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BackgroundAnimal studies have shown that exposure to organophosphate esters (OPEs) disturbs the composition of gut microbiome in rodents and zebrafish. However, current associated evidence in humans is limited. Considering the importance of gut microbiome in neonatal development, we need to investigate the impact of OPEs exposure on the early development stage of neonatal microbiome. ObjectiveTo investigate the associations between umbilical OPEs exposure and the diversity and composition of gut microbiome in newborns. MethodsBased on the Shanghai Maternal-Child Pairs Cohort (MCPC), 391 mother-infant pairs with comprehensive follow-up information and bio-samples were enrolled in this study. Concentrations of OPEs in neonatal cord blood were quantified using ultra performance liquid chromatography-tandem mass spectrometry. Meconium samples were collected after delivery and measured through 16S rRNA sequencing on the Illumina Miseq platform. Multiple linear regression models were used to assess the effects of OPEs exposure on the alpha diversity of meconium microbiome. Principal coordinate analysis and permutational multivariate analysis of variance based on unweighted UniFrac distance were used to compare the beta diversity differences between high and low exposure groups of OPEs. Linear discriminant analysis effect size (LEfSe) was utilized to analyze the differential gut microbiome taxa between high and low OPEs exposure groups. The functional pathways involved in the meconium microbiome were predicted based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and multivariate analysis by linear models (MaAsLin2) were conducted to explore the effects of OPEs exposure on gut microbiome pathways. ResultsSeven OPEs were detectable in the neonatal cord blood samples, of which four were detected higher than 50% including tributyl phosphate (TBP), tris (2-butoxyethyl) phosphate (TBEP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tris (2-chloro-1 (chloromethyl) ethyl) phosphate (TDCPP), and the median concentrations of these four congeners were as follows: 0.52 μg·L−1 for TBP, 2.41 μg·L−1 for TBEP, 0.13 μg·L−1 for EHDPP, and 2.23 μg·L−1 for TDCPP. A significant association was observed between umbilical TBEP and TDCPP exposure and alpha diversity indices in neonatal meconium microbiome. Beta diversity significantly differed across varied high and low OPEs exposure groups. The results of LEfSe analysis indicated a significant correlation between umbilical OPEs exposure and 27 genera, including Streptococcus, Corynebacterium, Neisseria, Haemophilus, and Parabacteroides. The MaAsLin2 analysis identified associations between OPEs exposure and upregulation of pathways related to linoleic acid metabolism, steroid biosynthesis, Toll and Imd signaling pathway, retinol metabolism, NOD like receptor signaling pathway, and fatty acid biosynthesis . ConclusionUmbilical OPEs exposure is associated increased alpha diversity indices, increased relative abundances of Neisseria, Streptococcus, Parabacteroides, and Corynebacterium in the gut microbiome, as well as predicted metabolic pathway alterations in linoleic acid metabolism, fatty acid biosynthesis, etc. These findings indicate that umbilical OPEs exposure may disrupt meconium microbiome equilibrium.

BackgroundIn recent years, ozone (O3) has gradually become a key air pollutant affecting public health. Studies have been conducted to evaluate O3 pollution-associated disease burden for general population, but there is a lack of research on O3 pollution-associated disease burden of gestational complications. ObjectiveTo assess the disease burden of O3 pollution on pregnancy complications in the Yangtze River Delta region and the changes in the disease burden resulting from the improvement of O3 pollution levels. MethodsThrough Chinese databases such as China National Knowledge Infrastructure (CNKI) and Wanfang, as well as English databases including PubMed and Web of Science, a systematic search was conducted to retrieve epidemiological studies investigating the association between O3 exposure and pregnancy complications from January 1, 2010 to February 28, 2023. Using predetermined inclusion and exclusion criteria, retrieved studies were screened and assessed for heterogeneity using the Higgins I2 statistic. The exposure increment was standardized to 10 µg·m−3, and a meta-analysis was conducted to evaluate the exposure-response relationship. Spatial analysis and environmental health risk assessment were then employed, using O3 monitoring data at national air monitoring stations, population data, and related disease burden parameters in the Yangtze River Delta region, to evaluate changes in the disease burden of pregnancy complications associated with improvements in O3 pollution levels. ResultsThe meta-analysis revealed a significant association between maternal O3 exposure and increased risks of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP), particularly in early pregnancy, and the related odds ratios (OR) and 95% confidence intervals (CI) were 1.028 (1.002, 1.055) and 1.031 (1.023, 1.040), respectively. The cities with higher attribution fractions (AF) of GDM and HDP related to O3 exposure in 2017 and 2020 in the Yangtze River Delta region were Xuzhou, Huaibei, Suzhou (Anhui Province), Changzhou, and Wuxi, with most cities showing a significant decrease in AF in 2020. Except for Hefei, the cases of GDM and HDP attributable to O3 exposure in the remaining cities of the Yangtze River Delta region decreased by 16.31% to 57.41% in 2020 compared to 2017. In addition, except for Hefei, Suqian, Anqing, and Wuxi, the direct medical costs attributed to O3 exposure in the remaining cities decreased by 1.12% to 45.36% in 2020 compared to 2017. ConclusionExposure to O3 during pregnancy is associated with increased risks of GDM and HDP. There are differences in the disease burden of GDM and HDP related to O3 pollution among cities in the Yangtze River Delta region in 2017 and 2020. In 2020, compared to 2017, the disease burden in most cities is decreased.