The HAPPI Kids (Harmonising Age Pathology Parameters in Kids) study

Abstract

The HAPPI Kids study aimed to establish continuous reference intervals for major biochemistry, haematology and immunology clinical tests using a prospective study design. Addressing the gap in comparative studies, this study specifically collected equal numbers of children from each year of life from newborns to 18 years and then separated samples into aliquots to facilitate head to head comparison across different commercially available analysers. Harmonising Age Pathology Parameters in Kids (HAPPI Kids) aims to collect paediatric blood samples from a range of children and determine the proper reference intervals for different age groups. This data can then be applied to the fields of haematology, immunology and biochemistry and provide health care professionals with a more accurate interpretation of vital clinical laboratory tests. For all clinical laboratory tests, it is vital that the reference intervals are established under the same conditions that the clinical test is performed. This means that the same reagents, analysers and assay techniques must be used in both conditions. ‘Unfortunately, age-appropriate reference intervals are often not available and therefore references intervals are established using different populations, reagents, analysers and assay techniques,’ explains Monagle. This then leads to scientists using inappropriate reference intervals for clinical tests, which results in incorrect results. This is particularly a problem for coagulation tests, or blood tests that provide information on blood clotting and bleeding disorders, which are extra sensitive to changes in analysers and reagents. ‘With incorrect interpretations of coagulation tests comes misdiagnoses and misclassifications of diseases, both of which can hold significant consequences for children who require blood thinning or blood clotting treatment’, he continues. One example of the results from the HAPPI Kids study is serum creatinine, a chemical waste molecule that is generated from muscle metabolism, and differs significantly in age groups and sexes. Serum creatinine is elevated and variable in newborns and then rapidly declines in the first month of life as renal function improves. Moreover, there is a continuous rise in serum creatinine from 1 month to 18 years of age, which reflects body growth and a change in muscle mass. When comparing males and females, median serum creatinine values are generally higher in males. Having a thorough understanding of the changes in serum creatinine throughout the body’s growth is vital for any test done on children, but in particular when monitoring children with kidney disease over time.