Original Study Premature Thelarche in Infants and Toddlers: Prevalence, Natural History and Environmental Determinants Alison L. Curfman BS 1 , Sophia M. Reljanovic BA 1 , Kera M. McNelis BA, BS 1 , Tina T. Dong MS 1 , Steven A. Lewis MS, MBA 2 , Leila W. Jackson PhD 1 , Barbara A. Cromer MD 1 ,3, * 1 Case Western Reserve University School of Medicine, Cleveland, Ohio, USA 2 Center for Health Care Research and Policy at Case Western Reserve University/MetroHealth Medical Center, Cleveland, Ohio, USA 3 Department of Pediatrics, MetroHealth Medical Center, Cleveland, Ohio, USA abstract Study Objective: The aim of this study was to measure the prevalence of premature thelarche in infant and toddler girls and to determine if environmental sources of estrogen were associated with early breast development. Design: Observational with mixed methods: Retrospective chart review, cross-sectional component involving an interview survey, along with longitudinal follow-up of girls with thelarche up to six months. Setting: A general pediatric clinic within a teaching hospital located in a large Midwestern city. Participants: Girls, between the ages of 12 and 48 months, and their mothers, presenting for well-child care. Interventions: None. Main Outcome Measures: Prevalence of premature thelarche; association of premature thelarche with selected environmental exposures. Results: Among the 318 subjects, the overall prevalence of premature thelarche was measured at 4.7% (n 5 15). The prevalence by race/ ethnicity was 4.2% among White Non-Hispanics, 4.6% among Blacks and 6.5% among White Hispanics. The peak prevalence occurred between 12e17 months of age. All thelarche cases were Tanner stage 2. No statistically significant relationship was found between premature thelarche and environmental exposures. Upon follow-up, 44% of the cases of premature thelarche had persistent breast development. Conclusions: Our study demonstrated a higher prevalence of premature thelarche than has been previously reported. This study lacked power because of the small number of premature thelarche cases, the ubiquitous presence of environmental exposure as well as the potentially small effect of each environmental factor. Future studies need to employ a very large sample in order to accurately analyze the relationship between environmental toxicants and premature thelarche. Key Words: Premature thelarche, Early puberty, Endocrine disruptors Introduction Epidemiologic evidence is accumulating that indicates a secular trend towards an increasing prevalence of prema- ture puberty, especially early breast development in school- aged girls. 1,2 This phenomenon may be attributed to in utero and childhood exposure to estrogen-like compounds in the environment, termed endocrine disruptors. 3,4 Synthetically produced endocrine disruptors are ubiquitous in the envi- ronment, and are present in many pesticides, plastics, and products used in daily life, such as some shampoos, scented products, and other beauty products. Beef from cattle fattened with subcutaneous estrogen pellets is a secondary source for exposure with exposed cattle having up to five times the tissue concentrations of estrogen when compared with untreated cattle. 5,6 Because of emerging evidence regarding potential expo- sure to endocrine disruptors for girls of all ages, we were curious about the occurrence of breast development in preschool-aged girls, known as premature thelarche. There are few data on the prevalence, natural history, and predic- tors of premature thelarche. Many pediatricians view premature thelarche as an isolated clinical finding with no pathological meaning; however, premature thelarche today may represent a response to environmental toxicants. Therefore, we designed a study to measure the prevalence, natural history, and environmental determinants of prema- ture thelarche in girls 1 to 4 years of age. Materials and Methods Overview The design of this study was observational and involved mixed methods, including retrospective and current chart review of mother and child pairs as well as a survey of the mother. The study took place in a general pediatric clinic within a teaching hospital located in a large Midwestern city. Using the pediatric continuity clinic as the recruiting base, girls and their biologic mothers were enrolled into the study from May 1, 2009, through December 18, 2009. Inclusion criteria for enrollment included girls between the ages of 12 and 48 months presenting for well-child care and * Address correspondence to: Barbara A. Cromer, MD, 2109 Riverside Drive, Lakewood OH, 44107. E-mail address: bac10@cox.net (B.A. Cromer). 1083-3188/$ - see front matter Ó 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. doi:10.1016/j.jpag.2011.01.003