BACKGROUND Globally, the ages at pubertal onset for girls and boys have been decreasing during recent decades, partly attributed to excess body fat accumulation. However, a growing body of literature has recognized that endocrine disrupting chemicals (EDCs) may play an important role in this global trend, but the association has not yet been fully established. OBJECTIVE AND RATIONALE EDCs can interfere with normal hormone function and metabolism and play a role in pubertal onset. We aimed to systematically identify and evaluate the current evidence on the timing of pubertal onset in girls and boys following prenatal or postnatal exposures to xenobiotic EDCs. SEARCH METHODS Following PRISMA guidelines, we performed a systematic literature search of original peer-reviewed publications in the PubMed database through a block search approach using a combination of index MeSH and free text search terms. Publications were considered if they covered biomarkers of prenatal or postnatal exposures to xenobiotic EDCs (European Commission's list of category 1 EDCs) measured in maternal or child biospecimen and pubertal onset defined by the progression of the following milestones (and assessed in terms of the following measures): menarche (age), thelarche (Tanner staging) and pubarche (Tanner staging), in girls, and genital stage (Tanner staging), testicular volume (ml) and pubarche (Tanner staging), in boys. OUTCOMES The literature search resulted in 703 references, of which we identified 52 publications fulfilling the eligibility criteria for the qualitative trend synthesis and 23 publications for the meta-analysis. The qualitative trend synthesis provided data on 103 combinations of associations between prenatal or postnatal exposure to EDC compounds groups and puberty outcomes and the meta-analysis enabled 18 summary risk estimates of meta-associations. WIDER IMPLICATIONS Statistically significant associations in the qualitative trend synthesis suggested that postnatal exposure to phthalates may be associated with earlier thelarche and later pubarche. However, we did not find consistent evidence in the meta-analysis for associations between timing of pubertal onset in girls and boys and exposures to any of the studied xenobiotic EDCs. We were not able to identify specific pre- or postnatal windows of exposure as particularly critical and susceptible for effects of EDCs. Current evidence is subject to several methodological challenges and inconsistencies and evidence on specific exposure-outcome associations remains too scarce to firmly confirm EDC exposure as a risk factor for changes in age of pubertal onset in the general child population. To create a more uniform foundation for future comparison of evidence and to strengthen pooled studies, we recommend the use of more standardized approaches in the choice of statistical analyses, with exposure transformations, and in the definitions and assessments of puberty outcomes. The impact of mixtures of EDC exposures on the association also remains unestablished and would be valuable to elucidate for prenatal and postnatal windows of exposure. Future large, longitudinal epidemiological studies are needed to clarify the overall association.

中文翻译：

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产前和产后接触内分泌干扰化学物质和女孩和男孩青春期开始的时间：系统回顾和荟萃分析。

背景技术在全球范围内，近几十年来女孩和男孩的青春期开始年龄一直在下降，部分原因是身体脂肪堆积过多。然而，越来越多的文献已经认识到内分泌干扰物 (EDC) 可能在这一全球趋势中发挥重要作用，但该关联尚未完全建立。目的和基本原理 EDCs 可以干扰正常的激素功能和代谢，并在青春期开始时发挥作用。我们的目的是系统地确定和评估关于在产前或产后接触外源性内分泌干扰物后女孩和男孩青春期开始时间的当前证据。搜索方法遵循 PRISMA 指南，我们通过使用索引 MeSH 和自由文本搜索术语的组合的块搜索方法，对 PubMed 数据库中的原始同行评审出版物进行了系统的文献搜索。如果出版物涵盖了产前或产后暴露于外源性内分泌干扰物（欧盟委员会的第 1 类内分泌干扰物清单）的生物标志物，这些生物标志物在母体或儿童生物样本中测量，青春期开始由以下里程碑的进展定义（并根据以下措施进行评估）：女孩的初潮（年龄）、初潮（Tanner 分期）和阴毛初现（Tanner 分期），男孩的生殖器阶段（Tanner 分期）、睾丸体积（ml）和阴毛初现（Tanner 分期）。结果 文献检索得到 703 篇参考文献，其中，我们确定了 52 篇符合定性趋势综合资格标准的出版物和 23 篇荟萃分析的出版物。定性趋势综合提供了产前或产后暴露于 EDC 化合物组与青春期结果之间关联的 103 种组合的数据，并且元分析启用了元关联的 18 种汇总风险估计。更广泛的意义 定性趋势综合中的统计学显着关联表明，出生后接触邻苯二甲酸盐可能与较早的阴毛初现和较晚的阴毛初现有关。然而，我们没有在荟萃分析中找到一致的证据，证明女孩和男孩青春期开始的时间与暴露于任何研究的外源性内分泌干扰物之间的关联。我们无法确定特定的产前或产后暴露窗口对 EDC 的影响特别重要和敏感​​。目前的证据受到一些方法学挑战和不一致的影响，关于特定暴露-结果关联的证据仍然太少，无法确定 EDC 暴露是一般儿童人群青春期开始年龄变化的风险因素。为了为未来的证据比较创造更统一的基础并加强汇总研究，我们建议在统计分析的选择、暴露转换以及青春期结果的定义和评估中使用更标准化的方法。EDC 暴露混合物对关联的影响也仍未确定，并且对于阐明产前和产后暴露窗口很有价值。未来需要进行大规模的纵向流行病学研究来阐明整体关联。