Inflammation During Pregnancy and its Association with Preterm Birth in Mexico City.

Preterm birth (PTB) is a global public health problem with significant short and long term effects. Preterm babies are at increased risk of neonatal mortality and long term morbidity. While the etiology of PTB is poorly understood, inflammation occurs frequently in the pathway between several identified risk factors and PTB. Inflammation is also a normal part of pregnancy. Therefore, longitudinal measures are required to evaluate when and what markers of inflammation are normal and what predict PTB. The objectives of this dissertation were to evaluate the expression of inflammatory biomarkers (specifically cytokines) during pregnancy, and to explore whether patterns of cytokine secretion can identify women at risk of PTB. Using longitudinal data from a pregnancy cohort in Mexico City, this dissertation 1) characterized 20 cervico-vaginal cytokines obtained during gestation and described cytokine patterns among 181 term births; 2) evaluated differences in concurrently measured systemic and reproductive tract cytokines, and evaluated the associations between air pollution exposure and serum and cervico-vaginal cytokines among 104 term births; and 3) compared cytokine expression between women who delivered term (n=78) and preterm (n=12); and evaluated associations between individual and patterns of cervico-vaginal cytokines at points in pregnancy and PTB. Among term births, mean cervico-vaginal cytokine concentrations were stable during gestation within cytokines but varied across cytokines; inflammation severity varied. Cervico-vaginal cytokines were uncorrelated with serum cytokines; air pollution was positively associated with serum but inversely associated with cervico-vaginal cytokines. Finally, cervico-vaginal cytokine concentrations differed between term and PTBs, and the first trimester was most predictive of PTB. This dissertation increases understanding of the role of inflammation and PTB. The range of cytokines in normal pregnancy is wide, such that deviation from ‘mean’ concentrations is an insufficient marker of risk; the effects of air pollution on these levels may be specific to serum or the cervico-vaginal cavity. Finally, early differences in cytokine levels between term and preterm births may be useful for risk identification. Future studies should use other cytokine categories, particularly ratios and inflammatory milieu, to assess for deviations from homeostasis, especially during the first trimester, to evaluate for preterm risk.PhDEpidemiological ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/120896/1/mabuxton_1.pd

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

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 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

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