{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T03:30:18Z","timestamp":1789356618314,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The research was supported by Basic and Frontier Research Project of Chongqing Science and Technology Commission","award":["Grant No. cstc2013jcyjA10001"],"award-info":[{"award-number":["Grant No. cstc2013jcyjA10001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Background: Precocious puberty (PP) currently affects 1 in 5000 children and is 10 times more common in girls. Existing studies have tried to detect an association between phathalic acid esters (PAEs) and PP, but the results did not reach a consensus. Objective: To estimate the association between PAEs and children with PP based on current evidence. Methods: Databases including PubMed (1978 to March 2015), OVID (1946 to March 2015), Web of Science (1970 to March 2015), EBSCO (1976 to March 2015), CNKI (1979 to March 2015), WANFANG DATA (1987 to March 2015), CBM (1978 to March 2015) and CQVIP (1989 to March 2015) were searched to identify all case-control studies that determined the exposure and concentration of PAEs and their metabolites in children with PP. Meta-analysis of the pooled standard mean difference (SMD) and odds ratio (OR) with 95% confidence intervals (CI) were calculated. Results: A total of 14 studies involving 2223 subjects were finally included. The pooled estimates showed that PP was associated with di-(2-ethylhexyl)-phthalate (DEHP) exposure (OR: 3.90, 95% CI: 2.77 to 5.49). Besides, the concentration of DEHP (SMD: 1.73, 95% CI: 0.54 to 2.91) and di-n-butyl phthalate (DBP) (SMD: 4.31, 95% CI: 2.67 to 5.95) in the PP group were significantly higher than those in the control group, respectively, while no difference was detected between case and control groups in either serum or urinary concentration of mono-(2-ethylhexyl)-phthalate (MEHP), monobutyl phthalate (MBP), mono(2-ethyl-5-oxohexyl) phthalate(MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), monomethyl phthalate (MMP), monobenzyl phthalate (MBzP) or monoethyl phthalate (MEP). Conclusions: Exposure of DEHP and DBP might be associated with PP risk for girls, however, there is no evidence to show an association between the exposure to most PAE metabolites and PP. Given the moderate strength of the results, well-designed cohort studies with large sample size should be performed in future.<\/jats:p>","DOI":"10.3390\/ijerph121214974","type":"journal-article","created":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T10:26:58Z","timestamp":1448965618000},"page":"15254-15268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Association of PAEs with Precocious Puberty in Children: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Yi","family":"Wen","sequence":"first","affiliation":[{"name":"School of Public Health and Management, Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health and Management, Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Lei","sequence":"additional","affiliation":[{"name":"School of Public Health and Management, Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Shuang","family":"Ling","sequence":"additional","affiliation":[{"name":"School of Public Health and Management, Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Public Health and Management, Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health and Management, Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/j.1552-6909.2007.00145.x","article-title":"Precocious puberty a comprehensive review of literature","volume":"36","author":"Cesario","year":"2007","journal-title":"J. Obstet. Gynecol. Neonatal Nurs."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/GCO.0000000000000099","article-title":"Precocious puberty","volume":"26","author":"Neely","year":"2014","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"211","DOI":"10.2165\/00148581-200406040-00002","article-title":"Central Precocious Puberty Current Treatment Options","volume":"6","author":"Antoniazzi","year":"2004","journal-title":"Paediatr. Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.envres.2014.08.010","article-title":"In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation","volume":"134","author":"Watkins","year":"2014","journal-title":"Environ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1078\/1438-4639-00309","article-title":"DEHP metabolites in urine of children and DEHP in house dust","volume":"207","author":"Becker","year":"2004","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1289\/ehp.6723","article-title":"Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999\u20132000","volume":"112","author":"Silva","year":"2004","journal-title":"Environ. Health Perspect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1897\/07-399.1","article-title":"Evaluation of estrogenic activity of phthalate esters by gene expression profiling using a focused microarray (EstrArray)","volume":"27","author":"Parveen","year":"2008","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1289\/ehp.0901690","article-title":"Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls","volume":"118","author":"Wolff","year":"2010","journal-title":"Environ. Health Perspect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1007\/s12010-012-9825-2","article-title":"Laccase-mediated transformations of endocrine disrupting chemicals abolish binding affinities to estrogen receptors and their estrogenic activity in zebrafish","volume":"168","author":"Viana","year":"2012","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1582-4934.2012.01649.x","article-title":"Molecular mechanism(s) of endocrine-disrupting chemicals and their potent oestrogencity in diverse cells and tissues that express oestrogen receptors","volume":"17","author":"Lee","year":"2013","journal-title":"J. Cell Mol. Med."},{"key":"ref_11","first-page":"895","article-title":"Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development","volume":"108","author":"Caro","year":"2000","journal-title":"Environ Health Perspect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jpeds.2009.09.047","article-title":"Phthalate exposure and precocious puberty in females","volume":"156","author":"Lomenick","year":"2010","journal-title":"J. Pediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1001\/archpedi.1994.02170040035006","article-title":"Laboratory Monitoring of Children with Precocious Puberty","volume":"148","author":"Lee","year":"1994","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_14","unstructured":"Wells, G., Shea, B.O., and Connell, D. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomized Studies in Meta-Analysis. Available online: http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.htm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1001\/archpsyc.63.5.530","article-title":"Depression and risk for Alzheimer disease: Systematic review, meta-analysis, and meta regression analysis","volume":"63","author":"Ownby","year":"2006","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_16","first-page":"5","article-title":"Estimating the mean and variance from the median, range, and the size of a sample","volume":"20","author":"Hozo","year":"2005","journal-title":"BMC Med. Res. Methodol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1136\/bmj.320.7249.1574","article-title":"Empirical assessment of effect of publication bias on meta-analyses","volume":"320","author":"Sutton","year":"2000","journal-title":"BMJ"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1515\/JPEM.2009.22.1.69","article-title":"Phthalate exposure in girls during early puberty","volume":"22","author":"Chou","year":"2009","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1080\/10934529.2013.762734","article-title":"Association between precocious puberty and some endocrine disruptors in human plasma","volume":"48","author":"Yum","year":"2013","journal-title":"J. Environ. Sci. Health A Tox Hazard Subst. Environ. Eng."},{"key":"ref_20","first-page":"26","article-title":"The relationship of the environment endocrine disruptors with precocious puberty","volume":"34","author":"Cai","year":"2013","journal-title":"Shanghai Med."},{"key":"ref_21","first-page":"4184","article-title":"Study on effect relationship between estrogen receptor \u03b1 gen polymorphism and environmental endocrine disruptors in precocious girls","volume":"28","author":"Ke","year":"2013","journal-title":"Matern. Child Health Care China"},{"key":"ref_22","unstructured":"Lin, Q. (2010). The Study on Relationship Urinary Phthalate Monoesters and house Dust Exposure for Precocious Puberty, National Cheng Kung University."},{"key":"ref_23","first-page":"288","article-title":"Determination of four kinds of environmental endocrine disruptors in blood serum of precocious puberty patients by high performance liquid chromatography","volume":"35","author":"Lu","year":"2006","journal-title":"J. Hyg. Res."},{"key":"ref_24","unstructured":"Wang, D.L. (2013). Association between 0 and 2 Year Old Girls with Premature Thelarche and Endocrine Disrupting Compounds Bisphenol A, Diethyl Phthalate, Nanchang University."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1093\/humrep\/det325","article-title":"Phthalates may promote female puberty by increasing kisspeptin activity","volume":"28","author":"Chen","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1365-2605.2012.01260.x","article-title":"High urinary phthalate concentration associated with delayed pubarche in girls","volume":"35","author":"Frederiksen","year":"2012","journal-title":"Int. J. Androl."},{"key":"ref_27","first-page":"736","article-title":"Analysis on the correlation between environmental endocrine disrupter chemicals and childhood precocious puberty","volume":"30","author":"Zhang","year":"2015","journal-title":"Matern. Child Health Care China"},{"key":"ref_28","first-page":"381","article-title":"Application of gas chromatography in the detection of DEHP and DBP in human serum","volume":"35","author":"Song","year":"2014","journal-title":"Med. J. Wuhan Univ. China"},{"key":"ref_29","first-page":"331","article-title":"Environmental Endocrine Disruptors in Serum of Sexually Precocious Girls","volume":"31","author":"Yang","year":"2014","journal-title":"J. Environ. Occup. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1289\/ehp.6008","article-title":"Blood lead levels and sexual maturation in US girls: The Third National Health and Nutrition Examination Survey, 1988\u20131994","volume":"111","author":"Wu","year":"2003","journal-title":"Environ. Health Perspect."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1095\/biolreprod.106.059303","article-title":"Early maturation of gonadotropin-releasing hormone secretion and sexual precocity after exposure of infant female rats to estradiol or dichlorodiphenyltrichloroethane","volume":"77","author":"Rasier","year":"2007","journal-title":"Biol. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"721","DOI":"10.3109\/09513590.2010.526666","article-title":"Peripheral precocious puberty in a 4 month old girl: Role of pesticides","volume":"27","author":"Gaspari","year":"2011","journal-title":"Gynecol Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1093\/humrep\/16.5.1020","article-title":"Sexual precocity after immigration from developing countries to Belgium: Evidence of previous exposure to organochlorine pesticides","volume":"16","author":"Charlier","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.neuro.2010.07.008","article-title":"The impact of neonatal bisphenol\u2014A exposure on sexually dimorphic hypothalamic nuclei in the female rat","volume":"32","author":"Adewale","year":"2011","journal-title":"Neurotoxicology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.reprotox.2007.07.010","article-title":"Human exposure to bisphenol A (BPA)","volume":"24","author":"Vandenberg","year":"2007","journal-title":"Reprod. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1289\/ehp.95103582","article-title":"A Variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic","volume":"103","author":"Jobling","year":"1995","journal-title":"Environ. Health Perspect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1289\/ehp.5658","article-title":"Mechanisms of phthalate ester toxicity in the female reproductive system","volume":"111","author":"Davis","year":"2003","journal-title":"Environ. Health Perspect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1289\/ehp.5799","article-title":"Assessing the effects of endocrine disruptors in the National Children\u2019s Study","volume":"111","author":"Landrigan","year":"2003","journal-title":"Environ. Health Perspect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1006\/taap.2001.9141","article-title":"Estrogenic activity and metabolism of n-butyl benzyl phthalate in vitro: Identification of the active molecule(s)","volume":"172","author":"Picard","year":"2001","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1289\/ehp.97105802","article-title":"The estrogenic activity of phthalate esters in vitro","volume":"105","author":"Harris","year":"1997","journal-title":"Environ. Health Perspect."},{"key":"ref_41","first-page":"282","article-title":"Examination of the in vitro and in vivo estrogenic activities of eight commercial phthalate esters","volume":"46","author":"Zacharewski","year":"1998","journal-title":"Toxicol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.envres.2008.08.007","article-title":"Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans","volume":"108","author":"Swan","year":"2008","journal-title":"Environ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1289\/ehp.9059","article-title":"Integrating biomonitoring exposure data into the risk assessment process: Phthalates [diethyl phthalate and di(2-ethylhexyl) phthalate] as a case study","volume":"114","author":"Calafat","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e624","DOI":"10.1542\/peds.2006-2188","article-title":"Weight status in young girls and the onset of puberty","volume":"119","author":"Lee","year":"2007","journal-title":"Pediatrics"},{"key":"ref_45","first-page":"1","article-title":"Association studies for asthma and atopic diseases: A comprehensive review of the literature","volume":"4","author":"Sabine","year":"2003","journal-title":"Respir. Res."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/12\/12\/14974\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:53:06Z","timestamp":1760215986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/12\/12\/14974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,1]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,12]]}},"alternative-id":["ijerph121214974"],"URL":"https:\/\/doi.org\/10.3390\/ijerph121214974","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,1]]}}}