Levels of Phthalate Metabolites in Urine of Pregnant Women and Risk of Clinical Pregnancy Loss

Abstract

Toxicological studies have shown that phthalate esters (PAEs), a class of widely used and environmentally prevalent chemicals, can increase the abortion rate in animals, but epidemiological evidence is scarce. This study aimed to explore the relationship between the urinary concentration of phthalate metabolites and the risk of clinical pregnancy loss. A total of 132 women who underwent clinical pregnancy loss (cases) and 172 healthy pregnant women (controls) were recruited from Beijing, China. Eight phthalate metabolites in urine were determined by ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Five phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono(2-ethlyhexyl) phthalate (MEHP), were detected in at least 95% of the urine samples, with the highest median concentration of 51.0 μg/g of creatinine for MnBP of all participants. The differences in urinary concentrations of phthalate metabolites between cases and controls were evaluated using the Mann-Whitney U test. The concentrations of MEP (median of 18.7 μg/g of creatinine), MiBP (23.3 μg/g of creatinine), and MnBP (58.2 μg/g of creatinine) detected in the cases were significantly higher than those (15.7 μg/g of creatinine for MEP, 19.4 μg/g of creatinine for MiBP, and 43.9 μg/g of creatinine for MnBP) in the controls (p < 0.05). Increasing risks of clinical pregnancy loss were observed from the first to fourth quartiles of the MEP, MiBP, and MnBP concentrations (p < 0.05 for trend). We concluded that exposure to MEP, MiBP, and MnBP was associated with an increased risk of clinical pregnancy loss.

Urinary Concentrations of Phthalate Metabolites and Pregnancy Loss Among Women Conceiving with Medically Assisted Reproduction

“…7,13,30 Our results are consistent with those of a Danish study by Toft and colleagues, who examined pregnancy loss, defined as subclinical embryonal losses and clinical losses combined. 7 The authors enrolled couples planning their first pregnancy after discontinuation of birth control, and followed them prospectively until a clinically recognized pregnancy occurred or for six menstrual cycles.…”

“…Three recent studies have examined the effect of various phthalates on pregnancy loss in couples conceiving naturally with conflicting results. 7,13,30 Others have investigated the effect of phthalates on gestational length 31–33 and preterm birth 34,35 with varying methods and conclusions.…”

Distribution patterns of phthalic acid esters in soil particle-size fractions determine biouptake in soil-cereal crop systems

“…Almost all of the non-cancer and carcinogenic risks to humans for PAEs were due to direct intake of the edible parts8. PAE intake may pose a special health hazard to vulnerable populations such as pregnant women and children454. Even when the overall health risk of PAE is low in maize and wheat crop systems, the potential damage of PAE to human health via long-term exposure to low doses may still deserve further attention.…”

Season-dependent concentrations of urinary phthalate metabolites among Chinese pregnant women: Repeated measures analysis

“…For instance, epidemiological studies revealed that in utero exposure to some phthalates was associated with pregnancy complications (e.g. spontaneous abortion and increased blood pressure) (Jukic et al, 2016;Mu et al, 2015;Toft et al, 2012;Werner et al, 2015), adverse birth outcomes (e.g. preterm birth, low birth weight and decreased birth length) Huang et al, 2009;Latini et al, 2003;Meeker et al, 2009;Minatoya et al, 2017;Philippat et al, 2012;Wolff et al, 2008;Zhang et al, 2009), and impaired children growth (Valvi et al, 2015) and neurodevelopment (e.g.…”