Summary:  Preterm birth is leading cause of death and disability in infants and children. Black and Latina women are at increased risk for preterm delivery compared to White women. While psychological stress has been shown to be associated with preterm birth, the mechanisms through which psychological stress causes preterm birth are unclear. The Saving Our Ladies from Early Births and Reducing Stress (SOLARS) study focuses on expanding our understanding of the relationship between psychological stress and preterm birth in 1,000 Black and Latina women in San Francisco, Oakland, and Fresno. The study has two primary research questions that examine the impact of individual, molecular, and social factors on psychological stress and preterm birth. The first question focuses on understanding patterns in all women in the study and the second focuses specifically on understanding why some women with high levels of psychological stress deliver preterm and some do not.

Introduction: More than one in ten Black and Latina pregnant women will have an infant born prematurely – that is, before 37 completed weeks of gestation. Infants born prematurely are at substantially increased risk for death within the first year of life and are more likely to have short- and long-term developmental and health challenges including, for example, intellectual delay, attention deficit hyperactivity disorder (ADHD), and asthma.

Rates of preterm birth in Black and Latina women have consistently been found to be 20 to 100% higher than in White women. Some data suggests that higher rates of preterm birth in women of color may be due to higher levels of stress – including higher levels of acute stress, accumulated lifetime exposure to stress, racism associated stress, and post-traumatic stress. Support for this explanation is driven by consistent findings showing an association between preterm birth and these different types of stress as measured by surveys, questionnaires and interviews.

Although studies have demonstrated specific links between multiple types of stress and preterm birth in women of color, what underlies this relationship remains unclear from a mechanistic point of view. For example, although cortisol is a key measure of biological stress, studies that have looked at the relationship between cortisol and preterm birth in women with both high and low levels of psychological stress have not observed a consistent link with preterm birth. The Saving Our Ladies from Early Births and Reducing Stress (SOLARS) study, funded by the UCSF California Preterm Birth initiative, is a prospective cohort study focused on expanding our understanding of the relationship between psychological stress, molecular signaling, and preterm birth in Black and Latina women in San Francisco, Oakland and Fresno.

Research questions: The SOLARS study focuses on two primary research aims including: 1) Evaluating whether individual, molecular, and social factors moderate or mediate the relationship between psychological stress and preterm birth in Black and Latina women (Aim 1); And, 2) Exploring the interrelationships of demographic, psychosocial, obstetric, and molecular risk and protective factors with preterm birth in Black and Latina women with high levels of psychological stress (Aim 2). Within Aim 1 we test three hypotheses: 1a, tests the hypotheses that social and individual risk and protective factors moderate the relationship between psychological stress and PTB;  Aim 1b, tests the hypothesis that individually-measured psychological resilience moderates the relationship between psychological stress and preterm birth; Aim 1c tests the hypothesis that molecular factors mediate the relationship between psychological stress and preterm birth. Whereas Aim 1 focuses on hypothesis testing, Aim 2 leverages advanced statistical techniques (i.e. machine learning) to determine whether or not there are factors within or across pregnancy that are associated with or predict  preterm birth in women with high levels of psychological stress. We believe that addressing these aims will lead to novel and actionable information that could eventually be translated into interventions for increasing gestational age and decreasing preterm birth in Black and Latina women in the geographies of focus and more broadly. In addition, we believe these efforts will contribute key data and biological resources for expanded and ongoing studies aimed at improving birth and developmental outcomes for women and children of color.

Addressing the SOLARS research aims requires intense work with participants and study partners throughout pregnancy and afterwards and includes the collection of survey data throughout pregnancy through the first year of life as well as biospecimens and hospital record data. Integration of the SOLARS study into the Eureka platform offers the opportunity to maximize engagement with women and study partners and we believe, could facilitate a more rapid cycling between discovery to interventions. In addition, use of the platform would offer the opportunity for developing nested studies that focus on other technologies including, for example, wearable activity and sleep tracking devices and contraction monitoring devices. In addition, leverage of the platform would eventually allow us to include more study sites across the United States and even worldwide as the effort progresses.

Study Sample: The SOLARS study will enroll 1,000 (500 Black and 500 Latina) women and their infants in San Francisco, Oakland and Fresno. The study pilot which aimed to assess methods for recruitment and retention and the acceptability of methods and measures among participants was conducted in March 2018-August 2018. We expect the full study to launch in the Fall of 2018 with enrollment extending over a three-year period (through 2021) and the full study extending through June 2023. Women are enrolled before 21 completed weeks of gestation at both UCSF and non-UCSF sites in all three geographies. All women included are self-identified as Black or Latina, are 18 years or older, are English and/or Spanish speaking, live or work full-time in one of the three geographies, and are expected to express a willingness to participate in all survey, biospecimen, and medical record review components of the study at all study time points in the prenatal period until the infant is one year of age. Women are not eligible for the study if they have active bipolar disorder or psychosis, if they are pregnant with a multiple gestation, if they are serving as birth surrogates, or if their pregnancy resulted from assisted reproductive technology.

Measurements: Participants complete online surveys and contribute biospecimens at up to 4 time points during pregnancy (11-14, 15-20, 24-26, 30-32). After birth, women complete surveys at 5-6 weeks, 6-months, and 12-months postpartum. Postpartum biospecimen collection is done at 5-6 weeks and 6-months. Hospital record review is done for all women from 1-year prior to pregnancy through 1-year after birth and for infants from birth through 12-months postpartum. Survey items focus on multiple components of psychological stress (e.g. childhood events, chronic strain, racism/discrimination), neighborhood and sociocultural factors (e.g. available healthcare, crime, poverty), individual factors (e.g. age, clinical factors, substance use/abuse), resiliency (e.g. mastery, self-efficacy, positive affect), and the current health status of the woman and infant (e.g. recent maternal and/or infant diagnoses). Required maternal biospecimen collection across time points include blood, urine and saliva. Molecular measures in biospecimens across time points include measures of the direct molecular stress response (cortisol and corticotropin-releasing hormone), measures of the immune response (cytokines, chemokines) and measures of placental health and growth (e.g. pregnancy-associated-protein-plasma protein A, nerve growth factor). We will also measure telomere length and target genetic markers (SNPs) with known associations to stress and/or preterm birth as well as lipids, proteins, metabolites and epigenetic signals in order to explore whether these pathways yield any useful information related to the link between stress and preterm birth. It is our belief that the Eureka platform would help facilitate all the survey measurement and hospital record review components of the study as well as online enrollment across sites and data visualization. We also believe that the Eureka platform might provide real-time specimen tracking capability across sites and might eventually provide a seamless way to share data with participants and partners.

Team: It is important to note that SOLARS study was designed from a reproductive justice perspective.This study was conceptualized, designed, and executed in a deeply engaged way with women of color serving in key leadership positions throughout the project. Project coordinators, graduate student researchers, and research assistants have been intentionally chosen to maximize the success of recruiting medically underserved women of color. We believe the integrity of the science and the quality of the data and their analyses are impacted by who, how, and why data are being collected.

The SOLARS team includes investigators across several schools and departments at UCSF and also includes investigators at UC Berkeley, UCSD, Stanford University, the University of Iowa, Cincinnati Children’s Hospital, and Fresno State University. The Primary Investigator on the study is Laura Jelliffe-Pawlowski, PhD – Director of Discovery and Precision Health within the UCSF California Preterm Birth Initiative. Dr. Jelliffe-Pawlowski has worked in the field of preterm birth for nearly two decades and is also the Mother of a daughter born preterm. Brittany Chambers, PhD, is one of two Co-Primary Investigators on the study and is an Assistant Professor in Epidemiology & Biostatistics at UCSF. Dr. Chambers’ research focuses on understanding the links between racism and preterm birth. Anu Gomez, PhD, is the other Co-Primary Investigator on the study and is an Assistant Professor in Sociology in the UC Berkeley School of Sociology. Dr. Gomez’ research focuses on understanding women’s contraception choices and on better understanding the reproductive experiences of Latina women.

Co-Investigators across UCSF include Dr. Larry Rand who is also the Primary Investigator of the UCSF California Preterm Birth Initiative, Drs. Monica McLemore, Elena Flowers, Kord Korber and Anatol Sucher in the School Nursing, Drs. Elizabeth Rogers and Matt Pantell in the Department of Pediatrics, Drs. Nancy Adler, Elissa Epel, and Jen Felder in the Department of Psychiatry, Dr. Nisha Parikh in the Department of Cardiology, and Dr. Charles McCulloch in the Department of Epidemiology & Biostatistics. This UCSF team works with closely with co-investigators at other institutions (Mike Snyder, PhD, at Stanford University, Christina Chambers, PhD at UCSD, Kelli Ryckman, PhD at the University of Iowa, Lou Muglia, MD, PhD, at Cincinnati Children’s Hospital, and Tania Pacheco, PhD at Fresno  State University). This transdisciplinary team also partners closely with women with lived experience and with community based organizations and clinics in San Francisco, Oakland and Fresno. The SOLARS team has a long-standing and ongoing relationship with the Community Advisory Board (CAB) of the California Preterm Birth Initiative. This CAB is composed mostly of Black and Latina women from San Francisco, Oakland and Fresno. All of the women on the CAB have either had a child with preterm birth or work closely with women at increased risk for preterm birth. These women have provided key input and suggestions at all phases of the SOLARS study and it is anticipated that they will remain involved as the study progresses. The study team also works closely with several organizations that serve low income women in one or more of the geographies of focus (e.g. Black Infant Health, La Clinica De La Raza). These partners assist with recruitment of women through their programs and provide feedback on study materials and methods.

Funding and Sustainability: The SOLARS study is funded by the UCSF California Preterm Birth Initiative. The UCSF Preterm Birth Initiative was funded by at $100 million gift from Marc and Lynn Benioff and Bill and Melinda Gates in 2015 and includes both a California arm and an East Africa arm. The California arm of the initiative will provide funding to the SOLARS project through fiscal year 2022-2023. Investigators are also seeking funding through the NIH and other entities to augment initiative costs and expand on the established research goals and infrastructure. It is also notable that the Eureka platform might eventually allow us to include women in Africa and other global locations in the study.

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