The association between prenatal phthalate mixture exposure and the risk of autism spectrum disorder (ASD) in children, as well as the potential mechanism and impact of maternal vitamin D, remains unclear. We analyzed data from 3209 mother-child pairs. The associations between prenatal phthalate exposure and autistic traits in children aged 1.5, 3, 5, and 6 years were explored. Furthermore, the modifying effects of maternal vitamin D and the adverse outcome pathway, which elucidates the contribution of phthalates to ASD, were estimated. Exposure to a phthalate mixture was associated with an increased risk of ASD in children aged 1.5-6 years. For mothers with 25(OH)D deficiency, an exposure‒response relationship was observed between phthalate mixtures in early to mid-pregnancy and autistic traits in children aged 3 years. However, this association was not observed for mothers with sufficient prenatal 25(OH)D levels. The potential mechanism of action of di(2-ethylhexyl) phthalate (DEHP) exposure may involve affecting GRIN2B, inhibiting NMDAR in the postsynaptic membrane, disrupting synaptic function, and impairing learning and memory, ultimately leading to ASD development. Importantly, maternal vitamin D supplementation was demonstrated to mitigate the risk of ASD associated with phthalate exposure. Reducing phthalate exposure during pregnancy may be associated with a decreased risk of autistic traits in children. Furthermore, adequate vitamin D supplementation could potentially mitigate the impact of phthalates on these traits. Additionally, the proposed biological mechanism provides insight into how phthalate exposure may contribute to the development of ASD.
Background: This study aims to investigate the association between sleep quality and infertility among women and to explore the mediating effects of DNA methylation in this association. Methods: This study is a population-based case–control study. The relationship between sleep quality and infertility was investigated in women with anovulatory infertility (n = 43) and healthy controls (n = 43). Genome-wide DNA methylation was profiled from peripheral blood samples using the Illumina Infinium Human Methylation 850k BeadChip. Differentially methylated CpGs between cases and controls were identified using the ChAMP R package. The mediating effect of DNA methylation between sleep quality and infertility among women was investigated using the Bayesian estimation method provided by the R package “mediation”. Results: The survey included 86 women of reproductive age, with 43 participants each in the case and control groups. The average age of the women was 27.6 ± 2.8 years (case group: 27.8 ± 3.0 years, control group: 27.4 ± 2.7 years). A total of 262 differentially methylated CpGs corresponding to 185 genes were identified. Difficulty falling asleep was a risk factor for infertility in women (OR = 3.69, 95%CI = 1.14, 11.99), and a causal mediation effect of DNA methylation CpGs was found. The mediating effect coefficient for cg08298632 was 0.10 (95%CI = 0.01–0.22), and the proportion of the total effect mediated by this methylation site increased to 64.3%. Conclusion: These results suggest that DNA methylation CpGs (cg08298632) play a significant role in the relationship between difficulty falling asleep and infertility in females. These findings contribute to our understanding of the underlying mechanisms that connect difficulty falling asleep and infertility in women. Further studies are necessary to fully understand the biological significance and potential therapeutic applications of these findings. The identified DNA methylation sites provide new and valuable insights and potential targets for future studies aiming to prevent and treat female infertility.
Background: Our previous study showed that antibiotic exposure was linked to depressive symptomatology in community-dwelling older adults in China. Our current study aims to explore the underlying mechanisms by assessing the intermediated effects of circulating short-chain organic acids (SCOAs) on this association. Methods: Depressive symptoms were screened by the 30-item Geriatric Depression Scale (GDS-30). Urinary concentrations of antibiotics and serum SCOAs were measured using a liquid chromatography–mass spectrometry method. Results: Increased exposure to sulfadiazine, azithromycin, tetracyclines, or veterinary antibiotics (VAs) was positively associated with GDS-30 scores. Tetracycline reduced levels of caproic acid, iso-butyric acid, and iso-caproic acid (iso-CA), with iso-CA concentration inversely correlating with GDS-30 scores, while β-hydroxybutyric acids showed a positive correlation. The mediating effect of serum iso-CA on the association between depression and ofloxacin, with a mediating effect of 25.3%, and the association between depression and tetracycline, with a mediating effect of 46.3%, were both statistically significant, indicating partial mediation. Conclusions: Antibiotics may affect the levels of SCOAs in older adults and could potentially contribute to depressive symptoms by influencing alterations in serum iso-CA levels.
13 March 2025 in Journal of the American Heart Association
Background: Animal studies suggest cardiovascular systems may be primary targets for barium toxicity. This study aims to examine longitudinal associations of prenatal and early childhood barium exposure with cardiometabolic risk (CMR) in preschoolers. Methods and Results: We determined serum or plasma barium concentrations during 3 trimesters, delivery, and early childhood (5 years) from 2291 mother–child dyads within the Ma'anshan Birth Cohort. CMR scores were calculated by summing standardized z scores for glucose, insulin, triglycerides, waist circumference, mean of blood pressure, and high‐density lipoprotein cholesterol among 5‐year‐old children. We employed multiple linear regression and multiple informant models to investigate whole pregnancy and stage‐specific associations of barium exposure with CMR scores and individual components and the modifying effects of sex. The ranges of log 10 ‐transformed barium from the first trimester to early childhood were 3.39 to 4.61 ng/L. Barium during the whole pregnancy showed positive associations with CMR scores, glucose, and triglycerides and negative association with high‐density lipoprotein cholesterol. These significant relationships of barium with CMR scores were mainly manifested in the second and third trimesters. Positive associations were observed between barium during the second and third trimesters and CMR scores, glucose, triglycerides, and negatively associated with high‐density lipoprotein cholesterol among boys. In girls, positive associations of barium during the third trimester with CMR scores, glucose, and triglycerides and a negative association with high‐density lipoprotein cholesterol were detected. Conclusions: Barium exposure during pregnancy, especially during the second and third trimesters, may increase CMR in preschoolers. Boys are more vulnerable than girls. These findings support the need for reductions in barium exposure during pregnancy.
Essential trace elements such as zinc (Zn), iron (Fe), and copper (Cu) play a critical role in neurodevelopment, influencing key processes like neurotransmitter regulation and neuronal signaling. To synthesize the existing evidence, we conducted a systematic review and meta-analysis of case–control studies investigating the associations between these trace elements and Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. A comprehensive literature search was performed up to March 2026 across multiple databases, including Web of Science, PubMed, and the Chinese National Knowledge Infrastructure. A total of 46 studies involving 5515 ADHD cases and 8166 controls were included. The results showed that Zn (SMD = −1.01, 95% CI: −1.51 to −0.52), Fe (SMD = −0.82, 95% CI: −1.52 to −0.11) and Ferritin (SMD = −0.54, 95% CI: −1.00 to −0.27) levels were significantly lower in children with ADHD than in controls, while no significant difference was observed for Cu levels (SMD = −0.55, 95% CI: −1.12 to 0.02). When the research subjects are limited to children ≤12 years old, the differences in Zn are more pronounced. Moreover, the differences in the levels of Zn, Fe, and Cu were more pronounced among children and adolescents from developing countries. These findings suggest that imbalances in Zn and Fe may be involved in the pathogenesis of ADHD. Further research is needed to validate early biomarkers of ADHD risk and to explore their potential application in clinical diagnosis and management, especially considering the high heterogeneity of the studies included in this study.