Li Xuesong, Ran Mingyue, Wang Mengyuan, Liu Ao, Qiao Bin, Han Bin, Wang Jianmei, Bai Zhipeng, Zhang Yujuan
Department of Family Planning, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
School of Chemical Engineering, Tianjin University, Tianjin, 300072, China.
Environ Health. 2025 Mar 7;24(1):7. doi: 10.1186/s12940-025-01160-z.
Elevated homocysteine (Hcy) is a pathogenic mechanism of adverse pregnancy outcomes and PM-induced cardiovascular diseases. We investigated the associations of fine particulate matter (PM) and chemical constituent exposures with maternal circulatory Hcy in early pregnancy.
Serum Hcy and 5-methyltetrahydrofolate in 324 women with pregnancy (162 normal early pregnancy [NEP] and 162 early pregnancy loss [EPL]) were measured by ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry. Daily exposures to PM and constituents (black carbon [BC], organic matter, nitrate, ammonium, and sulfate) were accessed using data of Tracking Air Pollution in China platform. Nonlinear and linear associations of average pollutant exposures during the post-conception period with serum Hcy were estimated using generalized additive models and multivariable linear regression models, respectively. Weekly cumulative and distributed lag associations between pollutant exposures within three months before serum collection and Hcy were analyzed by distributed lag nonlinear models combined with multivariable linear regression models. Sensitivity analyses were conducted using constituent residuals instead of constituent concentrations.
Three-month PM and the five constituent exposures were associated with elevated serum Hcy in all participants, EPL group, and NEP group, with 3-12 weeks before serum collection being the susceptible exposure time windows. Pollutants-related Hcy were generally higher in EPL group than in NEP group. Higher post-conception PM, BC, and sulfate exposures increased serum Hcy in lower but not in higher 5-methyltetrahydrofolate subgroup. Sulfate was the highest risk constituent with residual-related increased Hcy. BC residuals of both post-conception and three-month periods increased Hcy in EPL group but not in NEP group.
Maternal circulatory Hcy in early pregnancy increased with PM and constituent exposures, with sulfate being the highest risk constituent. BC-related increased Hcy may induce EPL.
The study protocol was registered for clinical trials (ChiCTR1900028619) on December 29, 2019.
同型半胱氨酸（Hcy）水平升高是不良妊娠结局和颗粒物（PM）诱发心血管疾病的致病机制。我们研究了早期妊娠时细颗粒物（PM）和化学成分暴露与母体循环中Hcy的关联。
采用超高效液相色谱-串联三重四极杆质谱法测定324名孕妇（162例正常早期妊娠[NEP]和162例早期妊娠丢失[EPL]）血清中的Hcy和5-甲基四氢叶酸。利用中国空气污染追踪平台的数据获取每日PM及其成分（黑碳[BC]、有机物、硝酸盐、铵和硫酸盐）的暴露量。分别使用广义相加模型和多变量线性回归模型估计受孕后期间平均污染物暴露量与血清Hcy的非线性和线性关联。通过分布滞后非线性模型结合多变量线性回归模型分析血清采集前三个月内污染物暴露与Hcy之间的每周累积和分布滞后关联。使用成分残差而非成分浓度进行敏感性分析。
在所有参与者、EPL组和NEP组中，三个月的PM和五种成分暴露均与血清Hcy升高有关，血清采集前3至12周是易受暴露的时间窗。EPL组中与污染物相关的Hcy通常高于NEP组。受孕后较高的PM、BC和硫酸盐暴露在5-甲基四氢叶酸水平较低而非较高的亚组中会使血清Hcy升高。硫酸盐是与残差相关的Hcy升高风险最高的成分。受孕后和三个月期间的BC残差在EPL组中会使Hcy升高，但在NEP组中不会。
早期妊娠时母体循环中的Hcy随PM和成分暴露增加，其中硫酸盐是风险最高的成分。与BC相关的Hcy升高可能导致早期妊娠丢失。
该研究方案于2019年12月29日在临床试验注册中心注册（ChiCTR1900028619）。
