Supplementary Material for: Effect of Growth Hormone Therapy on Pubertal Timing: Systematic Review and Meta-analysis

Introduction Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing. Methods Embase, Medline, and Cochrane library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children. Results Twenty-five articles (n=1,438 children) were identified describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n=6 studies), chronic renal failure (n=3), Noonan syndrome (n=1), and growth hormone deficiency (n=1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference=-0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total=402) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total=284). Conclusions Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls

Associations of appetitive traits with growth velocities from infancy to childhood.

Acknowledgements: The authors thank all the families who contributed to the study. The authors acknowledge the CBGS research nurses Suzanne Smith, Ann-Marie Wardell, and Karen Forbes, Department of Paediatrics, University of Cambridge. We are also very grateful to the midwives at the Rosie Maternity Hospital, Cambridge, and the staff at the NIHR-Wellcome Trust Clinical Research Facility, Cambridge, for their support. For the purpose of Open Access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.Funder: King Abdullah International Medical Research Center; doi: http://dx.doi.org/10.13039/501100013302Several studies have reported associations between appetitive traits and weight gain during infancy or childhood, but none have directly compared these associations across both age periods. Here, we tested the associations between appetitive traits and growth velocities from birth to childhood. Appetitive trait data were collected using the Children's Eating Behaviour Questionnaire (CEBQ) in 149 children from the Cambridge Baby Growth Study at age 9-17 years. These participants also provided anthropometric measurements during infancy (birth, 3, 12, 18, and 24 months) and childhood (5 to 11 years). Standardized growth velocities (in weight, length/height, BMI, and body fat percentage) for 0-3 months, 3-24 months, and 24 months to childhood were estimated using individual linear-spline models. Associations between each of the eight CEBQ traits and each growth velocity were tested in separate multilevel linear regression models, adjusted for sex, age at CEBQ completion, and the corresponding birth measurement (weight, length, BMI, or body fat percentage). The three food-approach traits (food responsiveness, enjoyment of food and emotional overeating) were positively associated with infancy and childhood growth velocities in weight, BMI, and body fat percentage. By contrast, only one of the food-avoidant traits, satiety responsiveness, was negatively associated with all growth velocities. Significant associations were mostly of similar magnitude across all age periods. These findings reveal a broadly consistent relationship between appetitive traits with gains in weight and adiposity throughout infancy and childhood. Future interventions and strategies to prevent obesity may benefit from measuring appetitive traits in infants and children and targeting these as part of their programs.The CBGS has been funded by the Medical Research Council (7500001180, G1001995), European Union Framework 5 (QLK4-1999-01422), the Mothercare Charitable Foundation (RG54608), Newlife Foundation for Disabled Children (07/20), and the World Cancer Research Fund International (2004/03). This research was also supported by the National Institute for Health Research/Wellcome Trust Clinical Research Facility at Cambridge University Hospitals NHS Foundation Trust and the NIHR Cambridge Comprehensive Biomedical Research Centre. DO, FD, TSC, AS and KO are supported by the Medical Research Council (Unit programmes MC_UU_00006/2 and MC_UU_00006/5). DO is also supported by a PhD studentship from the King Abdullah International Medical Research Center (KAIMRC), the Ministry of National Guard Health Affairs. The sponsors had no role in the study design, collection, analysis or interpretation of the data, the writing of the manuscript or the decision to submit it for publication

Associations of appetitive traits with growth velocities from infancy to childhood.

Several studies have reported associations between appetitive traits and weight gain during infancy or childhood, but none have directly compared these associations across both age periods. Here, we tested the associations between appetitive traits and growth velocities from birth to childhood. Appetitive trait data were collected using the Children's Eating Behaviour Questionnaire (CEBQ) in 149 children from the Cambridge Baby Growth Study at age 9-17 years. These participants also provided anthropometric measurements during infancy (birth, 3, 12, 18, and 24 months) and childhood (5 to 11 years). Standardized growth velocities (in weight, length/height, BMI, and body fat percentage) for 0-3 months, 3-24 months, and 24 months to childhood were estimated using individual linear-spline models. Associations between each of the eight CEBQ traits and each growth velocity were tested in separate multilevel linear regression models, adjusted for sex, age at CEBQ completion, and the corresponding birth measurement (weight, length, BMI, or body fat percentage). The three food-approach traits (food responsiveness, enjoyment of food and emotional overeating) were positively associated with infancy and childhood growth velocities in weight, BMI, and body fat percentage. By contrast, only one of the food-avoidant traits, satiety responsiveness, was negatively associated with all growth velocities. Significant associations were mostly of similar magnitude across all age periods. These findings reveal a broadly consistent relationship between appetitive traits with gains in weight and adiposity throughout infancy and childhood. Future interventions and strategies to prevent obesity may benefit from measuring appetitive traits in infants and children and targeting these as part of their programs.The CBGS has been funded by the Medical Research Council (7500001180, G1001995), European Union Framework 5 (QLK4-1999-01422), the Mothercare Charitable Foundation (RG54608), Newlife Foundation for Disabled Children (07/20), and the World Cancer Research Fund International (2004/03). This research was also supported by the National Institute for Health Research/Wellcome Trust Clinical Research Facility at Cambridge University Hospitals NHS Foundation Trust and the NIHR Cambridge Comprehensive Biomedical Research Centre. DO, FD, TSC, AS and KO are supported by the Medical Research Council (Unit programmes MC_UU_00006/2 and MC_UU_00006/5). DO is also supported by a PhD studentship from the King Abdullah International Medical Research Center (KAIMRC), the Ministry of National Guard Health Affairs. The sponsors had no role in the study design, collection, analysis or interpretation of the data, the writing of the manuscript or the decision to submit it for publication

Associations of appetitive traits with growth velocities from infancy to childhood

Abstract Several studies have reported associations between appetitive traits and weight gain during infancy or childhood, but none have directly compared these associations across both age periods. Here, we tested the associations between appetitive traits and growth velocities from birth to childhood. Appetitive trait data were collected using the Children’s Eating Behaviour Questionnaire (CEBQ) in 149 children from the Cambridge Baby Growth Study at age 9–17 years. These participants also provided anthropometric measurements during infancy (birth, 3, 12, 18, and 24 months) and childhood (5 to 11 years). Standardized growth velocities (in weight, length/height, BMI, and body fat percentage) for 0–3 months, 3–24 months, and 24 months to childhood were estimated using individual linear-spline models. Associations between each of the eight CEBQ traits and each growth velocity were tested in separate multilevel linear regression models, adjusted for sex, age at CEBQ completion, and the corresponding birth measurement (weight, length, BMI, or body fat percentage). The three food-approach traits (food responsiveness, enjoyment of food and emotional overeating) were positively associated with infancy and childhood growth velocities in weight, BMI, and body fat percentage. By contrast, only one of the food-avoidant traits, satiety responsiveness, was negatively associated with all growth velocities. Significant associations were mostly of similar magnitude across all age periods. These findings reveal a broadly consistent relationship between appetitive traits with gains in weight and adiposity throughout infancy and childhood. Future interventions and strategies to prevent obesity may benefit from measuring appetitive traits in infants and children and targeting these as part of their programs

Associations of appetitive traits with growth velocities from infancy to childhood

Acknowledgements: The authors thank all the families who contributed to the study. The authors acknowledge the CBGS research nurses Suzanne Smith, Ann-Marie Wardell, and Karen Forbes, Department of Paediatrics, University of Cambridge. We are also very grateful to the midwives at the Rosie Maternity Hospital, Cambridge, and the staff at the NIHR-Wellcome Trust Clinical Research Facility, Cambridge, for their support. For the purpose of Open Access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.Funder: King Abdullah International Medical Research Center; doi: http://dx.doi.org/10.13039/501100013302AbstractSeveral studies have reported associations between appetitive traits and weight gain during infancy or childhood, but none have directly compared these associations across both age periods. Here, we tested the associations between appetitive traits and growth velocities from birth to childhood. Appetitive trait data were collected using the Children’s Eating Behaviour Questionnaire (CEBQ) in 149 children from the Cambridge Baby Growth Study at age 9–17 years. These participants also provided anthropometric measurements during infancy (birth, 3, 12, 18, and 24 months) and childhood (5 to 11 years). Standardized growth velocities (in weight, length/height, BMI, and body fat percentage) for 0–3 months, 3–24 months, and 24 months to childhood were estimated using individual linear-spline models. Associations between each of the eight CEBQ traits and each growth velocity were tested in separate multilevel linear regression models, adjusted for sex, age at CEBQ completion, and the corresponding birth measurement (weight, length, BMI, or body fat percentage). The three food-approach traits (food responsiveness, enjoyment of food and emotional overeating) were positively associated with infancy and childhood growth velocities in weight, BMI, and body fat percentage. By contrast, only one of the food-avoidant traits, satiety responsiveness, was negatively associated with all growth velocities. Significant associations were mostly of similar magnitude across all age periods. These findings reveal a broadly consistent relationship between appetitive traits with gains in weight and adiposity throughout infancy and childhood. Future interventions and strategies to prevent obesity may benefit from measuring appetitive traits in infants and children and targeting these as part of their programs.</jats:p