Paediatric reference intervals an update. Tina Yen Harmonisation Workshop Sydney 18 th May 2017

Transcription

1 Paediatric reference intervals an update Tina Yen Harmonisation Workshop Sydney 18 th May 2017

2 Meeting of the AACB Paediatric SIG Tuesday 16 th May 2017 Prof Frank Bowling (NSW/ TAS) Prof Rita Horvath (NSW) Dr John Coakley (NSW) Ms Jenny Lee (NSW) Dr Jason Chung (NSW) Dr Sue Matthews (VIC) Mr Erik Haworth (VIC) Dr Nilika Wijeratne (VIC) Dr Tina Yen (VIC) Dr Tony Huynh (QLD) Dr Yael Grasko (QLD) Dr Michael Metz (SA) Dr Richard Mackay (Christchurch NZ) Dr Barry Lewis (WA)

3 Clin Biochem Rev (2014) 35 (4)

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8 Past Harmonisation Work by Paediatric SIG Paediatric EUC/ CMP/ ALP 2014 Implementation by laboratories/ feedback Review and Revise 2018?? Barriers to implementation Verification of AACB HRIC (harmonised RI in children) 2018

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10 Samples For each analyte, at least 20 samples will be required (in each age group). 20 samples are required from 14 different age-groups (280 samples). 20 samples = 10 male and 10 females.

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12 TOPIC 1. Revised Sweat Testing Guidelines Plasma ammonia clinical decision limits 3. Benchmarking project for paediatric transplantation (tacrolimus and others) 4. Paediatric Endocrinology Harmonisation of Endocrine Dynamic Testing (Paed-HDET) Reference intervals for hormones 5. AMH ref intervals in paediatrics 6. HAPPi kids 7. Glucose critical limits in paediatrics 8. Neonatal Bilirubin 9. Estimated GFR in children modified Schwartz equation 10. New Paediatric ref intervals for harmonisation albumin, AST, ALT.

13 Current gold standard for the diagnosis of cystic fibrosis (CF). CF unlikely with sweat Cl < 30 mmol/l, CF intermediate risk sweat Cl mmol/l. CF suggestive sweat Cl > 60 mmol/l. Within test variability 3.2 and +3.6 mmol/l (5 th and 95%th) Between test variability 18.2 and mmol/l

14 Ammonia clinical decision limits Plasma ammonia < 1 month < 100 umol/l > 1 month < 50 umol/l Most infants with inborn errors of metabolism present with plasma NH4 > 200 umol/l. NH4 levels rise with generalised illness in the neonatal period. sick premature neonates >150 μmol/l term neonates >100 μmol/l older infants and children >50 μmol/l should have further investigation.

15 Paediatric Renal Transplantation Dr Josh Kausman - differences in tacrolimus monitoring across transplant centres in ANZ paed neph association (ANZPNA). Survey of decision limits from clinicians in Australasian transplant network. Centre 0-4wk 4-8(12)wk 2(3)-6mth 6-12mth >12mth PMH - WA 3-5 Adelaide Monash MC RCH-Melb Sydney CH Westmead CH LCCH - Brisbane Starship ng/ml

16 Issues with tacrolimus decision limits Assay methodology - in original TDM papers, measurements were made with the locally available assays. Immunoassays TDX, IMX HPLC, LC-MS is there data on the difference in measurements between methods? what assays are currently used by the transplant centres in Australia? Impact of harmonisation of assay decision limits and database of methodologies have significant impact beyond Paediatric Nephrology (will translate to liver, heart & BMT services).

17 Current tacrolimus methods Centre Assay 0-4wk 4-8(12)wk 2(3)-6mth 6-12mth >12mth PMH LCMS 3-5 WCH Adelaide Architect (tbc) MonashCH Axsym RCH-Melb Architect SydneyCH LCMS WestmeadCH LCMS LadyCilentoCH LCMS Starship Roche

18 Harmonisation of Paediatric Endocrine Dynamic Testing Joint project of AACB/ RCPA/ APEG

19 Proposal for Paediatric Dynamic Endocrine Testing develop national guidelines and protocols related to the laboratory investigation of children with endocrine conditions with a particular focus on the appropriate clinical utilisation and analytical aspects of assays, tests, and protocols.

20 AMH testing in Paediatrics Ref Intervals AMH is measured in boys by paediatric endocrinologists where there may be a concern about pubertal development. disorders of male sexual development or delayed puberty.

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22 NORMAL: NEGATIVE correlation between serum AMH and testosterone except during fetal life and first few months due to physiological androgen insensitivity of Sertoli cells (have high androgens with high AMH). DISORDERS: Negative correlation will be present in precocious puberty. Negative correlation is lost in constitutional delay in puberty, or defective androgen production/ sensitivity.

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25 Summary New analytes for Harmonisation LFTs GGT, AST, ALT proposal next meeting Ammonia Neonatal BR continuation of discussion Immunosuppressants dialogue with Transplant Specialists Paediatric Dynamic Testing Protocols. Follow up verification of current Paediatric HRI.