Increased Risk of Phthalates Exposure for Recurrent Spontaneous Abortion in Reproductive-Aged Women: Taiwan Female Infertility Study (TIFF)

Abstract

Background/AimRecurrent spontaneous abortion (RSA) is the termination of pregnancies, usually before 20 weeks of gestation. Some studies indicated that phthalates may involve in the pathogenesis of RSA, and that Taiwan's reproductive-aged women were still exposed to high levels of DEHP and DBP after 2011 DEHP exposure episode. We aimed to assess the risk of phthalates in Taiwanese women with RSA using a case-control study design.MethodsWe recruited 103 RSA patients and 76 controls from the department of obstetrics and gynecology in a hospital in southern Taiwan from 2013 to 2017. Urine samples were analyzed for 11 phthalate metabolites through LC/MS-MS; subsequently, principal component analysis (PCA) and agglomerative hierarchical clustering analysis were performed to determine the main sources of phthalate exposure. Multivariate logistic regression was used to determine the RSA risk.ResultsMedian levels (ng/mL) of mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), ΣDBPm, and ΣDEHPm were 3.1/27.2, 5.3/9.8, 8.1/11.4, 9.5/12.9 ng/mL, 0.10/0.18 nmol/mL, and 0.12/0.15 nmol/mL respectively, in control/RSA. PCA revealed three primary components of phthalate exposure: DEP, DBP, and DEHP. Plastic food container use and medication use were identified as the main phthalate exposure sources. After adjustment for creatinine, age, age at menarche, educational level, plastic food container use, and food preservation bag use, we observed significantly high odds ratios for RSA: 3.15 (p= 0.03), 3.31 (p= 0.04), and 2.57 (p= 0.07) in the third tertile for MiBP, ΣDEHPm, and ΣDBPm, respectively.ConclusionsOur findings support the hypothesis that exposure to phthalates increases RSA risk in Taiwanese women. The development of the strategy to avoid using phthalate coatings for oral medications and plastic products among reproductive-aged women should be emphasized.