BACKGROUND:Increased placental oxidative stress is frequently documented in pregnant women with adverse maternal outcomes such as preeclampsia. However, environmental determinants of placental oxidative stress remain poorly understood. OBJECTIVES:To determine whether exposure to air pollution and polycyclic aromatic hydrocarbons (PAHs) are associated with placental levels of malondialdehyde (MDA), a biomarker of oxidative stress; to assess whether placental MDA reflects short-term (lag days 0-7) or longer-term (trimester-specific) exposure; and to evaluate whether these associations differ by fetal sex. METHODS:Participants were drawn from the UPSIDE ECHO BABIES cohort (n = 222). Placental MDA concentrations were quantified using an HPLC method. The ambient PM2.5 and NO2 exposures were estimated using high-resolution random forest models. PAH exposure was assessed using trimester-specific maternal blood concentration of PAH-hemoglobin adducts. Associations between exposure and placental MDA were evaluated using multivariable linear regression and distributed lag non-linear models (DLNMs), adjusting for maternal and demographic covariates. RESULTS:A 1-IQR increase in the second trimester, specifically month 5 p.m.2.5, was associated with a 24.8% (95% CI: 3.3-50.7), and 13.7% (95% CI: 0.1-29.16) increase in MDA concentration, respectively. Similarly, the second-trimester hemoglobin adduct of benzo [a]pyrene showed a positive, non-significant association with MDA. Although week-specific DLNM estimates were not statistically significant, the analysis showed that exposure to PM2.5 during gestational weeks 16-20 was positively associated with MDA concentration. When stratified by placenta sex, female placentas had increased MDA in the second trimester associated with PM2.5, and male placentas had increased MDA in the second trimester associated with PAH-hemoglobin adducts. No significant associations were observed for either pollutant when estimated one lag week before birth. No significant associations were observed for NO2 exposure. CONCLUSIONS:Second-trimester PM2.5 exposure was linked to elevated placental MDA concentration at delivery, indicating that placental MDA may reflect longer-term air pollution exposure. These findings emphasize the importance of investigating specific gestational windows through which air pollution induces oxidative injury to the placenta.

The rate of respiratory viral infection (RVI) associated with acute air pollution exposure is well established, but whether bacterial and viral infections respond similarly to traffic related air pollution (TRAP) exposure is less well understood. Using a novel seasonal time-stratified case-crossover design and conditional logistic regression, we separately estimated the rate of hospitalization for 465 patients with RVI, respiratory bacterial infection (RBI), or combined respiratory viral and bacterial infection (RVBI) associated with increased ambient particulate matter ≤2.5 µm (PM2.5), black carbon (BC), nitrogen dioxide (NO2) and carbon monoxide (CO) concentrations in the previous 1, 2, and 3 weeks (lag days 0-6, 7-13, 14-20). In a novel approach, a four-physician panel adjudicated each case of infection to accurately classify the type of infection present and only patients with the highest diagnostic certainty were enrolled in this study. Associations were strongest between TRAP and RVI at the 0-6 lag period, with fewer, less precise associations at later lag times for RVBI and RBI. Each 2.6 µg/m3 increase in PM2.5 on lag days 0-6 was associated with a 22.1% increased rate of RVI hospitalization (95% CI: 1.6%, 46.7%). Each 0.1 µg/m3 increase in BC was associated with a 30.0% increase (95% CI: 5.0%, 61.1%) in the rate of hospitalization for RVI. Rates of hospitalization for RVI associated with increased PM2.5 were generally largest for lag days 0-6 and 7-13. The RVI/BC rate ratio was larger for females than males for days 0-13, but not for PM2.5 and NO2. Short term increases in PM2.5, BC, NO2, and CO concentrations (markers of traffic pollution) were associated with an increased rate of RVI hospitalization, while sex-specific associations were observed between BC and RVI for females. Further study of the mechanism underlying the effect of TRAP on RVI is needed.

To study whether air pollution is detrimental to reproductive development is imperative. In the absence of randomized trials to study the effects of air pollution on human health, data from observational studies have been utilized in which the researchers attempted to capture the causal associations between air pollution and the health outcomes. Many of these studies rely on parametric assumptions which may be limiting. In this tutorial, we explain and implement the nonparametric empirical likelihood (EL) Algorithm within the causal inference framework of a classic methodology and a newer technique based on machine learning tools. We show the competitive results of the assumption free EL in simulations. We also apply the developed methods to study the causal association between PM2.5 and NO2 exposure and anogenital distance at birth, a marker of androgen activity.

Background: Sex steroid hormones are critical for maintaining pregnancy and optimal fetal development. Air pollutants are potential endocrine disruptors that may disturb sex steroidogenesis during pregnancy, potentially leading to adverse health outcomes. Methods: In the Environmental influences on Child Health Outcomes Understanding Pregnancy Signals and Infant Development pregnancy cohort (Rochester, NY), sex steroid concentrations were collected at study visits in early-, mid-, and late-pregnancy in 299 participants. Since these visits varied by the gestational age at blood draw, values were imputed at 14, 22, and 30 weeks gestation. Daily NO2 and PM2.5 concentrations were estimated using random forest models, with daily concentrations from each 1-km2 grid containing the subject’s residence. Associations between gestational week mean NO2 and PM2.5 concentrations and sex steroid concentrations were examined utilizing distributed lag nonlinear models. Results: Each interquartile range (IQR = 9 ppb) increase in NO2 during weeks 0–5 was associated with higher early-pregnancy total testosterone levels (cumulative β = 0.45 ln[ng/dl]; 95% CI = 0.07, 0.83), while each IQR increase in NO2 during weeks 12–14 was associated with lower early-pregnancy total testosterone levels (cumulative β = −0.27 ln[ng/dl]; 95% CI = −0.53, −0.01). Similar NO2 increases during gestational weeks 0–14 were associated with higher late-pregnancy estradiol concentrations (cumulative β = 0.29 ln[pg/ml]; 95% CI = 0.10, 0.49), while each IQR increase in NO2 concentrations during gestational weeks 22–30 was associated with lower late-pregnancy estradiol concentrations (cumulative β = −0.18 ln[pg/ml]; 95% CI = −0.34, −0.02). No associations with PM2.5 were observed, except for an IQR increase in PM2.5 concentrations (IQR = 4 µg/m3) during gestational weeks 5–11 which was associated with lower late-pregnancy estriol levels (cumulative β = −0.16 ln[ng/ml]; 95% CI = −0.31, −0.00). Conclusions: Residential NO2 exposure was associated with altered sex steroid hormone concentrations during pregnancy with some indication of potential compensatory mechanisms.

We examined the association between air pollution and neutralizing antibody responses to COVID-19 vaccination in participants enrolled in a phase 3 clinical trial. Seventy-four adults were vaccinated with two doses of the AstraZeneca ChAdOx1 vectored vaccine (AZD1222) (5 x 1010 viral particles) at baseline and day 29, between Aug 28, 2020, to Jan 15, 2021, in Monroe County, NY. SARS-CoV-2 pseudovirus neutralizing ID50 titers (NAb) and total spike protein IgG were assessed at baseline and 15, 29, 43, 57 and 90 days after vaccination. In this pilot study, each participant's dates of neutralization titers were matched to Monroe County ambient concentrations of fine particles (PM2.5; ≤ 2.5 µm), black carbon (BC; marker of traffic), among other particulate and gaseous pollutants. Using linear mixed models, we estimated the association between each interquartile range (IQR) difference in air pollutant concentrations in the 14 days prior to blood collection and antibody responses at each post vaccination timepoint. Though not statistically significant, we observed a 23% reduction in NAb titer (95% CI: -67%, 79%) measured on day 43 (i.e., 14 days after second vaccination) associated with each 0.32 µg/m3 increase in BC concentrations in the prior 14 days. We also observed a 42% increase in spike protein IgG (95% CI: -16%, 141%) measured on day 15 (i.e., 14 days after primary vaccination) associated with each 0.26 µg/m3 increase in BC concentrations in the 14 days prior. A similar pattern for total spike protein IgG was observed at day 29 (42%; 95% CI: -22%, 157%) and 90 (43%; 95% CI: -11%, 127%). Future research will need to explore the possible association between air pollution exposure and antibody response to SARS-CoV-2 vaccination given the potential for compromised vaccine efficacy.

Understanding health risks from methylmercury (MeHg) exposure is complicated by its link to fish consumption, which may confound or modify toxicities. One solution is to include fish intake and a biomarker of MeHg exposure in the same analytical model, but resulting estimates do not reflect the independent impact of accumulated MeHg or fish exposure. In fish-eating populations, this can be addressed by separating MeHg exposure into fish intake and average mercury content of the consumed fish. We assessed the joint association of prenatal MeHg exposure (maternal hair mercury level) and fish intake (among fish-eating mothers) with neurodevelopment in 361 children aged 8 years from the New Bedford Cohort (New Bedford, Massachusetts; born in 1993-1998). Neurodevelopmental assessments used standardized tests of IQ, language, memory, and attention. Covariate-adjusted regression assessed the association of maternal fish consumption, stratified by tertile of estimated average fish mercury level, with neurodevelopment. Associations between maternal fish intake and child outcomes were generally beneficial for those in the lowest average fish mercury tertile but detrimental in the highest average fish mercury tertile, where, for example, each serving of fish was associated with 1.3 fewer correct responses (95% CI, -2.2 to -0.4) on the Boston Naming Test. Standard analyses showed no outcome associations with hair mercury level or fish intake.This article is part of a Special Collection on Environmental Epidemiology.

Urinary hydroxylated-polycyclic aromatic hydrocarbons (PAHs), with half-life less than 2 days, are established biomarkers of short-term exposure to PAHs, a ubiquitous constituent of air pollution mixture. In this study, we explore the use of PAHs-hemoglobin adducts as biomarkers of longer-term exposure to air pollution by leveraging an extant resource of blood samples collected from 235 pregnant women residing in Rochester, NY. We measured red blood cells for benzo[a]pyrene-tetrols (BaPT) and phenanthrene-tetrols (PHET), both of which are hydrolysis products of PAH-hemoglobin adduct. We utilized previously estimated PM2.5 and NO2 concentrations within the 1 km2 grid surrounding each participant's residence, calculated for up to 20 weeks before the blood collection date. Associations between PAHs tetrols and cumulative exposures to ambient PM2.5 or NO2 over different time periods were examined using a linear mixed-effects model with participant-specific random intercepts adjusting for season, gestation age, maternal age, maternal income level, and pre-pregnancy BMI. We observed positive associations between PHET concentration and cumulative PM2.5 exposure over gestational weeks 12-17, and between BaPT concentration and cumulative PM2.5 exposure over gestational weeks 3-16 prior to sample collection. Each interquartile range (IQR) increase in 14 week PM2.5 exposure (1.26 μg m-3) was associated with a 9.02% (95% CI: 0.30%, 17.7%) increase in PHET and a 12.8% (95% CI: 1.09%, 23.5%) increase in BaPT levels. In contrast, no associations were observed between either biomarker and cumulative NO2 exposures. These findings underscore the potential of PAH-hemoglobin adducts as longer-term (weeks to 4 months) exposure biomarkers of ambient PM2.5.

BACKGROUND:Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) variations are linked to age-related diseases and are associated with environmental exposure and nutritional status. Limited data, however, exist on the associations with mercury exposure, particularly early in life. OBJECTIVE:We examined the association between prenatal mercury (Hg) exposure and TL and mtDNAcn in 1,145 Seychelles children, characterized by a fish-rich diet. METHODS:Total mercury (THg) was determined in maternal hair at delivery and cord blood. TL and mtDNAcn were determined relative to a single-copy hemoglobin beta gene in the saliva of 7-y-old children. Linear regression models assessed associations between THg and relative TL (rTL) and relative mtDNAcn (rmtDNAcn) while controlling for maternal and cord serum polyunsaturated fatty acid (PUFA) status and sociodemographic factors. Interactions between THg and child sex, PUFA, and telomerase genotypes were evaluated for rTL and rmtDNAcn. RESULTS:Higher THg concentrations in maternal hair and cord blood were associated with longer rTL [β=0.009; 95% confidence interval (CI): 0.002, 0.016 and β=0.002; 95% CI: 0.001, 0.003, respectively], irrespective of sex, PUFA, or telomerase genotypes. Maternal serum n-6 PUFA and n-6/n-3 ratio were associated with shorter [β=-0.24; 95% CI: -0.33, -0.15 and β=-0.032; 95% CI: -0.048, -0.016, respectively] and n-3 PUFA with longer (β=0.34; 95% CI: 0.032, 0.65) rTL. Cord blood n-6 PUFA was associated with longer (β=0.15; 95% CI: 0.050, 0.26) rTL. Further analyses revealed linoleic acid in maternal blood and arachidonic acid in cord blood as the main drivers of the n-6 PUFA associations. No associations were observed for THg and PUFA with rmtDNAcn. DISCUSSION:Our results indicate that prenatal THg exposure and PUFA status are associated with rTL later in childhood, although not consistently aligned with our initial hypothesis. Subsequent research is needed to confirm this finding, further evaluate the potential confounding of fish intake, and investigate the underlying molecular mechanisms to verify the use of rTL as a true biomarker of THg exposure. https://doi.org/10.1289/EHP14776.

Organophosphate esters (OPEs) are replacement flame retardants that have been implicated as metabolic disruptors and linked to birth size across a number of epidemiologic studies. Little is known about how OPEs impact maternal weight and body composition from pregnancy through the postpartum period. We measured OPE metabolites in mid-pregnancy urine samples from participants in a pregnancy cohort study based in Rochester, NY, USA. We calculated total gestational weight gain (GWG) based on clinical records (n = 278) and additionally measured weight retention and body fat percentage through bioelectric impedance at 6 (n = 205) and 12 months postpartum (n = 167). We fitted adjusted linear and logistic regression models examining OPE concentrations in relation to the outcome measures and secondarily, fitted models stratified by earliest pregnancy BMI (< 25 kg/m2 versus ≥ 25 kg/m2). In main models, most associations were null. Several highly prevalent OPEs such as bis(1,3-dichloro-2-propyl) phosphate (BDCPP; β: -1.02 lbs 95

Rationale: In 2017, introduction of Tier 3 light duty vehicles with reduced emissions began in NY State, with declining PM2.5 concentrations statewide. We hypothesized that Tier 3 vehicle controls would result in a reduction in the rates of hospitalization and emergency department (ED) visits for respiratory syncytial virus (RSV) associated with increased PM2.5. Methods: From the Statewide Planning and Research Cooperative System (SPARCS), we retained adult and pediatric patients hospitalized or having an ED visit for respiratory syncytial virus (RSV) living within 15 miles of the Buffalo, Rochester, Albany, Bronx, Manhattan, or Queens air quality monitoring sites. Using a case-crossover design and conditional logistic regression, we estimated the excess rates (ER) of RSV hospitalizations and ED visits associated with increased ambient PM2.5 concentrations in the previous 0-6 days in relation to age and sex. We then evaluated whether these relative rates differed in the period prior to the Tier 3 introduction (2014-2016) or after (2017-2019). Results: We observed a non-statistically significant increase in the rate of hospitalizations for RSV demonstrated in males within all age subgroups in 2017-2019 compared to 2014-2016. Specifically, adult males had 21.8% increased rate of RSV hospitalizations (95% CI: -9.5, 63.7) during 2017-2019 compared to a 13% decreased rate of hospitalizations (95% CI = -31.6,10.8) in 2014-2016 associated with a 4.6 ug/m3 increase in PM2.5 in the 0-6 day lag period. A similar non-statistical increase in ED visits for RSV was observed in 2017-2019 period compared to 2014-2016. In female patients, there generally appeared to be a decreased rate of hospitalizations and ED visits associated with IQR increases in PM2.5 at all lag periods and there were no consistent differences between periods. Conclusions: Despite the early implementation period of Tier 3 vehicles with lower pollutant emissions in 2017-2019, we did not observe a reduction in excess rates of hospitalizations and ED visits for RSV in males and females. Unexpectedly, the rate of healthcare encounters for males appeared to increase in the early implementation period compared with the period prior to implementation. A potential susceptibility of males to the change in the toxicity per unit mass of the PM mixture after the Tier 3 standards may explain the different pattern of hospitalizations and ED visits when comparing the sex-specific results.

Introduction: The risk of respiratory infection associated with air pollution exposure is well established in both epidemiologic and experimental studies. However, the precise timing of the period of risk for this association remains an area of active research. Methods: A total of 590 patients were enrolled from a prospective cohort study examining improved diagnostics for adult patients hospitalized with acute respiratory infections. Viral or bacterial infections were confirmed by a four-member adjudication panel of three infectious disease specialists and one pulmonary and critical care medicine specialist, using clinical histories, imaging, serum biomarkers and microbiologic samples. Using a modified time-stratified case crossover design and conditional logistic regression models, we separately estimated the rate of viral and bacterial infections associated with increased particulate matter ≤ 2.5µm (PM2.5), black carbon, nitrogen dioxide (NO2) and carbon monoxide (CO) concentrations in the previous 1 (lag days 0-6), 2 (lag days 7-13), and 3 weeks (lag days 14-20). To explore the timing of infection, we re-ran the analysis using patient reported symptom onset time instead of date of hospitalization. Results: Excess rates of viral infection hospitalization were generally largest for these traffic related pollutants at lag days 0-6, next largest at lag days 7-13 and null at lag days 14-20 (Figure 1). Each 2.5 µg/m3 increase in PM2.5 in lag days 0-6 was associated with a 16% increase in the rate of viral infection (95% CI: -0.5%, 35.2%), while each 0.1 µg/m3 increase in BC was associated with a 29.6% increase (95% CI: 7.3%, 56.5%) in the rate of viral infection. There were similar findings with NO2 and CO. However, although not statistically significant, we found increased rates of bacterial infection hospitalizations associated with increases in PM2.5, BC and NO2 on lag days 14-20, but decreased rate on lag days 0-13. Analyses using the symptom onset date generally yielded similar results in terms of magnitude and direction of effect. Conclusion: Short term increases in PM2.5, BC, NO2, and CO concentrations were associated with an increased rate of viral infection hospitalization, and suggestions of associations with bacterial infection hospitalizations. These association between traffic pollution exposure and respiratory viral infection appear to be strongest in the one week prior to hospitalization, but three weeks prior to hospitalization for bacterial infection. Future research on the timing of exposure for specific respiratory infections is warranted.

Pregnant people are ubiquitously exposed to endocrine-disrupting phthalates through consumer products and food. The placenta may be particularly vulnerable to the adverse effects of phthalates, with evidence from animal models suggesting impacts on placental development and vascularization. We translate this research to humans, examining gestational exposure to phthalates and phthalate replacements in relation to novel markers of chorionic plate surface vascularization. Phthalate and phthalate replacement metabolites were measured in first trimester urine from pregnant participants in the Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort (n = 154). At delivery, placentae underwent specialized 2D and 3D digital imaging to quantify chorionic plate surface vasculature. Using weighted quantile g-computation mixtures methods as well as multivariable linear regression models examining individual metabolites, we evaluated associations with overall chorionic plate surface area and five chorionic plate surface vascular measures, adjusting for covariates. We additionally examined interactions with placental sex. Exposure to a phthalate mixture was associated with longer total arterial arc length (β = 9.64 cm; 95%CI: 1.68, 17.59), shorter mean arterial arc length (β = −0.07 cm; 95%CI: −0.14, −0.01), and more arterial branch points (β = 5.77; 95%CI: 1.56, 9.98), but not chorionic plate surface area. In models considering individual metabolites and their molar sums, results were strongest for the metabolites of Di-isobutyl phthalate (DiBP), Di-isononyl phthalate (DiNP), and Di(2-ethylhexyl) phthalate (DEHP). Associations with metabolites of phthalate replacements tended to be in the same direction but weaker. Few sex differences were observed. Gestational phthalate exposure may be associated with alterations in placental chorionic plate surface vasculature characterized by more branching and shorter segments. These alterations may have implications for placental perfusion and suggest a placental mechanism by which phthalates may impact fetal development.

We examined associations between seven source-specific PM 2.5 concentrations and rates of asthma and COPD hospitalizations and emergency department (ED) visits in New York State and compared the changes in excess rates (ERs) between pre- (2014-2016) and post-implementation (2017-2019) of the Tier 3 automobile emission controls on new vehicles policy. A modified time-stratified case-crossover design and conditional logistic regression were employed to estimate the ERs of asthma and COPD hospitalizations and ED visits associated with interquartile range (IQR) increases in source-specific PM 2.5 concentrations. The 7 PM 2.5 sources were spark- ignition emissions (GAS), diesel (DIE), biomass burning (BB), road dust (RD), secondary nitrate (SN), secondary sulfate (SS), and pyrolyzed organic rich (OP). Residual PM 2.5 (PM2.5 - specific source [e.g., GAS]), daily temperature, relative humidity, weekday, and holidays were included in the model. IQR increases in GAS, SS, RD, BB, and SN were associated with increased ERs of asthma ED visits (highest ERs: 0.5 %-3.1 %), while a negative association was observed with DIE and OP. The rate of asthma hospitalizations was associated with increased RD concentrations (ERs: 1.3 %-1.7 %). Both COPD ED visit and hospitalization rates were associated with increased OP (ERs: 2.1 %-3.4 %), and increased SS was positively associated with COPD ED visits (ER = 3.8 %). In summary, after Tier 3 implementation (2017-2019), we found lower ERs for COPD admissions associated with BB, RD, SN, and SS compared to 2014-2016. However, rates of asthma ED visits associated with source-specific PM 2.5 concentrations were generally higher for all sources, except DIE, post- versus pre- implementation, requiring further research for validation.

BACKGROUND:Air pollution exposure during pregnancy has been associated with reduced fetal growth and birth weight, but mechanisms mediating this association are not well understood. OBJECTIVES:We examined whether pregnancy air pollution exposures were associated with altered placental vascularization. METHODS:We studied pregnant women (N = 163) from the UPSIDE cohort study, part of the Environmental Influences on Child Health Outcomes (ECHO) Study. Using placenta photographs taken at birth (gestational weeks 37-42), we derived seventeen chorionic plate surface vessel outcomes in 7 groups: arterial area, arterial branches, arterial arc length, arterial endpoint distance to perimeter, arterial branch angle, arterial tortuosity, and artery-vein distances. Distributed lag nonlinear models were used to determine if/when gestational week mean PM2.5 and NO2 concentrations were associated with the seventeen chorionic plate surface vessel outcomes. RESULTS:Placental measures were more strongly associated with weekly NO2 than PM2.5. Higher early-pregnancy NO2 concentrations were associated with lower measures of the arterial area and arterial endpoint distance to perimeter groups, and greater measures of the arterial tortuosity group (e.g., each 9-ppb increase in NO2 concentration in gestational weeks 0-12 was associated with lower arterial surface area; cumulative β = -1.46 cm2; 95 % CI = -2.73, -0.19). Higher NO2 in late-pregnancy was associated with increased measures of the arterial area, arc length, tortuosity, and artery-vein distances groups, and decreased measures of the arterial branch group (e.g., 9-ppb increases in NO2 concentration in gestational weeks 18-37 were associated with lower numbers of arterial generations; cumulative β = -1.30 generations; 95 % CI = -2.22, -0.38). CONCLUSION:Residential traffic pollution exposure in early-pregnancy was associated with altered chorionic surface arterial vasculature, potentially leading to worse perfusion, while late-pregnancy positive associations may represent a compensatory response.

Air pollution exposure during pregnancy has been associated with reduced fetal size and birth weight, but the sensitive exposure windows for these associations are not well established. We examined the association between gestational air pollution exposure and altered fetal size (femur length, biparietal diameter, head circumference, abdominal circumference, estimated fetal weight), measured in mid-pregnancy (week 20) and late-pregnancy (week 34), and attained size at birth (Z-scores of birth weight, length, and head circumference). Within the UPSIDE cohort study (N = 312 pregnant women) in Rochester, New York, we estimated residential, daily, ambient PM2.5 and NO2 concentrations using a spatial-temporal model. Distributed lag models estimated increases/decreases in each marker associated with interquartile range (IQR) increases in gestational week mean PM2.5 (3 µg/m3) and NO2 (9 ppb) concentrations, adjusting for child sex, maternal pre-pregnancy body mass index, race/ethnicity, and smoking during pregnancy. For birth measures, gestational age at birth was also included. Each IQR increase in NO2 in gestational weeks 18–33 was associated with decreased femur length at week 34 (-1.18 mm; 95

The introduction of Tier 3 light-duty vehicles with reduced emissions began in New York State (NYS) in 2017, with required compliance by 2025. We hypothesized that improved air quality during the early implementation of Tier 3 (2017-2019) would result in reduced rates of hospitalizations and emergency department (ED) visits for respiratory infection associated with increased PM2.5 compared to 2014-2016 (pre-Tier 3). Using data on adult patients hospitalized or having an ED visit for influenza, upper respiratory infection, culture-negative pneumonia, or respiratory bacterial infection, living within 15 miles of six air quality monitoring sites in NY, and a case-crossover design and conditional logistic regression, we estimated the rates of respiratory infection hospitalizations and ED visits associated with increased ambient PM2.5 concentrations in the previous 0-6 days and each week thereafter up to 1 month. Interquartile range (IQR) increases in PM2.5 in the previous 6 days were associated with 4.6% (95% CI: -0.5, 10.1) and 11.9% (95% CI = 6.1, 18.0) increased rates of influenza hospitalizations in 2014-2016 and 2017-2019, respectively. This pattern of larger relative rates in 2017-2019 observed at all lag times was only present in males hospitalized for influenza but not other infections or in females. The rates of respiratory infection visits associated with increased PM2.5 were generally not reduced in this early Tier 3 implementation period compared to 2014-2016. Limited fleet penetration of Tier 3 vehicles and differences in particle deposition, infection type, and sex by period may all have contributed to this lack of improvement.

Many types of health science learners, including clinical and translational scientists, students, researchers, and clinicians, seek to increase their knowledge of biostatistics. These learners are heterogeneous in their field, career stage and career focus. Based on the collective experience of an expert panel with over 115 years teaching statistics to health science learners, we propose a framework for considering the needs of health science learners motivated by their career goals. This framework defines four types of health science learners seeking statistical training: (a) consumers, (b) "milestone makers", (c) biomedical researchers with statistical support, and (d) biomedical researchers without statistical support. Each type of learner has different levels at which they need to understand statistical topics for their careers, such as when to use a particular statistical method or why a given method works; these differing levels of understanding are detailed in our proposed framework. Further, this framework identifies the expectations that each of these types of learners should have for gaining statistical knowledge in a single seminar, multiple seminars, a seminar series, an accredited course, or a certificate/degree program. Advantages and disadvantages of widely used educational formats for these learners are also described. From this work, health science learners seeking biostatistical training or those who are planning a training program for others can gain insight into identifying appropriate statistical training goals for the type of learner with which they identify. Statistical educators may also use these guidelines to help health science learners align expectations for various types of training.

Epidemiologic evidence has emerged showing an association between exposure to air pollution and increased risks of gestational diabetes mellitus (GDM). This study examines the effect of low-level air pollution exposure on a subclinical biomarker of hyperglycemia (i.e., HbA1c) in pregnant people without diabetes before conception. We measured HbA1c in 577 samples repeatedly collected from 224 pregnant people in Rochester, NY, and estimated residential concentrations of PM2.5 and NO2 using high-resolution spatiotemporal models. We observed a U-shaped trajectory of HbA1c during pregnancy with average HbA1c levels of 5.13 (±0.52), 4.97 (±0.54), and 5.43 (±0.40)% in early-, mid-, and late pregnancy, respectively. After adjustment for the U-shaped trajectory and classic GDM risk factors, each interquartile range increase in 10 week NO2 concentration (8.0 ppb) was associated with 0.09% (95% CI: 0.02 to 0.16%) and 0.18% (95% CI: 0.08 to 0.28%) increases in HbA1c over the entire pregnancy and in late pregnancy, respectively. These associations remained robust among participants without GDM. Using separate distributed lag models, we identified a period between 8th and 14th gestational weeks as critical windows responsible for increased levels of HbA1c measured at 14th, 22nd, and 30th gestational weeks. Our results suggest that low-level air pollution contributes to hyperglycemia in medically low-risk pregnant people.

Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM2.5), and nitrogen dioxide (NO2). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM2.5, NO2, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2 '-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM2.5 concentration (3.20 mu g/m3) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2nd (-7.99%, 95% CI: 13.8%, -2.23%) or 3rd trimester (-2.81%, 95% CI: 10.0%, 4.38%). The average cumulative PM2.5 exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM2.5 concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO2 exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM2.5 and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.

Fish and rice are the main dietary sources of methylmercury (MeHg); however, rice does not contain the same beneficial nutrients as fish, and these differences can impact the observed health effects of MeHg.