1 / 30

Auditing antenatal diagnoses – what is good practice?

Auditing antenatal diagnoses – what is good practice?. Sarah Ball, Tim Hutchin, George Gray, Linda Jenkinson, Mary Anne Preece West Midlands Laboratory for Inherited Metabolic Disorders, Birmingham Children’s Hospital. Summary. Purpose of antenatal audit

studs
Download Presentation

Auditing antenatal diagnoses – what is good practice?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Auditing antenatal diagnoses – what is good practice? Sarah Ball, Tim Hutchin, George Gray, Linda Jenkinson, Mary Anne Preece West Midlands Laboratory for Inherited Metabolic Disorders, Birmingham Children’s Hospital

  2. Summary • Purpose of antenatal audit • Practice at West Midlands Inherited Metabolic Disorders Laboratory • Audit outcome 1984 – 2005 • Details of 2 inconsistent audits and resultant change in practice • Suggested system for adoption by other laboratories

  3. Purpose of antenatal audit (1) • In utero diagnosis of inherited disease: most high risk test for genetic laboratories • Misdiagnosis  loss of a potentially healthy life birth of a child with a painful and crippling disease • Huge financial and social costs of misdiagnosis

  4. Purpose of antenatal audit (2) • Laboratory procedures to ensure reliability of test result – minimise pre-analytical, analytical and post-analytical errors • Potential sources of unexpected risks of misdiagnosis: • Genetics of the disease • Expression in utero (biochemical tests) • Technical problems with an established test • Inadequate test validation

  5. Purpose of antenatal audit (3) • To monitor the quality of our service we routinely attempt audit on ALL our antenatal diagnoses • Take action if there are anomalies

  6. Practice in the West Midlands Inherited Metabolic Disorders Laboratory • West Midlands population is 5.3million • Birth rate of 70000 per year • Since 1984 offered a regional service for co-ordinating prenatal tests for IMDs • Test may be performed: • In-house (DNA/biochemical) • UK biochemistry/molecular genetics network lab • Diagnostic lab abroad • Research lab in UK or abroad • National/international referral centre for some specialist biochemical and DNA tests

  7. Prenatal test and audit process (1) At time prenatal testing arranged • letter to clarify • Sample requirement and transport arrangements • Who will dissect sample • Tests to be done and by whom • Identify who will be giving results to the family • Advise that all prenatal tests are audited and recommend early discussion of audit with the family • All prenatal diagnoses are entered in a searchable database (Access)

  8. Prenatal test and audit process (2) Analytical process • Receive sample (CVS or AF – cultured or uncultured) • Perform analysis • Results reported and authorised

  9. Prenatal test and audit process (3) Final report letter = CHASE 1 • combines all results (eg MCC exclusion, uncultured and cultured CVS/AF results etc) • Requests appropriate audit sample • TOP: skin/placenta • Continuing pregnancy: blood/biochemistry or clinical report of healthy baby • Date of first chase letter recorded on database

  10. Prenatal test and audit process (4) Audit sample • Receive audit sample for testing and enter result on data base • Or receive clinical report (acceptable where condition manifest in neonatal period) • Result of audit sample testing or clinical report entered on database • CHASE 2 • If no audit sample received 3 months after the edd write to request appropriate samples

  11. Prenatal test and audit process (5) Unaudited prenatal test • If no response after 3 months of second chase letter then prenatal test recorded as unaudited

  12. Results of antenatal audit

  13. Completed Audits

  14. Uncompleted audits No sample received:-

  15. Inconsistent case 1 Index case • Baby boy with X-linked adrenoleukodystrophy (X-ALD) by plasma very long chain fatty acid quantification Prenatal test (1995) • VLCFA quantification in uncultured CVS • Predicted unaffected male foetus Audit • Neonatal plasma VLCFA indicated affected status • Audit trail on u-CVS – no evidence for sample swap • Reanalysis of c-CVS – variability of VLCFA levels with passage Conclusion • Result published and change of practice worldwide: VLCFA quantification AND oxidation of VLCFAs • Mutation analysis of ABCD1 gene – now preferred procedure for X-ALD prenatal diagnoses

  16. Inconsistent case 1 Index case • Baby boy with X-linked adrenoleukodystrophy (X-ALD) by plasma very long chain fatty acid quantification Prenatal test (1995) • VLCFA quantification in uncultured CVS • Predicted unaffected male foetus Audit • Neonatal plasma VLCFA indicated affected status • Audit trail on u-CVS – no evidence for sample swap • Reanalysis of c-CVS – variability of VLCFA levels with passage Conclusion • Result published and change of practice worldwide: VLCFA quantification AND oxidation of VLCFAs • Mutation analysis of ABCD1 gene – now preferred procedure for X-ALD prenatal diagnoses

  17. Inconsistent case 1 Index case • Baby boy with X-linked adrenoleukodystrophy (X-ALD) by plasma very long chain fatty acid quantification Prenatal test (1995) • VLCFA quantification in uncultured CVS • Predicted unaffected male foetus Audit • Neonatal plasma VLCFA indicated affected status • Audit trail on u-CVS – no evidence for sample swap • Reanalysis of c-CVS – variability of VLCFA levels with passage Conclusion • Result published and change of practice worldwide: VLCFA quantification AND oxidation of VLCFAs • Mutation analysis of ABCD1 gene – now preferred procedure for X-ALD prenatal diagnoses

  18. Inconsistent case 1 Index case • Baby boy with X-linked adrenoleukodystrophy (X-ALD) by plasma very long chain fatty acid quantification Prenatal test (1995) • VLCFA quantification in uncultured CVS • Predicted unaffected male foetus Audit • Neonatal plasma VLCFA indicated affected status • Audit trail on u-CVS – no evidence for sample swap • Reanalysis of c-CVS – variability of VLCFA levels with passage Conclusion • Result published and change of practice worldwide: VLCFA quantification AND oxidation of VLCFAs • Mutation analysis of ABCD1 gene – now preferred procedure for X-ALD prenatal diagnoses

  19. Inconsistent test 2 Index case • Neonatal hypoglycaemia, lactic acidosis • then hypotonia, liver failure, nystagmus and died • Fibroblast phosphoenolpyruvate carboxylasekinase (PEPCK) showed marked deficiency Prenatal test • PEPCK very rare no experience of prenatal testing worldwide • Testing lab agreed to test c-AF cells on research basis only • Parents counselled that experimental procedure • C-AF cell PEPCK within normal limits Audit • Baby born with same symptoms as index case • Fibroblast PEPCK within normal limits • Further studies suggested a possible mtDNA depletion disorder Conclusion • Involvement of PEPCK remains unknown • Availability of information on reliability of test crucial for informed genetic counselling

  20. Inconsistent test 2 Index case • Neonatal hypoglycaemia, lactic acidosis • then hypotonia, liver failure, nystagmus and died • Fibroblast phosphoenolpyruvate carboxylasekinase (PEPCK) showed marked deficiency Prenatal test • PEPCK very rare no experience of prenatal testing worldwide • Testing lab agreed to test c-AF cells on research basis only • Parents counselled that experimental procedure • C-AF cell PEPCK within normal limits Audit • Baby born with same symptoms as index case • Fibroblast PEPCK within normal limits • Further studies suggested a possible mtDNA depletion disorder Conclusion • Involvement of PEPCK remains unknown • Availability of information on reliability of test crucial for informed genetic counselling

  21. Inconsistent test 2 Index case • Neonatal hypoglycaemia, lactic acidosis • then hypotonia, liver failure, nystagmus and died • Fibroblast phosphoenolpyruvate carboxylasekinase (PEPCK) showed marked deficiency Prenatal test • PEPCK very rare no experience of prenatal testing worldwide • Testing lab agreed to test c-AF cells on research basis only • Parents counselled that experimental procedure • C-AF cell PEPCK within normal limits Audit • Baby born with same symptoms as index case • Fibroblast PEPCK within normal limits • Further studies suggested a possible mtDNA depletion disorder Conclusion • Involvement of PEPCK remains unknown • Availability of information on reliability of test crucial for informed genetic counselling

  22. Inconsistent test 2 Index case • Neonatal hypoglycaemia, lactic acidosis • then hypotonia, liver failure, nystagmus and died • Fibroblast phosphoenolpyruvate carboxylasekinase (PEPCK) showed marked deficiency Prenatal test • PEPCK very rare no experience of prenatal testing worldwide • Testing lab agreed to test c-AF cells on research basis only • Parents counselled that experimental procedure • C-AF cell PEPCK within normal limits Audit • Baby born with same symptoms as index case • Fibroblast PEPCK within normal limits • Further studies suggested a possible mtDNA depletion disorder Conclusion • Involvement of PEPCK remains unknown • Availability of information on reliability of test crucial for informed genetic counselling

  23. A system for antenatal audit • Database in place for audit • Facilitates running work lists regularly to chase audit gaps • Add data: • Before prenatal test • Final result of prenatal test: date of first chase • Date of second chase (if necessary) • Result of audit

  24. Minimum data required for audit database Before prenatal test • Mother’s name • Disease • Date of sampling procedure • Sample type

  25. Minimum data required for audit database After prenatal test • Result of diagnostic test • Date of first chase (i.e. final report letter) • Pregnancy continuing or termination of pregnancy

  26. Minimum data required for audit database Audit test • If termination of pregnancy: • Foetal skin/placenta • Result consistent or inconsistent • If pregnancy continuing: • Await appropriate sample from baby • Result of biochemistry or DNA analysis on neonatal sample • Result consistent or inconsistent

  27. Minimum data required for audit database Second chase • 3 months after live birth expected • If no audit sample or appropriate clinical report • Repeat request for audit sample • If still no reply or no sample after a further 3 months record as unaudited

  28. Conclusions (1) • Essential to ensure awareness of audit in clinical team and counsel family before prenatal test performed • Audit is routine • Attempt to audit all prenatal tests • Parents may decline audit specimen • Parents may chose not to be informed of the audit result if TOP

  29. Conclusions (2) • Clinical and lab audit is essential to good practice • Our results show value of antenatal audit • Systems are easily set up – high success rate of audit completion • Audit permits evaluation of new methods and checking performance of established methods • Failure to detect technical error (e.g. atypical enzyme deficiency or anomalous mutation test) would mean the same misdiagnosis could be repeated in subsequent pregnancies • Antenatal screening committee document on “Prenatal screening standards and protocols” April 2008 will have a standard on audit of amniocentesis and CVS diagnostic procedures and outcomes of pregnancy

  30. What is done in other labs? • What is the current practice in ACC and CMGS laboratories? • Are audits attempted on all antenatal diagnoses, some or none? • If only some, how are they selected?

More Related