ABSTRACT: Importance:There has been a worldwide secular trend toward earlier onset of puberty in the general population. However, it remains uncertain if these changes are paralleled with increased incidence of central precocious puberty (CPP) and normal variant puberty (ie, premature thelarche [PT] and premature adrenarche [PA]) because epidemiological evidence on the time trends in the incidence of these puberty disorders is scarce. Objective:To provide valid epidemiological data on the 20-year secular trend in the incidence rates of CPP and normal variant puberty. Design, Setting, and Participants:This population-based, 20-year cohort study used national registry data for all youth in Denmark registered with an incident diagnosis of CPP, PT, or PA in the Danish National Patient Registry from 1998 to 2017 (N?=?8596) using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). We applied the maximum diagnostic age limit for precocious puberty (ie, onset of puberty before age 8 years for girls and age 9 years for boys) with and without a 12-month lag to address time from first contact to final registration in the Danish National Patient Registry. Data analysis was conducted in 2019. Exposures:Diagnosis of CPP, PT, or PA. Main Outcomes and Measures:The age-specific and sex-specific incidence rates of first-time diagnosis of CPP, PT, and PA were estimated using data from the Danish National Patient Registry from 1998 to 2017, and information about the total number of children at risk within the same age groups and sex from Statistics Denmark. Incidences were stratified according to immigration group (Danish origin, first-generation immigrant, second-generation immigrant). Results:Overall a total 8596 children (7770 [90.4%] girls; median [interquartile] age at diagnosis for boys, 8.0 [7.1-9.0] years; for girls, 8.0 [7.6-8.5] years) were registered with an incident diagnosis of CPP, PT, or PA, of whom 7391 (86.0%) had Danish origin (6671 [90.3%] girls), corresponding to 370 new cases in children with Danish origin per year. The 20-year mean annual incidence rates of CPP, PT, PA, and all 3 conditions per 10?000 girls with Danish origin were 9.2 (95% CI, 8.0 to 10.3), 1.1 (95% CI, 0.7 to 1.5), 1.3 (95% CI, 0.9 to 1.7), and 11.5 (95% CI, 10.3 to 12.8), respectively. For boys with Danish origin, the 20-year mean annual incidence rates per 10?000 boys were lower: 0.9 (95% CI, 0.6 to 1.2), 0.2 (95% CI, 0.1 to 0.4), and 1.1 (95% CI, 0.7 to 1.4) for CPP, PA, and the sum, respectively. There was a 6-fold increase in incidence for girls with Danish origin (from 2.6 per 10?000 to 14.6 per 10?000) and a 15-fold increase for boys with Danish origin (from 0.1 per 10?000 to 2.1 per 10?000). The 20-year mean incidence of CPP and PA among girls in the first-generation and second-generation immigrant groups were greater than that of girls with Danish origin. The incidence rate for CPP per 10?000 girls in the first-generation and second-generation groups were 13.7 (95% CI, 9.3 to 18.2) and 14.2 (95% CI, 4.6 to 23.9), respectively; the incidence rate for PA per 10?000 girls in the first-generation and second-generation groups were 2.0 (95% CI, 0.3 to 3.6) and 1.5 (95% CI, -1.6 to 4.7), respectively. No differences associated with immigration status were observed among boys. Conclusions and Relevance:Our findings suggest that the annual incidence of CPP and normal variant puberty has substantially increased in Denmark during the last 20 years. These findings have implications for short-term and long-term health and potentially for the international classification of the reference age of puberty.
