Congenital heart defects (CHDs) are a major cause of death in infancy and childhood. Major risk factors for most CHDs, particularly those resulting from the combination of environmental exposures with social determinants and behaviors, are still unknown. This study evaluated the main effect of maternal environmental tobacco smoke (ETS), and its interaction with social-demographics and environmental factors on CHDs in China. A population-based, matched case-control study of 9452 live-born infants and stillborn fetuses was conducted using the Guangdong Registry of Congenital Heart Disease data (2004–2014). The CHDs were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia tomography/catheterization. Controls were randomly chosen from singleton newborns without any malformation, born in the same hospital as the cases and 1:1 matched by infant sex, time of conception, and parental residence (same city and town to ensure sufficient geographical distribution for analyses). Face-to-face interviews were conducted to collect information on demographics, behavior patterns, maternal disease/medication, and environmental exposures. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals of ETS exposure on CHDs while controlling for all risk factors. Interactive effects were evaluated using a multivariate delta method for maternal demographics, behavior, and environmental exposures on the ETS-CHD relationship. Mothers exposed to ETS during the first trimester of pregnancy were more likely to have infants with CHD than mothers who did not (aOR = 1.44, 95% CI 1.25–1.66). We also observed a significant dose-response relationship when mothers were exposed to ETS and an increasing number of risk factors and CHDs. There were greater than additive interactions for maternal ETS and migrant status, low household income and paternal alcohol consumption on CHDs. Maternal low education also modified the ETS-CHD association on the multiplicative scale. These findings may help to identify high-risk populations for CHD, providing an opportunity for targeted preventive interventions.

Air pollution is one of the leading preventable threats to public health. Emerging evidence indicates that exposure to environmental stressors is associated with abnormal foetal development. However, how prenatal exposure to diesel exhaust PM2.5 (DEP) predisposes adult offspring to the development of non-alcoholic fatty liver disease (NAFLD) remains unclear. To examine this, C57BL/6J mice were exposed to DEP or a vehicle before conception and during pregnancy and fed normal chow or a high-fat diet. Then, the hepatic fatty accumulation in the adult male offspring and possible molecular mechanisms were assessed. Our data showed that prenatal exposure to DEP on normal chow led to hepatic steatosis in adult male offspring with normal liver function. However, prenatal DEP exposure relieved the hepatic steatosis and liver function in offspring of mice fed a high-fat diet. Furthermore, prenatal exposure to DEP on normal chow increased lipogenesis and worsened fatty acid oxidation. The counteractive effect of prenatal DEP exposure on high-fat-diet-induced hepatic steatosis was produced through upregulated adenosine 5′-monophosphate-activated protein kinase, and this improved lipogenesis and fatty acid oxidation. Collectively, prenatal exposure to DEP programmed the development of NAFLD differently in the adult male offspring of mice fed normal chow and a high-fat diet, showing the pleotrophic effects of exposure to adverse environmental factors in early life.

Air pollution exposure during early-life is associated with altered brain development, but the precise periods of susceptibility are unknown. We aimed to investigate whether there are periods of susceptibility of air pollution between conception and preadolescence in relation to white matter microstructure and brain volumes at 9–12 years old. We used data of 3515 children from the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands (2002–2006). We estimated daily levels of nitrogen dioxide (NO2), and particulate matter (PM2.5 and PM2.5absorbance) at participants’ homes during pregnancy and childhood using land-use regression models. Diffusion tensor and structural brain images were obtained when children were 9–12 years of age, and we calculated fractional anisotropy and mean diffusivity, and several brain structure volumes. We performed distributed lag non-linear modeling adjusting for socioeconomic and lifestyle characteristics. We observed specific periods of susceptibility to all air pollutants from conception to age 5 years in association with lower fractional anisotropy and higher mean diffusivity that survived correction for multiple testing (e.g., −0.85 fractional anisotropy (95%CI -1.43; −0.27) per 5 μg/m³ increase in PM2.5 between conception and 4 years of age). We also observed certain periods of susceptibility to some air pollutants in relation to global brain and some subcortical brain volumes, but only the association between PM2.5 and putamen survived correction for multiple testing (172 mm³ (95%CI 57; 286) per 5 μg/m³ increase in PM2.5 between 4 months and 1.8 year of age). This study suggested that conception, pregnancy, infancy, toddlerhood, and early childhood seem to be susceptible periods to air pollution exposure for the development of white matter microstructure and the putamen volume. Longitudinal studies with repeated brain outcome measurements are needed for understanding the trajectories and the long-term effects of exposure to air pollution.

There is limited and equivocal epidemiological evidence relating to the association between maternal sulfur dioxide (SO₂) exposure and the risk of oral clefts (OCs) in offspring. We performed a population-based case-control study in Liaoning province to evaluate aforementioned relationship during 3 months before conception, the first trimester of pregnancy, and their single months. The study involved 3086 patients with OCs and 7950 controls. Data relating to SO₂ concentration was acquired from air monitoring stations throughout the study period. We used a multivariable logistic regression model to evaluate the association between exposure to SO₂ and the risk of OCs during the exposure windows. Maternal SO₂ exposure was positively related to OCs during the 3 months before conception (odds ratio = 1.38, 95% confidence interval: 1.15–1.65; P for trend < 0.01). Positive relationships were obtained from the first and second months before conception and the first month of pregnancy. Thus, our research reflects a relationship between SO₂ exposure and the risk of OCs. Future studies are now required to verify the association between SO₂ exposure and OCs during pregnancy and indicate the most relevant vulnerable exposure time windows.

Prenatal exposure to ambient air pollution has been associated with adverse perinatal outcomes in previous studies. However, few studies have examined the interaction between air pollution and the season of conception on term low birth weight (TLBW) or macrosomia. Birth registry data of singleton live births in Wenzhou, China, between January 2015 and December 2016 were accessed from the Wenzhou Maternal and Child Health Information Management platform, and data on the ambient air pollutants in Wenzhou were obtained from the Chinese Air Quality Online Monitoring and Analysis Platform. Single-/two-pollutant binary logistic regression models were used to assess the associations between ambient air pollutants (PM₂.₅, PM₁₀, NO₂, SO₂, and O₃) and TLBW/macrosomia, further exploring whether the season of conception interacts with air pollution to impact birth weight. Finally, 213,959 term newborns were selected, including 2452 (1.1%) infants with TLBW and 13,173 (6.1%) infants with macrosomia. In the single-/two-pollutant models, we observed an increased risk of TLBW associated with maternal exposure to PM₂.₅, PM₁₀, SO₂, and NO₂ during the entire pregnancy, especially in the 2nd trimester. Maternal exposure to O₃ during the 1st trimester was associated with increased macrosomia risk, and O₃ exposure during the 3rd trimester was associated with increased TLBW risk. Pregnant women who conceive in the warm season may experience a more adverse ambient air environment that is related to the risks of TLBW. These findings add to the evidence suggesting that air pollution and the season of conception may have synergistic effects on adverse perinatal outcomes, especially TLBW. Further prospective cohort studies are needed to validate our results.

Changes in the preconception ambient temperature (PAT) can affect the gametogenesis, disturbing the development of the embryo, but the health risks of PAT on the developing fetus are still unclear. Here, based on the National Free Preconception Health Examination Project in the rural areas of Henan Province, we evaluate the effects of PAT on preterm birth (PTB). Data of 1,231,715 records from self-reported interviews, preconception physical examination, early gestation follow-up, and postpartum follow-up were collected from 1 January 2013 to 31 December 2016. Generalized additive models were used to assess the cumulative and lag effects of PAT upon PTB. The significant cumulative effects of mean temperature within 2 weeks and 3 weeks on the risk of PTB, especially upon late PTB (34–36 weeks) (P < 0.05), were observed. Exposure to extreme heat (> 90th percentile) within 2 weeks (RR = 1.470) and 3 weeks (RR = 1.375) before conception could increase the risk of PTB. After stratifying PTB, exposure to extreme heat within 2 weeks before conception can increase the risks of early (< 34 weeks) and late PTB (P < 0.05). Besides, exposure to extreme cold (< 10th percentile) within 3 weeks or longer before conception can elevate the risk of PTB, especially late PTB. The significant lag effects of temperature changes on the risk of early PTB (lag-8 days or earlier) were observed. In conclusion, the risk of PTB was susceptible to PAT changes within 2 weeks or longer before conception. Our findings provide (i) guidance for rural couples to make pregnancy plans and (ii) scientific evidence for the government to formulate policies to prevent PTB.

Associations between maternal exposures to air pollutants and low birth weight (LBW) in offspring varied when different exposure windows were considered. Methods used in previous studies lacked flexibility in delineating exposure windows and did not consider time periods before conception, which may restrict the discoveries of critical exposure windows. This study introduces a novel method to identify critical windows of maternal air pollution exposures associated with LBW in offspring using massive georeferenced data. Through a case–control study based on birth data (94,106 LBW cases and 376,424 controls) and air quality monitoring data (367 chemicals) in Texas during 1996–2008, this study used the average ambient concentration measured by the monitoring site closest to the residence location of a mother during a time window as the maternal exposure to a specific chemical during that exposure window. Binary logistic regression was utilized to estimate air pollutant-LBW associations in different exposure windows. The odds ratios (ORs) were adjusted for child’s sex, gestational weeks, maternal age, race/ethnicity, and education. The adjusted ORs were plotted against the exposure window series of different sizes for each chemical, aiming at interactively visualizing and exploring the critical exposure windows across multiple temporal scales. This study identifies ten chemicals and seventeen corresponding critical exposure windows where strong air pollutant-LBW associations are detected. The ten identified chemicals are benzaldehyde, sum of Photochemical Assessment Monitoring Stations (PAMS) target compounds, n-undecane, m-tolualdehyde, organic carbon fraction 2 (OC2), ethylene dibromide, valeraldehyde, propionaldehyde, 4-methyl-1-pentene, and zirconium. Nine critical exposure windows involving six chemicals start more than five months prior to conception, seven windows involving five chemicals commence in the second and/or third trimester of pregnancy, and the remaining one window is located in other time periods. The novel method reveals a number of critical time windows of maternal exposure to ten chemicals that are positively associated with LBW in offspring. These ten chemicals were identified as LBW risk factors for the first time. Additional studies with more data are needed to validate the results in the future.

The potential association between maternal exposure to PM₁₀ ranging from 3 months prior to conception to the end of the early trimester and the risk of anorectal atresia/stenosis in offspring has not been established. Thus, we determined the association between maternal exposure to PM₁₀ and risk of anorectal atresia/stenosis in offspring in this study. We recruited 713 patients including 480 male and 233 female with anorectal atresia/stenosis and 7950 randomly selected healthy offspring from the Maternal and Child Health Certificate Registry of Liaoning Province and delivered between 1 January 2010 and 31 December 2015. Monthly PM₁₀ concentrations were retrieved from the Environment Protection Bureau of each city in Liaoning Province. We established a multivariable logistic regression model to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Maternal exposure to PM₁₀ was associated with an increased risk for anorectal atresia/stenosis in offspring during the 3 months prior to conception (per 10 μg/m³ increment: OR = 1.15, 95% CI = 1.03–1.20; per SD [27 μg/m³] increment: OR = 1.33, 95% CI = 1.09–1.63) and the first trimester (per 10 μg/m³ increment: OR = 1.08, 95% CI = 1.00–1.17; per SD [28 μg/m³] increment: OR = 1.26, 95% CI = 1.01–1.57). Evaluation of the association with a shorter exposure window (1 month) revealed a positive association between anorectal atresia/stenosis and PM₁₀ from the 3rd month prior to pregnancy to each month of the 1st trimester. Maternal exposure to PM₁₀ 3 months prior to conception and during the 1st trimester was associated with an increased risk of anorectal atresia/stenosis in the offspring. Future perspective cohort studies are needed to confirm our findings.