Pediatric reference values of alkaline phosphatase: Analysis from a German population-based cohort and influence of anthropometric and blood parameters.

BACKGROUND Due to different growth and metabolic processes, reference values of alkaline phosphatase (AP) for children aged 3 month to 18 years are dependent on age and sex. They are not constant and differ from those of adults due to the growth processes taking place. Accordingly, reference levels of AP continuous across these ages were generated for boys and girls based on of a large German health- and population-based study, LIFE Child. We considered AP at different growth and Tanner stages and additionally its association with other anthropometric parameters. The association between AP and BMI was of particulary great interest due to controversial literature on this topic. The role of AP in liver metabolism was investigated by examining ALAT, ASAT, and GGT. METHODS 3976 healthy children (12,093 visits) were included from the LIFE Child study from 2011 to 2020. The subjects´ age ranged from 3 months to 18 years. Serum samples from 3704 subjects (10,272 cases, 1952 boys and 1753 girls) were analysed for AP after applying specific exclusion criteria. After calculating of reference percentiles, associations between AP and height-SDS, growth velocity, BMI-SDS, Tanner stage and the liver enzymes ALAT, ASAT and GGT were examined via linear regression models. RESULTS In the continuous reference levels, AP showed a first peak during the first year of life, followed by a plateau at a lower level until the start of puberty. In girls, AP increased beginning at the age 8, with a peak around 11 years, in boys beginning at the age 9, with a peak around age 13. Afterwards, AP values decreased continuously until age 18. In Tanner stages 1 and 2, AP levels did not differ between the two sexes. We found a strong positive association between AP-SDS and BMI-SDS. We also observed a significantly positive association between AP-SDS and height-SDS, which was stronger in boys than in girls. We found different intensities in the associations of AP with growth velocity depending on age group and sex. Furthermore, we found a significantly positive association between ALAT and AP in girls but not in boys, whereas ASAT-SDS and GGT-SDS were significantly positively associated with AP-SDS in both sexes. CONCLUSION Sex and age, but also BMI may act as confounding factors for AP reference ranges. Our data confirm the remarkable association between AP and growth velocity (or height-SDS, respectively) during infancy and puberty. In addition, we were able to specify the associations between AP and ALAT, ASAT, and GGT and their differences in both sexes. These relations should be considered when evaluating liver and bone metabolism markers, especially in infancy.