Dynamic alterations in linear growth and endocrine parameters in children with obesity and height reference values

Elena Kempf; Mandy Vogel; Tim Vogel; Jürgen Kratzsch; Kathrin Landgraf; Andreas Kühnapfel; Ruth Gausche; Daniel Gräfe; Elena Sergeyev; Roland Pfäffle; Wieland Kiess; Juraj Stanik; Antje Körner

doi:10.1016/j.eclinm.2021.100977

Dynamic alterations in linear growth and endocrine parameters in children with obesity and height reference values

EClinicalMedicine. 2021 Jun 23:37:100977. doi: 10.1016/j.eclinm.2021.100977. eCollection 2021 Jul.

Authors

Elena Kempf¹, Mandy Vogel², Tim Vogel¹, Jürgen Kratzsch³, Kathrin Landgraf¹, Andreas Kühnapfel⁴, Ruth Gausche⁵, Daniel Gräfe⁶, Elena Sergeyev¹, Roland Pfäffle¹, Wieland Kiess^{1

2}, Juraj Stanik^{1

7}, Antje Körner^{1

2}

Affiliations

¹ University of Leipzig, Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, Liebigstr.19, Leipzig 04103, Germany.
² University of Leipzig, Medical Faculty, LIFE-Leipzig Research Center for Civilization Diseases, Philipp-Rosenthal-Str. 27, Leipzig 04103, Germany.
³ University of Leipzig, Medical Faculty, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Liebigstr. 27b, Leipzig 04103, Germany.
⁴ University of Leipzig, Medical Faculty, Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Härtelstr. 16-18, Leipzig 04107, Germany.
⁵ University of Leipzig, Medical Faculty, Growth Network CrescNet, Liebigstr. 20a, Leipzig 04103, Germany.
⁶ University of Leipzig, Medical Faculty, Pediatric Radiology, Liebigstr. 20a, Leipzig 04103, Germany.
⁷ Comenius University, Medical Faculty and Children Faculty Hospital, First Department of Pediatrics, Limbova 1, 833 40 Bratislava, Slovakia and Slovak Academy of Sciences, Biomedical Research Center, Institute of Experimental Endocrinology, DIABGENE Laboratory, Dúbravská cesta 9, Bratislava 845 05, Slovakia.

Abstract

Background: Obesity can affect linear growth of children but there is uncertainty regarding the dynamics and potential causes.

Methods: In the population-based LIFE Child and the obesity-enriched Leipzig Obesity Childhood cohorts (8,629 children, 37,493 measurements), recruited from 1999 to 2018 in Germany, we compared height, growth, and endocrine parameters between normal-weight and children with obesity (0-20 years). Derived from the independent German CrescNet registry (12,703 children) we generated height reference values specific for children with obesity (data collected from 1999 to 2020).

Findings: Children with obesity were significantly taller than normal-weight peers, differing at maximum by 7·6 cm (1·4 height, standard deviation scores or SDS) at age 6-8 years. Already at birth, children with obesity were slightly taller and thereafter had increased growth velocities by up to 1·2 cm/year. This growth acceleration was unrelated to parental height, but was accompanied by increased levels of insulin-like growth factor-1 (IGF-1), insulin and leptin. During puberty, children with obesity showed a catch-down in height SDS. The reduction in pubertal growth velocity by up to 25% coincided with a decrease in levels of IGF-1 (by 17%) and testosterone (by 62%) in boys and estradiol (by 37%) in girls. We confirmed these alterations in growth in the independent CrescNet cohort and furthermore provide height reference values for children with obesity for open access.

Interpretation: Dynamics of linear growth are altered distinctively in different developmental phases in children with obesity. Early emergence before other profound comorbidities implies predisposition, environmental, and/or endocrine factors affecting growth in early life. Height reference values for children with obesity may enhance the precision of clinical health surveillance.

Funding: German Research Foundation, German Diabetes Association, EU, ESF, ERDF, State of Saxony, ESPE, Hexal, Novo Nordisk, Pfizer Pharma.

Keywords: Children; Estradiol; Growth velocity; Height; IGF-1; Insulin; Leptin; Obesity; Testosterone.