Identifying underlying medical causes of pediatric obesity: Results of a systematic diagnostic approach in a pediatric obesity center

Lotte Kleinendorst; Ozair Abawi; Bibian van der Voorn; Mieke H.T.M. Jongejan; Annelies E. Brandsma; Jenny A. Visser; Elisabeth F.C. van Rossum; Bert van der Zwaag; Mariëlle Alders; Elles M.J. Boon; Mieke M. van Haelst; Erica L.T. van den Akker

doi:10.1371/journal.pone.0232990

Identifying underlying medical causes of pediatric obesity: Results of a systematic diagnostic approach in a pediatric obesity center

Lotte Kleinendorst
, Ozair Abawi
, Bibian van der Voorn
, Mieke H.T.M. Jongejan
, Annelies E. Brandsma
, Jenny A. Visser
, Elisabeth F.C. van Rossum
, Bert van der Zwaag
, Mariëlle Alders
, Elles M.J. Boon
, Mieke M. van Haelst
, Erica L.T. van den Akker^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: Underlying medical causes of obesity (endocrine disorders, genetic obesity disorders, cerebral or medication-induced obesities) are thought to be rare. Even in specialized pediatric endocrinology clinics, low diagnostic yield is reported, but evidence is limited. Identifying these causes is vital for patient-tailored treatment.

OBJECTIVES: To present the results of a systematic diagnostic workup in children and adolescents referred to a specialized pediatric obesity center.

METHODS: This is a prospective observational study. Prevalence of underlying medical causes was determined after a multidisciplinary, systematic diagnostic workup including growth charts analysis, extensive biochemical and hormonal assessment and genetic testing in all patients.

RESULTS: The diagnostic workup was completed in n = 282 patients. Median age was 10.8 years (IQR 7.7-14.1); median BMI +3.7SDS (IQR +3.3-+4.3). In 54 (19%) patients, a singular underlying medical cause was identified: in 37 patients genetic obesity, in 8 patients cerebral and in 9 patients medication-induced obesities. In total, thirteen different genetic obesity disorders were diagnosed. Obesity onset <5 years (p = 0.04) and hyperphagia (p = 0.001) were indicators of underlying genetic causes, but only in patients without intellectual disability (ID). Patients with genetic obesity with ID more often had a history of neonatal feeding problems (p = 0.003) and short stature (p = 0.005). BMI-SDS was not higher in patients with genetic obesity disorders (p = 0.52). Patients with cerebral and medication-induced obesities had lower height-SDS than the rest of the cohort.

CONCLUSIONS: To our knowledge, this is the first study to report the results of a systematic diagnostic workup aimed at identifying endocrine, genetic, cerebral or medication-induced causes of pediatric obesity. We found that a variety of singular underlying causes were identified in 19% of the patients with severe childhood obesity. Because of this heterogeneity, an extensive diagnostic approach is needed to establish the underlying medical causes and to facilitate disease-specific, patient-tailored treatment.

Original language	English
Article number	e0232990
Number of pages	22
Journal	PLoS ONE
Volume	15
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0232990
Publication status	Published - May 2020

Keywords

Adolescent
Ambulatory Care Facilities
Brain Diseases/complications
Child
Child, Preschool
Drug-Related Side Effects and Adverse Reactions/diagnosis
Endocrine System Diseases/complications
Female
Genetic Testing
Humans
Infant
Infant, Newborn
Intellectual Disability/complications
Male
Netherlands
Pediatric Obesity/diagnosis
Phenotype
Prospective Studies

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Kleinendorst, L., Abawi, O., van der Voorn, B., Jongejan, M. H. T. M., Brandsma, A. E., Visser, J. A., van Rossum, E. F. C., van der Zwaag, B., Alders, M., Boon, E. M. J., van Haelst, M. M., & van den Akker, E. L. T. (2020). Identifying underlying medical causes of pediatric obesity: Results of a systematic diagnostic approach in a pediatric obesity center. PLoS ONE, 15(5), Article e0232990. https://doi.org/10.1371/journal.pone.0232990

@article{87da4c8ee4b049a5b8584d4b6a4285da,

title = "Identifying underlying medical causes of pediatric obesity: Results of a systematic diagnostic approach in a pediatric obesity center",

abstract = "BACKGROUND: Underlying medical causes of obesity (endocrine disorders, genetic obesity disorders, cerebral or medication-induced obesities) are thought to be rare. Even in specialized pediatric endocrinology clinics, low diagnostic yield is reported, but evidence is limited. Identifying these causes is vital for patient-tailored treatment.OBJECTIVES: To present the results of a systematic diagnostic workup in children and adolescents referred to a specialized pediatric obesity center.METHODS: This is a prospective observational study. Prevalence of underlying medical causes was determined after a multidisciplinary, systematic diagnostic workup including growth charts analysis, extensive biochemical and hormonal assessment and genetic testing in all patients.RESULTS: The diagnostic workup was completed in n = 282 patients. Median age was 10.8 years (IQR 7.7-14.1); median BMI +3.7SDS (IQR +3.3-+4.3). In 54 (19\%) patients, a singular underlying medical cause was identified: in 37 patients genetic obesity, in 8 patients cerebral and in 9 patients medication-induced obesities. In total, thirteen different genetic obesity disorders were diagnosed. Obesity onset <5 years (p = 0.04) and hyperphagia (p = 0.001) were indicators of underlying genetic causes, but only in patients without intellectual disability (ID). Patients with genetic obesity with ID more often had a history of neonatal feeding problems (p = 0.003) and short stature (p = 0.005). BMI-SDS was not higher in patients with genetic obesity disorders (p = 0.52). Patients with cerebral and medication-induced obesities had lower height-SDS than the rest of the cohort.CONCLUSIONS: To our knowledge, this is the first study to report the results of a systematic diagnostic workup aimed at identifying endocrine, genetic, cerebral or medication-induced causes of pediatric obesity. We found that a variety of singular underlying causes were identified in 19\% of the patients with severe childhood obesity. Because of this heterogeneity, an extensive diagnostic approach is needed to establish the underlying medical causes and to facilitate disease-specific, patient-tailored treatment.",

keywords = "Adolescent, Ambulatory Care Facilities, Brain Diseases/complications, Child, Child, Preschool, Drug-Related Side Effects and Adverse Reactions/diagnosis, Endocrine System Diseases/complications, Female, Genetic Testing, Humans, Infant, Infant, Newborn, Intellectual Disability/complications, Male, Netherlands, Pediatric Obesity/diagnosis, Phenotype, Prospective Studies",

author = "Lotte Kleinendorst and Ozair Abawi and \{van der Voorn\}, Bibian and Jongejan, \{Mieke H.T.M.\} and Brandsma, \{Annelies E.\} and Visser, \{Jenny A.\} and \{van Rossum\}, \{Elisabeth F.C.\} and \{van der Zwaag\}, Bert and Mari{\"e}lle Alders and Boon, \{Elles M.J.\} and \{van Haelst\}, \{Mieke M.\} and \{van den Akker\}, \{Erica L.T.\}",

note = "Publisher Copyright: {\textcopyright} 2020 Kleinendorst et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2020",

month = may,

doi = "10.1371/journal.pone.0232990",

language = "English",

volume = "15",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

Kleinendorst, L, Abawi, O, van der Voorn, B, Jongejan, MHTM, Brandsma, AE, Visser, JA, van Rossum, EFC, van der Zwaag, B, Alders, M, Boon, EMJ, van Haelst, MM & van den Akker, ELT 2020, 'Identifying underlying medical causes of pediatric obesity: Results of a systematic diagnostic approach in a pediatric obesity center', PLoS ONE, vol. 15, no. 5, e0232990. https://doi.org/10.1371/journal.pone.0232990

TY - JOUR

T1 - Identifying underlying medical causes of pediatric obesity

T2 - Results of a systematic diagnostic approach in a pediatric obesity center

AU - Kleinendorst, Lotte

AU - Abawi, Ozair

AU - van der Voorn, Bibian

AU - Jongejan, Mieke H.T.M.

AU - Brandsma, Annelies E.

AU - Visser, Jenny A.

AU - van Rossum, Elisabeth F.C.

AU - van der Zwaag, Bert

AU - Alders, Mariëlle

AU - Boon, Elles M.J.

AU - van Haelst, Mieke M.

AU - van den Akker, Erica L.T.

N1 - Publisher Copyright: © 2020 Kleinendorst et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2020/5

Y1 - 2020/5

N2 - BACKGROUND: Underlying medical causes of obesity (endocrine disorders, genetic obesity disorders, cerebral or medication-induced obesities) are thought to be rare. Even in specialized pediatric endocrinology clinics, low diagnostic yield is reported, but evidence is limited. Identifying these causes is vital for patient-tailored treatment.OBJECTIVES: To present the results of a systematic diagnostic workup in children and adolescents referred to a specialized pediatric obesity center.METHODS: This is a prospective observational study. Prevalence of underlying medical causes was determined after a multidisciplinary, systematic diagnostic workup including growth charts analysis, extensive biochemical and hormonal assessment and genetic testing in all patients.RESULTS: The diagnostic workup was completed in n = 282 patients. Median age was 10.8 years (IQR 7.7-14.1); median BMI +3.7SDS (IQR +3.3-+4.3). In 54 (19%) patients, a singular underlying medical cause was identified: in 37 patients genetic obesity, in 8 patients cerebral and in 9 patients medication-induced obesities. In total, thirteen different genetic obesity disorders were diagnosed. Obesity onset <5 years (p = 0.04) and hyperphagia (p = 0.001) were indicators of underlying genetic causes, but only in patients without intellectual disability (ID). Patients with genetic obesity with ID more often had a history of neonatal feeding problems (p = 0.003) and short stature (p = 0.005). BMI-SDS was not higher in patients with genetic obesity disorders (p = 0.52). Patients with cerebral and medication-induced obesities had lower height-SDS than the rest of the cohort.CONCLUSIONS: To our knowledge, this is the first study to report the results of a systematic diagnostic workup aimed at identifying endocrine, genetic, cerebral or medication-induced causes of pediatric obesity. We found that a variety of singular underlying causes were identified in 19% of the patients with severe childhood obesity. Because of this heterogeneity, an extensive diagnostic approach is needed to establish the underlying medical causes and to facilitate disease-specific, patient-tailored treatment.

AB - BACKGROUND: Underlying medical causes of obesity (endocrine disorders, genetic obesity disorders, cerebral or medication-induced obesities) are thought to be rare. Even in specialized pediatric endocrinology clinics, low diagnostic yield is reported, but evidence is limited. Identifying these causes is vital for patient-tailored treatment.OBJECTIVES: To present the results of a systematic diagnostic workup in children and adolescents referred to a specialized pediatric obesity center.METHODS: This is a prospective observational study. Prevalence of underlying medical causes was determined after a multidisciplinary, systematic diagnostic workup including growth charts analysis, extensive biochemical and hormonal assessment and genetic testing in all patients.RESULTS: The diagnostic workup was completed in n = 282 patients. Median age was 10.8 years (IQR 7.7-14.1); median BMI +3.7SDS (IQR +3.3-+4.3). In 54 (19%) patients, a singular underlying medical cause was identified: in 37 patients genetic obesity, in 8 patients cerebral and in 9 patients medication-induced obesities. In total, thirteen different genetic obesity disorders were diagnosed. Obesity onset <5 years (p = 0.04) and hyperphagia (p = 0.001) were indicators of underlying genetic causes, but only in patients without intellectual disability (ID). Patients with genetic obesity with ID more often had a history of neonatal feeding problems (p = 0.003) and short stature (p = 0.005). BMI-SDS was not higher in patients with genetic obesity disorders (p = 0.52). Patients with cerebral and medication-induced obesities had lower height-SDS than the rest of the cohort.CONCLUSIONS: To our knowledge, this is the first study to report the results of a systematic diagnostic workup aimed at identifying endocrine, genetic, cerebral or medication-induced causes of pediatric obesity. We found that a variety of singular underlying causes were identified in 19% of the patients with severe childhood obesity. Because of this heterogeneity, an extensive diagnostic approach is needed to establish the underlying medical causes and to facilitate disease-specific, patient-tailored treatment.

KW - Adolescent

KW - Ambulatory Care Facilities

KW - Brain Diseases/complications

KW - Child

KW - Child, Preschool

KW - Drug-Related Side Effects and Adverse Reactions/diagnosis

KW - Endocrine System Diseases/complications

KW - Female

KW - Genetic Testing

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Intellectual Disability/complications

KW - Male

KW - Netherlands

KW - Pediatric Obesity/diagnosis

KW - Phenotype

KW - Prospective Studies

UR - https://www.scopus.com/pages/publications/85084359255

U2 - 10.1371/journal.pone.0232990

DO - 10.1371/journal.pone.0232990

M3 - Article

C2 - 32384097

AN - SCOPUS:85084359255

SN - 1932-6203

VL - 15

JO - PLoS ONE

JF - PLoS ONE

IS - 5

M1 - e0232990

ER -

Identifying underlying medical causes of pediatric obesity: Results of a systematic diagnostic approach in a pediatric obesity center

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