Early Puberty During the COVID-19 Pandemic in a Multi-Ethnic, Population-Based Cohort of Children and Adolescents - PROJECT SUMMARY Early puberty is associated with adverse health outcomes over the life course, including psychopathology in adolescence, and reproductive cancers, diabetes, and cardiovascular disease in adulthood. The age of pubertal onset has declined dramatically over the past 40 years in the United States (US), with alarming racial/ethnic disparities. These disparities may amplify future health inequities in chronic conditions, yet remain poorly understood. During the COVID-19 pandemic, pediatric endocrinology centers across twelve countries reported large increases in the incidence of central precocious puberty (CPP), a rare condition characterized by developing secondary sexual characteristics before age eight in girls and nine in boys. However, existing studies are subject to limitations such as small samples from specialty care settings, insufficient power to examine trends in boys, and reliance on diagnostic criteria for CPP. In addition to CPP, it is important to examine normative timing of early pubertal milestones, including onset of pubic hair and breasts/testes development, because they represent the earliest observable markers of underlying hormones and may play differential roles in the etiology of health outcomes. Moreover, no studies have investigated whether the pandemic exacerbated pre-existing racial/ethnic or neighborhood-level disparities in pubertal timing. To fill gaps in current knowledge, this study will leverage electronic health records from Kaiser Permanente Northern California (KPNC) to conduct the first population-based study on the pandemic and pubertal timing in the US. KPNC comprises ~32% of the northern California population and has 4.4 million members. In 2010, KPNC began systematically documenting routine pubertal development assessments for all children aged 6 years and older, thereby facilitating the study of trends in both CPP incidence and normative pubertal timing in a population with considerable racial/ethnic, socioeconomic, and geographic diversity. First, we will estimate pre–post pandemic changes in incident CPP diagnoses at KPNC medical centers using an interrupted time series design, using data from 2017–2023 (Aim 1). Second, we will use survival analysis techniques to estimate pre–post pandemic changes in the timing of normative pubertal milestones (including onset of pubic hair development, breast/testes development, and menses) in a representative population cohort of approximately 103,000 boys and 72,000 girls (Aim 2). Finally, we will examine the differential impact of the pandemic on CPP and normative pubertal timing across diverse racial/ethnic groups and neighborhood conditions (Aim 3). Study strengths and innovations include the use of a robust quasi-experimental design, longitudinal assessment of a large and representative population of boys and girls, and investigation of several important hallmarks of puberty. Examination of racial/ethnic and place-based disparities will guide the design of upstream health equity interventions and inform both clinical practice and future pandemic response. This study also provides a foundation for future research to determine whether earlier puberty has lasting health consequences for today’s children as they transition to adulthood.