Effects of childhood obesity and related genetic factors on precocious puberty: protocol for a multi-center prospective cohort study

Tingting Yu, Ying Yu, Xiaoqing Li, Peng Xue, Xiaodan Yu, Yao Chen, Huijun Kong, Cuilan Lin, Xiumin Wang, Hao Mei, Dan Wang, Shijian Liu, Tingting Yu, Ying Yu, Xiaoqing Li, Peng Xue, Xiaodan Yu, Yao Chen, Huijun Kong, Cuilan Lin, Xiumin Wang, Hao Mei, Dan Wang, Shijian Liu

Abstract

Background: Childhood obesity has important effects on the onset and development of puberty. Although a number of studies have confirmed the relationship between obesity and precocious puberty, little is known about the pleiotropic genes of obesity and precocious puberty and the interaction between genes and environment. There are four objectives: (1) to analyze the incidence of precocious puberty in the general population in China; (2) to verify the direct effect of obesity on children's precocious puberty using a variety of methods; (3) to verify the effect of obesity and its risk gene polymorphism on precocious puberty in a prospective cohort study; and (4) to analyze the interaction effect of genes and environment on pubertal development.

Methods: We will conduct a multi-center prospective cohort study in three cities, which are selected in southern, central, and northern China, respectively. Primary schools in these cities will be selected by a stratified cluster random sampling method. Primary school students from grade 1 to grade 3 (6 to 10 years old) will be selected for the cohort with extensive baseline data collection, including assessment of pubertal development, family demographic information, early development, sleep pattern, dietary pattern, and physical activity. Participants will be followed up for at least three years, and long-term follow-up will depend on future funding.

Discussion: The findings of this multicenter prospective population-based cohort study may expand previous related puberty development research as well as provide important information on the mechanism of early puberty. Targeted interventions can also be developed to improve adolescent health problems related to puberty development based on the available evidence.

Trial registration: ClinicalTrials.gov Identifier: NCT04113070 , prospectively registered on October 2, 2019.

Keywords: Cohort study; Obesity; Precocious puberty; Single nucleotide polymorphism.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flow chart of the prospective cohort study

References

    1. WHO. Obesity and overweight. World Health Organization (WHO) 2017.
    1. Gaete X, Garcia R, Riquelme J, et al. Age of onset of puberty in Chilean boys according to testicular volume and Tanner stage. Rev Med Chil. 2015;143:297–303. doi: 10.4067/S0034-98872015000300003.
    1. Brix N, Ernst A, Lauridsen LLB, et al. Timing of puberty in boys and girls: a population-based study. Paediatr Perinat Epidemiol. 2019;33:70–78. doi: 10.1111/ppe.12507.
    1. Biro FM, Greenspan LC, Galvez MP, et al. Onset of breast development in a longitudinal cohort. Pediatrics. 2013;132:1019–1027. doi: 10.1542/peds.2012-3773.
    1. Mendle J, Ryan RM, McKone KMP. Age at menarche, depression, and antisocial behavior in adulthood. Pediatrics. 2018;141:e20171703. doi: 10.1542/peds.2017-1703.
    1. Golub MS, Collman GW, Foster PMD, et al. Public health implications of altered puberty timing. Pediatrics. 2008;121:S218. doi: 10.1542/peds.2007-1813G.
    1. Silveira LG, Noel SD, Silveira-Neto AP, et al. Mutations of the KISS1 gene in disorders of puberty. J Cli Endocrinol Metab. 2010;95:2276–2280. doi: 10.1210/jc.2009-2421.
    1. Liu R, Kinoshita M, Adolfi MC, et al. Analysis of the role of the Mc4r system in development, growth, and puberty of Medaka. Front Endocrinol. 2019;10:213. doi: 10.3389/fendo.2019.00213.
    1. Haldar A, French MC, Brauning R, et al. Single-nucleotide polymorphisms in the LEPR gene are associated with divergent phenotypes for age at onset of puberty in Davisdale ewes. Biol Reprod. 2014;90:33. doi: 10.1095/biolreprod.113.115923.
    1. Villamor E, Jansen EC. Nutritional determinants of the timing of puberty. Ann Rev Pub Health. 2016;37:33–46. doi: 10.1146/annurev-publhealth-031914-122606.
    1. Boynton-Jarrett R, Harville EW. A prospective study of childhood social hardships and age at menarche. Ann Epidemiol. 2012;22:731–737. doi: 10.1016/j.annepidem.2012.08.005.
    1. Chen C, Zhang Y, Sun W, et al. Investigating the relationship between precocious puberty and obesity: a cross-sectional study in Shanghai. China BMJ Open. 2017;7:e014004–e014e04. doi: 10.1136/bmjopen-2016-014004.
    1. Crocker MK, Stern EA, Sedaka NM, et al. Sexual dimorphisms in the associations of BMI and body fat with indices of pubertal development in girls and boys. J Cli Endocrinol Metab. 2014;99:E1519–E1529. doi: 10.1210/jc.2014-1384.
    1. Al-Awadhi N, Al-Kandari N, Al-Hasan T, et al. Age at menarche and its relationship to body mass index among adolescent girls in Kuwait. BMC Public Health. 2013;13:29. doi: 10.1186/1471-2458-13-29.
    1. Lundeen EA, Norris SA, Martorell R, et al. Early life growth predicts pubertal development in south African adolescents. J Nutr. 2016;146:622–629. doi: 10.3945/jn.115.222000.
    1. Tomova A, Robeva R, Kumanov P. Influence of the body weight on the onset and progression of puberty in boys. J Pediatr Endocrinol Metab. 2015;28:859–865. doi: 10.1515/jpem-2014-0363.
    1. Lee JM, Wasserman R, Kaciroti N, et al. Timing of puberty in overweight versus obese boys. Pediatrics. 2016;137:e20150164. doi: 10.1542/peds.2015-0164.
    1. Kleber M, Schwarz A, Reinehr T. Obesity in children and adolescents: relationship to growth, pubarche, menarche, and voice break. J Pediatr Endocrinol Metab. 2011;24:125–130. doi: 10.1515/jpem.2011.089.
    1. Martos-Moreno GA, Barrios V, Argente J. Normative data for adiponectin, resistin, interleukin 6, and leptin/receptor ratio in a healthy Spanish pediatric population: relationship with sex steroids. Eur J Endocrinol. 2006;155:429–434. doi: 10.1530/eje.1.02227.
    1. Tabassum R, Mahendran Y, Dwivedi OP, et al. Common variants of IL6, LEPR, and PBEF1 are associated with obesity in Indian children. Diabetes. 2012;61:626–631. doi: 10.2337/db11-1501.
    1. Almeida SM, Furtado JM, Mascarenhas P, et al. Association between LEPR, FTO, MC4R, and PPARG-2 polymorphisms with obesity traits and metabolic phenotypes in school-aged children. Endocrine. 2018;60:466–478. doi: 10.1007/s12020-018-1587-3.
    1. EPITOOLS. Sample size for a Cohort study. . Accessed 10 Apr 2022.
    1. Chen C, Jin Z, Yang Y, et al. Prevalence of grade 1, 2 and 3 thinness is associated with lower socio-economic status in children in Shanghai. China Public Health Nutr. 2016;19:2002–2010. doi: 10.1017/S1368980016000045.
    1. Cole TJ, Bellizzi MC, Flegal KM, et al. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ Clin Res. 2000;320:1240–1243. doi: 10.1136/bmj.320.7244.1240.
    1. Cole TJ, Flegal KM, Nicholls D, et al. Body mass index cut offs to define thinness in children and adolescents: international survey. BMJ Clin Res. 2007;335:194. doi: 10.1136/bmj.39238.399444.55.
    1. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child. 1970;45:13–23. doi: 10.1136/adc.45.239.13.
    1. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44:291–303. doi: 10.1136/adc.44.235.291.
    1. Bridges NA, Christopher JA, Hindmarsh PC, et al. Sexual precocity: sex incidence and aetiology. Arch Dis Child. 1994;70:116–118. doi: 10.1136/adc.70.2.116.
    1. Lebrethon MC, Bourguignon JP. Management of central isosexual precocity: diagnosis, treatment, outcome. Curr Opin Pediatr. 2000;12:394–399. doi: 10.1097/00008480-200008000-00020.
    1. Kaplowitz PB. Update on precocious puberty: who should be treated? Adv Pediatr Infect Dis. 2020;67:93–104.
    1. Wang Y. Is obesity associated with early sexual maturation? A comparison of the Association in American Boys Versus Girls. Pediatrics. 2002;110:903. doi: 10.1542/peds.110.5.903.
    1. Sun Y, Tao F-B, Su P-Y, et al. National estimates of the pubertal milestones among urban and rural Chinese girls. J Adolesc Health. 2012;51:279–284. doi: 10.1016/j.jadohealth.2011.12.019.
    1. Sun Y, Tao F, Su P-Y, et al. National estimates of pubertal milestones among urban and rural Chinese boys. Ann Hum Biol. 2012;39:461–467. doi: 10.3109/03014460.2012.712156.
    1. Ong KK, Bann D, Wills AK, et al. Timing of voice breaking in males associated with growth and weight gain across the life course. J Cli Endocrinol Metab. 2012;97:2844–2852. doi: 10.1210/jc.2011-3445.
    1. García CJ, Espinoza A, Dinamarca V, et al. Breast US in children and adolescents. Radiographics. 2000;20:1605–1612. doi: 10.1148/radiographics.20.6.g00nv171605.
    1. Y. Chen HH, L. Shen and Y. LV. Urine bisphenol-a level and habits of life in relation to precocious puberty in girls. Chin. J Child Health Care. 2013;21:237–240.
    1. Song Y, Dong S, Jiang Y, et al. Association between television viewing and dietary patterns among preschool children. Chin J Eviden Based Pediatrics. 2014;9:447–451.
    1. Kantomaa MT, Stamatakis E, Kankaanpää A, et al. Physical activity and obesity mediate the association between childhood motor function and adolescents' academic achievement. Proc Natl Acad Sci U S A. 2013;110:1917–1922. doi: 10.1073/pnas.1214574110.
    1. Chan NPT, Sung RYT, Nelson EAS, et al. Measurement of pubertal status with a Chinese self-report pubertal development scale. Matern Child Health J. 2010;14:466–473. doi: 10.1007/s10995-009-0481-2.
    1. Speliotes EK, Willer CJ, Berndt SI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010;42:937–948. doi: 10.1038/ng.686.
    1. Liu S, Wilson JG, Jiang F, et al. Multi-variant study of obesity risk genes in African Americans: the Jackson heart study. Gene. 2016;593:315–321. doi: 10.1016/j.gene.2016.08.041.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi