Prenatal ambient air pollutants exposure and the risk of stillbirth in Wuhan, central of China.

BACKGROUND: The existing studies on the relationships of prenatal ambient air pollutants exposure with stillbirth in the Chinese population are very limited and the results are inconsistent, and the susceptible windows and potential modifiers for air pollutants exposure on stillbirth remain unanswered. OBJECTIVE: We aimed to determine the relationships between exposure to ambient air pollutants and stillbirth, and explored the susceptible windows and potential modifiers for air pollutants exposure on stillbirth. METHODS: A population-based cohort was established through the Wuhan Maternal and Child Health Management Information System involving 509,057 mother-infant pairs in Wuhan from January 1, 2011 through September 30, 2017. Personal exposure concentrations of fine particles (PM2.5), inhalable particles (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) for mothers were estimated based on their residential address during pregnancy using the inverse distance weighted (IDW) method. We used the logistic regression models to determine the associations at different stages of pregnancy with adjustment for confounding factors. RESULTS: There were 3218 stillbirths and 505,839 live births among the participants. For each 100 µg/m3 of CO and 10 µg/m3 of O3 increase in the first trimester (conception to 13+6 weeks), the risk of stillbirth increased by 1.0% (OR = 1.01, 95%CI: 1.00-1.03) and 7.0% (OR = 1.07, 95%CI: 1.05-1.09). In the second trimester (14 weeks-27+6 weeks), PM2.5, PM10, CO, and O3 exposure were closely related to the risk of stillbirth (P＜0.05). In the third trimester (28 weeks to delivery), for each 10 µg/m3 increase in exposure concentrations of PM2.5, SO2, and O3, the risk of stillbirth increased by 3.4%, 5.9%, and 4.0%, respectively. O3 exposure was positively relevant to the risk of stillbirth (OR = 1.11, 95%CI: 1.08-1.14) in the whole pregnancy. Exposure to NO2 was not significantly associated with the risk of stillbirth. Stratified analyses also presented a stronger association among mothers with boy infant, living in rural areas, delivering between 2011 and 2013, and those without gestational hypertension and history of stillbirth. CONCLUSION: This study provides evidence that maternal exposure to PM2.5, PM10, SO2, CO, and O3 were related to the increased risk of stillbirth. Both the second and third trimesters might be vital susceptible windows for stillbirth. Our findings expand the evidence base for the important impacts of air pollution on fetal growth.

Effect of maternal ozone exposure before and during pregnancy on wheezing risk in offspring: A birth cohort study in Guangzhou, China.

Ozone (O3) exposure may lead to the development and exacerbation of asthma or wheezing in postnatal children; however, it has rarely been studied before and during pregnancy. Wheezing is one of the most common symptoms when diagnosing of asthma; thus, we investigated the associations of O3 exposure before and during pregnancy with wheezing in preschool children and the potential susceptible exposure windows from a heavily polluted city in China. This population-based birth cohort study, which included 3725 mother-child pairs from Guangzhou, began in 2016, and the follow-up period ended on July 31, 2020. We used a spatiotemporal land-use-regression model combined with activity patterns to estimate the daily O3 exposure levels during the pre-pregnancy period and each trimester, and wheezing was recorded by reviewing medical records. We used the Cox proportional hazard model to quantify the effects of O3 exposure on childhood wheezing adjusted for potential confounders. No significant association was detected between pre-pregnancy exposure to O3 and childhood wheezing. However, increased ambient O3 exposures throughout pregnancy and in the second trimester were positively associated with the risk of childhood wheezing, with hazard ratios (HRs) and 95% confident intervals (CIs) per interquartile range (IQR) increment of 1.22 (95% CI: 1.04-1.44) and 1.31 (95% CI: 1.09-1.58), respectively. The effects of maternal O3 exposure on childhood wheezing risk was stronger when the exposure occurred in the warm conception season (P < 0.05). Significant childhood wheezing risk could be attributable to maternal O3 exposure, especially during the second trimester and with warm-season conception in Guangzhou. Further cohorts of children, particularly school age children who have more robust asthma diagnoses, should be investigated in the future.

Third trimester as the susceptibility window for maternal PM2.5 exposure and preterm birth: A nationwide surveillance-based association study in China.

Maternal PM2.5 exposure has been identified as a potential risk factor for preterm birth, yet the inconsistent findings on the susceptible exposure windows may be partially due to the influence of gaseous pollutants. This study aims to examine the association between PM2.5 exposure and preterm birth during different susceptible exposure windows after adjusting for exposure to gaseous pollutants. We collected 2,294,188 records of singleton live births from 30 provinces of China from 2013 to 2019, and the gridded daily concentrations of air pollutants (including PM2.5, O3, NO2, SO2, and CO) were derived by using machine learning models for assessing individual exposure. We employed logistic regression to develop single-pollutant models (including PM2.5 only) and co-pollutant models (including PM2.5 and a gaseous pollutant) to estimate the odds ratio for preterm birth and its subtypes, with adjustment for maternal age, neonatal sex, parity, meteorological conditions, and other potential confounders. In the single-pollutant models, PM2.5 exposure in each trimester was significantly associated with preterm birth, and the third trimester exposure showed a stronger association with very preterm birth than that with moderate to late preterm birth. The co-pollutant models revealed that preterm birth might be significantly associated only with maternal exposure to PM2.5 in the third trimester, and not with exposure in the first or second trimester. The observed significant associations between preterm birth and maternal PM2.5 exposure in the first and second trimesters in single-pollutant models might primarily be influenced by exposure to gaseous pollutants. Our study provides evidence that the third trimester may be the susceptible window for maternal PM2.5 exposure and preterm birth. The association between PM2.5 exposure and preterm birth could be influenced by gaseous pollutants, which should be taken into consideration when evaluating the impact of PM2.5 exposure on maternal and fetal health.

Effects of prenatal exposure to air particulate matter on the risk of preterm birth and roles of maternal and cord blood LINE-1 methylation: A birth cohort study in Guangzhou, China.

BACKGROUND: Epidemiological studies have found that increased risk of preterm birth (PTB) is associated with higher prenatal exposure to PM10 and PM2.5, but few studies have been conducted to assess the impacts of extremely fine particulate matter (PM1) which may have more toxic effects than other types of ambient particulate air pollution (PM). Several studies have separately investigated the associations between DNA methylation and PTB risk and PM. Maternal LINE-1 methylation level negatively correlated with prenatal exposure to PM and risk of PTB. A comprehensive picture is lacking regarding the associations between prenatal exposure to PM, LINE-1 methylation, and risk of PTB. OBJECTIVES: This study aimed to estimate the effects of exposure to ambient PM (PM10, PM2.5, and PM1) of different sizes during pregnancy on risk of PTB, identify susceptible exposure windows, and illustrate the roles of LINE-1 methylation in the associations between PM and PTB risk. METHODS: The Birth Cohort Study on Prenatal Environments and Offspring Health (PEOH) has been ongoing since 2016 in Guangzhou, China. A total of 4928 pregnant women were recruited during early pregnancy, and 4278 (86.8%) were successfully followed-up. Each individual weekly exposure to PM10 and PM2.5 from 3 months before pregnancy to childbirth was assessed using a spatiotemporal land use regression model, and the weekly PM1 exposure was estimated by employing a generalized additive model. Maternal and cord blood LINE-1 methylation levels (%5mC) were tested using bisulfite-PCR pyrosequencing. A distributed lag nonlinear model incorporated with a Cox proportional hazard model was applied to assess the effect of weekly-specific maternal PM exposure on PTB risk, and a multiple-linear regression model was employed to investigate the associations between PM exposure and LINE-1 methylation levels of maternal and cord bloods. We also assessed the associations between LINE-1 methylation levels and PTB risk by using a logistic regression model. RESULTS: The risk of PTB was positively associated with PM2.5 and PM1 concentrations during the 12th to 20th gestational weeks, and the strongest association was in the fourth quartile (Q4) versus the first quartile (Q1) and observed during the 16th gestational week (PM2.5: harzard ratio [HR] = 1.18, 95%CI: 1.04-1.35, IQR = 11.94 µg/m3. PM1: HR = 1.20, 95%CI: 1.03-1.39, IQR = 11.36 µg/m3). We observed significantly negative associations of PM10(ß = -0.51%5mC per 10 µg/m3, P = 0.014), PM2.5 (ß = -0.66%5mC per 10 µg/m3, P = 0.032) and PM1 (ß = -0.67%5mC per 10 µg/m3, P = 0.032) concentrations with cord blood LINE-1 methylation levels, and a negative association between PM1 concentration and maternal LINE-1 methylation level (ß = -0.86%5mC per 10 µg/m3, P = 0.034). CONCLUSION: Higher prenatal exposure to PM1 and PM2.5 during the 12th to 20th gestational weeks was associated with increased risk of PTB. Maternal and fetal LINE-1 methylation alternation might be an underlying mechanism of PM that increasing the risk of PTB.

Identifying windows of susceptibility for maternal exposure to ambient air pollution and preterm birth.

Maternal exposure to ambient air pollution has been associated with preterm birth (PTB), however, entire pregnancy or trimester-specific associations were generally reported, which may not sufficiently identify windows of susceptibility. Using birth registry data from Guangzhou, a megacity of southern China (population ~14.5 million), including 469,975 singleton live births between January 2015 and July 2017, we assessed the association between weekly air pollution exposure and PTB in a retrospective cohort study. Daily average concentrations of PM2.5, PM10, NO2, SO2, and O3 from 11 monitoring stations were used to estimate district-specific exposures for each participant based on their district residency during pregnancy. Distributed lag models (DLMs) incorporating Cox proportional hazard models were applied to estimate the association between weekly maternal exposure to air pollutant and PTB risk (as a time-to-event outcome), after controlling for temperature, seasonality, and individual-level covariates. We also considered moderate PTB (32-36 gestational weeks) and very PTB (28-31 gestational weeks) as outcomes of interest. Hazard ratios (HRs) and 95% confidential intervals (95% CIs) were calculated for an interquartile range (IQR) increase in air pollutants during the study period. An IQR increase in PM2.5 exposure during the 20th to 28th gestational weeks (27.0 µg/m3) was significantly associated with PTB risk, with the strongest effect in the 25th week (HR = 1.034, 95% CI:1.010-1.059). The significant exposure windows were the 19th-28th weeks for PM10, the 18th-31st weeks for NO2, and the 23rd-31st weeks for O3, respectively. The strongest associations were observed in the 25th week for PM10 (IQR = 37.0 µg/m3; HR = 1.048, 95% CI:1.034-1.062), the 26th week for NO2 (IQR = 29.0 µg/m3; HR = 1.060, 95% CI:1.028-1.094), and in the 28th week for O3 (IQR = 90.0 µg/m3; HR = 1.063, 95% CI:1.046-1.081). Similar patterns were observed for moderate PTB (32-36 gestational weeks) and very PTB (28-31 gestational weeks) for PM2.5, PM10, NO2 exposure, but the effects were greater for very PTB. We did not observe any association between pregnancy SO2 exposure and the risk of PTB. Our results suggest that middle to late pregnancy is the most susceptible air pollution exposure window for air pollution and PTB among women in Guangzhou, China.