The pregnancy research on inflammation, nutrition, & city environment: systematic analyses study (PRINCESA) cohort, 2009-2015.

The Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses Study (PRINCESA) cohort was set up to evaluate associations between air pollution and birth outcomes among pregnant persons in Mexico City. Specifically, the study was designed to improve air pollution exposure assessment and elucidate biological mechanisms underlying associations between maternal exposures and adverse pregnancy outcomes. Pregnant persons (all women) (N = 935) between ages 18-45 who lived and/or worked in metropolitan Mexico City, Mexico, from 2009 to 2015 and liveborn singleton infants (N = 815) of participants who completed follow-up were enrolled in the cohort. We followed participants monthly from enrollment to delivery and the following categories of data were obtained: demographic, medical and obstetric history, geo-referenced data, repeated measures on daily activity patterns, reported food intake, anthropometric, clinical and obstetric data, 20 serum and 20 cervicovaginal cytokines, and lower reproductive tract infection. Repeated ultrasound measures of fetal parameters and infant birth data are also included in the study's database. In addition, PRINCESA investigators calculated air pollution exposure measures for six pollutants measured by the Mexico City Atmospheric Monitoring System (SIMAT). These estimates utilize participants' addresses to account for spatial variation in exposure (nearest monitor, inverse distance weighting, and kriging) and are available daily during pregnancy for participants. To date, associations between environmental and nutritional impacts on maternal and child health outcomes have been evaluated. PRINCESA has a comprehensive database of maternal and infant data and biological samples and offers collaboration opportunities to study associations between environmental and other factors, including nutrition and pregnancy outcomes.

Particulate matter exposure, dietary inflammatory index and preterm birth in Mexico city, Mexico.

BACKGROUND: Particulate matter ≤10 µm in aerodynamic diameter (PM10) and diet quality are risk factors for systemic inflammation, which is associated with preterm birth (PTB). PM10 and a pro-inflammatory diet (assessed by the Dietary Inflammatory Index [DII®]) have been individually evaluated as causes of PTB and differences by offspring sex have been reported for the DII. However, additional studies are needed to evaluate joint effects of these associations to inform intervention efforts. OBJECTIVES: To evaluate the independent and joint effects of PM10 and energy-adjusted DII (E-DII) on PTB risks. METHODS: PM10 estimates were generated from daily citywide averages for 1216 pregnant women from three subcohorts of the Early Life Exposures in Mexico to Environmental Toxicants study using data from the Mexico City Outdoor Air Monitoring Network. Among a subset of participants (N = 620), E-DII scores were calculated using a validated food frequency questionnaire. Cox Proportional Hazards models were run for select periods during pregnancy and entire pregnancy averages for E-DII and PM10. We assessed for potential non-linear associations using natural splines. RESULTS: In adjusted models, PM10 exposure was associated with increased risks of PTB for a range of values (58-72 µg/m3) during the second trimester, while negative associations were seen during the second (≥74 µg/m3) and third trimesters (55-65 µg/m3). Analyses conducted using distributed lag models for periods closer to delivery (max lag = 90) did not show negative associations between PM10 exposure and preterm birth, and indeed positive significant associations were observed (estimates and figures). E-DII was not associated with PTB and there was no evidence of effect modification by infant sex. There was no evidence of interaction between PM10 and E-DII and the risk of preterm birth. DISCUSSION: Associations between PM10 and PTB in Mexico City varied over time and across levels of PM10. Our findings of negative associations in the second and third trimesters, which are contrary to the hypothesized relationship between PM10 and PTB, may be due to a number of factors, including live birth bias and the exposure period evaluated. Differences in results for the periods evaluated suggest that PM10 from shorter exposure windows may play a more proximal role in initiating preterm labor.

Repeated Measures of Cervicovaginal Cytokines during Healthy Pregnancy: Understanding "Normal" Inflammation to Inform Future Screening.

OBJECTIVE: This study aimed to describe characteristics of cervicovaginal cytokines obtained during pregnancy from women who subsequently delivered at term. STUDY DESIGN: We used repeated measures of 20 cervicovaginal cytokines, collected on average on a monthly basis, from the second to the ninth month of gestation among 181 term pregnancies in the Mexico City Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses cohort (2009-2014). Cytokines were quantified using multiplex assay. RESULTS: Cytokine distributions differed more between than within cytokines. Across trimesters, cytokines interleukin (IL)-1Ra, IL-1α, and IL-8 consistently had high concentrations compared with other measured cytokines. Cytokine intraclass correlation coefficients ranged from 0.41 to 0.82. Spearman's correlation coefficients among cytokine pairs varied but correlation directions were stable; 95.3% of the 190 correlation pairs remained either negative or positive across trimesters. Mean longitudinal patterns of log-transformed cytokines from Tobit regression varied across but less within cytokines. CONCLUSION: Although mean concentrations of cervicovaginal cytokines among term pregnancies were high, they were largely stable over time. The high cytokine concentrations corroborate that pregnancy is associated with an active inflammatory state. These characterizations may serve as a baseline for comparison to other obstetric outcomes, which may be helpful in understanding deviations from normal gestational inflammation.

Effects of PM10 Airborne Particles from Different Regions of a Megacity on In Vitro Secretion of Cytokines by a Monocyte Line during Different Seasons.

Several epidemiological studies have demonstrated that particulate matter (PM) in air pollution can be involved in the genesis or aggravation of different cardiovascular, respiratory, perinatal, and cancer diseases. This study assessed the in vitro effects of PM10 on the secretion of cytokines by a human monocytic cell line (THP-1). We compared the chemotactic, pro-inflammatory, and anti-inflammatory cytokines induced by PM10 collected for two years during three different seasons in five different Mexico City locations. MIP-1α, IP-10, MCP-1, TNF-α, and VEGF were the main secretion products after stimulation with 80 µg/mL of PM10 for 24 h. The THP-1 cells showed a differential response to PM10 obtained in the different sites of Mexico City. The PM10 from the north and the central city areas induced a higher pro-inflammatory cytokine response than those from the south. Seasonal pro-inflammatory cytokine secretion always exceeded anti-inflammatory secretion. The rainy-season-derived particles caused the lowest pro-inflammatory effects. We concluded that toxicological assessment of airborne particles provides evidence supporting their potential role in the chronic exacerbation of local or systemic inflammatory responses that may worsen the evolution of some chronic diseases.

Staying cool in a changing climate: Reaching vulnerable populations during heat events.

The frequency and intensity of hot weather events are expected to increase globally, threatening human health, especially among the elderly, poor, and chronically ill. Current literature indicates that emergency preparedness plans, heat health warning systems, and related interventions may not be reaching or supporting behavior change among those most vulnerable in heat events. Using a qualitative multiple case study design, we comprehensively examined practices of these populations to stay cool during hot weather ("cooling behaviors") in four U.S. cities with documented racial/ethnic and socio-economic disparities and diverse heat preparedness strategies: Phoenix, Arizona; Detroit, Michigan; New York City, New York; and Philadelphia, Pennsylvania. Based on semi-structured in-depth interviews we conducted with 173 community members and organizational leaders during 2009-2010, we assessed why vulnerable populations do or do not participate in health-promoting behaviors at home or in their community during heat events, inquiring about perceptions of heat-related threats and vulnerability and the role of social support. While vulnerable populations often recognize heat's potential health threats, many overlook or disassociate from risk factors or rely on experiences living in or visiting warmer climates as a protective factor. Many adopt basic cooling behaviors, but unknowingly harmful behaviors such as improper use of fans and heating and cooling systems are also adopted. Decision-making related to commonly promoted behaviors such as air conditioner use and cooling center attendance is complex, and these resources are often inaccessible financially, physically, or culturally. Interviewees expressed how interpersonal, intergenerational relationships are generally but not always protective, where peer relationships are a valuable mechanism for facilitating cooling behaviors among the elderly during heat events. To prevent disparities in heat morbidity and mortality in an increasingly changing climate, we note the implications of local context, and we broadly inform heat preparedness plans, interventions, and messages by sharing the perspectives and words of community members representing vulnerable populations and leaders who work most closely with them.

Structural racism, air pollution and the association with adverse birth outcomes in the United States: the value of examining intergenerational associations.

Structurally racist policies and practices of the past are likely to be a driving factor in current day differences in exposure to air pollution and may contribute to observed racial and ethnic disparities in adverse birth outcomes in the United States (U.S.). Non-Hispanic Black women in the U.S. experience poorer health outcomes during pregnancy and throughout the life course compared to non-Hispanic White women. This disparity holds even among non-Hispanic Black women with higher socioeconomic status. Reasons for this finding remain unclear, but long-term environmental exposure, either historical exposure or both historical and ongoing exposure, may contribute. Structural racism likely contributes to differences in social and environmental exposures by race in the U.S. context, and these differences can affect health and wellbeing across multiple generations. In this paper, we briefly review current knowledge and recommendations on the study of race and structural racism in environmental epidemiology, specifically focused on air pollution. We describe a conceptual framework and opportunities to use existing historical data from multiple sources to evaluate multi-generational influences of air pollution and structurally racist policies on birth and other relevant health outcomes. Increased analysis of this kind of data is critical for our understanding of structural racism's impact on multiple factors, including environmental exposures and adverse health outcomes, and identifying how past policies can have enduring legacies in shaping health and well-being in the present day. The intended purpose of this manuscript is to provide an overview of the widespread reach of structural racism, its potential association with health disparities and a comprehensive approach in environmental health research that may be required to study and address these problems in the U.S. The collaborative and methodological approaches we highlight have the potential to identify modifiable factors that can lead to effective interventions for health equity.

Associations between Air Pollution Exposure and Blood Pressure during Pregnancy among PRINCESA Cohort Participants.

High blood pressure (BP) is a risk factor for hypertensive disease during pregnancy. Exposure to multiple toxic air pollutants can affect BP in pregnancy but has been rarely studied. We evaluated trimester-specific associations between air pollution exposure and systolic (SBP) and diastolic BP (DBP). Ozone (O3), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), and particulate matter less than 10 and 2.5 µm in aerodynamic diameter (PM10, PM2.5) in the Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses (PRINCESA) study. Multipollutant generalized linear regression models with each pollutant and O3 were fit. Due to nonlinear pollution/BP associations, results are presented for "below the median" or "above the median", where the beta estimate is the change in BP at a pollutant's median versus BP at the pollutant's minimum or maximum, respectively. Associations varied across trimesters and pollutants, and deleterious associations (higher blood pressure with higher pollution) were found only at pollutant values below the median: for SBP with NO2 in the second and third trimesters, and PM2.5 during the third trimester, and for DBP, PM2.5, and NO2 in the second and third trimesters. Findings suggest that minimizing prenatal exposure to air pollution may reduce the risks of changes in BP.

Timing of Cervico-Vaginal Cytokine Collection during Pregnancy and Preterm Birth: A Comparative Analysis in the PRINCESA Cohort.

Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, is a major cause of infant morbidity and mortality. Inflammation is an important component in the physiopathologic pathway leading to PTB but results from cross-sectional studies on associations between inflammation, as measured by cytokines, and PTB are inconsistent. Timing of cytokine measurement during pregnancy varies between studies and may contribute to inconsistent findings. We investigated the effects of timing on associations between 16 cervico-vaginal cytokines (Eotaxin, IL-10, IL-12p40, IL-17, IL-1RA, sIL-2rα, IL-1a, IL-1ß, IL-2, IL-6, IP-10, MCP-1, MIP-1α, MIP-1ß, TNFα, and VEGF) and PTB among 90 women throughout pregnancy. We used logistic regression to compare associations between concentrations of cervico-vaginal cytokines from periods in pregnancy and PTB. Trimester 1 cytokines had the strongest positive associations with PTB; for example, OR = 1.76 (95% confidence interval: 1.28, 2.42) for IL-6. Second and third trimester associations were weaker but largely positive. IL-1α was the only cytokine with a negative association (trimesters 2, 3 and overall pregnancy). Strong first trimester associations between cytokines and PTB suggest that measuring cytokines early in pregnancy may hold promise for early identification of PTB risk. Variations in cytokine measurement during pregnancy may contribute to inconsistencies among studies.

Air pollution and inflammation: Findings from concurrent repeated measures of systemic and reproductive tract cytokines during term pregnancy in Mexico City.

BACKGROUND: Environmental exposures are associated with a number of outcomes including adverse pregnancy outcomes. Although inflammation is hypothesized to play a role, the mechanistic pathways between environmental exposures and adverse health outcomes, including associations between exposures and longitudinal measures of systemic and reproductive tract inflammation, need elucidation. OBJECTIVES: This study was conducted to evaluate whether exposure to air pollution is associated with immunologic responses in the systemic circulation and lower reproductive tract, and to evaluate whether systemic and reproductive tract immunologic responses are similar. METHODS: We quantified repeated measures of cytokines from cervico-vaginal exudates and serum obtained concurrently among 104 women with term pregnancies and estimated PM10 and CO exposure using the monitor nearest each participant's residence. Serum and cervico-vaginal cytokines were compared using Wilcoxon signed-ranks test and Spearman rank correlations for select gestational months. We used intraclass correlation coefficients (ICCs) to quantify reproducibility of cytokine measurements, and Tobit regression to estimate associations between air pollution and cytokines. RESULTS: Median cervico-vaginal levels of IL-6, Eotaxin, IP-10, MCP-1, MIP-1α, MIP-1ß, and TNFα were higher than corresponding serum cytokines, significantly so for IL-6 and IP-10. Cervico-vaginal and serum cytokines were not correlated, but cytokines from the same fluid were correlated. ICCs for most serum cytokines were ≤0.40, while ICCs were higher in cervico-vaginal cytokines (range 0.52-0.83). IP-10 and Eotaxin had the highest ICCs for both cytokine sources. In adjusted models, PM10 was positively associated with serum cytokines IL-6, IP-10, MIP-1ß and Eotaxin but inversely associated with cervico-vaginal cytokine TNFα, IP-10, MIP-1ß, MCP-1 and Eotaxin, controlling for false discovery rate. CO was inversely associated with cervico-vaginal TNFα, IL-6, MIP-1ß, MCP-1 and Eotaxin. CONCLUSIONS: Inflammatory processes are compartment-specific. Systemic inflammatory markers may provide information on immunologic processes and response to environmental exposures, but are not proxies for lower reproductive tract inflammation.

Strategies to reduce the harmful effects of extreme heat events: a four-city study.

Extreme heat events (EHEs) are becoming more intense, more frequent and longer lasting in the 21st century. These events can disproportionately impact the health of low-income, minority, and urban populations. To better understand heat-related intervention strategies used by four U.S. cities, we conducted 73 semi-structured interviews with government and non-governmental organization leaders representing public health, general social services, emergency management, meteorology, and the environmental planning sectors in Detroit, MI; New York City, NY; Philadelphia, PA and Phoenix, AZ-cities selected for their diverse demographics, climates, and climate adaptation strategies. We identified activities these leaders used to reduce the harmful effects of heat for residents in their city, as well as the obstacles they faced and the approaches they used to evaluate these efforts. Local leaders provided a description of how local context (e.g., climate, governance and city structure) impacted heat preparedness. Despite the differences among study cities, political will and resource access were critical to driving heat-health related programming. Upon completion of our interviews, we convened leaders in each city to discuss these findings and their ongoing efforts through day-long workshops. Our findings and the recommendations that emerged from these workshops could inform other local or national efforts towards preventing heat-related morbidity and mortality.

Air pollution, inflammation and preterm birth: a potential mechanistic link.

Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth.

Air pollution, inflammation and preterm birth in Mexico City: study design and methods.

Preterm birth is one of the leading causes of perinatal mortality and is associated with long-term adverse health consequences for surviving infants. Preterm birth rates are rising worldwide, and no effective means for prevention currently exists. Air pollution exposure may be a significant cause of prematurity, but many published studies lack the individual, clinical data needed to elucidate possible biological mechanisms mediating these epidemiological associations. This paper presents the design of a prospective study now underway to evaluate those mechanisms in a cohort of pregnant women residing in Mexico City. We address how air quality may act together with other factors to induce systemic inflammation and influence the duration of pregnancy. Data collection includes: biomarkers relevant to inflammation in cervico-vaginal exudate and peripheral blood, along with full clinical information, pro-inflammatory cytokine gene polymorphisms and air pollution data to evaluate spatial and temporal variability in air pollution exposure. Samples are collected on a monthly basis and participants are followed for the duration of pregnancy. The data will be used to evaluate whether ambient air pollution is associated with preterm birth, controlling for other risk factors. We will evaluate which time windows during pregnancy are most influential in the air pollution and preterm birth association. In addition, the epidemiological study will be complemented with a parallel toxicology invitro study, in which monocytic cells will be exposed to air particle samples to evaluate the expression of biomarkers of inflammation.