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      Worldwide Secular Trends in Age at Pubertal Onset Assessed by Breast Development Among Girls : A Systematic Review and Meta-analysis

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          Key Points

          Questions

          Has the age at onset of thelarche in girls changed within the past 4 decades?

          Findings

          This systematic review and meta-analysis found that age at pubertal onset, with thelarche assessed by physical or clinical examination of the breast, decreased by a mean of almost 3 months per decade from 1977 to 2013.

          Meaning

          In most textbooks, thelarche among girls younger than 8 years is considered pathologic and warrants further investigations; therefore, a younger age at thelarche in girls in the general population will change current diagnostic decision-making in girls suspected to have puberty disorders.

          Abstract

          Importance

          The initial clinical sign of pubertal onset in girls is breast gland development (thelarche). Although numerous studies have used recalled age at menarche (first menstruation) to assess secular trends of pubertal timing, no systematic review has been conducted of secular trends of thelarche.

          Objectives

          To systematically evaluate published data on pubertal timing based on age at thelarche and evaluate the change in pubertal onset in healthy girls around the world.

          Data Sources

          A systematic literature search was performed in PubMed and Embase of all original peer-reviewed articles published in English before June 20, 2019.

          Study Selection

          Included studies used clinical assessment of breast development in healthy girls and used adequate statistical methods, including the reporting of SEs or CIs. The quality of the articles was evaluated by assessing study design, potential sources of bias, main characteristics of the study population, and methods of statistical analysis.

          Data Extraction and Synthesis

          In accordance with PRISMA guidelines, all articles were assessed for eligibility independently by 2 authors. Weighted regression analysis was performed using a random-effects model.

          Main Outcomes and Measures

          Studies examining age at thelarche (development of Tanner breast stage 2) in healthy girls.

          Results

          The literature search resulted in a total of 3602 studies, of which 30 studies fulfilled the eligibility criteria. There was a secular trend in ages at thelarche according to race/ethnicity and geography. Overall, the age at thelarche decreased 0.24 years (95% CI, −0.44 to −0.04) (almost 3 months) per decade from 1977 to 2013 ( P = .02).

          Conclusions and Relevance

          The age at thelarche has decreased a mean of almost 3 months per decade from 1977 to 2013. A younger age at pubertal onset may change current diagnostic decision-making. The medical community needs current and relevant data to redefine “precocious puberty,” because the traditional definition may be outdated, at least in some regions of the world.

          Abstract

          This systematic review and meta-analysis evaluates published data on pubertal timing based on age at thelarche and evaluates the change in pubertal onset in healthy girls around the world.

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          Author and article information

          Journal
          JAMA Pediatr
          JAMA Pediatr
          JAMA Pediatr
          JAMA Pediatrics
          American Medical Association
          2168-6203
          2168-6211
          April 2020
          10 February 2020
          10 February 2021
          : 174
          : 4
          : e195881
          Affiliations
          [1 ]Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
          [2 ]The International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
          [3 ]Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
          [4 ]Division of Adolescent and Transition Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
          [5 ]Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio
          [6 ]Institute of Child Health, University College London Hospital, London, United Kingdom
          Author notes
          Article Information
          Accepted for Publication: November 26, 2019.
          Corresponding Author: Camilla Eckert-Lind, MB, Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark ( camilla.eckert-lind@ 123456regionh.dk ).
          Published Online: February 10, 2020. doi:10.1001/jamapediatrics.2019.5881
          Author Contributions: Ms Eckert-Lind and Dr Petersen had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
          Concept and design: Eckert-Lind, Busch, Bräuner, Juul.
          Acquisition, analysis, or interpretation of data: All authors.
          Drafting of the manuscript: Eckert-Lind, Busch, Biro, Bräuner, Juul.
          Critical revision of the manuscript for important intellectual content: All authors.
          Statistical analysis: Eckert-Lind, Petersen.
          Obtained funding: Eckert-Lind, Juul.
          Administrative, technical, or material support: Biro, Juul.
          Supervision: Busch, Petersen, Bräuner, Juul.
          Conflict of Interest Disclosures: Ms Eckert-Lind and Dr Bräuner reported receiving grants from the Research Council at Rigshospitalet during the conduct of the study. No other disclosures were reported.
          Funding/Support: During the preparation of this systematic review, Ms Eckert-Lind was supported by a scholarship from the Research Council at Rigshospitalet.
          Role of the Funder/Sponsor: Rigshospitalet had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
          Article
          PMC7042934 PMC7042934 7042934 poi190101
          10.1001/jamapediatrics.2019.5881
          7042934
          32040143
          feaaf4ab-6cff-48fe-a57d-1e5875d6c5e5
          Copyright 2020 American Medical Association. All Rights Reserved.
          History
          : 24 August 2019
          : 26 November 2019
          Categories
          Research
          Research
          Original Investigation
          Online First
          Online Only
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