B3909 - The tempo of childhood growth and physical and neurocognitive development - 27/10/2021

B number: 
Principal applicant name: 
Yee-Ming Chan | Boston Children's Hospital (United States)
Title of project: 
The tempo of childhood growth and physical and neurocognitive development
Proposal summary: 

In our research and clinical experience, we have found that children with delayed puberty often have delays in other aspects of childhood growth and development, including later emergence of adult teeth (secondary tooth eruption), slower growth in childhood, and delayed appearance of changes driven by hormones from the adrenal glands, such as pubic hair, underarm hair, and body odor. These observations suggest that some "master" mechanism (currently unknown) dictates the tempo of childhood growth and development.

This master mechanism may also affect aspects of neurocognitive development, as we have observed high rates of attention-deficit/hyperactivity disorder in children with delayed puberty - over 35%, compared to 5% to 10% in the general population. Alternatively, it has been proposed that ADHD medications may affect the timing of puberty (perhaps through suppression of appetite, or by stimulating production of the hormone cortisol), though studies that have formally examined this possibility have not found evidence for this.

Our above studies focused on children with delayed puberty. In this project, we seek to examine relationships between these childhood milestones in a more general population. We also seek to identify the genetic factors that control the tempo of childhood growth and development.

Impact of research: 
As a pediatric endocrinologist, I routinely evaluate children with concerns about rapid or slow growth and with concerns about precocious and delayed puberty. However, we have an extremely limited understanding of the mechanisms that regulate childhood growth and development, and this hampers our ability to distinguish benign variation from pathological conditions and, in turn, to decide whether reassurance vs. intervention is needed. A more complete understanding of determinants of the tempo of childhood growth will not only shed light on a fascinating and mysterious process, it will also permit a more physiologically informed approach to evaluation and management of children with atypical growth and/or pubertal timing. We also intend to use findings from this project to develop clinical tools, such as a tool to estimate when a child with delayed puberty will eventually enter puberty, which would in turn help to guide management decisions. The connection between growth, pubertal timing, ADHD, and ADHD medications has long been discussed, but the mechanisms underlying all of these - much less linking all of these - remain elusive. Understanding these mechanisms may lead to new approaches to diagnose and manage these concerns.
Date proposal received: 
Friday, 15 October, 2021
Date proposal approved: 
Wednesday, 27 October, 2021
Endocrinology, Learning difficulty, Puberty, growth, adrenarche, other developmental milestones, ADHD, Statistical methods, Latest class/factor/trajectory analyses, polygenic risk score analysis, Mendelian randomization, BMI, Cognition - cognitive function, Development, Genetics, Genomics, Growth, Hormones - cortisol, IGF, thyroid, Mendelian randomisation, Puberty, Sex differences