Ambient fine particulate matter exposures and human early placental inflammation

The effect of fine particulate matter (PM_2.5) on human early maternal-fetal interface is unknown. We explored the association between maternal exposure to ambient PM_2.5 and inflammation in placental villus of 114 women with clinically recognized early pregnancy loss (CREPL) and 114 women with normal early pregnancy (NEP). Temporally-adjusted land use regression models were used to estimate maternal daily PM_2.5 exposure during pregnancy. Villus interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured using multiplex cytokines detection platform. Single-day lag effect of PM_2.5 exposure within ten days before early placental villus collection was estimated using multivariable linear regression model. Distributed lag and net cumulative effects of PM_2.5 exposures within ten and 30 days before villus collection, as well as five single weeks during the periovulatory period, were estimated using distributed lag non-linear models. In all 228 subjects, after adjusting for group (CREPL or NEP), temporal confounders, and demographic characteristics, both single-day and distributed lag effects of PM_2.5 exposure at lag 8 significantly increased villus IL-6; distributed lag effects of PM_2.5 exposure in the first and second weeks before ovulation increased IL-1β, and PM_2.5 exposure in the third week after ovulation increased IL-6 and TNF-α. In CREPL, single-day lag effect significantly increased IL-1β (at lag 1), IL-6 (at lag 8), and TNF-α (at lag 5); distributed lag effect increased IL-6 (at lag 4-lag 8) and TNF-α (at lag 4-lag 6); and cumulative effect within ten days before villus collection increased IL-6. There was no statistically significant cumulative effect in NEP. In summary, maternal PM_2.5 exposure was associated with placental inflammation in human early pregnancy, particularly with increased villus IL-6 in CREPL. Whether maternal-fetal interface inflammation related to PM_2.5 exposure during the periovulatory period or later contributes to CREPL or other adverse pregnancy outcomes requires further study.