A group of clinical biochemists and laboratory medicine scientists across Canada, led by Dr. Khosrow Adeli of The Hospital for Sick Children, are developing a comprehensive database of updated paediatric reference intervals for various chemicals.
In order to make a correct diagnosis, it’s important to know what the normal blood levels of various analytes are for a child of a certain age. When a child undergoes a diagnostic blood test, physicians rely heavily on the presence of reference intervals to accurately diagnose potential illnesses.
The quality of paediatric health care depends on the availability of precise and accurate reference intervals for different groups of the population. A child’s growth and development profoundly influences the various biomarkers tested in laboratories. Under- or over-estimating reference intervals can lead to the misdiagnosis of patients, resulting in costly and unnecessary medical follow-ups. Unfortunately, most currently available laboratory reference intervals are incomplete, cover a limited paediatric age interval, and are derived mostly from Caucasian hospital patients. The paucity of information on the effects of various factors such as age, sex, ethnic background, and sexual development on paediatric reference intervals can compromise the ability of clinicians to accurately diagnose patients.
Current reference intervals also lack reference intervals for emerging biomarkers including cardiovascular disease and cancer. For instance, in paediatric neoplasms, genetic factors are more important than environmental factors and many emerging tumour markers, such as alpha-fetoprotein, have been identified for cancer that could facilitate the process of diagnosis. But no reference intervals currently exist for these markers. Similarly, the lack of age-adjusted cut offs for thyroid stimulating hormone (TSH) during neonatal screening for congenital hypothyroidism has led to an increase in the frequency of false positive results and excessive unnecessary follow-ups.
Through the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) Project, Adeli’s group at The Hospital for Sick Children was able to recruit more than 2,200 healthy participants across ages, sex and ethnicities to submit blood for the study. Six other Canadian pediatric hospitals are collaborating on the CALIPER Project: the Eastern Health/Janeway Children’s Health & Rehabilitation Centre, CHU Sainte-Justine, Children’s Hospital of Eastern Ontario, McMaster Children’s Hospital, Royal University Hospital and B.C. Children’s Hospital.
The CALIPER group has recently published a new database of 40 biochemical markers which is available to clinicians and general public. The next phase of the project includes establishing reference intervals for 30 additional biochemical markers, and conducting a transference study to make the reference intervals obtained at Hospital at Sick Children adaptable to different instruments used in hospitals across the nation. The transference study will account for inter-instrumental differences and analytical methods, and validation studies will verify the transference and will ensure that the reference intervals are comparable.
The CALIPER project could provide clinicians and diagnosticians with an updated and more accurate knowledge of paediatric reference intervals for healthy populations, potentially leading to better diagnoses and care.