Systematic review and meta-analysis of early life exposure to di(2-ethylhexyl) phthalate and obesity related outcomes in rodents

Abstract

Background: It has been suggested that the plasticizer di(2-ethylhexyl) phthalate (DEHP) exerts obesogenic effects after pre- or perinatal exposure. Objective: A systematic review with meta-analyses was conducted of early life exposure to DEHP, or its biologically active metabolite mono(2-ethylhexyl) phthalate (MEHP), on the obesity related outcome measures body weight, fat (pad) weight, triglycerides, free fatty acids and leptin in experimental rodent studies. Methods: The applied methodology was pre-specified in a rigorous protocol. Relevant articles were identified using PubMed and EMBASE and meta-analyses were performed using mean differences (MD) and random effects model when at least five studies could be included per outcome measure. Risk of bias and the quality of evidence was assessed using established methodologies. Results: Overall, 31 studies could be included and meta-analyses could be performed for body weight and fat weight. Early life exposure to DEHP was significantly associated with increased fat weight (MD ¼ 0.02; 95% CI: 0.00, 0.03), while a non-significant association was estimated for body weight (MD ¼ 0.14; 95% CI: 0.32, 0.04). There was substantial heterogeneity across studies and the information was insufficient to assess the risk of bias for most studies. No meta-analyses could be conducted for other outcome measures, because too few studies were available. Conclusions: The results of this systematic review indicate that early life exposure to DEHP is potentially associated with increased adiposity in rodents. More data is needed to strengthen the evidence base.