Introduction

With the development of economy, air pollution has become an inseparable topic with people’s health.Air pollution, especially fine particle pollutants, is considered to be one of the main causes of the global burden of disease, such as respiratory diseases1,2,cardiovascular diseases3,4,bowel disease5and adverse pregnancy outcomes6,7, etc.Abortion, stillbirth and birth defects are the most common adverse pregnancy outcomes8. Pregnancy is the process of embryonic and fetal growth and development in the mother9. The commonly used diagnostic methods are pregnancy test and ultrasound examination. Spontaneous abortion accounts for 15-25% of all pregnancies10.Spontaneous abortion has a great impact on the physical and mental health of women of childbearing age11.Exploring the risk factors of spontaneous abortion is great significance to women ‘s health and fetus. There are many risk factors for spontaneous abortion, including age12, history of spontaneous abortion13, vaginal microbiome14, genetic factors, environmental factors and immune factors15,16.

Baoji City is located in the northwest of China. Its geological structure is complex, surrounded by mountains on three sides, and developed along the river valley with the Weihe River as the central axis. During winter, the consumption of coal for home heating time (From November 15 to March 15 of the following year) increases the concentraiotn of atmospheric pollutants. Through the analysis of five kinds of air pollutants and maternal data in Baoji City from 2018 to 2019, this study explores the relationship between the exposure of pregnant women to air pollutants in the first trimester(the first 14 weeks of gestation is called first trimester17)and the occurrence of spontaneous abortion.

Research methods

Collection of cases

The general data and pregnancy data of pregnant women admitted to the Department of Obstetrics and Gynecology of Baoji Central Hospital and Baoji People ‘s Hospital from 2018 to 2019 were collected. Demographic and clinical data of patients included: age, occupation, gravidity (number of pregnancies), parity (number of deliveries), previous caesarean section (number of cesarean sections), season of last mentruation, regular or irregular menses, pregnancy complications, pregnancy comorbidities, hypertensive disorders of pregnancy. The population was divided into two groups, the case group was the people of spontaneous abortion and the control group was the full-term birth population. Miscarriages cases were matched for maternal age with ongoing pregnancies to term in a one to four case-control study. Taking age as the matching factor, the interference of maternal age on the research results was removed.

Pregnancy complications are conditions in which a pregnant woman develops a series of diseases caused by pregnancy, including hyperemesis gravidarum, ectopic pregnancy, placenta previa, premature rupture of membranes, amniotic fluid embolism, fetal distress, and so on. Pregnancy comorbidities refer to the diseases existing before pregnancy or occurred during pregnancy due to non-pregnancy causes, which include combined heart disease, combined hematological disease, combined respiratory disease, combined gastrointestinal disease, combined urological disease, combined endocrine disease, combined infectious disease and combined tumor. Hypertensive disorders of pregnancy is a group of diseases in which pregnancy coexist with elevated blood pressure, including gestational hypertension, preeclampsia, eclampsia, chronic hypertension with superimposed preeclampsia as well as chronic hypertension in pregnancy, which seriously affects maternal and infant health.

Cases with no communication disorder (including impairments in social cognition, the ability to recognize others’ emotions and infer others’ thoughts, which can have profound negative effects on communication functions18), local residence time more than one year and detailed address were collected. And those cases of assisted conception, non-spontaneous abortion and spontaneous abortion caused by genetic problems were excluded.

Approval to conduct this study was obtained from Medical ethics committee of Medical School of Yan’an University (NO.2018051).Informed consent was provided by all participants at enrollment. All of the methods were performed in accordance with the relevant guidelines and regulations. And in line with Declaration of Helsinki.

Exposure assessment of atmospheric pollutants

The air quality monitoring stations in the urban area of Baoji City are mainly distributed in the east-west downtown area along the Weihe River (Fig. 1 ).The daily average concentrations of five conventional air pollutants PM2.5, PM10, SO2, NO2 and O3 in Baoji City from 2017 to 2019 were collected and sorted out ( except that O3 is an 8-hour moving average, the other four pollutants are 24-hour moving average ).Taking the first trimester as the exposure window, the outdoor air pollutant exposure value of each pregnant woman during pregnancy was calculated. The global average method and the nearest monitoring station method were used to evaluate the exposure level of each pregnant woman in the first trimester. The global average method does not consider the distance between the maternal address and the monitoring site, adding the pollutant data during exposure window of all monitoring sites to calculate the mean value. The nearest monitoring station method bases on the address of the pregnant woman’s place of residence during pregnancy, and then the latitude and longitude of her place of residence were obtained from Gaode Map. The distance from the latitude and longitude of the place of residence to the latitude and longitude of the monitoring station was calculated, and the pollutant mass concentration of the nearest monitoring station to the place of residence was selected as the individual’s exposure mass concentration. After dividing exposure window according to the date of the last menstrual period of pregnant women, the mass concentration of pollutants in exposure window was calculated.

Figure 1
figure 1

Distribution of air quality monitoring stations and topographic map of Baoji.

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Statistical method

The case-control method of group design was used to analyze the risk factors of gravidity, parity, previous caesarean section, occupation, season of last mentruation, menstrual cycle, pregnancy complications, pregnancy comorbidities and hypertensive disorders of pregnancy by chi-square test. Excel was used for data collation, and IBM SPSS20 was used for data analysis. We performed the pollutant data for normality with K-S test, if the data met the normal distribution, the mean and standard deviation were used to describe, and difference within the group was tested by the t-test. If not, the median and upper and lower quartiles were chosen to describe the data, and difference between groups was judged using Mann-Whitney test. The difference of pollutant concentration between the case group and the control group in the exposure window was compared. The conditional logistic model was used to analyze each pollutant, and the OR value and its 95% confidence interval (95% CI) were used to represent the correlation strength between each pollutant and spontaneous abortion. Then the relevant risk factors were introduced to establish the model, and the data of each pollutant were substituted into the model to explore the relationship between each pollutant in the first trimester and spontaneous abortion.

Result

Maternal information

During the study period we collected 154 cases of spontaneous abortion and 616 cases of full-term birth in the control group, with a total of 770 cases, ranging from 19 to 44 years old. Table 1 reports the comparison between the main democrophic and clinical data of cases and controls. It was concluded that the differences in parity, previous caesarean section, occupation, last menstrual season, pregnancy complications, pregnancy comorbidities between the spontaneous abortion group and the full-term delivery group were significantly different between cases and controls (P < 0.05). These factors will be included in the model as risk factors. There was no significant difference in gravidity, menstrual cycle and hypertensive disorders of pregnancy between the two groups. It can also be found that people who are pregnant in spring and winter have a higher incidence of spontaneous abortion than those in summer and autumn (Table 1).

Table 1 Comparison of demographic and clinical data of cases and controls (numbers and percentages in brakets).
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Atmospheric pollutant data

The daily average concentrations of outdoor PM2.5, PM10, SO2, NO2 and O3 in Baoji City from 2017 to 2019 were collected and sorted out. It can be seen that the concentrations of these five pollutants in Baoji City showed obvious seasonal changes (Fig. 2). In terms of annual unit, the concentrations of PM2.5, PM10, SO2 and NO2 in Baoji City showed a trend of decreasing first and then increasing. The concentration of pollutants was higher in spring and winter, but lower in summer and autumn. The change of O3 concentration is opposite, showing a trend of increasing first and then decreasing. The concentration is higher in spring and summer, with the highest value, and relatively low in autumn and winter.

Figure 2
figure 2

The daily average concentration changes of five air pollutants in Baoji City from 2017 to 2019. (The x axis represents date and the y axis represents pollutant concentration (ug/m 3 )).

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Analysis results of global average method

The K-S test indicated that the data did not fit to the normal distribution, so the median and upper and lower quartiles were used to describe the contaminant data. We chose the rank sum test to judge the variability. The data were organized in Table 2: There was no significant difference in the exposure doses of the five pollutants between the groups (P > 0.05), and the median exposure doses of PM2.5 and NO2 in the case group(48.74ug/m3,37.06ug/m3) were higher than those in the control group(47.22ug/m3,36.83ug/m3).

Table 2 Exposure levels of pollutants during first trimester in the study population (ug/m3) (Differential testing of contaminant exposure).
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Logistic regression analysis showed that (Table 3), before adjustment, PM2.5 ( OR = 1.016,95% CI = 1.005 ~ 1.027 ) and SO2 ( OR = 1.164,95% CI = 1.096 ~ 1.236 ) were statistically significant. In analyses after combining other risk factors, exposure to PM2.5 (OR = 1.156,95% CI = 1.074 ~ 1.254), SO2 (OR = 1.432,95% CI = 1.209 ~ 1.695) and NO2 (OR = 1.121,95% CI = 1.004 ~ 1.204) in the first trimester was associated with the occurrence of spontaneous abortion, while PM10 (P > 0.05) and O3 (OR = 0.93) were not significantly correlated.

Table 3 Logistic regression analysis of risk factors related to first trimester pollutants (associations between pollutants and spontaneous abortion).
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Analysis results of nearest monitoring station method

The K-S test indicated that the data did not fit to the normal distribution, so the median and upper and lower quartiles were used to describe the contaminant data. We used the rank sum test to judge the variability. As shown in Table 4: There were significant differences in the exposure levels of NO2(P = 0.01 < 0.05)and O3(P = 0.02 < 0.05) between the case group and the control group. The median of PM10 and O3 exposure concentration in the full-term group (105.08ug/m3,101.16ug/m3) was higher than that in the spontaneous abortion group (103.90ug/m3,96.49ug/m3),and the median of PM2.5, SO2 andNO2 exposure doses in the case group (46.85ug/m3,7.44ug/m3,36.40ug/m3)were higher than those in the control group(46.82ug/m3,7.42ug/m3,34.50ug/m3).

Table 4 Exposure levels of pollutants during first trimester in the study population (ug/m3) (Differential testing of contaminant exposure)
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Analysis concluded (Table 5), before adjustment, exposure to PM2.5 (OR = 1.013, 95% CI = 1.004–1.022), SO2 (OR = 1.117, 95% CI = 1.073–1.162) and NO2 (OR = 1.056, 95% CI = 1.030–1.082) in the first trimester was associated with the occurrence of spontaneous abortion. After adjusting the relevant risk factors, It indicate that pregnant women exposure to PM2.5 ( OR = 1.036,95% CI = 1.009 ~ 1.064 ), SO2 ( OR = 1.429,95% CI = 1.189 ~ 1.718 ) and NO2 ( OR = 1.159,95% CI = 1.074 ~ 1.251 ) during first trimester may increase the risk of spontaneous abortion, while PM10 ( P > 0.05 ) and O3 ( OR = 0.924 ) did not show significant correlation.

Table 5 Logistic regression analysis of risk factors related to first trimester (associations between pollutants and spontaneous abortion).
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Discussion

This study is a retrospective case-control study. Through the analysis of maternal data and five air pollutants in Baoji City from 2017 to 2019, it was found that parity, previous caesarean section, occupation, last menstrual season, pregnancy complications and pregnancy comorbidities were listed as other risk factors (P < 0.05). Other studies have similar findings. As demonstrated by Magnus MC et al., the risk of miscarriage varies greatly with maternal age19. Moradinazar, M. et al. found that age and diabetes can increase the miscarriage rate in pregnant women20.

Although existing studies have shown the relationship between air pollution and spontaneous abortion21, studies in different regions have shown inconsistent results due to differences in research methods and research sites22.In this study, the two exposure evaluation methods showed that the exposure of atmospheric pollutants PM2.5, SO2 and NO2 in the first trimester had an effect on the occurrence of spontaneous abortion, but there was no significant correlation between spontaneous abortion and PM10 or O3. A case-control study in China found that exposure to NO2 during first trimester was associated with increased risk of spontaneous abortion23, which is similar to the results of this study. Nevertheless, as a result of the selection of exposure window period, research methods and regional differences, a study in Mongolia shows that seasonal environmental air pollution is closely related to spontaneous abortion in Mongolia, which is reflected in the strong dose-response correlation of SO2, PM2.5, PM10 and NO2, but the correlation of O3 has not been studied24.Also a study in Chongqing showed that high levels of exposure to PM2.5, PM10, NO2 and SO2 during pregnancy increased the risk of spontaneous abortion25. The difference is that this study did not find the correlation between PM10 and spontaneous abortion. Other researchers have found that exposure to SO2 and PM10 during pregnancy in Ahwas, Iran, is significantly directly related to the occurrence of spontaneous abortion26, which is different from the results of this study.

Through the analysis of pollutants from 2017 to 2019 (Fig. 2), it is concluded that the concentrations of PM2.5, SO2 and NO2 are higher in spring and winter and the analysis of maternal data found that the incidence of spontaneous abortion in spring and winter is also relatively high, which could be a good evidence of the association between PM2.5, SO2, NO2 and spontaneous abortion. Further comparison of the maternal pollutant exposure data estimated by global average method and the nearest monitoring station method (Tables 2 and 4) found that there was difference. Obviously, the first trimester pollutant exposure values are different between the two methods. Contaminants in the case group with a median exposure higher than that in the control group may increase the risk of spontaneous abortion in the first trimester: PM2.5, NO2 in the global average method and PM2.5, SO2, NO2 in the nearest monitoring station method. What’s more, there was no significant difference in the exposure level of any pollutant in the global average method, but a significant difference in the exposure level of NO2 (P = 0.01 < 0.05) and O3 (P = 0.02 < 0.05) in the nearest monitoring station method. The reason for this difference still needs further study, probably because the data obtained by the global average method are susceptible to extreme values, while the nearest monitoring station method does not take into account the influence of space when the pregnant women are out or at work.

As for the mechanism of air pollution on spontaneous abortion, Xu Q et al. proposed that air pollution exposure affects spontaneous abortion by affecting pregnancy hormones27.Some pointed out that contamants affect embryo normality by affecting oxidative stress28.Others considered that exposure to ambient air pollution leads to abnormal placental development that leads to adverse pregnancy outcomes29.Studies have also found that air pollution may lead to spontaneous abortion by affecting the methylation level of the IGF2BP1 promoter30 and PM2.5 may cause spontaneous abortion by causing inflammation in women31.

This study also has shortcomings: First of all, not taking into account the exposure of air pollutants in the indoor environment of pregnant women. Secondly, only one exposure window in the first trimester was explored and the sample size was relatively small, which made the research results less supported by some data. In addition, contaminant data derived from the global average method and the nearest monitoring station method used the same analysis method, and the retrospective nature of the study does not allow to distinguish between association and causal relationship. Subsequently, different methods can be used to analyze the data. Inverse distance weighting method, land regression utilization model and linear diffusion model can also be used to evaluate pollutant exposure concentration.