Association between exposures to phthalate metabolites and preterm birth and spontaneous preterm birth: A systematic review and meta-analysis.

Emerging evidence from observational studies proves the association between preterm birth (PTB) and phthalate metabolites; however, such findings are inconsistent and inconclusive. This meta-analysis aimed to clarify this association by accessing the connection between 11 phthalate metabolites and PTB, and 6 phthalate metabolites and spontaneous PTB. The PubMed, Embase, and WOS (Web of Science) databases were searched up to July 2020. Seven prospective studies met the inclusion criteria. Pooled odds ratios (OR) with 95 % confidence intervals (CIs) were calculated for risk estimation. Our results indicated that mono-n-butyl phthalate (MBP), sum of di-2-ethylhexyl phthalate (ΣDEHP), and mono 3-carboxypropyl phthalate (MCPP) significantly correlated with the risk of PTB (MBP: OR = 1.23, 95 % CI = 1.05-1.45; ΣDEHP: OR = 1.21, 95 % CI =1.01-1.44; MCPP: OR = 1.09, 95 % CI = 1.00-1.19). Pooled results showed that spontaneous PTB was associated with higher urinary levels of mono-ethyl phthalate (MEP), MCPP, mono-isobutyl phthalate (MIBP), and MBP (MBP: OR = 1.27, 95 % CI = 1.02-1.58; MEP: OR = 1.19, 95 % CI = 1.01-1.40; MCPP: OR = 1.15, 95 % CI = 1.02-1.30; MIBP: OR = 1.38, 95 % CI = 1.12-1.71). Overall, we conclude that during pregnancy, MBP, ΣDEHP, and MCPP levels are associated positively with PTB. MBP, MEP, MCPP, and MIBP levels had increased odds of spontaneous PTB. No significant associations were observed between other phthalate metabolites and PTB or spontaneous PTB. Further research is needed to verify these findings and elucidate the association of phthalate levels and PTB.