Abstract
Accumulating evidence suggests that air pollution increases pregnancy loss; however, most previous studies have focused on case identification from medical records, which may underrepresent early pregnancy losses. Our objective was to investigate the association between acute and chronic exposure to ambient air pollution and time to pregnancy loss among women undergoing assisted reproductive technologies (ART) who are closely followed throughout early pregnancy. We included 275 women (345 human chorionic gonadotropin (hCG)-confirmed pregnancies) undergoing ART at a New England academic fertility center. We estimated daily nitrogen dioxide (NO(2)), ozone (O(3)), fine particulate matter <2.5 μm (PM(2.5)), and black carbon (BC) exposures using validated spatiotemporal models estimated from first positive hCG test until day of failure or live birth. Air pollution exposures were averaged over the past week and the whole pregnancy. Multivariable Cox proportional hazards models were used to estimate the hazards ratio (HR) for pregnancy loss for an interquartile range (IQR) increase in pollutant exposure. We tested for violation of proportional hazards by considering an interaction between time (in days) since positive hCG (<30 days vs. ≥30 days) and air pollution. The incidence of pregnancy loss was 29 per 100 confirmed pregnancies (n = 99). Among pregnancies not resulting in live birth, the median (IQR) time to loss was 21 (11, 30) days following positive hCG. Average past week exposures to NO(2), O(3), PM(2.5), and BC were not associated with time to pregnancy loss. Exposure throughout pregnancy to NO(2) was not associated with pregnancy loss; however, there was a statistically significant interaction with time (p-for-interaction<0.001). Specifically, an IQR increase in exposure to NO(2) was positively associated with pregnancy loss after 30 days (HR = 1.34, 95% CI: 1.13, 1.58), but not in the first 30 days after positive hCG (HR = 0.83, 95% CI: 0.57, 1.20). Overall pregnancy exposure to O(3), PM(2.5), and BC were not associated with pregnancy loss regardless of timing. Models evaluating joint effects of all pollutants yielded similar findings. In conclusion, acute and chronic exposure to NO(2), O(3), PM(2.5), and BC were not associated with risk of pregnancy loss; however, higher exposure to NO(2) throughout pregnancy was associated with increased risk of loss 30 days after positive hCG. In this cohort, later pregnancy losses appeared more susceptible to the detrimental effects of air pollution exposure.