A Natural History of Genetic and Environmental Predictors of Pubertal Timing Among Youth With Obesity

Background:

Obesity affects 1 in 5 children in the United States. Childhood obesity often persists into adolescence and adulthood. It can also raise the risk of sleep apnea, fatty liver disease, and fluid buildup in the brain and lead to early-onset puberty. This natural history study will explore how factors such as genes, hormones, diet, and chemical exposures affect puberty in children with obesity.

Objective:

To learn which factors predict the early start of puberty in children with obesity vs those of normal weight.

Eligibility:

Children aged 5 to 7 years with obesity or of normal weight.

Design:

Participants will have clinic visits every 6 months until they reach age 12.

Each clinic visit will include these tests and procedures:

A physical exam.

Collection of blood, urine, and saliva samples. Some samples will be used for genetic tests.

Questions about medical history and medications and supplements.

A questionnaire about their physical activity over the previous week.

A silicone wrist band. Participants will wear a soft wristband for a week prior to each visit. It will tell researchers what chemicals the children were exposed to during that time.

Breast ultrasound, for girls. A gel will be applied, and a wand will be pressed against the skin. The wand uses sound waves to see the tissue inside the breast.

DXA whole body scan. Once a year, participants will have a DXA (dual energy X-ray absorptiometry) scan. This scan measures the amount of bone, muscle, and fat in the body.

Optional food diary. Parents may record everything the participant eats for two 24-hour periods

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Study Overview

• Status: Not yet recruiting
• Conditions: Obesity
• Intervention / Treatment: Behavioral: No Weight loss intervention; Behavioral: Weight loss intervention

Detailed Description

Study Description:

This is a longitudinal study to predict pubertal timing in 5-12-year-old girls and boys with obesity. We hypothesize that: 1) Children with obesity with exposure to estrogenic environmental compounds will demonstrate earlier puberty than those without such an exposure. 2) A polygenic risk score (PRS) of alleles that confer risk for voice break in boys will associate with age at Tanner II pubertal development in boys with obesity. 3) A polygenic risk score (PRS) of alleles that confer risk for menarche in girls will associate with age at stage II pubertal development in girls with obesity. 4) Children with obesity who demonstrate a decrease in BMI percentile of > 5 percentage points will demonstrate later stage II pubertal development than children with no change or an increase in BMI percentile but will demonstrate earlier pubertal development than peers of normal weight.

Objectives:

• Primary Objective: To identify predictors of pubertal timing in 5-12-year old children with obesity.
• Secondary Objectives: To determine the effect of obesity on reproductive hormones and adrenarche.

Endpoints:

• Primary Endpoint: pubertal markers by questionnaire, physical exam (testicular volume, breast development), and ultrasound (breast morphological stage). Pubertal development will be defined as breast morphological stage B and a testicular volume of 4 cc.
• Secondary Endpoints: Tanner pubic hair staging, reproductive hormones (luteinizing hormone (LH), Follicle-stimulating hormone (FSH), estradiol, total testosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione)

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: NIEHS Join A Study Recruitment Group; Phone Number: (855) 696-4347; Email: myniehs@nih.gov
• Study Contact Backup: Name: Natalie D Shaw, M.D.; Phone Number: (984) 287-3716; Email: natalie.shaw@nih.gov

Study Locations

• United States
  • North Carolina
    • Research Triangle Park, North Carolina, United States, 27709
      • National Institute of Environmental Health Sciences Clinical Research Unit
      • Contact: Natalie Shaw, M.D.; Phone Number: 984-287-3716; Email: natalie.shaw@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children from the community and the Obesity Weight Management Clinic within the greater Raleigh, Durham, Chapell Hill North Carolina area.

Description

• INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet all of the following criteria:

1. Stated willingness to comply with all study procedures and availability for the duration of the study, including sharing medical records
2. Male or female, aged 5 to 7 years at the screening visit
3. Normal weight (defined as BMI > 5th percentile and <85th percentile for age and sex) or Obese weight (defined as BMI > 95th percentile for age and sex)
4. Ability of parent or guardian to understand and willingness to sign a written informed consent document. And ability of the participant (child) to provide verbal assent and/or to sign a written assent document.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Known diagnosis of syndromic/genetic form of obesity
2. Current use of medications or supplements that affect reproductive hormones (e.g., estrogen, progesterone, testosterone, puberty blockers, regular use of lavender oil or tea tree oil)
3. Chronic medical conditions (e.g., type 1 or type 2 diabetes, cancer, renal failure, lupus, etc.), at the discretion of the Principal Investigator
4. Clinically significant abnormal laboratory values, at the discretion of the Principal Investigator
5. International adoptee (associated with earlier puberty)

Individuals who do not meet the criteria for participation in this study (screen failure) because of an acute, reversible or transient medical reason may be rescreened upon reversal, improvement or stabilization of their clinical status. Participants who develop an acute, reversible or transient medical condition during the study may return upon reversal, improvement or stabilization of their clinical status.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal weight children; BMI > 5th percentile and <85th percentile for age and sex	Behavioral: No Weight loss intervention; No strategies for weight loss
Obese weight children; BMI > 95th percentile for age and sex	Behavioral: No Weight loss intervention; No strategies for weight loss; Behavioral: Weight loss intervention; Pediatric Weight Management Clinic, which utilizes multiple, individualized strategies to effect weight loss (such as nutrition, behavioral therapy, exercise programs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify predictors of pubertal timing in 5-12-year-old children with obesity	1. pubertal markers by questionnaire, physical exam (testicular volume, Tanner breast staging), and 2. ultrasound (breast morphological stage).	1. Every 6 months2. Every 6 - 12 months, investigator discretion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the effect of obesity on reproductive hormones and adrenarche.	Tanner pubic hair staging, reproductive hormones	Every 6 months

Collaborators and Investigators

• Sponsor: National Institute of Environmental Health Sciences (NIEHS)
• Investigators: Principal Investigator: Natalie D Shaw, M.D., National Institute of Environmental Health Sciences (NIEHS)

Publications and helpful links

General Publications

• Li W, Liu Q, Deng X, Chen Y, Liu S, Story M. Association between Obesity and Puberty Timing: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2017 Oct 24;14(10):1266. doi: 10.3390/ijerph14101266.
• Ortega MT, McGrath JA, Carlson L, Flores Poccia V, Larson G, Douglas C, Sun BZ, Zhao S, Beery B, Vesper HW, Duke L, Botelho JC, Filie AC, Shaw ND. Longitudinal Investigation of Pubertal Milestones and Hormones as a Function of Body Fat in Girls. J Clin Endocrinol Metab. 2021 May 13;106(6):1668-1683. doi: 10.1210/clinem/dgab092.
• Carlson L, Flores Poccia V, Sun BZ, Mosley B, Kirste I, Rice A, Sridhar R, Kangarloo T, Vesper HW, Duke L, Botelho JC, Filie AC, Adams JM, Shaw ND. Early breast development in overweight girls: does estrogen made by adipose tissue play a role? Int J Obes (Lond). 2019 Oct;43(10):1978-1987. doi: 10.1038/s41366-019-0446-5. Epub 2019 Aug 28.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Estimated): June 14, 2026
• Primary Completion (Estimated): December 23, 2036
• Study Completion (Estimated): December 23, 2036

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: February 23, 2026

More Information

Terms related to this study

• Keywords: Obesity; Puberty; Reproductive Hormones; ADRENARCHE; Environmental predictors
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity
• Other Study ID Numbers: 10002237; 002237-E

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified/coded Individual participant data: Demographics, Clinical Data (medical history, medications, phenotypic data, questionnaire data, physical exam, lab tests), Genomic Data (DNA and RNA sequencing), Exposomic data, and Metabolomic data.
• IPD Sharing Time Frame: Starting 6 months after publication, aggregated and summarized data would be made available.
• IPD Sharing Access Criteria: Data could be made available for sharing upon request, with requesters securing appropriate IRB approvals, and following establishment of a data transfer agreement. @@@@@@@@@@@@WES/WGS and RNAseq data are planned to be deposited in dbGaP, a controlled access database, at the time of publication for those subjects who consented to deposit data in dbGaP. @@@@@@
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No