Association between phthalate exposure and risk of spontaneous pregnancy loss: A systematic review and meta-analysis

Numerous studies suggested that phthalates might be associated with increased risk of spontaneous pregnancy loss. However, these results were conflicting and inconclusive. Thus we performed this systematic review and meta-analysis to assess the relationship between phthalate exposure and risk of pregnancy loss. We searched PubMed, EMBASE, Web of Science and major Chinese literature databases for studies investigating phthalates and spontaneous pregnancy loss. Pooled odds ratio (OR) with 95% confident interval (CI) were calculated for risk estimate. A total of 8 studies involving 4713 participants (including 651 cases and 4062 controls) were enrolled in the present meta-analysis. Our pooled results showed that spontaneous pregnancy loss was associated with higher urinary levels of monobutyl phthalate (MBP) (OR: 1.34, 95% CI: 1.04-1.72), mono(2-ethylhexyl) phthalate (MEHP) (OR: 1.57, 95% CI: 1.29-1.90), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (OR: 1.59, 95% CI: 1.23-2.07) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) (OR: 1.47, 95% CI: 1.15-1.89). Indirect estimate of di-2-ethylhexyl phthalate (DEHP) levels, which were pooled from molar sum of urinary DEHP metabolites and hair DEHP, were also correlated with elevated risk of spontaneous pregnancy loss (OR: 1.79, 95% CI: 1.27-2.53). No significant association was found regarding urinary concentrations of monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP) or mono(2-ethyl-5-carboxypentyl) phthalate (MECPP). Our findings indicate that phthalate exposure might be a risk factor for spontaneous pregnancy loss. Given indirect estimate of phthalate exposure by evaluating its metabolite levels, our results should be interpreted with caution.