Perinatal exposure to traffic related air pollutants and the risk of infection in the first six months of life: a cohort study from a low-middle income country.

OBJECTIVE: There is limited study from low-and-middle income countries on the effect of perinatal exposure to air pollution and the risk of infection in infant. We assessed the association between perinatal exposure to traffic related air pollution and the risk of infection in infant during their first six months of life. METHODS: A prospective cohort study was performed in Jakarta, March 2016-September 2020 among 298 mother-infant pairs. PM2.5, soot, NOx, and NO2 concentrations were assessed using land use regression models (LUR) at individual level. Repeated interviewer-administered questionnaires were used to obtain data on infection at 1, 2, 4 and 6 months of age. The infections were categorized as upper respiratory tract (runny nose, cough, wheezing or shortness of breath), lower respiratory tract (pneumonia, bronchiolitis) or gastrointestinal tract infection. Logistic regression models adjusted for covariates were used to assess the association between perinatal exposure to air pollution and the risk of infection in the first six months of life. RESULTS: The average concentrations of PM2.5 and NO2 were much higher than the WHO recommended levels. Upper respiratory tract infections (URTI) were much more common in the first six months of life than diagnosed lower respiratory tract or gastro-intestinal infections (35.6%, 3.5% and 5.8% respectively). Perinatal exposure to PM2.5 and soot suggested increase cumulative risk of upper respiratory tract infection (URTI) in the first 6 months of life per IQR increase with adjusted OR of 1.50 (95% CI 0.91; 2.47) and 1.14 (95% CI 0.79; 1.64), respectively. Soot was significantly associated with the risk of URTI at 4-6 months age interval (aOR of 1.45, 95%CI 1.02; 2.09). All air pollutants were also positively associated with lower respiratory tract infection, but all CIs include unity because of relatively small samples. Adjusted odds ratios for gastrointestinal infections were close to unity. CONCLUSION: Our study adds to the evidence that perinatal exposure to fine particles is associated with respiratory tract infection in infants in a low-middle income country.

Long-term exposure to air pollution and chronic kidney disease-associated mortality-Results from the pooled cohort of the European multicentre ELAPSE-study.

Despite the known link between air pollution and cause-specific mortality, its relation to chronic kidney disease (CKD)-associated mortality is understudied. Therefore, we investigated the association between long-term exposure to air pollution and CKD-related mortality in a large multicentre population-based European cohort. Cohort data were linked to local mortality registry data. CKD-death was defined as ICD10 codes N18-N19 or corresponding ICD9 codes. Mean annual exposure at participant's home address was determined with fine spatial resolution exposure models for nitrogen dioxide (NO2), black carbon (BC), ozone (O3), particulate matter ≤2.5 µm (PM2.5) and several elemental constituents of PM2.5. Cox regression models were adjusted for age, sex, cohort, calendar year of recruitment, smoking status, marital status, employment status and neighbourhood mean income. Over a mean follow-up time of 20.4 years, 313 of 289,564 persons died from CKD. Associations were positive for PM2.5 (hazard ratio (HR) with 95% confidence interval (CI) of 1.31 (1.03-1.66) per 5 µg/m3, BC (1.26 (1.03-1.53) per 0.5 × 10- 5/m), NO2 (1.13 (0.93-1.38) per 10 µg/m3) and inverse for O3 (0.71 (0.54-0.93) per 10 µg/m3). Results were robust to further covariate adjustment. Exclusion of the largest sub-cohort contributing 226 cases, led to null associations. Among the elemental constituents, Cu, Fe, K, Ni, S and Zn, representing different sources including traffic, biomass and oil burning and secondary pollutants, were associated with CKD-related mortality. In conclusion, our results suggest an association between air pollution from different sources and CKD-related mortality.

Long-term exposure to air pollution and incidence of gastric and the upper aerodigestive tract cancers in a pooled European cohort: The ELAPSE project.

Air pollution has been shown to significantly impact human health including cancer. Gastric and upper aerodigestive tract (UADT) cancers are common and increased risk has been associated with smoking and occupational exposures. However, the association with air pollution remains unclear. We pooled European subcohorts (N = 287,576 participants for gastric and N = 297,406 for UADT analyses) and investigated the association between residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone in the warm season (O3w) with gastric and UADT cancer. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. During 5,305,133 and 5,434,843 person-years, 872 gastric and 1139 UADT incident cancer cases were observed, respectively. For gastric cancer, we found no association with PM2.5, NO2 and BC while for UADT the hazard ratios (95% confidence interval) were 1.15 (95% CI: 1.00-1.33) per 5 µg/m3 increase in PM2.5, 1.19 (1.08-1.30) per 10 µg/m3 increase in NO2, 1.14 (1.04-1.26) per 0.5 × 10-5 m-1 increase in BC and 0.81 (0.72-0.92) per 10 µg/m3 increase in O3w. We found no association between long-term ambient air pollution exposure and incidence of gastric cancer, while for long-term exposure to PM2.5, NO2 and BC increased incidence of UADT cancer was observed.

Air pollution and human health: a phenome-wide association study.

OBJECTIVES: To explore the associations of long-term exposure to air pollution with onset of all human health conditions. DESIGN: Prospective phenome-wide association study. SETTING: Denmark. PARTICIPANTS: All Danish residents aged ≥30 years on 1 January 2000 were included (N=3 323 612). After exclusion of individuals with missing geocoded residential addresses, 3 111 988 participants were available for the statistical analyses. MAIN OUTCOME MEASURE: First registered diagnosis of every health condition according to the International Classification of Diseases, 10th revision, from 2000 to 2017. RESULTS: Long-term exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were both positively associated with the onset of more than 700 health conditions (ie, >80% of the registered health conditions) after correction for multiple testing, while the remaining associations were inverse or insignificant. As regards the most common health conditions, PM2.5 and NO2 were strongest positively associated with chronic obstructive pulmonary disease (PM2.5: HR 1.06 (95% CI 1.05 to 1.07) per 1 IQR increase in exposure level; NO2: 1.14 (95% CI 1.12 to 1.15)), type 2 diabetes (PM2.5: 1.06 (95% CI 1.05 to 1.06); NO2: 1.12 (95% CI 1.10 to 1.13)) and ischaemic heart disease (PM2.5: 1.05 (95% CI 1.04 to 1.05); NO2: 1.11 (95% CI 1.09 to 1.12)). Furthermore, PM2.5 and NO2 were both positively associated with so far unexplored, but highly prevalent outcomes relevant to public health, including senile cataract, hearing loss and urinary tract infection. CONCLUSIONS: The findings of this study suggest that air pollution has a more extensive impact on human health than previously known. However, as this study is the first of its kind to investigate the associations of long-term exposure to air pollution with onset of all human health conditions, further research is needed to replicate the study findings.

Long-term exposure to ambient air pollution and risk of leukemia and lymphoma in a pooled European cohort.

Leukemia and lymphoma are the two most common forms of hematologic malignancy, and their etiology is largely unknown. Pathophysiological mechanisms suggest a possible association with air pollution, but little empirical evidence is available. We aimed to investigate the association between long-term residential exposure to outdoor air pollution and risk of leukemia and lymphoma. We pooled data from four cohorts from three European countries as part of the "Effects of Low-level Air Pollution: a Study in Europe" (ELAPSE) collaboration. We used Europe-wide land use regression models to assess annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) at residences. We also estimated concentrations of PM2.5 elemental components: copper (Cu), iron (Fe), zinc (Zn); sulfur (S); nickel (Ni), vanadium (V), silicon (Si) and potassium (K). We applied Cox proportional hazards models to investigate the associations. Among the study population of 247,436 individuals, 760 leukemia and 1122 lymphoma cases were diagnosed during 4,656,140 person-years of follow-up. The results showed a leukemia hazard ratio (HR) of 1.13 (95% confidence intervals [CI]: 1.01-1.26) per 10 µg/m3 NO2, which was robust in two-pollutant models and consistent across the four cohorts and according to smoking status. Sex-specific analyses suggested that this association was confined to the male population. Further, the results showed increased lymphoma HRs for PM2.5 (HR = 1.16; 95% CI: 1.02-1.34) and potassium content of PM2.5, which were consistent in two-pollutant models and according to sex. Our results suggest that air pollution at the residence may be associated with adult leukemia and lymphoma.

Long-term exposure to several constituents and sources of PM2.5 is associated with incidence of upper aerodigestive tract cancers but not gastric cancer: Results from the large pooled European cohort of the ELAPSE project.

It is unclear whether cancers of the upper aerodigestive tract (UADT) and gastric cancer are related to air pollution, due to few studies with inconsistent results. The effects of particulate matter (PM) may vary across locations due to different source contributions and related PM compositions, and it is not clear which PM constituents/sources are most relevant from a consideration of overall mass concentration alone. We therefore investigated the association of UADT and gastric cancers with PM2.5 elemental constituents and sources components indicative of different sources within a large multicentre population based epidemiological study. Cohorts with at least 10 cases per cohort led to ten and eight cohorts from five countries contributing to UADT- and gastric cancer analysis, respectively. Outcome ascertainment was based on cancer registry data or data of comparable quality. We assigned home address exposure to eight elemental constituents (Cu, Fe, K, Ni, S, Si, V and Zn) estimated from Europe-wide exposure models, and five source components identified by absolute principal component analysis (APCA). Cox regression models were run with age as time scale, stratified for sex and cohort and adjusted for relevant individual and neighbourhood level confounders. We observed 1139 UADT and 872 gastric cancer cases during a mean follow-up of 18.3 and 18.5 years, respectively. UADT cancer incidence was associated with all constituents except K in single element analyses. After adjustment for NO2, only Ni and V remained associated with UADT. Residual oil combustion and traffic source components were associated with UADT cancer persisting in the multiple source model. No associations were found for any of the elements or source components and gastric cancer incidence. Our results indicate an association of several PM constituents indicative of different sources with UADT but not gastric cancer incidence with the most robust evidence for traffic and residual oil combustion.

Long-Term Exposure to Low-Level PM2.5 and Mortality: Investigation of Heterogeneity by Harmonizing Analyses in Large Cohort Studies in Canada, United States, and Europe.

BACKGROUND: Studies across the globe generally reported increased mortality risks associated with particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) exposure with large heterogeneity in the magnitude of reported associations and the shape of concentration-response functions (CRFs). We aimed to evaluate the impact of key study design factors (including confounders, applied exposure model, population age, and outcome definition) on PM2.5 effect estimates by harmonizing analyses on three previously published large studies in Canada [Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE), 1991-2016], the United States (Medicare, 2000-2016), and Europe [Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), 2000-2016] as much as possible. METHODS: We harmonized the study populations to individuals 65+ years of age, applied the same satellite-derived PM2.5 exposure estimates, and selected the same sets of potential confounders and the same outcome. We evaluated whether differences in previously published effect estimates across cohorts were reduced after harmonization among these factors. Additional analyses were conducted to assess the influence of key design features on estimated risks, including adjusted covariates and exposure assessment method. A combined CRF was assessed with meta-analysis based on the extended shape-constrained health impact function (eSCHIF). RESULTS: More than 81 million participants were included, contributing 692 million person-years of follow-up. Hazard ratios and 95% confidence intervals (CIs) for all-cause mortality associated with a 5-µg/m3 increase in PM2.5 were 1.039 (1.032, 1.046) in MAPLE, 1.025 (1.021, 1.029) in Medicare, and 1.041 (1.014, 1.069) in ELAPSE. Applying a harmonized analytical approach marginally reduced difference in the observed associations across the three studies. Magnitude of the association was affected by the adjusted covariates, exposure assessment methodology, age of the population, and marginally by outcome definition. Shape of the CRFs differed across cohorts but generally showed associations down to the lowest observed PM2.5 levels. A common CRF suggested a monotonically increased risk down to the lowest exposure level. https://doi.org/10.1289/EHP12141.

Multiple myeloma risk in relation to long-term air pollution exposure - A pooled analysis of four European cohorts.

BACKGROUND: Air pollution is a growing concern worldwide, with significant impacts on human health. Multiple myeloma is a type of blood cancer with increasing incidence. Studies have linked air pollution exposure to various types of cancer, including leukemia and lymphoma, however, the relationship with multiple myeloma incidence has not been extensively investigated. METHODS: We pooled four European cohorts (N = 234,803) and assessed the association between residential exposure to nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), and ozone (O3) and multiple myeloma. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 4,415,817 person-years of follow-up (average 18.8 years), we observed 404 cases of multiple myeloma. The results of the fully adjusted linear analyses showed hazard ratios (95% confidence interval) of 0.99 (0.84, 1.16) per 10 µg/m³ NO2, 1.04 (0.82, 1.33) per 5 µg/m³ PM2.5, 0.99 (0.84, 1.18) per 0.5 10-5 m-1 BCE, and 1.11 (0.87, 1.41) per 10 µg/m³ O3. CONCLUSIONS: We did not observe an association between long-term ambient air pollution exposure and incidence of multiple myeloma.

Long-term air pollution exposure and malignant intracranial tumours of the central nervous system: a pooled analysis of six European cohorts.

BACKGROUND: Risk factors for malignant tumours of the central nervous system (CNS) are largely unknown. METHODS: We pooled six European cohorts (N = 302,493) and assessed the association between residential exposure to nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) and malignant intracranial CNS tumours defined according to the International Classification of Diseases ICD-9/ICD-10 codes 192.1/C70.0, 191.0-191.9/C71.0-C71.9, 192.0/C72.2-C72.5. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 5,497,514 person-years of follow-up (average 18.2 years), we observed 623 malignant CNS tumours. The results of the fully adjusted linear analyses showed a hazard ratio (95% confidence interval) of 1.07 (0.95, 1.21) per 10 µg/m³ NO2, 1.17 (0.96, 1.41) per 5 µg/m³ PM2.5, 1.10 (0.97, 1.25) per 0.5 10-5m-1 BC, and 0.99 (0.84, 1.17) per 10 µg/m³ O3. CONCLUSIONS: We observed indications of an association between exposure to NO2, PM2.5, and BC and tumours of the CNS. The PM elements were not consistently associated with CNS tumour incidence.

Long-term exposure to air pollution and risk of SARS-CoV-2 infection and COVID-19 hospitalisation or death: Danish nationwide cohort study.

BACKGROUND: Early ecological studies have suggested links between air pollution and risk of coronavirus disease 2019 (COVID-19), but evidence from individual-level cohort studies is still sparse. We examined whether long-term exposure to air pollution is associated with risk of COVID-19 and who is most susceptible. METHODS: We followed 3 721 810 Danish residents aged ≥30 years on 1 March 2020 in the National COVID-19 Surveillance System until the date of first positive test (incidence), COVID-19 hospitalisation or death until 26 April 2021. We estimated residential annual mean particulate matter with diameter ≤2.5 µm (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) in 2019 by the Danish DEHM/UBM model, and used Cox proportional hazards regression models to estimate the associations of air pollutants with COVID-19 outcomes, adjusting for age, sex, individual- and area-level socioeconomic status, and population density. RESULTS: 138 742 individuals were infected, 11 270 were hospitalised and 2557 died from COVID-19 during 14 months. We detected associations of PM2.5 (per 0.53 µg·m-3) and NO2 (per 3.59 µg·m-3) with COVID-19 incidence (hazard ratio (HR) 1.10 (95% CI 1.05-1.14) and HR 1.18 (95% CI 1.14-1.23), respectively), hospitalisations (HR 1.09 (95% CI 1.01-1.17) and HR 1.19 (95% CI 1.12-1.27), respectively) and death (HR 1.23 (95% CI 1.04-1.44) and HR 1.18 (95% CI 1.03-1.34), respectively), which were strongest in the lowest socioeconomic groups and among patients with chronic respiratory, cardiometabolic and neurodegenerative diseases. We found positive associations with BC and negative associations with O3. CONCLUSION: Long-term exposure to air pollution may contribute to increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection as well as developing severe COVID-19 disease requiring hospitalisation or resulting in death.

Early-Life Exposure to Ambient Air Pollution from Multiple Sources and Asthma Incidence in Children: A Nationwide Birth Cohort Study from Denmark.

BACKGROUND: Ambient air pollution exposure has been associated with childhood asthma, but previous studies have primarily focused on prevalence of asthma and asthma-related outcomes and urban traffic-related exposures. OBJECTIVE: We examined nationwide associations between pre- and postnatal exposure to ambient air pollution components and asthma incidence in children age 0-19 y. METHODS: Asthma incidence was identified from hospital admission, emergency room, and outpatient contacts among all live-born singletons born in Denmark between 1998 and 2016. We linked registry data with monthly mean concentrations of particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5) and PM with aerodynamic diameter ≤10µm (PM10), nitrogen dioxide (NO2), nitrogen oxides, elemental carbon, and organic carbon (OC), sulfur dioxide, ozone, sulfate, nitrate, ammonium, secondary organic aerosols, and sea salt. Associations were estimated with Cox proportional hazard models using fixed prenatal exposure means and time-varying postnatal exposures. RESULTS: Of the 1,060,154 children included, 6.1% had asthma during the mean follow-up period of 8.8 y. The risk of asthma increased with increasing prenatal exposure to all pollutants except for O3 and sea salt. We also observed increased risk after restriction to asthma after age 4 y, after additional adjustment for area-specific socioeconomic status, and for postnatal exposure to most pollutants. The hazard ratio (HR) associated with an interquartile range increase of 2.4 and 8.7 µg/m3 in prenatal exposure was 1.06 [95% confidence interval (CI): 1.04, 1.08] for PM2.5 and 1.04 (95% CI: 1.02, 1.05) for NO2, respectively. This association with PM2.5 was stable after adjustment for NO2, whereas it attenuated for NO2 to 1.01 (95% CI: 0.99, 1.03) after adjustment for PM2.5. For a 0.5-µg/m3 increase in prenatal OC exposure, for which biomass is an important source, the HR was 1.08 (95% CI: 1.06, 1.10), irrespective of adjustment for PM2.5. DISCUSSION: These findings suggest that early-life exposure to ambient air pollution from multiple sources contributes to asthma development. https://doi.org/10.1289/EHP11539.

Exposure to ambient air pollution and elevated blood levels of gamma-glutamyl transferase in a large Austrian cohort.

Gamma glutamyl transferase (GGT) is related to oxidative stress and an indicator for liver damage. We investigated the association between air pollution and GGT in a large Austrian cohort (N = 116,109) to better understand how air pollution affects human health. Data come from voluntary prevention visits that were routinely collected within the Vorarlberg Health Monitoring and Prevention Program (VHM&PP). Recruitment was ongoing from 1985 to 2005. Blood was drawn and GGT measured centralized in two laboratories. Land use regression models were applied to estimate individuals' exposure at their home address for particulate matter (PM) with a diameter of <2.5 µm (PM2.5), <10 µm (PM10), fraction between 10 µm and 2.5 µm (PMcoarse), as well as PM2.5 absorbance (PM2.5abs), NO2, NOx and eight components of PM. Linear regression models, adjusting for relevant individual and community-level confounders were calculated. The study population was 56 % female with a mean age of 42 years and mean GGT was 19.0 units. Individual PM2.5 and NO2 exposures were essentially below European limit values of 25 and 40 µg/m3, respectively, with means of 13.58 µg/m3 for PM2.5 and 19.93 µg/m3 for NO2. Positive associations were observed for PM2.5, PM10, PM2.5abs, NO2, NOx, and Cu, K, S in PM2.5 and PM10 fractions and Zn mainly in PM2.5 fraction. The strongest association per interquartile range observed was an increase of serum GGT concentration by 1.40 % (95 %-CI: 0.85 %; 1.95 %) per 45.7 ng/m3 S in PM2.5. Associations were robust to adjustments for other biomarkers, in two-pollutant models and the subset with a stable residential history. We found that long-term exposure to air pollution (PM2.5, PM10, PM2.5abs, NO2, NOx) as well as certain elements, were positively associated with baseline GGT levels. The elements associated suggest a role of traffic emissions, long range transport and wood burning.

Association between exposure to multiple air pollutants, transportation noise and cause-specific mortality in adults in Switzerland.

BACKGROUND: Long-term exposure to air pollution and noise is detrimental to health; but studies that evaluated both remain limited. This study explores associations with natural and cause-specific mortality for a range of air pollutants and transportation noise. METHODS: Over 4 million adults in Switzerland were followed from 2000 to 2014. Exposure to PM2.5, PM2.5 components (Cu, Fe, S and Zn), NO2, black carbon (BC) and ozone (O3) from European models, and transportation noise from source-specific Swiss models, were assigned at baseline home addresses. Cox proportional hazards models, adjusted for individual and area-level covariates, were used to evaluate associations with each exposure and death from natural, cardiovascular (CVD) or non-malignant respiratory disease. Analyses included single and two exposure models, and subset analysis to study lower exposure ranges. RESULTS: During follow-up, 661,534 individuals died of natural causes (36.6% CVD, 6.6% respiratory). All exposures including the PM2.5 components were associated with natural mortality, with hazard ratios (95% confidence intervals) of 1.026 (1.015, 1.038) per 5 µg/m3 PM2.5, 1.050 (1.041, 1.059) per 10 µg/m3 NO2, 1.057 (1.048, 1.067) per 0.5 × 10-5/m BC and 1.045 (1.040, 1.049) per 10 dB Lden total transportation noise. NO2, BC, Cu, Fe and noise were consistently associated with CVD and respiratory mortality, whereas PM2.5 was only associated with CVD mortality. Natural mortality associations persisted < 20 µg/m3 for PM2.5 and NO2, < 1.5 10-5/m BC and < 53 dB Lden total transportation noise. The O3 association was inverse for all outcomes. Including noise attenuated all outcome associations, though many remained significant. Across outcomes, noise was robust to adjustment to air pollutants (e.g. natural mortality 1.037 (1.033, 1.042) per 10 dB Lden total transportation noise, after including BC). CONCLUSION: Long-term exposure to air pollution and transportation noise in Switzerland contribute to premature mortality. Considering co-exposures revealed the importance of local traffic-related pollutants such as NO2, BC and transportation noise.

Comparison of traditional Cox regression and causal modeling to investigate the association between long-term air pollution exposure and natural-cause mortality within European cohorts.

Most studies investigating the health effects of long-term exposure to air pollution used traditional regression models, although causal inference approaches have been proposed as alternative. However, few studies have applied causal models and comparisons with traditional methods are sparse. We therefore compared the associations between natural-cause mortality and exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) using traditional Cox and causal models in a large multicenter cohort setting. We analysed data from eight well-characterized cohorts (pooled cohort) and seven administrative cohorts from eleven European countries. Annual mean PM2.5 and NO2 from Europe-wide models were assigned to baseline residential addresses and dichotomized at selected cut-off values (PM2.5: 10, 12, 15 µg/m³; NO2: 20, 40 µg/m³). For each pollutant, we estimated the propensity score as the conditional likelihood of exposure given available covariates, and derived corresponding inverse-probability weights (IPW). We applied Cox proportional hazards models i) adjusting for all covariates ("traditional Cox") and ii) weighting by IPW ("causal model"). Of 325,367 and 28,063,809 participants in the pooled and administrative cohorts, 47,131 and 3,580,264 died from natural causes, respectively. For PM2.5 above vs. below 12 µg/m³, the hazard ratios (HRs) of natural-cause mortality were 1.17 (95% CI 1.13-1.21) and 1.15 (1.11-1.19) for the traditional and causal models in the pooled cohort, and 1.03 (1.01-1.06) and 1.02 (0.97-1.09) in the administrative cohorts. For NO2 above vs below 20 µg/m³, the HRs were 1.12 (1.09-1.14) and 1.07 (1.05-1.09) for the pooled and 1.06 (95% CI 1.03-1.08) and 1.05 (1.02-1.07) for the administrative cohorts. In conclusion, we observed mostly consistent associations between long-term air pollution exposure and natural-cause mortality with both approaches, though estimates partly differed in individual cohorts with no systematic pattern. The application of multiple modelling methods might help to improve causal inference. 299 of 300 words.

Comparing "causal" and "traditional" approaches in the association of long-term exposure to ambient air pollution on mortality: How sensitive are the results?

BACKGROUND: Few comparisons between causal inference and traditional approaches have been performed. We applied "causal" and "traditional" methods to investigate the association between long-term air pollution exposure (PM2.5 and NO2) and mortality. METHODS: We analyzed pooled data from eight well-characterized cohorts and one administrative cohort. We defined the generalized propensity score (GPS) as the conditional likelihood of exposure given confounders, and derived corresponding inverse-probability weights (IPW). We applied Cox-proportional hazard models weighted by IPW, adjusted for GPS, and directly adjusting for all confounders. RESULTS: In IPW models, PM2.5 5 µg/m3 increases were associated with hazard ratios (HR) = 1.141 (95% confidence interval (CI): 1.107, 1.176) and 1.050 (1.014, 1.088) in the pooled and administrative cohorts. Corresponding estimates for traditional Cox models were 1.132 (1.107, 1.158) and 1.057 (1.025, 1.089). Almost identical results were found for all approaches and both pollutants, when unbalanced covariates were adjusted for in causal models. CONCLUSIONS: Traditional and causal approaches provided consistent associations between long-term exposure to air pollution and mortality.

The effect of exposure to traffic related air pollutants in pregnancy on birth anthropometry: a cohort study in a heavily polluted low-middle income country.

BACKGROUND: Ambient air pollution has been recognized as one of the most important environmental health threats. Exposure in early life may affect pregnancy outcomes and the health of the offspring. The main objective of our study was to assess the association between prenatal exposure to traffic related air pollutants during pregnancy on birth weight and length. Second, to evaluate the association between prenatal exposure to traffic related air pollutants and the risk of low birth weight (LBW). METHODS: Three hundred forty mother-infant pairs were included in this prospective cohort study performed in Jakarta, March 2016-September 2020. Exposure to outdoor PM2.5, soot, NOx, and NO2 was assessed by land use regression (LUR) models at individual level. Multiple linear regression models were built to evaluate the association between air pollutants with birth weight (BW) and birth length (BL). Logistic regression was used to assess the risk of low birth weight (LBW) associated with all air pollutants. RESULTS: The average PM2.5 concentration was almost eight times higher than the current WHO guideline and the NO2 level was three times higher. Soot and NOx were significantly associated with reduced birth length. Birth length was reduced by - 3.83 mm (95% CI -6.91; - 0.75) for every IQR (0.74 × 10- 5 per m) increase of soot, and reduced by - 2.82 mm (95% CI -5.33;-0.30) for every IQR (4.68 µg/m3) increase of NOx. Outdoor air pollutants were not significantly associated with reduced birth weight nor the risk of LBW. CONCLUSION: Exposure to soot and NOx during pregnancy was associated with reduced birth length. Associations between exposure to all air pollutants with birth weight and the risk of LBW were less convincing.