CLB-08745; No. of pages: 2; 4C: Clinical Biochemistry xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem
Session 7
KiGGS — The German survey on children's health as data base for reference intervals and beyond Klaus P. Kohse Faculty of Medicine and Health Sciences, University of Oldenburg, Germany Institute for Laboratory Diagnostics and Microbiology, Klinikum Oldenburg, Germany
Introduction Age specific reference intervals for results of clinical laboratory investigations are an essential prerequisite for a judgment on a child's health status, since the different phases of physiological development of the healthy child from or even before birth to adolescence are reflected in rather different concentrations of a variety of clinical laboratory analytes in blood. Validated and reliable statistical methods are needed to establish these reference intervals [1]. In recent years, a variety of activities for the establishment of reference intervals have been performed in several regions of the world, studying a substantial number of healthy children in each age group and using well-characterized or traceable methods, such as the NORICHILD initiative of the Scandinavian Societies of Clinical Chemistry, or the CALIPER initiative carried out in Canada. In the United States of America, the National Children's Study, a long-term project, has been started a few years ago and will eventually yield clinical laboratory results on more than 100,000 children. In Germany, the German Health Interview and Examination Survey for Children and Adolescents (“KiGGS”) has recently provided a set of reference intervals for many parameters used in routine laboratory investigations, based on a large number of children with well characterized health status. Pediatric laboratories in Germany will be able to rely on these data, and it may be anticipated that these data can eventually merged into an international “reference interval pool”. Methods The subjects for the KiGGS study had been randomly selected from the official registers of local residents, and 167 study locations (sample points) had been chosen all over Germany [2]. The health status of the children was thoroughly evaluated using questionnaires filled in by parents and (using parallel questionnaires) by the children aged 11 years and older. Physical examinations and other tests as well as computer-assisted personal interviews were carried out by a study team of physicians and health workers. Since the study had been designed to comprise a number of 1000 children per age group comprising one year, about 18,000 children from age 0 to 18 years participated in the study. As a result, ca. 14,000 EDTA blood samples, ca. 14,000 serum samples and ca. 14,000 urine samples were collected from children older than 1 year. In younger
children, the design of the study did not permit collection of blood and urine samples. Following a strict preanalytical protocol, the laboratory investigations were carried out at central laboratories using well-defined standardized methods (e.g., IFCC reference methods) when available [3].
Results and discussion Laboratory parameters to be investigated in the KiGGS study were focussed on general health indices (such as clinical chemistry analytes, red blood count, and urine status), markers of the nutritional state, iron metabolism as well as that of the thyroid, indices for atopic sensitization (allergy-specific IgE), and markers of past infections, or the immunization status. After the initial evaluation of the data, a comprehensive overview of results for ca. 25 analytes of the study has been published in German [4]. It contains age dependent percentiles (from 3rd to 97th) in table as well as graphic form which were obtained using elaborate statistical methods in order to deal with nonparametric distributions. These data may already serve as a basis for age specific reference intervals, although it may still be necessary to examine the clinical data of the children studied and maybe rule out some of the results. On the other hand, since a variety of clinical information is available for these children, it will be possible to study the influence of parameters like body weight or other biometric and physiological data on some of the laboratory parameters investigated. Upon submittal of a request containing the intended use, the data obtained during the KiGGS study are available from the Robert Koch-Institute as Public Use files for scientists with a documented interest in the field of pediatric medicine. The scientific output of this has already been documented in several publications [5–15]. Thus, in the years following their collection, the data obtained during the KiGGS study have been further evaluated in numerous projects e.g., investigations on the interrelationships of endocrinological parameters such as thyroid hormone concentrations and iodine status [6], or assessment of seropositivity rates for several viral infective agents [11–13]. Furthermore, correlations of the data obtained in the laboratory with clinical parameters have been investigated, such as vitamin D concentrations and endurance performance [9], or thyroid hormone concentrations and blood pressure [15].
http://dx.doi.org/10.1016/j.clinbiochem.2014.05.039 0009-9120/© 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Please cite this article as: Kohse KP, KiGGS — The German survey on children's health as data base for reference intervals and beyond, Clin Biochem (2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.05.039
2
K.P. Kohse / Clinical Biochemistry xxx (2014) xxx–xxx
In conclusion, the results of the KiGGS study still serve as an invaluable tool for researchers trying to solve specific problems related to children's health.
[8]
[9]
References [1] Daly CH, Liu X, Grey VL, Hamid JS. A systematic review of statistical methods used in constructing pediatric reference intervals. Clin Biochem 2013;46:1220–7. [2] http://www.kiggs-studie.de/english/home.html. [3] Thierfelder W, Dortschy R, Hintzpeter B, Kahl H, Scheidt-Nave C. Biochemical measures in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2007;50:757–70. [4] Dortschy R, Schaffarth Rosario A, Scheidt-Nave C, Thierfelder W, Thamm M, Gutsche J, et al. Bevölkerungsbezogene Verteilungswerte ausgewählter Laborparameter aus der Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland (KiGGS). Beiträge zur Gesundheitsberichterstattung des Bundes. Berlin: Robert Koch-Institut; 2009. [5] Schwab KO, Doerfer J, Scheidt-Nave C, Kurth BM, Hungele A, Scheuing N, et al. Algorithm-based cholesterol monitoring in children with type 1 diabetes. J Pediatr 2014;S0022-3476:1584–9. [6] Johner SA, Thamm M, Stehle P, Nöthlings U, Kriener E, Völzke H, et al. Interrelations between TSH levels and iodine status in thyroid-healthy children. Thyroid Feb 18 2014 [Epub ahead of print]. [7] Schmitz R, Ellert U, Kalcklösch M, Dahm S, Thamm M. Patterns of sensitization to inhalant and food allergens — findings from the German Health Interview and
[10]
[11]
[12]
[13]
[14]
[15]
Examination Survey for Children and Adolescents. Int Arch Allergy Immunol 2013;162:263–70. Haar K, Bremer V, Houareau C, Meyer T, Desai S, Thamm M, et al. Risk factors for Chlamydia trachomatis infection in adolescents: results from a representative population-based survey in Germany, 2003–2006. Euro Surveill 2013;18:20562. Lämmle L, Bergmann K, Bös K, Koletzko B. Predictors of differences in vitamin D levels in children and adolescents and their relation to endurance performance. Ann Nutr Metab 2013;62:55–62. Truthmann J, Richter A, Thiele S, Drescher L, Roosen J, Mensink GB. Associations of dietary indices with biomarkers of dietary exposure and cardiovascular status among adolescents in Germany. Nutr Metab (Lond) 2012;9:92. Dehnert M, Fingerle V, Klier C, Talaska T, Schlaud M, Krause G, et al. Seropositivity of Lyme borreliosis and associated risk factors: a population-based study in Children and Adolescents in Germany (KiGGS). PLoS One 2012;7:e41321. Poethko-Müller C, Mankertz A. Seroprevalence of measles-, mumps- and rubellaspecific IgG antibodies in German children and adolescents and predictors for seronegativity. PLoS One 2012;7:e42867. Poethko-Müller C, Mankertz A. Sero-epidemiology of measles-specific IgG antibodies and predictive factors for low or missing titres in a German population-based crosssectional study in children and adolescents (KiGGS). Vaccine Oct 19 2011;29:7949–59. Langen U. Classification of specific IgE antibodies in children with hay fever and other atopic diseases in Germany. Results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz Mar 2012;55:318–28. Ittermann T, Thamm M, Wallaschofski H, Rettig R, Völzke H. Serum thyroidstimulating hormone levels are associated with blood pressure in children and adolescents. J Clin Endocrinol Metab Mar 2012;97:828–34.
Please cite this article as: Kohse KP, KiGGS — The German survey on children's health as data base for reference intervals and beyond, Clin Biochem (2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.05.039
Contents lists available at ScienceDirect
Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem
Session 7
KiGGS — The German survey on children's health as data base for reference intervals and beyond Klaus P. Kohse Faculty of Medicine and Health Sciences, University of Oldenburg, Germany Institute for Laboratory Diagnostics and Microbiology, Klinikum Oldenburg, Germany
Introduction Age specific reference intervals for results of clinical laboratory investigations are an essential prerequisite for a judgment on a child's health status, since the different phases of physiological development of the healthy child from or even before birth to adolescence are reflected in rather different concentrations of a variety of clinical laboratory analytes in blood. Validated and reliable statistical methods are needed to establish these reference intervals [1]. In recent years, a variety of activities for the establishment of reference intervals have been performed in several regions of the world, studying a substantial number of healthy children in each age group and using well-characterized or traceable methods, such as the NORICHILD initiative of the Scandinavian Societies of Clinical Chemistry, or the CALIPER initiative carried out in Canada. In the United States of America, the National Children's Study, a long-term project, has been started a few years ago and will eventually yield clinical laboratory results on more than 100,000 children. In Germany, the German Health Interview and Examination Survey for Children and Adolescents (“KiGGS”) has recently provided a set of reference intervals for many parameters used in routine laboratory investigations, based on a large number of children with well characterized health status. Pediatric laboratories in Germany will be able to rely on these data, and it may be anticipated that these data can eventually merged into an international “reference interval pool”. Methods The subjects for the KiGGS study had been randomly selected from the official registers of local residents, and 167 study locations (sample points) had been chosen all over Germany [2]. The health status of the children was thoroughly evaluated using questionnaires filled in by parents and (using parallel questionnaires) by the children aged 11 years and older. Physical examinations and other tests as well as computer-assisted personal interviews were carried out by a study team of physicians and health workers. Since the study had been designed to comprise a number of 1000 children per age group comprising one year, about 18,000 children from age 0 to 18 years participated in the study. As a result, ca. 14,000 EDTA blood samples, ca. 14,000 serum samples and ca. 14,000 urine samples were collected from children older than 1 year. In younger
children, the design of the study did not permit collection of blood and urine samples. Following a strict preanalytical protocol, the laboratory investigations were carried out at central laboratories using well-defined standardized methods (e.g., IFCC reference methods) when available [3].
Results and discussion Laboratory parameters to be investigated in the KiGGS study were focussed on general health indices (such as clinical chemistry analytes, red blood count, and urine status), markers of the nutritional state, iron metabolism as well as that of the thyroid, indices for atopic sensitization (allergy-specific IgE), and markers of past infections, or the immunization status. After the initial evaluation of the data, a comprehensive overview of results for ca. 25 analytes of the study has been published in German [4]. It contains age dependent percentiles (from 3rd to 97th) in table as well as graphic form which were obtained using elaborate statistical methods in order to deal with nonparametric distributions. These data may already serve as a basis for age specific reference intervals, although it may still be necessary to examine the clinical data of the children studied and maybe rule out some of the results. On the other hand, since a variety of clinical information is available for these children, it will be possible to study the influence of parameters like body weight or other biometric and physiological data on some of the laboratory parameters investigated. Upon submittal of a request containing the intended use, the data obtained during the KiGGS study are available from the Robert Koch-Institute as Public Use files for scientists with a documented interest in the field of pediatric medicine. The scientific output of this has already been documented in several publications [5–15]. Thus, in the years following their collection, the data obtained during the KiGGS study have been further evaluated in numerous projects e.g., investigations on the interrelationships of endocrinological parameters such as thyroid hormone concentrations and iodine status [6], or assessment of seropositivity rates for several viral infective agents [11–13]. Furthermore, correlations of the data obtained in the laboratory with clinical parameters have been investigated, such as vitamin D concentrations and endurance performance [9], or thyroid hormone concentrations and blood pressure [15].
http://dx.doi.org/10.1016/j.clinbiochem.2014.05.039 0009-9120/© 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Please cite this article as: Kohse KP, KiGGS — The German survey on children's health as data base for reference intervals and beyond, Clin Biochem (2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.05.039
2
K.P. Kohse / Clinical Biochemistry xxx (2014) xxx–xxx
In conclusion, the results of the KiGGS study still serve as an invaluable tool for researchers trying to solve specific problems related to children's health.
[8]
[9]
References [1] Daly CH, Liu X, Grey VL, Hamid JS. A systematic review of statistical methods used in constructing pediatric reference intervals. Clin Biochem 2013;46:1220–7. [2] http://www.kiggs-studie.de/english/home.html. [3] Thierfelder W, Dortschy R, Hintzpeter B, Kahl H, Scheidt-Nave C. Biochemical measures in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2007;50:757–70. [4] Dortschy R, Schaffarth Rosario A, Scheidt-Nave C, Thierfelder W, Thamm M, Gutsche J, et al. Bevölkerungsbezogene Verteilungswerte ausgewählter Laborparameter aus der Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland (KiGGS). Beiträge zur Gesundheitsberichterstattung des Bundes. Berlin: Robert Koch-Institut; 2009. [5] Schwab KO, Doerfer J, Scheidt-Nave C, Kurth BM, Hungele A, Scheuing N, et al. Algorithm-based cholesterol monitoring in children with type 1 diabetes. J Pediatr 2014;S0022-3476:1584–9. [6] Johner SA, Thamm M, Stehle P, Nöthlings U, Kriener E, Völzke H, et al. Interrelations between TSH levels and iodine status in thyroid-healthy children. Thyroid Feb 18 2014 [Epub ahead of print]. [7] Schmitz R, Ellert U, Kalcklösch M, Dahm S, Thamm M. Patterns of sensitization to inhalant and food allergens — findings from the German Health Interview and
[10]
[11]
[12]
[13]
[14]
[15]
Examination Survey for Children and Adolescents. Int Arch Allergy Immunol 2013;162:263–70. Haar K, Bremer V, Houareau C, Meyer T, Desai S, Thamm M, et al. Risk factors for Chlamydia trachomatis infection in adolescents: results from a representative population-based survey in Germany, 2003–2006. Euro Surveill 2013;18:20562. Lämmle L, Bergmann K, Bös K, Koletzko B. Predictors of differences in vitamin D levels in children and adolescents and their relation to endurance performance. Ann Nutr Metab 2013;62:55–62. Truthmann J, Richter A, Thiele S, Drescher L, Roosen J, Mensink GB. Associations of dietary indices with biomarkers of dietary exposure and cardiovascular status among adolescents in Germany. Nutr Metab (Lond) 2012;9:92. Dehnert M, Fingerle V, Klier C, Talaska T, Schlaud M, Krause G, et al. Seropositivity of Lyme borreliosis and associated risk factors: a population-based study in Children and Adolescents in Germany (KiGGS). PLoS One 2012;7:e41321. Poethko-Müller C, Mankertz A. Seroprevalence of measles-, mumps- and rubellaspecific IgG antibodies in German children and adolescents and predictors for seronegativity. PLoS One 2012;7:e42867. Poethko-Müller C, Mankertz A. Sero-epidemiology of measles-specific IgG antibodies and predictive factors for low or missing titres in a German population-based crosssectional study in children and adolescents (KiGGS). Vaccine Oct 19 2011;29:7949–59. Langen U. Classification of specific IgE antibodies in children with hay fever and other atopic diseases in Germany. Results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz Mar 2012;55:318–28. Ittermann T, Thamm M, Wallaschofski H, Rettig R, Völzke H. Serum thyroidstimulating hormone levels are associated with blood pressure in children and adolescents. J Clin Endocrinol Metab Mar 2012;97:828–34.
Please cite this article as: Kohse KP, KiGGS — The German survey on children's health as data base for reference intervals and beyond, Clin Biochem (2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.05.039
