Ambient Ultrafine Particles and Hypertensive Disorders of Pregnancy: A Mediation Analysis of Homocysteine in a Birth Cohort

While the link between ambient air pollution and hypertensive disorders of pregnancy (HDP) is well-established, evidence regarding ultrafine particulate matter (UFP), which may exhibit greater toxicity than PM2.5, remains limited, and the underlying mechanisms are poorly understood. We examined the associations of prepregnancy and gestational exposure to UFP and the risk of HDP and its subtypes. Additionally, we investigated the potential mediating role of homocysteine (Hcy) and assessed effect modification by Hcy-related nutrients. We analyzed data from a birth cohort conducted in Shanghai, China, between 2017 and 2018 (N = 7569). Individual UFP exposure was estimated using a high-spatiotemporal-resolution prediction model based on participants’ residential addresses. Data on HDP diagnosis and subtypes were obtained from the Hospital Information System. The levels of serum Hcy, folic acid, and vitamin B12 (VB12) were measured during early pregnancy. Poisson regression models with robust error variance were used to evaluate associations between UFP exposure and HDP and its subtypes. Mediation analysis was performed to assess the role of Hcy during the first trimester in the association between UFP and pre-eclampsia (PE). Stratified analysis was conducted to examine potential effect modification by B-group vitamins. Positive associations were observed between UFP exposure during the prepregnancy period, the first trimester, and the second trimester, and the risks of HDP and PE. Per interquartile range (IQR) increase in UFP, relative risks (RRs) ranged from 1.15 to 1.23 for HDP and 1.29 to 1.41 for PE. UFP exposure during prepregnancy and the first trimester was positively associated with Hcy levels, which in turn were associated with increased PE risk (RR = 1.49, 95% CI: 1.04–2.13). Mediation analysis indicated that Hcy mediated 8.87% and 2.51% of the associations between PE and prepregnancy and first-trimester UFP exposure, respectively. Stratified analysis by VB12 levels showed that the association between UFP and PE was significant only in the low-VB12 group and not in the high-VB12 group. Ambient UFP exposure is associated with an increased risk of HDP and PE. Hcy partially mediates the relationship between UFP exposure and PE. Adequate VB12 levels in early pregnancy may mitigate the risk of UFP-related HDP.