Associations between the exposure to organophosphate flame retardants during early pregnancy and the risk of spontaneous abortion based on metabolomics combined with tandem mass spectrometry

BACKGROUND: As potential substitutes for polybrominated diphenyl ethers (PBDEs), organophosphate flame retardants (OPFRs) have been frequently detected in the environment. They have been suggested to impair fetal growth and development in toxicological studies. However, there are few studies on their maternal effects before or during early pregnancy. METHODS: This study was designed to investigate whether exposure to OPFRs before or during early pregnancy is associated with the risk of spontaneous abortion (SAB), using a nested case-control design based on the case data from clinical examinations in Shanghai, China. A total of 110 cases from this cohort project in 2019–2020 were included. The concentrations of OPFRs in maternal urine samples collected in early pregnancy were determined using Ultra high performance liquid chromatography- triple quadrupole mass spectrometer (UHPLC-MS/MS), and pregnancy outcomes were extracted from the medical records. Meanwhile, ultra high performance liquid chromatography time-of-flight mass spectrometer (UHPLC-Q-TOF/MS)-based metabonomics was used to obtain urine metabolic profiles of 110 women in early pregnancy. RESULTS: According to the quantitative results, the content of bis(1-chloro-2-propyl)phosphate (BCIPP) in urine was significantly different between the SAB patients and the healthy pregnant women. Besides, metabolic profile analysis showed a significant difference in the urine metabolism profile in early pregnancy between SAB cases and controls. Twenty-five different metabolites were screened out, which showed different degrees of correlation with the urinary BCIPP concentration. CONCLUSIONS: Based on these results, it suggests that there may be a certain correlation between BCIPP concentration in the urine and the risk of SAB from a metabolomics perspective, and its effect may be related to the metabolism of tryptophan and fatty acids.