU and MCADD screening is provided from within the Willink laboratory using tandem mass spectrometry technology. Members of staff from the laboratory also provide support for the mail sorting and punching (sampling) of newborn screening cards. All results produced by the Willink Laboratory are inputted directly into the dedicated screening IT system using file transfer and are subsequently reported to child health departments by senior staff within the Newborn Screening Laboratory. 9

12 Analysis and Reporting Bloodspot samples are used for all tests. PKU and MCADD screening is carried out using the method of tandem mass spectrometry (Waters instrumentation). CHT and CF screening are carried out using analysis of TSH (CHT) and IRT (CF) on the AutoDELFIA automated immunoassay analyser (Perkin Elmer ) with second line genetic testing for CF being carried out within the molecular genetics laboratory (St Mary s Hospital, Manchester). SCD screening is carried out using a high performance liquid chromatography system (HPLC) (Biorad Variant NBS) with confirmatory testing for SCD being carried out within the Haematology Department at Manchester Royal Infirmary using an iso-electric focussing method. The reporting of results for all 5 screening programs is carried out using a dedicated IT system (Specimen Gate Laboratory IT system, Perkin Elmer). A summary district report is generated and ed on each working day to the individual Child Health Records Departments. Individual A5 reports are generated for incorporation in the babies personal record (red book) and are sent by first class post. 10

13 3. Clinical Governance Accreditation The Newborn Screening Laboratory is accredited with CPA as part of Clinical Biochemistry. The Willink Laboratory is currently accredited separately as a stand alone laboratory in its own right, but will move to a joint inspection of the Genomic Diagnostics Laboratory (along with molecular genetics and cytogenetics) in the next inspection cycle. Both laboratories have full CPA accreditation status. External Quality Assessment Both laboratories participated in the combined UK NEQAS scheme for Newborn Screening for TSH, IRT, PKU and MCADD, achieving satisfactory results. The Newborn Screening Laboratory also takes part in the UK NEQAS Newborn Sickle Screening scheme and have reported results that agree with the consensus for all samples. The laboratory has also taken part in the CDC EQA scheme for IRT analysis and has received satisfactory reports for this scheme. Governance Arrangements Programme Specific Operational and Quality Groups for Cystic Fibrosis, Sickle and Metabolic screening which include all stakeholders meet on a 6-monthly basis. Matters in relation to Congenital Hypothyroid Screening are discussed as part of weekly MDT meeting with paediatric endocrinology. All groups report to the Trust Newborn Screening Board. The Newborn Screening Laboratory also reports to the Greater Manchester and Cumbria and Lancashire Quality and Commissioning Groups. National, Regional and Local Audit Data is submitted annually to the UK Newborn Screening Programme Centre regarding performance of the newborn bloodspot programme in relation to key process and clinical referral standards. Performance data is also collated quarterly and reports are presented to the Greater Manchester and Cumbria and Lancashire Commissioning and Quality Groups. Other local audits are performed on an on-going basis to assess specific aspects of the programme (both generic and programme specific). A list of audits completed in 2012/13 is provided in Appendix 1. 11

14 Research and Development The laboratory is committed to on-going research and development both independently and in collaboration with clinical colleagues, other screening laboratories within the UK Newborn Screening Laboratory Network (UKNSLN) and UK National Screening Programme Centre and National Sickle Cell and Thalassaemia Programme. Details of oral presentations, posters and publications in 2012/13 is provided in Appendix 1. Training and Education The laboratory continues to have a commitment to teaching and training both laboratory scientists and other groups of health professionals involved in delivery of the newborn bloodspot screening programme. Pre-Registration Clinical Scientist trainees rotate through the department, spending 4 weeks within the newborn screening laboratory and 4 weeks in the Willink laboratory. A Higher Specialist Trainee post specialising in paediatric and metabolic biochemistry is shared jointly between Clinical Biochemistry and the Willink Laboratory. Clinical Scientists from the Newborn Screening and Willink Laboratories together deliver the teaching elements of newborn screening for the MSc in Clinical Biochemistry (University of Manchester). The Newborn Screening Laboratory Leads contribute to regional screening training and update days organised by the North West Regional Antenatal and Newborn Screening Team and the Sickle Cell and Thalassaemia Centre for screening link health visitors, child health staff and staff within NICU units throughout the region, as well as providing the opportunity for midwives, health visitors and CHRD staff to visit the laboratory. The aim of these visits is to improve understanding of laboratory processes and issues around sample quality. In addition to these regular sessions, in July 2012 and February 2013 educational days for newborn screening were organised for trainee midwives from Salford University. 12

15 4. Summary of Programme Performance The laboratory is required to submit screening data to the UKNSPC each year at the end of July, for the previous 12 months of screening. The Standards and Guidelines for Newborn Bloodspot Screening were revised by the UK Newborn Screening Program Centre (UKNSPC) in 2008 and can be found at There are 9 standards for newborn screening and the laboratory reported results against standards 2 (enhanced tracking abilities), 3 (timely sample collection), 4 (timely sample dispatch), 5 (quality of bloodspot sample) and 7 (timely processing of screen positive samples). The data submitted by this laboratory, in addition to other data collected as part of our continuous audit (insufficient rates etc) is summarised and discussed below and covers the time period from April 2012 through to March Data was collected and analysed both by PCT and hospital of birth. For the sake of brevity only the analysis by PCT is included within the body of the document but tables and charts relating to analysis by hospital of birth can be found in Appendix 3. The UKNSPC standards are as follows: Standard 2: Core standard: Enhanced tracking abilities: 100% of bloodspot cards include the babies NHS number This standard states that 100% of samples should include babies NHS number. The data for this standard is shown graphically in Figure 1 and tabulated in table 1. This standard is applied to all samples (including repeats). Performance against this standard was similar to 2011/12 with the highest percentage being 99.9% and the average for the region 99.4%. Figure 1 also shows the number of samples that included a bar coded label detailing the NHS number. The percentage of samples that included an NHS number bar coded label varied dramatically throughout the region and ranged from 0.1% to 85% (average 51%). Overall there has been very little increase in the usage of bar-coded labels. 13

16 PCT Number of all samples (including repeats) Number of blood spot cards including babies' NHS number Number of blood spot cards including ISB label barcoded babies' NHS number Percentage with NHS number Percentage with barcoded NHS number AW&L % 7.49% Blackburn % 80.42% Blackpool % 68.95% Bolton % 58.37% Bury % 62.42% C Lancs % 58.70% Cumbria (South) % 0.12% E Lancs % 84.75% Manchester % 34.24% N Lancs % 34.09% Oldham % 64.33% Rochdale % 64.81% Salford % 41.01% Stockport % 74.03% Tameside % 63.50% Trafford % 24.86% Out of region % 29.07% Total % 51.26% Table 1: Data for standard 2 showing number of cards that include NHS number 14

17 Standard 2: Inclusion of NHS number Percentage with NHS number Percentage with bar-coded NHS number 100% 98.75% 99.85% 99.48% 99.61% 99.67% 99.48% 98.82% 99.82% 99.07% 99.12% 99.66% 99.54% 99.39% 99.40% 99.26% 99.36% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% AW&L Blackburn Blackpool Bolton Bury C Lancs Cumbria (South) E Lancs Manchester N Lancs Oldham Rochdale Salford Stockport Tameside Trafford PCT Figure 1: Graph to show percentage of cards that included NHS number for period April 2012 March

18 Standard 3: Core standard: Timely sample collection 95% of first samples taken 5-8 days after birth The data corresponding to this standard is shown in Figure 2. Whilst average performance against this standard was the same as 2011/12 (97.4%) one PCT (Blackburn) failed to meet the standard. Blackburn and East Lancs PCTs showed a greater than 2% increase in the number of samples taken on or after day 9. Some units have implemented vetting of samples prior to despatch in order to reduce their avoidable repeat rate. This may have had a detrimental effect on this standard as samples taken at the appropriate time but discarded will not have been recorded. 16

19 Number of first samples taken Percentage of first samples taken PCT on or before day 4 on day 5 on day 6 on day 7 on day 8 on or after day 9 on or before day 4 on day 5 on day 6 on day 7 on day 8 AW&L % 65.60% 22.40% 8.58% 1.57% 1.38% Blackburn % 28.23% 41.17% 18.94% 5.95% 5.46% Blackpool % 61.66% 23.01% 10.88% 2.04% 1.88% Bolton % 51.38% 27.85% 12.41% 3.88% 4.09% Bury % 66.84% 24.24% 5.44% 1.53% 1.68% C Lancs % 32.93% 49.64% 13.27% 2.05% 1.87% Cumbria (South) % 84.99% 10.40% 2.66% 0.71% 1.04% E Lancs % 53.03% 33.14% 8.19% 1.51% 3.97% Manchester % 83.64% 11.35% 2.30% 0.73% 1.58% N Lancs % 70.59% 18.87% 6.64% 1.42% 2.15% Oldham % 87.96% 8.66% 1.28% 0.55% 1.40% Rochdale % 88.01% 8.20% 1.45% 0.33% 1.94% Salford % 79.12% 13.72% 3.11% 1.08% 2.54% Stockport % 86.01% 10.12% 2.14% 0.38% 1.16% Tameside % 86.89% 7.49% 1.90% 1.08% 2.14% Trafford % 85.71% 8.94% 2.09% 0.60% 2.17% Out of region % 54.52% 29.68% 7.10% 1.94% 5.16% Total % 68.32% 20.94% 6.49% 1.62% 2.31% on or after day 9 Table 2: Data for Standard 3 showing the number of cards taken in a timely manner (between Day 5-8) 17

20 % of samples collected day 5-8 Standard 3: Timely sample collection 100% 99% 98% 97% 96% 95% 94% 93% 92% AW&L Blackburn Blackpool Bolton Bury C Lancs Cumbria (South) E Lancs Manchester N Lancs Oldham Rochdale Salford Stockport Tameside Trafford PCT Figure 2: Graph to show percentage of samples taken 5-8 days after birth 18

21 Standard 4: Core standard: Timely sample dispatch 100% of samples to be received by laboratory within 4 working days. The data corresponding to this standard is shown in Figure 3. The percentages range from 97.5% to 99.8% with an average of 98.9%. There has been a significant improvement in performance against this standard compared with 2011/12. The data collected for standard 4 now excludes day 0 pre-transfusion samples which has contributed to the improvement against this standard. The developmental target for standard 4 is that 100% of cards are received within 3 working days. The percentage of cards that were received within 3 working days ranged from 91% to 99%. PCT Number of samples received in 3 or fewer working days of sample being taken in 4 or fewer working days of sample being taken on or after 5 working days of sample being taken Percentage of samples received In 3 or fewer working days of sample being taken In 4 or fewer working days of sample being taken On or after 5 working days of sample being taken AW&L % 98.93% 1.07% Blackburn % 99.57% 0.43% Blackpool % 98.77% 1.23% Bolton % 99.07% 0.93% Bury % 98.69% 1.31% C Lancs % 99.24% 0.76% Cumbria (South) % 97.80% 2.20% E Lancs % 99.75% 0.25% Manchester % 98.89% 1.11% N Lancs % 97.52% 2.48% Oldham % 98.82% 1.18% Rochdale % 99.04% 0.96% Salford % 99.36% 0.64% Stockport % 98.03% 1.97% Tameside % 99.32% 0.68% Trafford % 98.90% 1.10% Out of region % 96.73% 3.27% Total % 98.91% 1.09% Table 3: Data for standard 4 showing the number of samples despatched in a timely manner 19

22 Standard 4: Timely sample transport Samples received within 3 working days Samples received within 4 working days 100% 99.6% 99.8% 98.9% 98.8% 99.1% 99.2% 98.7% 98.9% 98.8% 99.0% 99.4% 98.0% 99.3% 98.9% 98% 97.8% 97.5% 96% 94% 92% 90% 88% 86% AW&L Blackburn Blackpool Bolton Bury C Lancs Cumbria (South) E Lancs Manchester N Lancs Oldham Rochdale Salford Stockport Tameside Trafford PCT Figure 3: Graph to show percentage of samples received within 3 and 4 working days of being taken 20

23 Standard 5: Quality of bloodspot sample Core standard: The avoidable repeat rate is less than or equal to 2%. Reporting against this standard came into effect for the data collected for An avoidable repeat can be classified as follows: Sample taken too soon (< 5 days) Sample taking too long to reach the laboratory (> 14 days) Sample taken too soon after a transfusion (within 72 hrs) Insufficient blood/unsatisfactory quality (eg, multilayered) No NHS number Contamination (discrepant IRT) Table 4 shows the number of samples received in each category. Insufficient and poor quality samples remain by far the biggest contributor to the avoidable repeat rate. The number of insufficient/poor quality samples was 2288 samples this year (4.0%) which is a slight improvement over last year s figure of 4.3%. Please note, calculation of the avoidable repeat rate now includes repeat samples in addition to first samples. Currently samples taken too soon (<5 days) and samples taken too soon after a transfusion (within 72 hours) are not included. REASON FOR REPEAT NUMBER OF SAMPLES Taken too soon (<5 days) 153 Taken too long to reach the laboratory (>14 days) 31 Taken too soon after a transfusion (with 72 hours) 173 Poor quality or insufficient quantity of blood 2288 No valid NHS number 368 Contamination (discrepant IRT) 81 Table 4: Data to show the number of avoidable repeats in each category 21

24 Figure 4 shows the avoidable repeat rate per PCT and also shows how the number of insufficient samples contributes to the overall avoidable repeat rate. This data is also tabulated in table 5. The maximum rate for avoidable repeats is 2% according to standard 5, no PCT achieved this standard but it can be seen that three (Bury, Oldham and East Lancs) are quite close. The percentage overall avoidable repeat rate ranges from 2.3% to 7.9% which compares favourably with 2011/12 figures of 2.5% to 9.0%. Previous data analysis exercises have demonstrated that the number of insufficient samples taken from babies that were in hospital at the time of sample is much higher that those taken on babies within the community. This continues to be the case this year although there is some improvement. 9% of all samples that were taken within the hospital setting were insufficient (compared with 14% in 2011/12). Table 6 shows the insufficient rate for each hospital within the area of coverage. This data is also displayed graphically in Figure 5. The rate ranges from 0% to 46%. 22

25 PCT Number of first samples received/ babies tested Too soon after transfusion (<72 hours)* Too young for reliable screening ( 4 days)* Insufficient/ multi-layered sample >14 days in transit No NHS number Contaminated (discrepant IRT) Number of Avoidable Repeat Requests Avoidable Repeat Requests Rate AW&L % Blackburn % Blackpool % Bolton % Bury % C Lancs % Cumbria (South) % E Lancs % Manchester % N Lancs % Oldham % Rochdale % Salford % Stockport % Tameside % Trafford % Out of region % Total % Table 5: Data for Standard 5 showing avoidable repeat rate *Not currently included in calculation of avoidable repeat rate 23

26 Standard 5: Avoidable repeats % Avoidable repeats (all) % Insufficient % No NHS number 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% AW&L Blackburn Blackpool Bolton Bury C Lancs Cumbria (South) E Lancs Manchester N Lancs Oldham Rochdale Salford Stockport Tameside Trafford PCT Figure 4: Graph to show avoidable repeat rate for each PCT 24

27 Current Hospital Insufficient sample from in-patients Total number of samples From in-patients % Insufficient or multi-layered Blackburn Blackpool Bolton Burnley Furness North Manchester Ormskirk RMCH Royal Lancaster Royal Oldham Royal Preston St Mary's Stepping Hill Tameside Westmorland Wigan Wythenshawe Not stated Total Table 6: The proportion of insufficient samples collected from babies in hospital 25

28 % Insufficient or multi-layered Insufficient rate for in-patient samples Blackburn Blackpool Bolton Burnley Furness North Manchester Ormskirk RMCH Royal Lancaster Royal Oldham Royal Preston St Mary's Stepping Hill Tameside Westmorland Wigan Wythenshawe Not stated Current Hospital Figure 5: Graph to show percentage of insufficient samples taken within each acute Trust, whilst the baby was in hospital Key: RMCH Royal Manchester Children s Hospital 26

29 Cases per 10, Clinical Referral Data A comparison of the number of cases referred for each condition since 2007 is shown in Figure 6. Rate of screen positive babies per 10, CHT PKU MCADD CF Condition Screened Figure 6: Rate of screen positive babies (per 10000) from 2007 onwards. Positive Cases PKU Screening Eight cases of confirmed raised phenylalanine were followed up clinically by medical staff at the Willink Unit. There were 7 confirmed as PKU cases, giving an estimated incidence of 1:8111. This figure was calculated based on the number of first samples received by the laboratory which may not truly reflect the birth rate. The remaining positive screen was confirmed as a case of galactosaemia. According to the UKNSPC clinical referral guidelines, 100% of positive screening results should be referred within four working days of sample receipt. All eight cases were referred within 3 working days. The age at referral ranged from 8-12 days. 7/8 babies had their first clinical appointment by 14 days of age (range days). 27

30 MCADD Screening There were 6 screen positives for MCADD and all six were confirmed as MCADD cases, giving an estimated incidence of 1 in All screen positives were referred within 3 working days. The age at referral ranged from 8-13 days. All babies had their first clinical appointment by 14 days. CHT Screening All raised TSH levels (>5mU/L) were checked in duplicate on the original sample and the average result was taken. Samples with confirmed levels > 20mU/l were treated as positive and urgent follow up was arranged at RMCH, unless the baby was still in a local hospital in which case follow up was initiated by the corresponding medical team. There were 34 such cases and all were confirmed as congenital hypothyroid cases following clinical referral. The bloodspot TSH in these cases ranged from 20 miu/l to >264 miu/l. One further case had a normal blood spot TSH concentration on the initial sample (7mIU/l on day 7) but a repeat was required as it had been collected within 72 hours of a transfusion (and the sample was also insufficient). The repeat sample collected on day 16 had a blood spot TSH concentration of 37mIU/l. This baby was referred on day 22. There was one case of a screen positive result on a premature repeat sample, collected on day 33 (blood spot TSH concentration 26 miu/l) and referred on day 43. This baby was also reported with last year s figures, which were collated by date of birth rather than date of sample receipt. All figures are now collected by date of sample receipt. Confirmed TSH levels between 8 and 20 miu/l were treated as borderline and a repeat sample was requested, to be taken no sooner than one week later to allow for normalisation of transient increases. If the borderline result was persistent or had moved into the positive range (>20 miu/l) clinical follow up was initiated at RMCH. Of the 94 initial borderline results (using a local cut off of 8mIU/l as opposed to the national cut off of 10mIU/l), 13 (13.8%) were treated as positive following repeat sampling with a TSH ranging from 9 to 48 miu/l on repeat. A further persistent borderline positive result was obtained on a baby following a normal bloodspot TSH on a poor quality initial sample (day 6). The repeat sample on day 15 had a blood spot TSH of 8mIU/l and the TSH concentration of the second repeat on day 29 was 12mIU/l. This baby was referred on day

31 The number of positive cases per PCT is shown in Table 7. The national standards for clinical referral of positive CHT babies currently state that 98% of babies should have clinical referral initiated by 14 days of age. However following consultation in May/June 2012 new clinical referral guidelines were published in January 2013 for implementation in March These state that for babies identified as CHT positive on the initial screening sample 100% should be on treatment by 17 days of age (acceptable standard). Ages for positive CHT babies, identified on the first sample are shown in figure 7 and table 7. The median age for referral was 13 days (range days). 29 babies (85%) were referred by 14 days and 32 babies (94%) were referred by 17 days. The sample from the baby referred at 19 days took 6 days to arrive in the laboratory (4 working days) and referral was delayed by a bank holiday. The sample from the baby referred aged 20 days took 7 working days to arrive in the laboratory. In the fiscal year April 2012 to March 2013 there were no separate standards with respect to babies identified as CHT positive on a repeat blood spot sample that follows a borderline TSH. However the January 2013 guidelines state that for these babies 100% should be on treatment by 24 days of age (acceptable standard). The referral ages for babies referred following a second sample are shown in table 8 and detailed as the darker (purple) bars in figure 7. The median age at referral was 23 days (range 16-54; excluding the premature repeat screen positive result, the double borderline case due to an initial sample of insufficient quality and the frank positive case following a repeat sample due to transfusion within 72 hours, all detailed above). Four babies (31%) were referred by 21 days and 8 babies (62%) were referred by 24 days. The sample from the baby referred on day 27 was not received in the laboratory until day 24 (collected aged 18 days). The two babies referred at 54 days were twins who did not have their repeat samples collected until day 48. A clinical incident was raised in relation to these babies (incident number ). The national guidelines for clinical referral of CHT babies state that parents should be offered an appointment within three days of being informed about their baby s positive screening result. All babies referred by our screening laboratory are given an appointment within 1 day of the parents being informed of the result. The guidelines also state that clinical referral should be initiated within four working days of sample receipt by the laboratory for 100% of cases. All 50 positive CHT cases were referred within 4 working days. 29

32 Number of cases Referral age distribution for CHT babies First Sample Repeat Sample Age at referral (days) Figure 7: Graph to show age (in days) of each positive CHT referral case First sample: babies referred on first sample (TSH >20mIU/l); Repeat sample: detected on repeat sample. 30

33 PCT Number of cases Age at referral (days) AW&L 1 16 Blackburn 2 11, 13 Bolton 1 14 Bury 2 13, 13 C Lancs 2 12, 13 Cumbria (South) 2 17, 19 E Lancs 3 10, 11, 12 Manchester 5 11, 11, 11, 13, 14 N Lancs 1 13 Oldham 8 10, 11, 13, 14, 14, 14, 15, 20 Rochdale 1 11 Salford 3 11, 11, 12 Tameside 2 12, 13 Trafford 1 11 Table 7: Location and age at referral of positive CHT babies identified on the first sample PCT Number of cases Age at referral (days) AW&L 1 22 Blackburn 1 19 Bolton 1 22 Bury 2 54 C Lancs 1 35 E Lancs 1 20 Manchester 2 22, 23 Oldham 1 18 Rochdale 2 27, 43 Salford 1 25 Stockport 1 16 Tameside 1 25 Trafford 1 24 Table 8: Positive CHT babies identified on a second sample and age of referral 31

34 CF Screening CF screening process is carried out according to the national algorithm as detailed on the UKNSPC website ( and involves the analysis of IRT on the initial bloodspot sample taken at day 5-8 followed by DNA mutational analysis if the initial IRT is raised. If no mutations are identified yet the initial IRT is greatly elevated (>120ng/ml) a second IRT sample is requested to be taken between days If this is raised the baby is reported as CF suspected. Referrals are carried out by liaison with the CF centre at Royal Manchester Children s Hospital. The data for CF screening is shown in tables 9, 10 and 11. Comparative data for 2010/11 and 2011/12 is shown in table 9 and summary data since the programme was implemented in 2007 in table / / /2013 Screening data (first sample) CF not suspected Number of babies screened for CF Number 99.5th centile sent for mutation analysis 307* Total number of second samples requested Number with first IRT 99.5th centile and one mutation Number with first IRT 99.9th centile and no mutation found Number with first IRT < 99.5th centile Number with first IRT 99.5th centile but < 99.9th, no mutations detected (2nd sample not required) Number with first IRT 99.9th centile, no mutations detected and second sample IRT below cut-off 2 Number with first IRT 99.5th centile and two mutations detected Number with first IRT 99.5th centile and two mutations detected on the four mutation panel CF suspected Number with first IRT 99.5th centile and two mutations detected, with the second mutation detected on the extended mutation panel Number with first IRT 99.5th centile, one mutation and second sample IRT above cut-off 2 Number with first IRT 99.9th centile, no mutations detected and second sample IRT above cut-off Total number of 'CF suspected' babies Carrier Number with first IRT 99.5th centile and one mutation found and second sample IRT below cut-off Table 9: Summary of screening results for cystic fibrosis. A second IRT sample is requested if no mutations were identified and the initial IRT result was greater than the 99.9 th centile (currently 120) OR if one mutation was identified. If the second IRT sample was greater than cut off 2 (currently 60) then that baby was reported as CF suspected. *Includes some repeat samples 32

35 07/08 08/09 09/10 10/11 11/12 12/13 Babies Screened Samples referred for DNA 116 (0.43%) 232 (0.42%) 263 (0.46%) 307 (0.54%) 257 (0.45%) 226 (0.40%) CF Suspected 11 (11) 17 (23) 24 (23) 23 (23) 21 (23) 26 (23) 2 mutations on 4 mutation panel 2 mutations on extended panel 1 mutation + 2 nd IRT >cut-off 2 No mutation + 2 nd IRT>cut-off 2 6 (8) 12 (17) 11 (17) 14 (17) 16 (20) 16 (20) 1 (1) 1 (3) 5 (3) 4 (3) 1 (3) 6 (3) 0 (1) 3 (3) 2 (3) 1 (3) 1 (3) 2 (3) 4 (0) 1 (1) 6 (1) 4 (1) 3 (1) 2 (1) CF probable carriers 5 (13) 13 (28) 16 (28) 22 (28) 12 (29) 6 (28) Table 10: CF Outcome Data for CF Since Programme Implementation Figures in parentheses are numbers predicted from the national algorithm The percentage of samples referred for DNA testing remains close to the target of 0.5%. The total number of babies who are screen positive is similar to the figure predicted from the national algorithm although as in previous years the number of samples with two raised IRTs and no mutation detected is higher than predicted. The number of carriers identified decreased significantly in 2011/12 and has decreased even further this year. The age of referral of positive CF cases is represented graphically in figure 8. The cases that have been referred following analysis of a second IRT are shown to the right of the chart. The median age for referral of all babies was 19 days (range days). According to the clinical referral guidelines for cystic fibrosis, CF referrals for cases identified as positive on the first sample (ie, two mutations) should be referred by the age of 28 days and those identified as positive from the second IRT sample should be referred by 35 days. Table 11 and figure 8 detail the age of each baby at referral. All double mutation cases except one were referred by day 28, thus achieving this standard. In the case of the baby who was referred on day 34, from Blackburn, the first sample was not collected until age 22 days. 33

36 PCT Number of cases Age at referral AW&L 4 18, 19, 19, 30 Blackburn 3 15, 19, 34 Blackpool 1 33 Bolton 2 18, 20 C Lancs 2 21, 22 E Lancs 1 16 Manchester 5 14, 15, 16, 16, 54 N Lancs 3 13, 17, 19 Oldham 1 20 Rochdale 1 17 Salford 1 19 Stockport 1 20 Tameside 1 31 Table 11: Location of CF cases identified by screening and age at referral The referral ages shown in bold represent those cases that were identified following receipt of a second samples for IRT analysis. Of the cases that were referred following receipt of a second sample for IRT, (shown in bold in table 11, and to the right of figure 8), one case was referred beyond the recommended 35 day timeframe. This Manchester baby had a repeat sample collected aged 47 days, rather than the recommended days. 34

37 Number of cases Referral age distribution for positive CF babies 1st sample 2nd sample Age at referral (days) Figure 8: Graph to show the age at referral of all CF cases. Those that were referred following receipt of a second bloodspot are shown to the right of the graph. 35

38 Number of babies In 2012/13 a total of 189 babies missed CF screening which is a significant reduction from 2011/ babies were movers in ; it would be important to establish whether these babies arrived in the UK too late to be screened for CF or whether there was a delay in the collection of their screening samples. Of the remaining 41 babies, 36 were born in the UK and in 5 cases it was not clear from the details provided on the blood spot card whether they were born within or outside of the UK. Figures 9 and 10 give a breakdown of babies who missed CF screening by PCT (excluding the 5 cases where the place of birth was not stated). In figure 10 the numbers are expressed as a rate per 10,000 babies screened to enable better comparison between the PCTs. Born in UK Born Outside UK AW&L Blackburn Blackpool Bolton Bury C Lancs Cumbria South E Lancs Manchester N Lancs Oldham Rochdale Salford Stockport Tameside Trafford Out of region Figure 9: The number of babies who missed CF screening sorted by PCT. 36

39 Rate per 10,000 babies screened 60 Born in UK Born Outside UK AW&L Blackburn Blackpool Bolton Bury C Lancs Cumbria South E Lancs Rochdale Manchester N Lancs Oldham Salford Stockport Tameside Trafford Figure 10: The number of babies who missed CF screening per 10,000 babies screened by each PCT. 37

40 Screening for Sickle Cell disease and other Haemoglobinopathies Screening for sickle cell and other haemoglobinopathies is carried out within the laboratory using high performance liquid chromatography (HPLC) as a first line test and any variants that have been identified are confirmed by second line iso-electric focussing which is carried out within the haematology department of Manchester Royal Infirmary. The laboratory sent 659 samples for confirmatory testing, 76 of which were subsequently reported as not suspected (FA). A summary of all diseases (both clinically and not clinically significant) and carriers identified following confirmatory testing is provided in table 12. There were 17 babies identified as having sickle cell disease (13 FS and 4 FSC) and 4 babies identified as thalassaemia cases (HbF). Other clinically significant disorders were also identified as shown in table 11 (FD, FSA). Data on the ethnic origin of babies identified with sickle cell disease or other clinically significant haemoglobinopathies is shown in table 13 and age at referral for those babies in table 14. National standard P3 stipulates that 90% of positive screening results for sickle disease should be communicated to parents by 4 weeks of age. The within laboratory turnaround time was the subject of a specific local audit in March As a result processes were modified and local laboratory turnaround time standards agreed: L1: receipt of sample in NBS Lab to referral of sample to haematology lab for isoelectric focusing 3 working days. L2: Receipt of sample in haematology lab to entry of IEF result into screening information system 5 working days. L3: Entry of IEF result into screening information system to printing of referral letters 1 working day. The Manchester Sickle Cell and Thalassaemia Centre (MSCTC) agreed to inform parents of positive screening results within 5 days of receiving the results or sooner if the baby is approaching 4 weeks of age. Therefore, to meet Standard P3, the NBS lab should aim to report results to the MSCTC before the baby reaches 24 days of age. Of the clinically significant disorders identified 75% were reported by 24 days of age. Of the 17 babies positive for sickle cell disease 76% were referred by 24 days of age. In total 7 babies were referred at 24 days or later. In all cases the time of receipt of the sample in 38

41 the haematology lab to entry of the IEF result into the screening information system exceeded 5 working days (mean 10 working days). In one case the time from receipt of sample in NBS Lab to referral of sample to haematology lab for isoelectric focusing was 4 working days. All of the late referrals were prior to November 2012 when further changes were made to working practices to improve turnaround times. A further audit is planned and it will be important to include the final stage of the pathway; the communication of results to parents. PCT Significant diseases FS FSC FSA FE F only Nonsignificant diseases Carriers FC FD FAS FAC FAD FAE AW&L Blackburn Blackpool Bolton Bury C Lancs Cumbria (South) E Lancs Manchester N Lancs Oldham Rochdale Salford Stockport Tameside Trafford Out of region Total Table 12: Results obtained for sickle cell and haemoglobinopathy screening. FS = sickle cell disease FSC = SC type sickle cell disease FSA = possible heterozygote for sickle cell/ thalassaemia FE = HbE disease F only = β thalassaemia major FAS = sickle cell carrier FAC = HbC carrier FAD = HbD carrier FAE = HbE carrier 39

42 Ethnic origin Significant diseases FS FSC FSA FE F Only Nonsignificant diseases Carriers FC FD FAS FAC FAD FAE White British White Irish Any other White background White and Black Caribbean White and Black African White and Asian Any other mixed background Indian Pakistani Bangladeshi 1 35 Any other Asian background Black Caribbean 15 5 Black African Any other Black background Chinese 1 Any other ethnic category Not stated Totals Table 13: Distribution of babies with sickle cell disease and other clinically significant haemoglobinopathies by ethnic origin 40

43 Age in days Sample collection Receipt of sample in lab Positive result reported Screening result FS FSC FSC FS FS FS FS F FS F F FS FSA FS FS FS FSA FSC FSC F FS FS FS FSA Table 14: Age at referral for babies with sickle cell disease and other clinically significant haemoglobinopathies 41