Establishment Of Pediatric Reference Intervals For Liver Function Tests Among 2 To 14 Years Old Healthy Han Children In Changchun

Objective: Reference intervals are basic dimension to explain laboratory tests.Proper and accurate laboratory tests and reference intervals are vitally necessary for medical assessment and care of patients.The liver function reference intervals are basis of disease diagnostic and health assessment.As a completely different group,children have different physical size,organ maturity,and nutrition status with adults.The development and growth of children make reference intervals moving targets.Thus,it is necessary to establish liver function pediatric reference intervals.The aim of this study is to establish and validate pediatric reference intervals of liver function tests among healthy Han children in Changchun.Methods: The study is recommended by the guidelines of International federation of clinical chemistry and laboratory medicine and clinical and laboratory standards institute.The 2 to 14 years old healthy individuals were selected from the Changchun City Hospital Medical Center and Maternal and Child Health Hospital through the questionnaire survey,physical examination and screening criteria to select.Then the reference individual blood sample were collected and detected.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),?-glutamyltransferase(GGT),alkaline phosphatase(ALP),total protein(TP),albumin(ALB),total bilirubin(TBIL)and direct bilirubin(DBIL)were measured on Hitachi 7600-210 automatic biochemical analyzer.The Shanghai Branch of Biological Engineering Company limited provided reagents and standards.Statistical analysis was performed with EXCEL?R language 3.0 and SPSS 21.0 software.The data outliers were removed;distribution was identified.The reference interval of each group was calculated using the nonparametric method to calculate the lower and higher reference limits respectively.For each reference interval,90% confidence intervals were calculated for either ends?The age and gender specific reference intervals were partitioned using Harris and Boyd' s test and calculated using nonparametric rank method.The pediatric reference intervals were validated in five representative hospitals located in different areas in Changchun.Analyze the trend of serum liver function with age in 2 to 14 years old children,and analyze the correlation between serum liver function and age and sex.The established reference intervals were compared with national industry standard and children's reference range result of other studies.Results: A total of 1394 samples from 649 males and 745 females(2-14 years)were used to calculate age and gender specific reference intervals,and the male: female ratio was 1: 1.15.All the analytes required some levels of age partitioning.All the analytes required a minimum of 2 age specific reference intervals.Only enzymes required some levels of sex partitioning.The four enzymes(ALT?AST?GGT?ALP)required no gender partition within the initial several age groups and required partitioning in the later age groups.However,bilirubins(TBIL?DBIL)and proteins(TP?ALB)displayed no gender partition in the whole groups.Different analytes showed different moving trends with age.TP,TBIL,and DBIL showed steady increases,and AST showed apparent decreases in analytes concentration over time,whereas ALT,GGT,ALP,and albumin demonstrated complex trends of change in these times.ALT and GGT increased sharply in males from 11 years to juveniles.However,ALP markedly declined in females from 13 years to 14 years.ALT,AST,GGT,ALP,TP,ALB,TBIL and DBIL were significantly correlated with age(P <0.05).AST and GGT were significantly correlated with sex,while TP,ALB,TBIL and DBIL were not correlated with sex(P > 0.05).All five laboratories passed the validation for each age and gender subgroup of pediatric reference intervals and all the validation data fell within the range of intervals for those liver function analytes.The number of measured values falling outside the reference limit does not exceed 10% of the number of validated cases.The newly reference intervals are applicable in most representative laboratories in Changchun.In the present study,the reference range of liver function in children aged 2 to 14 years old in Changchun was different from that in the standard of Chinese adult population.The serum ALT,GGT and TP reference in children aged 2 to 14 years were significantly lower than those in adults,and serum total bilirubin reference the lower limit of reference and the upper limit were lower than that of adult.The lower limit of reference value and reference limit of serum ALP were higher than that of adult.The reference limit and reference upper limit of 2 to 6 years old children were higher than those of adults.The reference section of pediatric reference intervals for liver function tests among healthy Han children in Changchun is different in age and gender from domestic and overseas.Conclusions: 1.There were apparent age or gender variations of the pediatric reference intervals for liver function tests among healthy Han children in Changchun.When establishing pediatric reference intervals,partitioning according to age and gender is frequently necessary.2.The marked differences reference intervals between pediatrics and adults highlight the importance of establishing specific pediatric reference intervals of liver function to enhance diagnostic safety.3.Our established pediatric reference intervals for liver function tests among healthy Han children in Changchun can be applied to most laboratories in Changchun City.