Systematic review and meta-analysis of early-life exposure to bisphenol a and obesity-related outcomes in rodents

BACKGROUND: Early-life exposure to bisphenol A (BPA) has been implicated to play a role in the development of obesity. OBJECTIVE: A systematic review with meta-analyses of experimental rodent studies was conducted to answer the following question: does early-life exposure to BPA affect the obesity-related outcomes body weight, fat (pad) weight, and circulating and tissue levels of triglycerides, free fatty acids (FFA), and leptin? METHODS: The methodology was prespecified in a rigorous protocol using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) approach. Using PubMed and EMBASE, we identified 61 articles that met the inclusion criteria. The risk of bias and the methodological quality of these articles were assessed using the SYRCLE Risk of Bias tool, and a confidence-rating methodology was used to score the quality of evidence. Meta-analyses were performed using random effect models and standardized mean differences (SMDs), or, where possible, mean differences (MDs) were calculated. RESULTS: Overall summary estimates indicated significant positive associations between BPA and fat weight [SMD = 0:67 (95% CI: 0.53, 0.81)], triglycerides [SMD = 0:97 (95% CI: 0.53, 1.40)], and FFA [SMD = 0:86 (95% CI: 0.50, 1.22)], and a nonsignificant positive association with leptin levels [MD = 0:37 (95% CI: −0:14, 0.87)] and a significant negative association with body weight were estimated [MD = − 0:22 (95% CI: −0:37, −0:06)]. Subgroup analyses revealed stronger positive associations for most outcome measures in males and at doses below the current U.S. reference dose of 50 μg/kg/d compared with doses above the reference dose. It should be noted that there was substantial heterogeneity across studies for all outcomes assessed and that there was insufficient information to assess risk of bias for most studies. CONCLUSIONS: Findings from our systematic review suggest that early-life exposure to BPA may increase adiposity and circulating lipid levels in rodents