Early Breast Growth in Girls Aged 6 to 8 Years in the Current Environmental Context

Study Overview
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Brief Summary
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Various studies show an increase in the number of cases of early puberty in girls with breast development with a variable clinical presentation and evolution. This increasing phenomenon concerns girls between 6 and 8 years old. In a large number of cases, from 70 to 95% depending on the series, no medical cause is found and environmental factors are suspected to be involved. Descriptive studies of these patients are scarce and not always provide an overview of all the parameters in line with the concept of the exposome. The PENELOPE clinical trial will allow to analyze a large number of parameters, including the adipose tissue, its metabolism, the endocrine disruptors, and the epigenetic modifications, and to study the impact of environmental health measures in the evolution of these parameters. The data from the analyses of the endocrine disruptors of the patients will be explored in parallel in experimental models (amphibians, murine, cellular) in order to test potential mechanistic hypotheses.

Official Title
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Early Breast Growth in Girls Aged 6 to 8 Years in the Current Environmental Context: Clinical and Biological Parameters, Level of Impregnation With Endocrine Disruptors and Evaluation of the Impact of Environmental Health Measures

Conditions
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Puberty, Precocious, Breast, Environmental Exposure

Intervention / Treatment
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* Other: Environmental health measures


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Girls aged 6 to 8 years Presenting a breast development (isolated or not) Undergoing scheduled pediatric day hospital care (HDJ) Who agree to participate in the study Whose parents agree to their child's participation in the study French speaking Whose parents speak French Affiliated to social security Exclusion Criteria: Organic brain causes of precocious puberty: History of neurocerebral disease (malformations, developmental abnormalities) Organic causes of precocious puberty: Mac Cune Albright syndrome, ovarian cyst or tumor and adrenal hyperplasia History of chemotherapy or radiation therapy Presenting with a communication disorder Pregnancy Persons under protective measures Persons deprived of liberty for judicial or administrative reasons

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 8 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 6 to 8 years old girls, presenting with a breast flare-up<br>Girls aged 6 to 8 years old with breast flare (isolated or not) and scheduled for pediatric day hospital stay | Other: Environmental health measures<br>* MRI will be used to confirm the presence of breast buds, to measure the size of the ovaries and uterus, as well as the fraction of fat mass (abdominal, subcutaneous, liver and bone marrow). The bood and urine tests will allow to measure different biological and metabolic parameters. The presence of endocrine disruptors will be determined in the hair. The bone age x ray will be estimate the maturity of the child's skeletal system.<br>* Other names: Bone age x ray;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of the size of the breast development measured by Magnetic Resonance Imaging | This parameter will allow to describe the clinical evolution of breast development after application of environmental health measures | Baseline, 3 months | 
| Change from baseline of the size of ovaries/uterus measured by Magnetic Resonance Imaging | This parameter will allow to describe the clinical evolution of ovaries and uterus after application of environmental health measures | Baseline, 3 months, | 
| Change from baseline of the abdominal fat surface measured by Magnetic Resonance Imaging | This parameter will allow to describe the clinical evolution of the abdominal fat surface after application of environmental health measures | Baseline, 3 months | 
| Change from baseline of the weight | This parameter will allow to describe the clinical evolution of the weight after application of environmental health measures | Baseline, 3 months, 6 months | 
| Change from baseline of the height | This parameter will allow to describe the clinical evolution of the height after application of environmental health measures | Baseline, 3 months, 6 months | 
| Body mass index (BMI) | This parameter will allow to describe the clinical evolution of the BMI after application of environmental health measures | Baseline, 3 months, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of endocrine disruptors in hair | Describe the evolution of the amount of endocrine disruptors in hair after the implementation of environmental health measures. from 70 to 100 mg of hair will cut as close as possible to the scalp at the posterior vertex, and stored at room temperature to measure endocrine disruptors such as parabens, phthalates, bisphenols and pesticides. | Change from baseline at 90 days | 
| Tanner scale | The Tanner scale is a scale of physical development as children transition into adolescence and then adulthood. The scale defines physical measurements of development based on external primary and secondary sex characteristics. Breast: Tanner I: no glandular tissue Tanner II: breast bud forms, areola begins to widen Tanner III: breast begins to become more elevated, and extends beyond the borders of the areola, Tanner IV: increased breast sizing and elevation; areola and papilla form a secondary mound projecting from the contour of the surrounding breast Tanner V: breast reaches final adult size Pubis hair: Tanner I: no pubic hair Tanner II: small amount of long, downy hair Tanner III: hair becomes more coarse and curly, and begins to extend laterally Tanner IV: adult-like hair quality, extending across pubis but sparing medial thighs Tanner V: hair extends to medial surface of the thighs | Change from baseline at 90 and 180 days | 
| Bone age determination by X ray | Determination of bone age to determine the maturity of the child's skeletal system. | Change from baseline at 90 | 
| Degree of severity of teeth hypomineralisation | The dree of severity is determine according to a scale: 1: <30% of the tooth's enamel surface area visibly disrupted, 2: 31 to 49% of the tooth's enamel surface area visibly disrupted, 3: >50% of the tooth's enamel surface area visibly disrupted | Baseline, 3 months | 
| Follicle-stimulating hormone (FSH) level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Estradiol (E2) level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Testosterone Level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| 17 hydroxyprogesterone level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Dehydroepiandrosterone sulfate level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Sex Hormone-Binding Globulin level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Thyroid Stimulating Hormone level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| FT4 (Free Thyroxine hormone) level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Androstenedione level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Insulin level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Glycated hemoglobin (HbA1C) level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Insulin-like Growth Factor-1 level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Leptine level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Luteinizing hormone (LH) level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 
| Glycemia level | Blood test for determining the evolution of this parameter from baseline | Change from baseline at 90 days and 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Girls, Early puberty, Endocrine disruptors, Breast growth, Environmental Health Measure