Clinical trial NCT04113070: Overweight and Obesity and Puberty Development Cohort Study
Official title: The Effect of Childhood Overweight and Obesity and Genetic Factors on Puberty Development: a Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Precocious Puberty
Overweight and Obesity
Keywords: Child health care
Weight status
Environment
puberty
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Shanghai Children's Medical Center
name: BoAi Hospital of Zhongshan
name: QuFu People's Hospital
name: Inner Mongolia People's Hospital
First posted: 2019-10-02
Enrollment: 14100
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: A stratified random sample of children over 6 years old from grade 1 to 3 of selected primary schools in three cities in China

Brief summary: Precocious puberty and childhood overweight and obesity are important public health problems that both had adverse effects, which including psychological symptom in childhood, short final height or reproductive dysfunction in adulthood, on children's physical and psychological development.The prevalence of precocious puberty and childhood overweight and obesity are both high, and a growing body of epidemiological studies suggested that there was a close relationship of childhood overweight and obesity with puberty development, especially in girls. However, the underlying mechanism between them is unclear. Existing evidence shows that the occurrence of precocious puberty and overweight and obesity are the result of interaction of multiple factors, which consists growth environment and genetics, and many previous studies provided that more overlapping genes existed between obesity and precocious puberty patients, suggesting that common genes may result in these diseases. Therefore, based on a case control study, which will investigate the associations between obesity pleiotropic genes and early puberty, the researchers will collect information related to obesity, growth environment factors and risk genes in this study to evaluate the relationships of these related factors and precocious puberty, and to further explore whether there exists biological interaction effects of these risk factors on sexual precocity. This project has been approved by the Ethics Committee of Shanghai Children's Medical Center.

Detailed description: 1. Purpose: A prospective cohort study. The aim of this study is to investigate the effect of pediatric weight status and childhood growth environment on puberty development.
2. Participants: Participants are primary school children aged 6- to 12-year-old, and their parents must be willing to engage in this study and comply with study requirements.
3. Study Procedure: According to geographic and population distribution, about 40 schools included in this study by stratified, random clustering sampling in three cities of China, including Qufu, Zhongshan and Huhhot. Participant will accept anthropometric measuring by clinicians from the three collaborated hospitals, including BoAi Hospital of Zhongshan, QuFu People' s Hospital and Inner Mongolia People's Hospital. This study will be conducted among children of grade 1 to 3 from selected schools in 2019 and the first, secondary and third follow-up will be conducted one, two and three year later respectively.
4. Exposures: Participants with overweight or obesity will be included in overweight and obesity group at baseline.
5. Related risk factors: Childhood growth and family environmental information, including physical activity, diet habit, sleep duration, family structure and family social-economic status, will be collected by parent-reported questionnaire;
6. Outcomes measures: Participants' puberty stage will be evaluated by secondary sexual characteristics development by physician palpation.

Eligibility criteria: Inclusion Criteria:

* Children over 6 years old from grade 1, 2 and 3 in selected primary schools in Zhongshan, Qufu and Huhhot since 2019

Exclusion Criteria:

* Children with overweight or obesity had a history of hormone drug treatment last for 6 months

Primary outcomes:
measure: Rate of precocious puberty
timeFrame: 1 year
Secondary outcomes:
measure: Rate of early puberty
timeFrame: 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Shanghai Children's Medical Center
name: Shijian Liu, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen C, Zhang Y, Sun W, Chen Y, Jiang Y, Song Y, Lin Q, Zhu L, Zhu Q, Wang X, Liu S, Jiang F. Investigating the relationship between precocious puberty and obesity: a cross-sectional study in Shanghai, China. BMJ Open. 2017 Apr 11;7(4):e014004. doi: 10.1136/bmjopen-2016-014004.
citation: Colmenares A, Gunczler P, Lanes R. Higher prevalence of obesity and overweight without an adverse metabolic profile in girls with central precocious puberty compared to girls with early puberty, regardless of GnRH analogue treatment. Int J Pediatr Endocrinol. 2014;2014(1):5. doi: 10.1186/1687-9856-2014-5. Epub 2014 Apr 17.
citation: Wang M, Zhang Y, Lan D, Hill JW. The Efficacy of GnRHa Alone or in Combination with rhGH for the Treatment of Chinese Children with Central Precocious Puberty. Sci Rep. 2016 Apr 13;6:24259. doi: 10.1038/srep24259.
citation: Luke B. Adverse effects of female obesity and interaction with race on reproductive potential. Fertil Steril. 2017 Apr;107(4):868-877. doi: 10.1016/j.fertnstert.2017.02.114.
citation: Deng F, Tao FB, Liu DY, Xu YY, Hao JH, Sun Y, Su PY. Effects of growth environments and two environmental endocrine disruptors on children with idiopathic precocious puberty. Eur J Endocrinol. 2012 May;166(5):803-9. doi: 10.1530/EJE-11-0876. Epub 2012 Feb 8.
citation: Boyne MS, Thame M, Osmond C, Fraser RA, Gabay L, Reid M, Forrester TE. Growth, body composition, and the onset of puberty: longitudinal observations in Afro-Caribbean children. J Clin Endocrinol Metab. 2010 Jul;95(7):3194-200. doi: 10.1210/jc.2010-0080. Epub 2010 Apr 28.
citation: Biro FM, Khoury P, Morrison JA. Influence of obesity on timing of puberty. Int J Androl. 2006 Feb;29(1):272-7; discussion 286-90. doi: 10.1111/j.1365-2605.2005.00602.x. Epub 2005 Dec 20.
citation: Kaplowitz PB. Link between body fat and the timing of puberty. Pediatrics. 2008 Feb;121 Suppl 3:S208-17. doi: 10.1542/peds.2007-1813F.
citation: Abdel Ghany SM, Sayed AA, El-Deek SEM, ElBadre HM, Dahpy MA, Saleh MA, Sharaf El-Deen H, Mustafa MH. Obesity risk prediction among women of Upper Egypt: The impact of serum vaspin and vaspin rs2236242 gene polymorphism. Gene. 2017 Aug 30;626:140-148. doi: 10.1016/j.gene.2017.05.007. Epub 2017 May 4.
citation: Grarup N, Moltke I, Andersen MK, Dalby M, Vitting-Seerup K, Kern T, Mahendran Y, Jorsboe E, Larsen CVL, Dahl-Petersen IK, Gilly A, Suveges D, Dedoussis G, Zeggini E, Pedersen O, Andersson R, Bjerregaard P, Jorgensen ME, Albrechtsen A, Hansen T. Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. Nat Genet. 2018 Feb;50(2):172-174. doi: 10.1038/s41588-017-0022-7. Epub 2018 Jan 8.
citation: Wasim M, Awan FR, Najam SS, Khan AR, Khan HN. Role of Leptin Deficiency, Inefficiency, and Leptin Receptors in Obesity. Biochem Genet. 2016 Oct;54(5):565-72. doi: 10.1007/s10528-016-9751-z. Epub 2016 Jun 16.
citation: Euling SY, Selevan SG, Pescovitz OH, Skakkebaek NE. Role of environmental factors in the timing of puberty. Pediatrics. 2008 Feb;121 Suppl 3:S167-71. doi: 10.1542/peds.2007-1813C.
citation: Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969 Jun;44(235):291-303. doi: 10.1136/adc.44.235.291. No abstract available.
citation: Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child. 1970 Feb;45(239):13-23. doi: 10.1136/adc.45.239.13.
citation: Bridges NA, Christopher JA, Hindmarsh PC, Brook CG. Sexual precocity: sex incidence and aetiology. Arch Dis Child. 1994 Feb;70(2):116-8. doi: 10.1136/adc.70.2.116.
citation: Lebrethon MC, Bourguignon JP. Management of central isosexual precocity: diagnosis, treatment, outcome. Curr Opin Pediatr. 2000 Aug;12(4):394-9. doi: 10.1097/00008480-200008000-00020.
citation: Klein KO. Precocious puberty: who has it? Who should be treated? J Clin Endocrinol Metab. 1999 Feb;84(2):411-4. doi: 10.1210/jcem.84.2.5533. No abstract available.
citation: Sun Y, Tao FB, Su PY, Mai JC, Shi HJ, Han YT, Wang H, Lou XM, Han J, Liu J. National estimates of the pubertal milestones among urban and rural Chinese girls. J Adolesc Health. 2012 Sep;51(3):279-84. doi: 10.1016/j.jadohealth.2011.12.019. Epub 2012 Mar 15.
citation: Sun Y, Tao F, Su PY; China Puberty Research Collaboration. National estimates of pubertal milestones among urban and rural Chinese boys. Ann Hum Biol. 2012 Nov-Dec;39(6):461-7. doi: 10.3109/03014460.2012.712156. Epub 2012 Aug 6.
citation: Ong KK, Bann D, Wills AK, Ward K, Adams JE, Hardy R, Kuh D; National Survey of Health and Development Scientific and Data Collection Team. Timing of voice breaking in males associated with growth and weight gain across the life course. J Clin Endocrinol Metab. 2012 Aug;97(8):2844-52. doi: 10.1210/jc.2011-3445. Epub 2012 May 31.
citation: Yu T, Yu Y, Li X, Xue P, Yu X, Chen Y, Kong H, Lin C, Wang X, Mei H, Wang D, Liu S. Effects of childhood obesity and related genetic factors on precocious puberty: protocol for a multi-center prospective cohort study. BMC Pediatr. 2022 May 27;22(1):310. doi: 10.1186/s12887-022-03350-x.