PM_2.5 constituent exposures and maternal circulatory homocysteine in early pregnancy

Elevated homocysteine (Hcy) is a pathogenic mechanism of adverse pregnancy outcomes and PM_2.5-induced cardiovascular diseases. We investigated the associations of fine particulate matter (PM_2.5) 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_2.5 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_2.5 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_2.5, 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_2.5 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.