Minipuberty of Infancy and the Timing of Pubertal Development in Adolescence: a Follow-up of the Infant Feeding and Early Development (IFED) Cohort

Study Description: Our overarching hypothesis is that endogenous and exogenous factors related to hypothalamic-pituitary-gonadal (HPG) axis activity during minipuberty of infancy are associated with childhood growth, the timing of pubertal development, and HPG axis activity in adolescence. To examine this hypothesis, we will conduct an observational follow-up study of children previously enrolled as infants in the Infant Feeding and Early Development (IFED) cohort. This follow-up study will be conducted remotely with data collection via email/online, mail and telephone by contractors at DLH, working on behalf of NIEHS.

Objectives: Primary Objective: To assess whether endogenous (e.g. hormone concentrations and size of hormone-sensitive organs) and exogenous (e.g. infant feeding method, exposure to endocrine disrupting chemicals) factors during minipuberty of infancy are related to a) growth, b) timing of pubertal development, and c) HPG axis activity in adolescence.

Endpoints: Primary Endpoints:

• Height, weight and body mass index (BMI)
• Onset of breast, pubic hair and/or genital development
• Urinary metabolites of reproductive hormones (e.g. gonadotropins and sex steroids)

• INCLUSION CRITERIA:

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

• Completion of the original IFED study, defined as participants who did not withdraw from the study or were not withdrawn by the investigator prior to the end of original follow-up (up to 7 months in males and 9 months in females) and who provided at least the minimum number of blood samples (3 for boys, 4 for girls) across the original study period (N=283 eligible families).
• Ability of subject and mother to understand and the willingness to review informed assent and consent documents, respectively, and indicate agreement to participate.

Exclusion criteria

We will not exclude any participants that meet the inclusion criteria from participating in the study overall or in any of the study procedures. We will collect information, via maternal report and linked medical records, on relevant medical diagnoses and the use of medications that may affect hormone levels, growth, and pubertal development. We may exclude participants with reported conditions or medication use (listed below) from analyses of some study aims or in sensitivity analyses.

Diagnoses/conditions:

• Central or peripheral precocious puberty
• Delayed puberty
• Growth hormone deficiency
• Stunted or delayed growth
• Idiopathic short stature
• Hypopituitarism
• Thyroid conditions, such as hyperthyroid, hypothyroid, Graves disease, Hashimoto's thyroiditis
• Genetic conditions, such as Prader-Willi syndrome, Turner syndrome, and Noonan syndrome

Medications:

• Gonadotropin-Releasing Hormone Agonists (e.g., leuprolide acetate (Lupron Depot), triptorelin (Triptodur), histrelin implant (Supprelin LA))
• Hormone therapy (e.g., testosterone, estrogen)
• Synthetic human growth hormone or IGF-1
• Synthetic thyroid hormone (e.g., levothyroxine)
• Anti-thyroid medications (e.g., methimazole, propylthiouracil) or radioactive iodine treatment