An earlier age at pubertal development is associated with increased breast cancer risk, and Westernized countries are observing earlier ages of pubertal timing in girls. While increased rates of childhood obesity are associated with earlier ages of pubertal development, earlier ages of puberty are also observed in countries that are not experiencing high rates of childhood obesity. Prior evidence from a birth cohort in Hong Kong suggests that early life infections, as measured by hospitalizations, is associated with pubertal onset. Emerging evidence suggests that early life and childhood exposures to infection may impact pubertal development. Therefore, we aimed to assess whether indirect measures of infections in infancy (birth-12 months) and early childhood (1-5 years) are associated with the age of onset of puberty (menarche and breast and pubic hair development). We used data from the Infection Questionnaire from the multisite prospective LEGACY Girls Study where mothers/guardians reported on daughters’ indirect exposure to infection (daycare attendance, antibiotic use, physician visit due to fever, hospitalization due to infection) and specific exposure to infections (e.g., tonsillitis, cold sores). Mothers/guardians reported on daughters’ age at first menses and the onset of breast and pubic hair development using Tanner Staging (as defined as Tanner Stage 2 or higher). We used Cox Proportional Hazard Ratio (HR) models to examine the prospective association between infection history and pubertal timing. We considered site, race/ethnicity, and maternal education as possible confounders. In 615 girls (average age (SD) 9.5 (2.4) years) whose mother/guardians completed the Infection Questionnaire, 65% were white non-Hispanic, 18% were Hispanic, 5% were Black non-Hispanic, and 9% were Asian. Sixty-nine percent of mothers/guardians had a college degree or higher. We assessed frequency of infectious exposures across infancy and early childhood where 73% of girls ever used antibiotics, 59% of girls ever had an ear infection, 59% of girls ever attended daycare over 10 hours per week, 29% of girls visited a physician due to fever (measured in childhood only), 36% of mothers reported girls having 2 or more infections, and 6% of girls were ever hospitalized due to infection. In multivariable models controlled for socioeconomic and maternal factors, earlier age of pubic hair development was associated with hospitalization due to infection compared to never hospitalized (HR=1.53, 95% CI=1.07-2.21) and ever antibiotic use compared to never antibiotic use (HR=1.31, 95% CI=1.03-1.68). Compared to never, multivariable models suggested that earlier age at menarche was associated with physician visit due to fever (HR=1.30, 95% CI=1.04-1.63). We observed no association between infectious exposures and earlier breast development. These results suggest that infancy and childhood infectious exposures may be related to earlier pubertal development, but more studies are needed to confirm these findings.

Citation Format: Yun Huang, Irene L. Andrulis, Angela R. Bradbury, Saundra S. Buys, Mary B. Daly, Esther M. John, Lisa A. Schwartz, Mary Beth Terry, Jasmine A. McDonald. Infancy and childhood infections and pubertal timing in the LEGACY Girls’ Study [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A14.