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.

Background: Epidemiological studies reporting the effect of small fetuses (SF) on puberty development have shown inconsistent results. Objective: To examine current study evidence and determine the strength and direction of the association between SF and puberty timing. Methods: PubMed, OVID, Web of Science, EBSCO, and four Chinese databases were searched from their date of inception to February 2016. All cohort studies that examined the association between SF and puberty timing in children were identified. Two reviewers independently screened the studies, assessed the quality of included studies, and extracted the data. The quality of the included cohort studies was assessed by the Newcastle–Ottawa Scale. Risk ratio (RR), Weighted Mean Difference (WMD), and 95% confidence intervals (CIs) were calculated and pooled by RevMan5.3 (Cochrane Collaboration, London, UK). Results: A total of 10 cohort studies involving 2366 subjects was included in the final analysis. The pooled estimates showed that SF did not significantly increase the number of pubertal children in boys (RR: 0.97; 95% CI: 0.82 to 1.15), or in girls (RR: 0.91; 95% CI: 0.79 to 1.04). Compared with the control group, the SF group had an earlier onset of puberty in girls (WMD: −0.64; 95% CI: −1.21 to −0.06), and in precocious pubarche (PP) girls (WMD: −0.10; 95% CI: −0.13 to −0.07). There was no difference in the onset of puberty in boys (WMD: −0.48; 95% CI: −1.45 to 0.50) between SF and control groups. The pooled result indicated an earlier age at menarche in girls born small for gestational age (WMD: −0.30; 95% CI: −0.58 to −0.03), but no difference in the age at menarche in the SF group of PP girls. Conclusions: SF may be associated with an earlier age of onset of puberty, especially among girls, as well as earlier age at menarche for girls. Well-designed studies with larger sample sizes and long-term follow-up among different countries and ethnicities are needed.