Research Areas.

Methodology: Measurement, Recruitment, Sampling, Study Design, and Analyses

Faculty Lead: Matthew Fox

Faculty active in this cluster: Alana Brennan, Ann Aschengrau, Anthony Rosellini, Avron Spiro, Bernard Harlow, Collette Ncube, Eleanor Murray, Jacob Bor, Jaimie Gradus, Jennifer Weuve,  Kenneth Rothman, Koichiro Shiba, Lauren Wise, Leonardo Martinez, Marcia Pescador Jimenez, Maria Glymour, Martha Werler, Mary Willis, Salma Abdalla,  Samantha Parker Kelleher,  Ziming Xuan

Research methods are central to epidemiology and methodology is the largest research cluster within the department, with the majority of faculty tackling one or more methodologic challenges in their work. Epidemiologic methods are a long-standing strength of the department, with two of the leading textbooks in the field authored by our faculty (Aschengrau, Rothman) and many additional textbook chapters authored by faculty. Dr. Fox is among the preeminent scholars in measurement error and quantitative bias analysis and has published two editions of a textbook on these methods. Two cohorts led or co-led by departmental faculty (PRESTO and the BWHS) have established field-standards for novel recruitment methods. These recruitment methods address two of the most important challenges in field epidemiology: increasing sample size of individuals when there is no sampling frame, and recruiting individuals underrepresented in research. Research in PRESTO was complemented by systematic evaluation of potential biases introduced by the recruitment approach and further research to enhance the types of data that could be collected. For example, in a particularly innovative set of projects, PRESTO embedded randomized trials within the observational cohort. Measurement innovations are drawing on high-density data flows such as ongoing blood pressure monitors, electronic health record data, online panel data fielded for measurement harmonization, and spatial data, linked to outcomes assessed in cohorts or in administrative data. Machine learning approaches are being used to identify strong predictors of health outcome, particularly in mental health. Study design innovations include evidence triangulation across econometric approaches (e.g., instrumental variables, regression discontinuity designs), innovative approaches to conventional epidemiologic studies (e.g., novel confounder control methods like G-methods and marginal structural models) and integration of randomization into long-term observational studies. As the field moves to more computationally intensive and data-driven analytic approaches, department faculty are advancing methods in both causal inference and machine learning (Gradus, Murray, Rosellini, Shiba).

Externally funded research within this cluster often has a strong applied bent, with a focus on solving methodologic problems in a specific area.  Examples include: 

  • The Methods in Longitudinal research on Dementia (MELODEM) Initiative: an NIA-funded workshop grant providing a platform for developing and disseminating research methodologies for improved cognitive aging and dementia research. The workshop has also served as a venue to identify and support emerging scholars as they engage with dementia research. (PI: Weuve)
  • Pregnancy Study Online (PRESTO): This extremely influential web-based North American cohort of pregnancy planners addresses key methodologic challenges in research on fertility, including misclassification, selection bias, and reverse causation. The cohort’s prospective design, cost-efficient web-based infrastructure for participant recruitment and follow-up, geographic and racial/ethnic heterogeneity make it a model for the future of cohort-based research. (PI: Wise)

Examples of recent published scholarship in this area include:

  • Fox MP, MacLehose RF, Lash TL. SAS and R code for probabilistic quantitative bias analysis for misclassified binary variables and binary unmeasured confounders. Int J Epidemiol. 2023 Oct 05; 52(5):1624-1633. PMID: 37141446.
  • Murray EJ, Carr KC. Measuring Racial Sentiment Using Social Media Is Harder Than It Seems. Epidemiology. 2024 Jan 01; 35(1):60-63. PMID: 37756311.
  • Rosellini, A. J., & Brown, T. A. (2021). Developing and validating clinical questionnaires. Annual Review of Clinical Psychology, 17, 55-81.
  • Jimenez MP, Aris IM, Rifas-Shiman S, Young J, Tiemeier H, Hivert MF, Oken E, James P. Early life exposure to greenness and executive function and behavior: An application of inverse probability weighting of marginal structural models. Environ Pollut. 2021 Dec 15; 291:118208. PMID: 34740291.
  • Schwartz GL, Maria Glymour M. Bridging the Divide: Tackling Tensions Between Life-Course Epidemiology and Causal Inference. Annual Review of Developmental Psychology. 2023 Aug 24;5.
  • Jiang T, Gradus JL, Rosellini AJ. Supervised machine learning: a brief primer. Behavior Therapy. 2020 Sep 1;51(5):675-87.
  • Shiba K, Daoud A, Kino S, Nishi D, Kondo K, Kawachi I. Uncovering heterogeneous associations of disaster‐related traumatic experiences with subsequent mental health problems: A machine learning approach. Psychiatry and clinical neurosciences. 2022 Apr;76(4):97-105.

Example Project: Internet-based study of time to pregnancy and miscarriage

This NIH-funded prospective cohort study is recruiting Danish and North American women via the internet to study risk factors for delayed time to pregnancy and miscarriage. Over 14,000 women have enrolled so far and are being followed for up to twelve months or until they become pregnant. An additional 1,600 male partners have been enrolled to obtain male factor data. The primary risk factors of interest include dietary intake, medication use, environmental toxins, and male factors. We have published on caffeine and alcohol consumption, smoking, medication use, physical activity, depression and body mass index. The extensive system of medical registries in Denmark, including birth, medication, and medical registries allow for data linkage to assess the validity of the using the internet for epidemiologic research and to study other health outcomes. Birth registry linkage in selected US states and Canadian provinces is underway, permitting the assessment of adverse birth outcomes. Epidemiology faculty: Elizabeth Hatch, Lauren Wise, and Ken Rothman

Example Project: A Conceptual Model for the Design and Interpretation of Biomarker Studies

Observational studies are often used to identify biomarkers that could stratify patients in terms of risk of cancer progression, and therefore inform subsequent management decisions. However, the selection of the appropriate patient populations for these studies, particularly with respect to whether patients have been treated or untreated, is not always tied to the specific clinical question of interest. We developed a framework for designing and interpreting biomarker studies of prostate cancer, the ABC Model of Prostate Cancer. Ongoing studies will use the ABC Model to evaluate existing prostate cancer biomarker signatures, some of which are now commercially available, to inform clinical application.

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Health Equity: Structural and Social Determinants of Health

Faculty Lead: Maria Glymour,

Faculty active in this cluster: Koichiro Shiba, Yvette Cozier, Jonathan Jay, Salma Abdalla, Collette Ncube, Leonardo Martinez, Daniel Brooks, Ziming Xuan, Jacob Bor, Lauren Wise, Rhoda Au, Emilia Benjamin, Jennifer Weuve, Amelia Wesselink, Samantha Parker Kelleher, Sandro Galea,  Marcia Pescador Jimenez, Mary Willis

Social inequalities affect nearly every health outcome, and department faculty are considering both individual and structural social determinants of health. Half of the primary faculty in the department incorporate health equity as a component of their research. Research considers health equity along socioeconomic status, geography, and racial/ethnic identity and most importantly social policies. Social and structural determinants of health shape the distribution of many other exposures, including environmental risk factors, behavioral patterns, stress, and access to health care. Specific projects related to health equity include work on social inequalities in the perinatal period (Ncube, Parker, Wise, Wesselink), social and structural determinants of fertility (Ncube, Wesselink, Willis, Wise), major chronic conditions in adulthood (Cozier, Shiba), and healthy aging (Glymour, Jimenez, Shiba, Weuve). A distinctive feature of our Social and Structural Determinants cluster is the emphasis on rigorous research methods applied to health equity problems. By bringing the strongest methodologic approaches to our questions about health equity, we aim to deliver evidence that is most likely to translate to health improvements. 

Externally funded research within this cluster includes:

  • Understanding racial and ethnic disparities in preterm birth: a systems science approach. This research aims to address significant gaps in our understanding of how structural and intermediary determinants of health interact and function interdependently to generate and perpetuate racial/ethnic preterm birth disparities, as well as inform strategies to address these disparities. (PI: Ncube)
  • Postpartum remote blood pressure monitoring program: study of reducing severe maternal morbidity among Black and Latina women by incorporating patient experiences and systems science. Cardiovascular complications are the leading cause of postpartum maternal morbidity and are more common among Black and Hispanic women compared to White women. The proposed project will evaluate an innovative postpartum blood pressure monitoring program aimed at improving blood pressure management, decreasing health emergencies, and reducing population rates of cardiovascular related severe maternal morbidity among women of color. (PI: Parker)
  • An assessment of neighborhood and environmental determinants of subfertility in the Black Women’s Health Study. This study aims to assess the extent to which environmental and neighborhood-level exposures are related to time-to-pregnancy and infertility risk in Black women. This is the first study focused on structural determinants of infertility in Black women. (PI: Wesselink)

Examples of recent published scholarship in this area include:

  • Martinez L, et al. Global, regional, and national estimates of tuberculosis incidence and case detection among incarcerated individuals from 2000 to 2019: a systematic analysis. The Lancet Public Health. 2023 Jul; 8(7):e511-e519.
  • Nakagomi A, Tsuji T, Saito M, Ide K, Kondo K, Shiba K. Social isolation and subsequent health and well-being in older adults: A longitudinal outcome-wide analysis. Soc Sci Med. 2023 Jun; 327:115937. PMID: 37167920
  • Matthay EC, Glymour MM. Causal inference challenges and new directions for epidemiologic research on the health effects of social policies. Current Epidemiology Reports. 2022 Mar;9(1):22-37.
  • Willis MD, Orta OR Ncube C, Wesselink AK, Doan LN, Kirwa K, Boynton-Jarrett R, Hatch EE, Wise LA. Association between neighborhood disadvantage and fertility among pregnancy planners in the US. JAMA Netw Open. 2022 Jun; 5(6): e2218738. PMID: 35771576

 

Black Women’s Health Study (BWHS)

The BWHS is the largest follow-up study of the health of African-American women yet conducted. The purpose is to identify and evaluate causes and preventives of cancers and other serious illnesses in African-American women. Among the diseases being studied are breast cancer, colon cancer, hypertension, type 2 diabetes, uterine fibroids, systemic lupus erythematosus, rheumatoid arthritis, and sarcoidosis. The study began in 1995, when 59,000 black women from all parts of the United States enrolled through postal questionnaires. The women provided demographic and health data on the 1995 baseline questionnaire, including information on weight, height, smoking, drinking, contraceptive use, use of other selected medications, illnesses, reproductive history, physical activity, diet, use of health care, and other factors. The participants are followed through biennial questionnaires to determine the occurrence of cancers and other illnesses and to update information on risk factors. Completion of follow-up questionnaires by members of the 1995 cohort has exceeded 80% in each cycle of follow-up. Information on outcomes is validated through medical record review. Validation studies of diet, anthropometric measures, and physical activity have been completed. In a genetic component, saliva samples have been obtained from participants; DNA from the samples will serve as a resource for testing hypotheses about gene-environment interactions. Epidemiology faculty: Lynn Rosenberg, Julie Palmer, Yvette Cozier, Lauren Wise, Patricia Coogan, and Edward Ruiz-Narvaez.

SEE ALSO:

Coronary Heart Disease in US Black Women—entry under “Cardiovascular & Respiratory Research”

Chicago Health and Aging Project—entry under “Aging Research”

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Environmental Determinants of Health

Faculty Lead: Jennifer Weuve

Active faculty in this cluster: Mary Willis, Marcia Pescador Jimenez, Kenneth Rothman, Lauren Wise, Ann Aschengrau, Amelia Wesselink, Jonathan Jay, Avron Spiro

The physical environment and community infrastructure influence health via many pathways, and as the environment changes, so too do the consequences for health. The complexity of environmental exposures poses many epidemiologic challenges related to study design, data collection, and causal inference. Our faculty are leaders on methods to characterize exposures in the physical environment, including drinking water pollution (Aschengrau), traffic patterns (Willis), noise (Weuve), air pollution (Weuve, Wesselink), heat (Wesselink), greenspace (Jimenez), energy use (Willis), consumer product chemicals (Wesselink, Wise), infrastructure change (Jimenez, Willis), and occupational exposures (Weuve). Population growth, migration, and climate change will all drive new patterns of environmental exposure and therefore have important consequences for health. Faculty in this research cluster collaborate extensively with the Department of Environmental Health, and the Center for Climate and Health.. 

Examples of externally funded scholarship in this domain include:

  • Air Pollution And Noise Exposures In Relation To Dementia: From Brain Imaging Markers To Clinical Disease (PI: Weuve)
  • A Preconception Cohort Study on Oil and Gas Development, Fertility, and Pregnancy (PI: Willis)
  • A preconception cohort study of air pollution, fertility, and miscarriage (PI: Wise, Hatch)
  • Chronic kidney diseases of uncertain etiology (CKDu) in agricultural communities (CURE) research consortium – Scientific and Data Coordinating Center (Subaward PI: Brooks)

Examples of recently published scholarship:

  • Wesselink AK, Hystad P, Kirwa K, Kaufman JD, Willis MD, Wang TR, Szpiro AA, Levy JI, Savitz DA, Rothman KJ, Hatch EE, Wise LA. Air pollution and fecundability in a North American preconception cohort study. Environ Int. 2023 Nov; 181:108249. PMID: 37862861.
  • Zhang B, Weuve J, Langa KM, D’Souza J, Szpiro A, Faul J, Mendes de Leon C, Gao J, Kaufman JD, Sheppard L, Lee J, Kobayashi LC, Hirth R, Adar SD. Comparison of Particulate Air Pollution From Different Emission Sources and Incident Dementia in the US. JAMA Intern Med. 2023 Oct 01; 183(10):1080-1089. PMID: 37578757.
  • Willis MD, Buonocore JJ. Fossil Fuel Racism: The Ongoing Burden of Oil and Gas Development in the Shadows of Regulatory Inaction. Am J Public Health. 2023 Nov; 113(11):1176-1178. PMID: 37651657.
  • Doran CR, Aschengrau A. Prenatal and early childhood exposure to tetrachloroethylene-contaminated drinking water and the risk of poor sleep quality during adulthood: a retrospective cohort study. Environ Health 2022, 21:15.
  • Daneshvar DH, Nair E, Baucom Z, Rasch A, Abdolmohammadi B, Uretsky M, Saltiel N, Shah A, Jarnagin J, Baugh CM, Martin BM, Palmisano JN, Cherry JD, Alvarez VE, Huber BR, Weuve J, Nowinski CJ, Cantu RC, Zafonte RD, Dwyer B, Crary JF, Goldstein LE, Kowall NW, Katz DI, Stern RA, Tripodis Y, Stein TD, McClean M, Alosco ML, McKee AC, Mez J. Leveraging football accelerometer data to quantify associations between repetitive head impacts and chronic traumatic encephalopathy. Nature Communications 2023 Jun 20;14(1):3470. PMC10281995

Example Project: Effects of Endocrine Disrupting Chemicals (EDCs) on Fertility and Thyroid Hormones

With support from the National Toxicology Program, and grants from the Oak Foundation and NICHD, we are evaluating the association of several classes of EDCs, including phthalates, poly-flouro-alkyl substances, and phenols with fertility in our Danish and North American prospective cohorts of pregnancy planners.  We have also measured over 130 chemicals in a sub-study of our Danish cohort to describe levels and patterns of co-exposure in this population (Rosofsky et al, 2017).  With a pilot grant from BUSPH, we will be evaluating levels of EDCs during the preconception and pregnancy time periods with levels of maternal thyroid hormones.  Epidemiology faculty: Elizabeth Hatch and Lauren Wise; Environmental Health faculty: Patricia Janulewicz

Example Project: Validation of Portable Methods of Measuring Cumulative Exposures to Heavy Metals

Exposures to heavy metals at low levels over an extended period of time appear to be related to chronic disease health outcomes, such as cardiovascular and renal disease, later in life.  A critical challenge to identifying these effects is the lack of practical measures that capture exposures over the long term.  We are currently validating a portable x-ray fluorescence instrument for the purpose of in vivo quantification of lead in bone and both manganese and mercury in toenail.  Such a device, if shown to be accurate and precise, could be used for large-scale studies in almost any setting, including people’s homes.  Epidemiology faculty: Jennifer Weuve

Example Project: Health Impacts of Exposure to PCE-Contaminated Drinking Water *completed*

We have conducted a series of studies to investigate the health impacts of exposure to tetrachloroethylene (PCE)-contaminated drinking water. These studies have been conducted among residents of the Cape Cod region of Massachusetts where thousands of residents were exposed to PCE during the 1960s-1990s when it leached into the drinking water from vinyl-lined water pipes. Our research has focused on whether PCE exposure during pregnancy may have increased the risk of pregnancy loss or having a child with birth defects and whether exposure to PCE has influenced the long-term health of PCE exposed children.

We have found that exposure to PCE-contaminated drinking water during pregnancy does not appear to increase the risk of pregnancy loss, low birth weight or prematurity. Nor does it seem to increase the risk of learning problems in exposed children. However, our findings suggest that PCE exposure during pregnancy may increase the risks of having a stillborn child or a child born with oral clefts and neural tube defects. They also suggest that there may be behavioral health consequences later in life, such as drug abuse and an increased risk of bipolar disorder and post-traumatic stress disorder. SPH Investigators: Ann Aschengrau, Lisa Gallagher, Patricia Janulewicz, Thomas Webster, David Ozonoff, Roberta White, Janice Weinberg, Michael Winter

SEE ALSO: Chicago Health and Aging Project—entry under “Aging Research” above.

Example Project: Impact of Early Life Exposure to Environmental and Social Stressors

Tetrachloroethylene (PCE) is a solvent commonly used in metal degreasing, textile processing, and dry cleaning. Because it is often used in poorly controlled settings, it is a common ground water and Superfund site contaminant. Our prior research found that early life exposure to PCE-contaminated drinking water was associated with substance use during adolescence and adulthood. However, early life exposure to social stressors is widely thought to influence this behavior and so we are now conducting a retrospective cohort study to examine the combined impact of early life exposure to PCE-contaminated drinking water and social stressors on the subsequent occurrence of illicit drug use and unhealthy alcoholic beverage consumption. Epidemiology faculty: Ann Aschengrau

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Stress, Trauma, and Mental Health

Faculty Lead: Anthony Rosellini,

Active faculty in this cluster: Jaimie Gradus, Jennifer Weuve, Maria Glymour, Marcia Pescador Jimenez, Salma Abdalla, Yvette Cozier, Koichiro Shiba, Ann Aschengrau, Avron Spiro, Bernard Harlow, Eleanor Murray

This research cluster includes both psychosocial exposures and psychiatric outcomes. The creation of the Center for Trauma and Mental Health crystallized the department’s strength in these areas. Our scholarship encompasses challenging conventional narrow definitions of trauma and mental health (i.e., extending beyond DSM/ICD diagnostic codes), understanding the myriad health effects of individual and mass trauma, and evaluating how social and psychosocial adversity, including exposure to racism and other stressors, influences mental and physical health outcomes. The department’s faculty use exceptional data sets and collaborative efforts to conduct work that would not otherwise be possible, such as understanding the health consequences of having a family member die by suicide.  

 

Examples of current externally funded scholarship in this domain include:

  • Identifying Cardiotoxic Manifestations Of Posttraumatic Psychopathology: A Population-Based Longitudinal Investigation (PI: Gradus)
  • Testing The Effectiveness Of An Evidence-Based Transdiagnostic Cognitive Behavioral Therapy Approach For Improving HIV Treatment Outcomes Among Violence-Affected And Virally Unsuppressed Women In South Africa (PI: Fox)
  • Examining the Physical and Mental Health Outcomes of Suicide Loss (MPI: Rosellini/Gradus)
  • Exposure to Suicide Among Post 9/11 Veterans: Prevalence, Correlates and Treatment Needs (Site PI: Gradus)
  • Real-World Effectiveness of Long-Acting Injectable Versus Oral Naltrexone for Co-Occurring Posttraumatic Stress Disorder and Alcohol Use Disorder (Site PI: Gradus)
  • Suicidal risk modification by statin prescriptions in US Veterans with common inflammation-mediated clinical conditions- a controlled, quasi- randomized epidemiological approach. (Site PI: Gradus)

 

Examples of recently published scholarship in this area (*Denotes work led by a trainee):

  • Shiba K, Daoud A, Hikichi H, Yazawa A, Aida J, Kondo K, Kawachi I. Uncovering Heterogeneous Associations Between Disaster-Related Trauma and Subsequent Functional Limitations: A Machine-Learning Approach. Am J Epidemiol. 2023 Feb 01; 192(2):217-229. PMID: 36255224.
  • *Yamin N, Brown TA, Rosellini AJ. Longitudinal associations of chronic health stress and COVID-19-related anxiety among outpatients with anxiety and mood disorders. Clin Psychol Psychother. 2023; 30(5):1020-1028. PMID: 37073862.
  • Matthay EC, Smith ML, Glymour MM, White JS, Gradus JL. Opportunities and challenges in using instrumental variables to study causal effects in nonrandomized stress and trauma research. Psychological Trauma: Theory, Research, Practice, and Policy. 2023 Sep;15(6):917.
  • Sabbath EL, Willis MD, Wesselink AK, Wang TR, McKinnon CJ, Hatch EE, Wise LA. Association between job control and time to pregnancy in a preconception cohort. Fertil Steril. 2023 Nov 28. PMID: 38036244.
  • Gradus, J. L., Smith, M. L., Szentkúti, P., Rosellini, A. J., Horváth-Puhó, E., Lash, T. L., Galea, S., Schnurr, P. P., Sumner, J. A., Sørensen, H. T., (2023). Anti-hypertensive medications and PTSD incidence in a trauma cohort. Journal of Clinical Psychiatry, 84(5), 22m14767.
  • *Smith, M. L., Seegulam, V., Szentkúti, P., Horváth-Puhó, E., Galea, S., Lash, T. L., Rosellini, A. J., Schnurr, P. P., Sørensen, H. T., Gradus, J. L. (2023). Risk of psychopathology following traumatic events among immigrants and native-born persons in Denmark. Social Psychiatry and Psychiatric Epidemiology, 58(9), 1305-1316.
  • *Sampson, L., Gradus, J. L., Cabral, H. J., Rosellini, A. J., Fink, D. S., Cohen, G. H., Liberzon, I., Galea, S. (2023) Stressful life events and incident depression among U.S. military personnel. Social Psychiatry and Psychiatric Epidemiology, 58(7), 1009-1018.
  • *Jiang, T., Nagy, D., Rosellini, A. J., Horváth-Puhó, E., Keyes, K. M., Lash, T. L., Galea, S., Sørensen, H. T., Gradus, J. L. (published online ahead of print; 2023). Prediction of suicide attempts among persons with depression: A population-based case cohort study. American Journal of Epidemiology. doi:10.1093/aje/kwad237
  • Shiner, B., Park, J. A., Rozema, L., Hoyt, J. E., Watts, B. V., Gradus, J. L. (2023) Safety of Glecaprevir/Pibrentasvir for Hepatitis C in patients with posttraumatic stress disorder: A post-marketing surveillance study.  General Hospital Psychiatry, 84, 268-270.
  • Aschengrau A, Winter M, Shea MG. Associations between resilience promotion factors during childhood and drug use disorder. Addiction Substance Abuse 2023, (2(1):1-9.

Example Project: Examining the Physical and Mental Health Outcomes of Suicide Loss

The impact of suicide reaches well-beyond individual suicide decedents. For each suicide death, an estimated 135 people are exposed to the potential trauma of suicide loss. Research indicates that exposure to suicide loss can result in mental and physical health distress, with those experiencing adverse outcomes called “suicide loss survivors.” At the same time, the literature is severely limited by a lack of appropriate comparison groups, examining a limited number of outcomes without considering comorbidity, and focusing on one type of familial relation (e.g., spouses) while ignoring non-familial loss survivors (e.g., cohabitants). The goal of this project is to use Danish national registry data to document the mental and physical health outcomes and comorbidities among the population of individuals exposed to suicide loss over a 30-year period. We will determine if adverse outcomes are specific to suicide loss, or unexpected loss in general, and further examine how outcomes and comorbidities vary across relationship types (e.g., spouses, children, roommates) and sex.

Example Project: Mental Health and Service Utilization among Reserve and National Guard Forces

The reliance on U.S. Reserve and National Guard forces has become greater than ever during the conflicts in Iraq and Afghanistan through Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn. The purpose of this project is to assess mental health over time among a representative sample of Reserves and National Guard members within a causal framework that takes into account lifecourse experiences and circumstances together with combat history, other Reserve and National Guard experience (e.g. humanitarian activity), civilian traumatic event experiences, and genetic factors as determinants. The central goal is to identify modifiable factors that can foster resilience over time and hence may optimize mental health functioning and health behavior in these groups. This project is in collaboration with Uniformed Services University of the Health Sciences. Epidemiology faculty: Sandro Galea

Example Project: Hurricane Sandy Community Resilience Project

There is ample evidence that natural disaster experiences as well as characteristics of individuals shape postdisaster mental and behavioral health outcomes. Less is known about the characteristics of communities that promote postdisater resilience, and how community and individual characteristics work together to shape outcomes. Such information is crucial for community-level interventions that aim to promote recovery in the aftermath of disasters and mitigate risks of future disasters. The goal of this project is to assess community-level factors including economic development, information and communication, community competence, and social capital that promoted resilience in the aftermath of Hurricane Sandy so as to inform both ongoing recovery efforts and future disaster preparedness plans. Simulated agent-based models are built to demonstrate how manipulating key elements of community resilience may mitigate the consequences of disasters. Other organizations involved in this project include Montclair University and The Rand Corporation. Epidemiology faculty: Sandro Galea

 

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Infectious Disease Research

Faculty Lead: Bob Horsburgh

Alana Brennan, Benjamin Linas, Eleanor Murray, Jacob Bor, Leonardo Martinez, Maria Glymour,  Matthew Fox,

The department has cutting edge research in tuberculosis, HIV, and COVID and faculty collaborate on critical epidemiologic modeling projects to predict the trajectory of epidemics and generate resources for allocating resources to mitigate the impacts. Much of the research focuses on HIV as this has been a leading cause of infectious disease morbidity and mortality for the last thirty years. Dr. Fox’s work in South Africa seeks to use novel observational datasets and clinical trials to identify ways to improve outcomes on and access to HIV treatment. Tuberculosis, which accounts for roughly 1.5 million deaths globally each year and is a major contributor to antimicrobial resistance, is another area of strength within the department. Dr. Martinez focuses much of his work on the strong intersection between social vulnerability and infectious diseases, for example among incarcerated populations who are especially adversely impacted by infection. Dr. Martinez works on TB control in incarcerated and other high-risk populations, optimizing screening programs, developing core infrastructure and research tools to monitor changes in population burden of TB,  and on evaluating the long term adverse effects of TB infections in children. This research directly informs policies to reduce TB burden and inequalities. Department faculty have been heavily involved in epidemiologic research around the COVID epidemic. Dr. Murray worked on a highly influential paper in the New England Journal of Medicine on the effects of lifting universal masking mandates in schools on COVID transmission and demonstrated increased transmission associated with the change using novel methods for causal inference.

Examples of externally funded scholarship: 

  • Testing The Effectiveness Of An Evidence-Based Transdiagnostic Cognitive Behavioral Therapy Approach For Improving HIV Treatment Outcomes Among Violence-Affected And Virally Unsuppressed Women In South Africa (MPI: Fox)
  • Identifying Effective And Efficient Approaches To Tuberculosis Screening In Brazilian Prisons (PI: Martinez)
  • DRAMATIC Phase 2 Duration Randomized MDR-TB Treatment Trial (MPI: Horsburgh)

Examples of recently published scholarship:

  • Martinez L, Gray DM, Botha M, Nel M, Chaya S, Jacobs C, Workman L, Nicol MP, Zar HJ. The long-term impact of early-life tuberculosis disease on child health: a prospective birth cohort study. American Journal of Respiratory and Critical Care Medicine. 2023 Apr 15;207(8):1080-8.
  • Aschmann HE, Riley AR, Chen R, Chen YH, Bibbins-Domingo K, Stokes AC, Glymour MM, Kiang MV. Dynamics of racial disparities in all-cause mortality during the COVID-19 pandemic. Proceedings of the National Academy of Sciences. 2022 Oct 4;119(40):e2210941119.
  • Esra RT, Carstens J, Estill J, Stoch R, Le Roux S, Mabuto T, Eisenstein M, Keiser O, Maskew M, Fox MP, De Voux L, Sharpey-Schafer K. Historical visit attendance as predictor of treatment interruption in South African HIV patients: Extension of a validated machine learning model. PLOS Glob Public Health. 2023; 3(7):e0002105. PMID: 37467217.
  • Shumba K, Bor J, Nattey C, Gareta D, Lauren E, Macleod W, Fox MP, Puren A, Mlisana K, Onoya D. Record linkage without patient identifiers: proof of concept using data from South Africa’s national HIV program. Res Sq. 2023 May 15. PMID: 37292689.
  • Cowger TL, Murray EJ, Clarke J, Bassett MT, Ojikutu BO, Sánchez SM, Linos N, Hall KT. Lifting universal masking in schools—COVID-19 incidence among students and staff. New England Journal of Medicine. 2022 Nov 24;387(21):1935-46.

Tuberculosis

Boston University School of Public Health participates in TB research through four Federally-funded research networks, the Tuberculosis Trials Consortium (TBTC), the Tuberculosis Epidemiologic Studies Consortium, both supported by the CDC and the TB Research Unit (TBRU), and RePORT India, funded by NIH. These consortia design and conduct clinical trials of new drugs and regimens for the treatment and prevention of TB and perform Epidemiologic studies of TB disease and Latent TB Infection (LTBI).

BUSPH is also performing the PREEMPT Study, a multicenter prospective observational cohort study to identify the causes of emergence of resistance during therapy for treatment of MDR-TB, with study sites in India and Brazil and South Africa (funded by NIH). Through RePORT India, the Department is participating in an observational cohort study of TB in India, and through TBRU, we are participating in a household contact study of TB transmission in South Africa. Additionally, we are performing two cohort studies of TB in South Africa focusing on the effects of alcohol and drug use on TB (funded by NIH). Lastly, we are performing cost-effectiveness studies of TB and HCV (funded by CDC), and mathematical modeling of TB transmission (funded by NIH).

BUSPH has also partnered with Boston Medical Center and Brown/Lifespan in the Providence/Boston Center for AIDS Research (CFAR, founded by NIH), with a Scientific Working Group that addresses TB/HIV co-infection. Epidemiology faculty: C. Robert Horsburgh Jr.

ENHANCE: Evaluation of South Africa’s National Adherence Guidelines

To address high levels of loss to follow up from HIV care and treatment, South Africa intends to roll out a package of interventions as part of its National Adherence Guidelines. The package of interventions includes fast track initiation counseling for patients eligible for ART, enhanced adherence counseling for unstable patients, adherence clubs for stable patients, decentralized medication delivery for stable patients and early tracing of all patients who miss an appointment by two weeks. To evaluate the impact of this strategy, we will work with the National Department of Health in South Africa and the World Bank to assess the effectiveness of the five interventions in the minimum package. We will also estimate for each study site an overall “adherence guideline impact” to provide an indication of the effectiveness of the package as a whole. In addition, we will estimate the cost of each of the interventions compared to standard of care. Finally, we will describe the cascade of care for tuberculosis, hypertension, and diabetes, three other chronic diseases for which little information currently exists. To evaluate these interventions, we will work with the National Department of Health (which will implement the interventions) to randomize 24 clinics in 4 provinces 1:1 to receive the interventions or continue standard of care. All evaluations will use data routinely collected by the clinics, with no study interaction with subjects. A total of 6,680 patients will be enrolled and followed for up to 20 months to estimate short- and long-term outcomes. Epidemiology faculty: Matthew Fox

Anti-retroviral Treatment (ART) for HIV in Zambia and South Africa *concluded*

Zambia, Factors Influencing Enrollment in Treatment for HIV/AIDs: Despite Zambia’s rapid scale-up of antiretroviral therapy, the number of Zambians on ART is thought to be only about half to two-thirds of the number of those who are medically eligible. To identify barriers to and facilitators of ART-seeking among those medically eligible, a cross-sectional survey was conducted among 400 patients on ART (able to access care) and 400 patients accessing home-based care without ART (either not able, chose not, or poor access to care) in two rural and two urban sites in Zambia. Patients in home-based care for HIV/AIDS (who never initiated ART) perceived greater financial and logistical barriers to seeking HIV care and had more negative perceptions about the benefits of the treatment. Future efforts to expand access to antiretroviral care should consider ways to reduce these barriers in order to encourage more of those medically eligible for ART to initiate care.

South Africa, Use and Outcomes of Second-and-Third Line HIV Treatment: As South Africa continues its rapid expansion of access to first-line antiretroviral therapy (ART), more patients will need to be switched to second-line therapy as these first-line regimens fail, and eventually may need third-line treatment regimens. However, with little experience with second- and third-line treatments in resource-limited settings and their high costs, it is critical to evaluate whether these medications can be delivered effectively as part of a large-scale public health response to HIV. To date there have been only a limited number of such evaluations, as they require large databases to conduct a robust evaluation. To evaluate the need for and effectiveness of second- and third-line ART, we have analyzed data from several large clinical HIV treatment databases in South Africa, including the Themba Lethu Clinical HIV Cohort, the Right to Care Clinical Cohort and the IeDEA-SA cohort. Our findings show that most patients on second-line ART are alive, engaged in care and are achieving viral load suppression in the year after being switched. However, the need for both second- and third-line ART is increasing over time. These studies are among the first of their kind and suggest that these regimens can effectively be delivered to patients who fail first-line treatments in such settings but they come at an increased cost compared to first-line ART. Epidemiology faculty: Matthew Fox

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Aging and Chronic Disease Research

Faculty lead: Maria Glymour (Interim)

Faculty Active in this Cluster: Marcia Pescador Jimenez, Jennifer Weuve, Mary Willis, Phillip Hwang, Emilia Benjamin, Rhoda Au, Daniel Brooks, Megan Healey, Alana Brennan, Avron Spiro, Koichiro Shiba, Salma Abdalla

Via strong links with the Framingham Heart Study and other studies, the department has historically been a leader in cardiovascular disease and stroke (Hwang). Additional work centering the experiences of Black women and seeking to fill the historical gap in research on the drivers of health in Black women draws on the Black Women’s Health Study to evaluate risk factors for cancer, sarcoidosis, inflammatory bowel disease, and myriad other chronic conditions (Cozier, Healey). Several outstanding research projects related to Alzheimer’s Disease and dementia are also housed in the department, with faculty including Drs. Jimenez (environmental exposome and dementia), Hwang (novel measurements of dementia risk, and behavioral risk factors for dementia), and Weuve (noise and dementia, research methods and dementia). Research into the causes of kidney disease occurring among young agricultural and other manual laborers throughout Central America focuses on both environmental and genetic contributors (Brooks).

 

Examples of externally funded scholarship: 

  • Building an unbiased pooled cohort for the study of lifecourse social and vascular determinants of Alzheimer’s Disease and Related Disorders (MPI: Glymour) 
  • Air Pollution and Alzheimer’s Dementia: Neuropathologic and Olfactory Mechanisms in Multi-Ethnic Longitudinal Cohorts (MPI: Weuve)
  • Neurodegenerative diseases and the role of green space: A deep learning assessment (PI: Jimenez)
  • Physical activity over the adult life course and cognitive resilience to Alzheimer’s disease and related dementias (PI: Hwang)
  • Social networks over the adult life course and cognitive resilience (PI: Hwang)
  • Impact of midlife and late-life intake of flavonoid-rich fruits on dementia risk in the Framingham Heart Study (PI: Hwang)
  • Early detection and monitoring of Alzheimer’s disease and related dementia using non-semantic linguistic and acoustic features of speech derived from hearing aids (Subaward PI: Hwang)
  • Risk of cardiovascular disease following different manifestations of posttraumatic psychopathology in a trauma cohort (PI: Gradus)
  • Role of genetic susceptibility in the Central American kidney disease epidemic (MPI: Brooks)
  • Chronic kidney diseases of uncertain etiology (CKDu) in agricultural communities (CURE) research consortium – Scientific and Data Coordinating Center (Subaward PI: Brooks)

 

Examples of recently published scholarship:

  • Hwang PH, Ang TFA, De Anda-Duran I, Liu X, Liu Y, Gurnani A, Mez J, Auerbach S, Joshi P, Yuan J, Devine S, Au R, Liu C. Examination of potentially modifiable dementia risk factors across the adult life course: The Framingham Heart Study. Alzheimers Dement. 2023 Jul; 19(7):2975-2983. PMID: 36656649.
  • Hikichi H, Shiba K, Aida J, Kondo K, Kawachi I. Association between sense of coherence and health and well-being among older survivors of a natural disaster: a prospective outcome-wide study. Sci Rep. 2023 Sep 29; 13(1):16385. PMID: 37773258.
  • Anyane-Yeboa A, Buadu MAE, Khalili H, Cozier YC. Epidemiology of Inflammatory Bowel Disease in a Cohort of US Black Women. Inflamm Bowel Dis. 2023 Oct 03; 29(10):1517-1523. PMID: 36946376.
  • Delgado, IS, Outterson A, Ramesh V, Amador Sanchez AG, Boza AC, Lopez-Pilarte D, Amador Velázquez JJ, Friedman DJ, Brooks DR, Scammell MK, Wang C. Ethical considerations for genetic research in low-income countries: Perceptions of informed consent, data sharing, and expectations in Nicaragua. Eur J Hum Genet. Published online December 2023, https://doi.org/10.1038/s41431-023-01505-7.
  • Wang J, Buto P, Ackley SF, Kobayashi LC, Graff RE, Zimmerman SC, Hayes-Larson E, Mayeda ER, Asiimwe SB, Calmasini C, Glymour MM. Association between cancer and dementia risk in the UK Biobank: evidence of diagnostic bias. European Journal of Epidemiology. 2023 Oct;38(10):1069-79.

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Example Project: Chicago Health and Aging Project

The Chicago Health and Aging Project (CHAP), which began in 1993, is a community-based study of aging set on the south side of Chicago and comprising more than 10,000 older adults, 60% of whom are African American.  CHAP is perhaps best known for its source as an estimate of Alzheimer’s dementia prevalence in the US. Among the currently funded investigations set in CHAP are: studies of community exposure to noise and its relation to blood pressure and cognitive aging; a study of racial differences in cognitive aging; and a study of dementia trends. Work on the health effects of air pollution exposure in older adults is ongoing. Epidemiology faculty: Jennifer Weuve

Example Project: The e-Cognitive Health Initiative (e-CHI)

The e-CHI seeks to create a comprehensive, open-access, high quality brain health data resource. Anchoring this research initiative is the Framingham Cognitive Aging Study program that boasts arguably the richest database of its kind, with up to 7 decades of prospective health and lifestyle measures, along with available genetic and other biomarkers to relate to brain health. The longitudinal assessment of brain health includes an extensive battery of neuropsychological testing, as well as neuroimaging via MRI. More recently, the assessment of cognitive performance has also included digital capture, starting with voice (2005) and extending to written performance (2011). Additional efforts are underway to expand the work beyond what is possible within the Framingham Cognitive Aging Study. The vision is to create a platform from which to validate new e-health measures against known gold standards, and then build and implement a scalable, e-digital health solution that integrates use of wearable/mobile and smart home technologies, collecting data continuously in real time and in natural settings—potentially transforming our understanding of how the brain ages. Central to achieving the goals of the e-CHI is the building of an ecosystem of multi-disciplinary, multi-sector collaborators that together can catalyze groundbreaking discoveries for cognitive impairment prevention, inform policies for reducing the economic cost and healthcare burden generally associated with progressive dementing disorders, such as Alzheimer’ disease, and identify determinants of sustained lifelong cognitive health. Epidemiology Faculty: Rhoda Au

Example Project: Coronary Heart Disease in US Black Women

This is a recently funded study (K01) of selected adverse pregnancy outcomes, such as gestational diabetes and preeclampsia, as risk factors for coronary heart disease (CHD) in black women. An accumulating body of evidence on this topic exists in predominantly white populations, but there is a dearth of evidence among black populations, despite persistent racial disparities in CHD morbidity and mortality. Identifying risk factors for CHD during pregnancy can provide an early window of opportunity to identify women at high-risk of CHD and translate to improvements in prevention and intervention. The study will also address mediation by clinical risk factors for CHD, including chronic hypertension and diabetes, and modification by life course measures of individual-level and neighborhood-level social determinants of health. The study is being conducted within the Black Women’s Health Study at the Slone Epidemiology Center. Epidemiology faculty: Samantha Parker

Example Project: Long-term follow-up of individuals exposed to diethylstilbestrol (DES)

This multi-center prospective cohort study follows over 10,000 mothers, daughters, sons and third generation granddaughters who were exposed to the pregnancy drug, DES. DES was originally used to prevent miscarriage and preterm birth between the early 1940’s and 1971. Not only was it not effective in preventing pregnancy problems, but it was also found cause a rare vaginal cancer and other health problems in the daughters who were exposed in utero. Participants in this study are being followed for breast and other cancers, as well as reproductive problems such as infertility and early menopause. Epidemiology faculty: Julie Palmer, Elizabeth Hatch, and Lauren Wise.

Example Project: Health Advocates as a Vehicle to Improve Treatment for Smokers in Public Housing

Quitting smoking is the most important step that smokers can take to benefit their health. However, low-income smokers are less successful in quitting than higher-income smokers. If these socioeconomic disparities in smoking and smoking cessation rates persist, low-income smokers will bear an increasingly disparate burden of smoking-related morbidity and mortality. Therefore, interventions to improve the rate of smoking cessation among low-income smokers are urgently needed. Smoking cessation treatment programs such as telephone quitlines and clinic-based programs exist but are underutilized, particularly by low-income smokers. A group-randomized trial is being conducted among public housing residents to test whether the use of resident Community Health Advocates with special training in smoking cessation (Tobacco Treatment Advocates (TTAs) can improve (1) utilization of quitlines and clinic-based programs and (2) smoking cessation rates among smokers in public housing. Epidemiology faculty: Daniel Brooks.

The project described above is supported by the National Cancer Institute. To read more about this research project and other NCI funded tobacco control research, please visit www.cancercontrol.cancer.gov/tcrb .

Example Project: Prostate Cancer Screening in Mexico

Effective cancer screening policy requires robust evidence of screening test efficacy as well as an understanding of healthcare capacity, and political and cultural factors. Through a collaboration with the Instituto Nacional de Salud Publica (Institute of Public Health) in Mexico, we conducted a pilot study of male teachers in Mexico. Our results indicated that prostate cancer screening with prostate specific antigen (PSA) was frequently occurring outside of national recommendations and among younger men. Our ongoing study will help us to understand the outcomes of opportunistic prostate cancer screening in Mexico and develop recommendations for screening policy. Epidemiology faculty: Jennifer Rider

Example Projet: The Detection and Outcomes of Prostate Cancer in HIV-infected Men

HIV-infected persons have a higher risk of a variety of malignancies due to immunospuppression or other mechanisms, and the cancer burden in HIV-infected populations is increasing as more effective HIV therapy extends life.  However, HIV-infected men have consistently lower rates of prostate cancer than the general population. Funded by a pilot grant from BUSPH, we will compare data from HIV-infected and HIV-uninfected men to explore potential differences in prostate cancer detection with PSA according to HIV status, as well as characterize differences in tumor biology reflected in tumor mRNA expression. The results of this study will contribute to evidence-based screening and treatment recommendations for HIV-infected men. Epidemiology faculty: Jennifer Rider

Example Project: Biomarkers of prostate cancer progression

There are few established risk factors for the development or the progression of prostate cancer, which limits efforts aimed at both prevention and therapy. Using cohorts from the U.S. and Sweden with long-term follow-up and archival tumor specimens, our ongoing work aims to use expression of mRNA and protein to provide clues into disease etiology and identify therapeutic targets. Some of these analyses investigate specific pathways, such as cholesterol metabolism, while other studies aim to relate lifestyle factors to biological changes in the prostate in order to clarify disease mechanism. Epidemiology faculty: Jennifer Rider

Example Project:

Example Boston Collaborative Drug Surveillance Program (BCDSP) continues its work in the area of pharmacoepidemiology and drug safety. We are conducting several studies on a diverse set of questions including continued research in the area of hormonal contraceptives in relation to risks of venous thromboembolism (VTE). We are also conducting studies on

  1. Drugs to treat psoriasis and risk of infection
  2. Maternal antidepressant drug use, depression and risk of autism in the offspring
  3. Changes in MS outcomes following newer MS treatments, and
  4. Iodine exposure in young children and risk of hypoglycemia.

We are also conducting research on

  1. Quantifying the effects of quinolones on tendon rupture,
  2. The importance of idiopathic cases selection in drug safety studies, and
  3. Comorbidities in patients with vasculitis

Epidemiology faculty: Susan Jick.

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Reproductive, Perinatal, Gynecologic, & Developmental Epi

Faculty lead: Samantha Parker Kelleher,

Active faculty in this cluster: Lauren Wise, Amelia Wesselink, Mary Willis, Collette Ncube, Martha Werler, Bernard Harlow, Eric Rubenstein, Ann Aschengrau, Kenneth Rothman

The department hosts field-leading research on fertility (notably via the PRESTO study and considering both male and female contributions); women’s health (the SELF cohort focusing on uterine fibroids, research on menstruation and menopause); adverse birth outcomes (eclampsia, birth defects, stillbirths); gynecologic outcomes (e.g., vulvodynia); and determinants of health and flourishing of individuals with developmental disorders, e.g., Down Syndrome. In the past year, department faculty have published extremely important work about the effects of COVID-19 vaccines on fertility and miscarriages, while continuing their ongoing work on diverse determinants of fertility. Department faculty (Rubenstein, Weuve) are also using Medicaid data to better understand the health needs of people living with Down Syndrome and, in collaboration with a co-research team of individuals with and without Down Syndrome, are delivering critical evidence on the long-term health of individuals with Down Syndrome.

Examples of externally funded scholarship in this domain include:

  • An internet-based preconception cohort study in North America (PI: Wise)
  • A Prospective Study Of Male Factors, Fertility, And Pregnancy Outcomes (Pi: Wise)
  • Down Syndrome: Toward Optimal Trajectories And Health Equity Using Medicaid Analytic Extract (Ds-To-The-Max) (Pi: Rubenstein)
  • A Prospective Study Of Heat Exposure And Miscarriage (PI: Wesselink)
  • Early Life Course Of Children With Congenital Structural Heart Anomalies (PI: Werler)
  • Impact of Postpartum Remote Blood Pressure Monitoring on Maternal Morbidity (Pi: Parker)
  • An assessment of neighborhood and environmental risk factors for subfertility in the Black Women’s Health Study (PI: Wesselink)
  • Environmental risk factors for uterine fibroids: a prospective ultrasound study (PI: Wise)

Examples of recently published scholarship:

  • Wesselink AK, Hatch EE, Rothman KJ, Wang TR, Willis MD, Yland JJ, Crowe HM, Geller RJ, Willis SK, Perkins RB, Regan AK, Levinson J, Mikkelsen EM, Wise LA. A Prospective Cohort Study of COVID-19 Vaccination, SARS-CoV-2 Infection, and Fertility, Am J Epidemiol, 2022 Aug; 191(8), 1383–1395. 
  • Rubenstein E, Tewolde S, Michals A, Fox M, Wang N. Prevalence of Autism Among Medicaid-Enrolled Adults. JAMA Psychiatry. 2023 Oct 04. PMID: 37792361.
  • Willis MD, Harris L, Campbell EJ, Chaskes M, Sawyer E, Harleman M, Ritz B, Hill EL, Hystad P. A population-based cohort study of electronic tolling, traffic congestion, and adverse birth outcomes. Environ Int. 2023 Nov 27; 183:108355. PMID: 38056094.
  • Geller RJ*, Wesselink AK, Koenig MR, Eisenberg ML, Tucker KL, Hatch EE, Wise LA. Association of male fatty acid intake with fecundability among couples planning pregnancy. 2023 Aug; Hum Reprod 38(8): 1601-1612.

Example Project: Best Treatment Practices in Opioid Dependent Pregnant Women & Their Infants

Opioid agonist therapy with methadone or buprenorphine improves pregnancy outcomes in opioid dependent women by preventing withdrawal and relapse with opioids. However, preventing maternal opioid relapse and withdrawal requires exposing the fetus to these potent therapies, which can cause neonatal opioid withdrawal (neonatal abstinence syndrome, NAS). Rising rates of opioid use in pregnant women and NAS in their neonates are major public health concerns. Investigators from the Departments of Epidemiology, Biostatistics, Internal Medicine, Obstetrics & Gynecology, and Pediatrics of Boston University Medical Campus have collaborated to establish a large prospective cohort of mother-neonate pairs. Data collection is ongoing with women enrolled in care at Boston Medical Center. For women in the study, we collect a large array of maternal medical information, pregnancy and delivery data, and neonatal outcome data. Epidemiology faculty: Martha Werler and Susan Brogly (Adjunct)

Example Project: Long-term follow-up of individuals exposed to diethylstilbestrol (DES)

This multi-center prospective cohort study follows over 10,000 mothers, daughters, sons and third generation granddaughters who were exposed to the pregnancy drug, DES. DES was originally used to prevent miscarriage and preterm birth between the early 1940s and 1971. Not only was it not effective in preventing pregnancy problems, but it was also found cause a rare vaginal cancer and other health problems in the daughters who were exposed in utero. Participants in this study are being followed for breast and other cancers, as well as reproductive problems such as infertility and early menopause. Males are also being followed for cancer and cardiovascular disease. A sub-study is evaluating hormonal and epigenetic changes the daughters exposed in utero.  Epidemiology faculty: Julie Palmer, Elizabeth Hatch, and Lauren Wise.

Example Project: Risk factors for spina bifida in the era of folic acid fortification

When folic acid intake was established as a protective factor for the development of spinal defects in the mid-1990s, the US Public Health Service formally recommended that all women of childbearing age ingest 400 micrograms of folic acid daily.  To help women achieve this, the cereal grain supply has been fortified with folic acid since 1998.  Although the prevalence of spina bifida has dropped, an estimated 800 pregnancies are affected each year in the US to women who ingested at least the recommended amount of folic acid.  Using data collected by the Slone Epidemiology Center Birth Defects Study, associations between spina bifida and maternal exposures and illnesses in pregnancy are evaluated according to level of folic acid intake.  This CDC-sponsored project has identified found evidence of folic acid reducing increased risks of spina bifida associated with assisted reproductive technologies, fever, diabetes, use of nitrosatable medications, and use of opioids. Epidemiology faculty: Martha Werler

Example Project: Hemifacial Microsomia: From Gestation to Young Adulthood

Hemifacial microsomia is a craniofacial malformation characterized by asymmetric development of the cheek, chin, mouth, ear, and/or eye. A first ever, large-scale, multi-center study of pregnancy risk factors for this birth defect was launched in 1997.  Over 200 cases and 800 controls were enrolled from craniofacial centers across the US and Canada.  Vasoactive exposures in pregnancy were observed to increase risk.  Cases and controls were subsequently assessed at elementary-school ages and at adolescence for psycho-social and cognitive outcomes.  Cases were identified as having more behavior problems and neurocognitive deficits than controls, but the majority of cases score in the normal range.  Plans are underway to follow the cohort into young adulthood to identify predictors of resilience.  Epidemiology faculty: Martha Werler

Example Project: Prospective Studies of Uterine Fibroids in Black Women

Black Women’s Health Study (BWHS): Uterine fibroids are the primary indication for hysterectomy in the US. Black women are 2–3 times more likely to be diagnosed with uterine fibroids than white women, and they tend to have earlier onset and greater symptoms at the time of diagnosis. Established risk factors for fibroids do not fully explain this black-white discrepancy in rates. GENETICS STUDY: We have compared genetic loci of Black Women’s Health Study (BWHS) participants with and without fibroids in an attempt to identify genes potentially involved in the etiology of fibroids. A total of 2500 cases (fibroids) and 2500 controls (without fibroids) will be studied. Differences will also be examined according to age at onset and disease severity. The DNA for these analyses will be obtained from saliva samples that have been provided by BWHS participants. PSYCHOSOCIAL FACTORS: Recent evidence in white populations suggests that psychosocial stress can increase the risk of fibroids, possibly by causing chronic dysregulation of the hypothalamic-pituitary-adrenal axis and alterations in ovarian hormones that could affect fibroid risk. We have planned analyses of BWHS data to identify whether various psychosocial stressors—including adverse socioeconomic conditions across the lifespan, abuse victimization across the lifespan, depressive symptoms, and caregiver responsibilities—influence the risk of fibroids. SPH Faculty: Lauren Wise, Edward Ruiz-Narvaez, Julie Palmer, Lynn Rosenberg.

Study of Environment Lifestyle and Fibroids (SELF): Sex steroid hormones are involved in the pathogenesis of fibroids. Given that endocrine disrupting chemicals (EDCs) can alter the functioning of hormones, we will evaluate fibroid risk in relation to 3 classes of EDCs: phthalates, polychlorinated biphenyls (PCBs), and phenols. This study will use data and biospecimens from SELF, a NIEHS-funded prospective cohort study of 1,300 African American women aged 23-34 and free of fibroids at baseline (2010-2012). Questionnaire data were collected at baseline and subjects are being followed for 5 years. Every 20 months, blood and urine were collected, and ultrasounds were performed by trained sonographers to detect fibroids. Non-persistent chemicals (e.g., phthalates) will be measured at baseline, 20 months, and 40 months. Persistent chemicals (e.g., PCBs) will be measured at baseline only. This project has many strengths that overcome the limitations of prior studies: large sample size, prospective data collection, state-of-the-art EDC measurement, serial ultrasound screening for fibroids, analysis of repeated EDC measures, innovative statistical approaches for evaluating EDC mixtures, and control for multiple confounders. The study of African Americans, a high-risk population for EDC exposure and fibroids, will provide informative data on the effects of widespread pollutants on fibroids and seek explanations for the racial disparity in fibroid incidence. SPH Faculty: Epidemiology: Lauren Wise, Jennifer Weuve. Environmental Health: Michael McClean, Birgit Claus Henn.

Example Project: Environmental Risk Factors for Birth Defects and Stillbirths

Our current research is examining environmental risk factors for three types of birth defects (oral clefts, neural tube defects and male genital defects) and stillbirths stemming from placental dysfunction. Environmental factors under investigation in this case-control study include PCE-contaminated drinking water, traffic related air pollution, and ambient temperature extremes. SPH Investigators: Ann Aschengrau, Lisa Gallagher, Patricia Fabian, Michael Winter

See also: Internet-based study of time to pregnancy—entry under “Epidemiologic Methods Research and Ethics”

Example Project: Chronic Kidney Disease of Unknown Etiology in Nicaragua

This project is attempting to determine the causes of an unexplained epidemic of chronic kidney disease (CKD) in western Nicaragua that has led to significant health, economic, and social strains. SPH has been working as part of a World Bank-organized mediation process that has brought together a Nicaraguan sugar company and a group of ex-workers and widows who have been affected by CKD to address these problems. A team of epidemiologists, environmental health faculty, and nephrologists is carrying out a number of activities intended to evaluate the potential causes of the excess of CKD in the area and whether work practices or chemicals used at the company is at least partly responsible for the occurrence of the disease. To date, two reports have been issued: (1) a review of the evidence available, proposed hypotheses, and recommendations for research activities; and (2) an evaluation of the current work practices at the company and a review of the literature on the renal effects of the agrichemicals that have been used. Potential causes being investigated include occupational, environmental, medical, and behavioral factors.  Some of the activities planned or in process include a record-based retrospective cohort study, environmental sampling, blood and urine testing of 1200 current workers, a urinalysis study among adolescents, and kidney biopsies. Epidemiology Faculty: Daniel Brooks, Ann Aschengrau

Example Project: The Prevention of Lower Urinary tract Symptoms (PLUS) Consortium

The PLUS Consortium will identify promising strategies for promoting bladder health and reducing lower urinary tract symptoms (LUTS) and conditions in women throughout the lifespan. Using both qualitative and quantitative research strategies, the Consortium will obtain information about girls and women in various age groups including prevalence and characteristics of those with no history of any LUTS, prevalence and characteristics of those with various LUTS, and potential protective and risk factors including such things as past or current health conditions, history of medical procedures, and toileting behaviors. Information to inform health promotion and prevention interventions will be obtained including knowledge, attitudes, beliefs, cultural norms, and environmental influences related to bladder health behaviors. The focus will be on obtaining the necessary information to plan for future prospective observational studies, and bladder health promotion educational efforts with the ultimate goal of reducing LUTS and their impact on overall health. Epidemiology Faculty: Bernard L Harlow

Example Project: Immunological Predictors of Unexplained Vulvar Pain (Vulvodynia)

Vulvodynia (“dynia” is the Greek word for pain) is suffered by women of various ages, races and ethnicities all over the world but it is a relatively unknown and under-studied disorder.  A community-based study of the prevalence and etiological predictors of unexplained vulvar pain that began with a screening of over 30,000 women 18-40 years of age who were part of the administrative database of a large health care network in the Minneapolis/St. Paul metropolitan area to establish prevalence. Clinical examinations confirmed 234 cases with vulvodynia and 234 controls with no history of vulvar discomfort for which details on symptoms, treatment, demographic factors, and psychosocial scales, and biospecimens were collected.  The rich data set is unique for exploring the etiology of this devastating condition..  A current focus is on how immunological factors such as thymic function, the composition of the vaginal microbiome, and immunohistological markers within the vulvar tissue itself play a role in vulvodynia etiology.  Epidemiology Faculty: Bernard L Harlow.

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