Prenatal exposure to phthalates with preterm birth and gestational age: A systematic review and meta-analysis

Phthalates are non-persistent chemicals used in products of daily necessities. The evidence on the relationship of prenatal phthalates exposure and preterm birth remain uncertain and dimed. We Searched Cochrane, EMBASE, PubMed and Qvid Medline and selected studies according to a priori defined inclusion criteria. A total of 20 relevant studies published before March 31, 2020, were included. The main methods to detect heterogeneity and publication bias of included studies were the Q-statistic and Begg's test. Overall summary estimates indicated positive association of prenatal exposure to di(2-ethylhexyl) phthalate [number of studies (n) = 11, odds ratio (OR) = 1.1; 95% confidence interval (CI): 0.89, 1.4], diethyl phthalate [n = 11, OR = 1.1; 95% CI: 0.92, 1.3], dibutyl phthalate [n = 10, OR = 1.1; 95% CI: 0.77, 1.4], butyl benzyl phthalate [n = 10, OR = 1.0; 95% CI: 0.91, 1.2], diisobutyl phthalate [n = 9, OR = 1.1; 95% CI: 0.92, 1.3], diisononyl phthalate [n = 4, OR = 1.1; 95% CI: 0.85, 1.3], and phthalates were negatively associated with gestational age except di(2-ethylhexyl) phthalate and diisononyl phthalate. Most of them were not statistically significant. Subgroup analysis indicated that the heterogeneity was mainly found in the studies conducted in China and matrix collected at first trimester of pregnancy. Substantial heterogeneity and inconsistency of research methods may lead to inconsistent results of maternal phthalates exposure with preterm birth. We recommend a multicenter cohort study with a consistent approach to unravel the complex associations of prenatal phthalates exposure with birth outcomes.