To the best of our knowledge, this is the first study systematically investigating the relationship of prenatal exposure to air pollutants with SGA over the entire and trimester-specific pregnancy in Xuzhou in the northern Jiangsu province in China. In our study, a total of six kinds of air pollutants exposure were examined to test the effects on SGA, of which the SO2 was the most significant representative air pollutant, to which our calculated odds ratio reached up 1.382(95% confidence interval:1.177–1.623) during the third trimester.
The incidence of SGA varied greatly among different areas, of which the 6.93% in Xuzhou while 15.4% in the southern district of Israel and 5.74% in Beijing of China and 11.1% in a multicenter study in American [26–28]. The reasons for these differences may be diverse selection of research objects, sample size and economic and medical development of the studied regions. For example, Beijing, a political, economic and cultural center in China, has a relatively better medical and health care level and people have a higher health quality. The selected subjects may have different levels of physical activity and education, as well as socioeconomic status, which can affect the health of the new infants. Lee reported that high levels of occupational physical activity were significantly associated with SGA while a completely opposite opinion was performed a study in Brazil , the relative physical activity level with adverse birth outcome also needed to be furthered.
All our air pollutants exception NO2 and O3 were observed adversely weak or strong association over the entire or trimester-specific pregnancy. Although there were many studies investigating the association between exposure to SO2 and being born to SGA, the results remained still inconsistent. While adverse effects of exposure to SO2 during pregnancy with SGA were observed in some studies [31–33], other had the completely different conclusions with null even protective association [16, 34–37]. Similar to the study conducted in a multicenter study in US using Binary Poisson regression and a low urbanization of Italy using multivariate regression analysis [19, 31], we also found the susceptibly sensitive windows periods of gestation of maternal exposure to SO2 over the total and each trimester of pregnancy. Thus the varied studying population, research design, statistical methods, degree of exposure misclassification among various studies, we finally came to the same conclusion as above studies that exposure to SO2 during pregnancy will exert adverse effect on pregnant women and their babies in some extent. Especially, when we calculated whether there was exposure-response relationship between the SO2 and the SGA, we found that the risk of SGA became stronger per IQR increase from the point of Q3 concentration over the entire and during the 1st and 2nd trimester, suggesting that the risk of SGA could increase with a threshold at the range of the second and third quartile. Considering the inconsistent susceptible exposure windows and threshold effect, future studies needed to be conducted to precisely investigate the sensitive exposure windows to provide government prevention advices timely.
Completely inverse results from the study conducted in US investigating the relationship between prenatal exposure to O3 and SGA , we found null association during each trimester while adverse relationship was observed for O3 for SGA during the third trimester and protective effect was observed for PM2.5 and SGA over the entire pregnancy and the first and second trimester in their study. We also found that prenatal exposure to particulate matter with aerodynamics diameter less than 10µm and CO decreased the risk of SGA during the second and third trimester, which seems not biologically plausible and inconsistent with previous studies. Embryos sensitive to early air pollution may eventually be stillborn or die in the intrauterine phase, however, our study only included live births, which could be one reason and create selection bias. This discrepancy also may be due to our inconsistent adjustment of model covariates and exposure heterogeneity, our study did not consider factors such as socioeconomic and marital status, maternal education level and history of smoking, which are all significant factors analyzing the causes born to SGA in recent studies[38–40]. Considering the negative impacts of smoking and drinking on human health, it is necessary to adjust the effects of confounders. Furthermore, a large amount of studies have reported a strong correlation between PM2.5 and PM10 [41–43], we also found the similar effects on SGA between the two air pollutants in our study although only the positive relationship over the entire pregnancy. An OR increase was observed per IQR increase over the entire trimester, suggesting that there was no threshold effect of pollutants as the concentration of PM2.5 increased. The adverse effects attributed to PM2.5 exposure not only compromised SGA, but the prevalent low birth weight and preterm birth, which are all far-reaching consequences of air pollutants exposure [44, 45]. The possible biological mechanism of particulate matter on SGA may include immunity impairment and oxidative stress inflammation induced by PM2.5 [46, 47], which will cause endocrine disorder in pregnant women and hinder the essential nutrition and gases passing through the placenta.
In this cross sectional study in Xuzhou, we found null association of exposure to NO2 and moderate effect between CO and SGA over the entire pregnancy and the first trimester. Inconsistent with previous study conducted in meta analysis [32, 48], which may be due to that included a large number of black people, a relatively susceptible and understudied population, resulting the heterogeneity of studying population.
This study also has several strengthens. It is the first study on the relationship between air pollution and SGA in Xuzhou, and we found that SO2 is an independent risk factor for SGA. We included six pollutants to explore the possible relationship between air pollutants and adverse birth outcomes. Meanwhile, our study also have some limitations. The average exposure level of the monitoring site is for the population rather than the individual exposure level, which may cause exposure measurement bias and ultimately affect the determination of the relationship. We did not include indicators of and socioeconomic status and lifestyle factors related to smoking and alcohol consumption among pregnant women, which are all confounders of air pollutants and SGA.