Minipuberty of infancy: a critical period for growth and development in girls

About This Grant

PROJECT SUMMARY/ABSTRACT Age at onset of breast development (thelarche), a marker of pubertal onset in girls, has decreased dramatically in the past half-century. This trend has important public health implications as earlier puberty in girls is associated with adverse health consequences across the lifecourse, including increased risks of cardiovascular disease and breast and other hormonal cancers. Pubertal onset is triggered by the re-activation of the hypothalamic-pituitary- gonadal (HPG) axis in childhood, a process that is poorly understood. Increased understanding of HPG axis activity and function in early life is crucial for identifying risk factors for early puberty that may be amenable to interventions. The HPG axis is active for a brief period during infancy, known as minipuberty, before it is silenced until pubertal onset. The function of HPG axis activity during minipuberty in girls remains unclear. In this K99/R00 research, I will examine the overarching hypothesis that minipuberty is a critical window of programming with short- and long-term effects on endocrine-sensitive processes including growth, breast development, and pubertal development. To do so, I will use data from 136 girls in the Infant Feeding and Early Development (IFED) study, a prospective cohort of infants previously followed from birth to age 9 months with repeated assessments of serum sex steroid concentrations, anthropometrics, and ultrasound measures of breast bud diameter. In the K99 phase, I will examine longitudinal associations of sex steroid concentrations during minipuberty with breast bud diameter (Aim 1) and velocity of linear growth and weight gain into late infancy (Aim 2). I will also conduct a longitudinal follow-up of the former IFED infants (born 2010-2013) as they transition through pubertal maturation. Combining these unique repeated measures data captured during minipuberty and adolescent puberty, I will evaluate whether sex steroid concentrations during minipuberty are associated with the timing of pubertal development, as assessed by ages at thelarche and menarche, and sex steroid concentrations across the pubertal transition (Aim 3, R00). This research will provide novel insights into the role of minipuberty in shaping breast development and growth into adolescence, which has implications for the etiology, screening and ultimately prevention of early puberty and its long-term sequelae. To achieve these research aims, I will combine prior epidemiologic training with new experiential and didactic training in pediatric and reproductive endocrinology, advanced statistical methods for longitudinal biomarker data, cohort development and implementation, and professional development. My K99 training will take place within the interdisciplinary environment of the Intramural Research Program at the National Institute of Environmental Health Sciences with the support of a mentoring team of outstanding scientists. This career development award will provide me with the necessary experience to launch my independent research program focused on applying innovative epidemiologic approaches to understand how exogenous and endogenous hormonal factors during critical periods of early life affect growth, breast development, and women’s health across the lifecourse.