In China, there exists a long-standing registry for all types of births, including fetal death and selective termination of pregnancy. The timing of exposure within the critical window of fetal development and an extended exposure window at 3 months before conception was explored in order to better identify underlying factors. In the present study, from 2006 to 2015, exposure to higher levels of PM10 at both 3 months preconception and early pregnancy significantly increased the risk of CAs among offspring in Liaoning Province. The study results also revealed that the most crucial time windows for susceptibility were 3 months before pregnancy and the first trimester of gestation. In addition, this association did not appear to be substantially influenced by a shorter time scale of 1 month.
This study provides evidence of a robust association between maternal exposure to ambient PM10 and the risks of CAs in offspring. A recent systematic review reported evidence of an association between ambient pollutants (including PM10) and CAs, although the results were limited and inconsistent . Previous reviews of the effects of air pollution on birth outcomes demonstrated a clear association between PM10 exposure and risks of CAs [20, 21]. Nonetheless, it is worth noting that most studies conducted over the past decade have shown an association between prenatal PM10 exposure and the risk of some specific defects, especially cardiovascular malformations [8–13], but not CAs overall. Consistent with the findings of the present study, statistically significant associations between overall CAs and PM10 have been observed in only three studies conducted in Israel and China. Of these, Farhi et al. (2014) found that higher levels of PM10 exposure in all stages of pregnancy were positively associated with slightly increased risks of overall CAs (OR = 1.06 [95% CI = 1.01–1.11] for an increase of 10 µg/m3 and OR = 1.10 (95% CI = 1.01–1.20) for the high vs. low tertile) . However, this association was less evident in the first trimester (OR = 1.01 [95% CI = 0.98–1.03]). Furthermore, Liang et al. (2014) reported that exposure to PM10 during the second and third month of pregnancy was associated with increased risks of total CAs (gestational month 2: OR = 1.039 [95% CI = 1.016–1.063]; gestational month 3: OR = 1.066 [95% CI = 1.043–1.090]) . Wang et al. (2019) reported that PM10 exposure during the first trimester increased the risk of all CAs by 3.4% per increment of 10 µg/m3 (relative risk [RR] = 1.034, 95% CI = 1.019–1.049) and the highest risks were observed in the second month of pregnancy (RR = 1.031, 95% CI = 1.020–1.042) . More positive associations between PM10 exposure and overall CAs have been observed in Korea and Italy, but these associations were not statistically significant [25, 26]. Moreover, studies that included the full spectrum of CAs found little evidence of such associations [15, 13, 17]. A possible explanation for these inconsistent findings could be due to differences in sample sizes, air pollutant levels, exposure assignments, and confounders [22, 19, 17]. Notably, the cohort of the present study was a population exposed to relatively high mean PM10 levels of 90.264–93.626 µg/m3, while all of the above-mentioned studies, which were conducted in areas with relatively low mean PM10 levels of ≤ 40 µg/m3, reported irrelevant or negative associations. Given the limited number of studies, these findings should be interpreted with caution.
A great deal of evidence suggests that oxidative stress , pulmonary and placental inflammation , blood coagulation , endothelial function , and hemodynamic responses  are involved in the mechanisms underlying the effects of air pollution. In addition, maternal exposure to PM10 may affect embryos and fetuses by influencing transplacental transport of oxygen and nutrients . Recent studies have suggested that prenatal PM10 exposure during the last trimester of pregnancy may cause mitochondrial dysfunction and shorten the lengths of telomeres in the cells of newborns [33, 34, 35]. Despite this evidence, the effects of air pollutants remain uncertain.
There were several limitations to this study that should be addressed. First, assessment of the dosage of prenatal exposure may have been inaccurate because the method used to measure PM10 concentrations may have affected the accuracy of exposure estimation and led to misclassification. In the present study, the monthly average of prenatal PM10 exposure concentrations was calculated from daily readings of all air monitoring stations throughout Liaoning Province. However, the municipal exposure level estimates are generally lower than those based on personal assessment of exposure . Second, the time that people spend indoors was not taken into consideration, which may explain the difference between personal and municipal exposure. However, this error was assumed to be irrelevant with respect to the differentiation between cases and controls. Such misclassification would lead to underestimation of the effect estimates . Third, although any random migration would reduce the accuracy of prenatal exposure assessment, the median distance of migration in this study tended to be short and, therefore, was not likely to result in misclassification . Fourth, some of the potential risk factors for CAs, such as smoking, alcohol consumption, and folic acid use, were not included in multivariate analyses. Although it is unlikely that these factors were associated with exposure to PM10, they were partially accounted for by adjusting for the educational level of the mother . Fifth, the study design only tested associations for a single pollutant, as the co-effects of other air pollutants, such as carbon monoxide, nitrogen dioxide, and ozone, which may be associated with CAs, were not considered in the analyses . Hence, future studies should include mixtures of pollutants.
In general, the results of the present study demonstrated a strong association between maternal exposure to environmental PM10 and the risk of CAs in offspring. However, additional studies are needed to elucidate the underlying mechanisms in order to further explore the impact of maternal PM10 exposure on CAs.