PTBi-CA Research Award Recipients

Since 2016, PTBi California has distributed over $2 million in awards for 24 discovery and interventions research projects.

Discovery Research

Identifying biological drivers of preterm birth among women with insomnia

Aric Prather, PhD | Department of Psychiatry, UCSF School of Medicine

The goal of the proposed project is to identify the biological processes that lead women with insomnia to deliver preterm. Clinical insomnia negatively affects the immune system often leading to high levels of inflammation, which has been linked to preterm birth. Unfortunately, prior studies of sleep and preterm birth have focused on one or two biomarkers, even though preterm birth is complex and involves multiple biological pathways. To improve our understanding, we will comprehensively examine blood samples from 150 women, including women with and without insomnia who either experienced a preterm birth or delivered at term. These blood samples are directly linked to birth records and hospital discharge data via the California Biobank Program. Using cutting edge technology and advanced statistical methods, we will be able to determine which biological pathways are most associated with preterm birth among women with insomnia. Findings from this project will lead to a critical advancement in our understanding of how insomnia “gets under the skin” to affect preterm birth and highlight new biological targets for prevention of preterm birth among women with insomnia.

Testing exposure to local immigration enforcement as a structural determinant of preterm birth disparities in California counties

Jaqueline Torres, PhD | Center for Health and Community, UCSF School of Medicine

Although Latinas overall have similar or lower rates of preterm birth compared to non-Latina whites, there has been limited understanding about how preterm birth among Latinas might differ based on exposure to societal stressors. Enhanced local immigration enforcement efforts are one such societal stressor that may have negative health impacts for Latinas, as these efforts have been linked to widespread fear of arrest and deportation among Latino communities. Nationally, over half of foreign and U.S.-born Latinos report worrying about deportation for themselves or for family or community members. Our team will evaluate the impact of local immigration enforcement efforts from 2009 to 2015 on differences in preterm birth between Latina and non-Latina white women in California counties. We will use monthly data on arrests and deportations made within each county under the “Secure Communities” program in combination with California birth data and other county-level characteristics.

Persistent human cytomegalovirus infection of the amnion in preterm birth and intrauterine growth restriction

Takako Tabata, PhD | Cell & Tissue Biology, UCSF School of Dentistry

Human cytomegalovirus (HCMV) infection during pregnancy is a leading cause of birth defects and preterm birth, and African American and Hispanic women are at four- to five-fold greater risk for infection during reproductive years than white women, contributing to racial disparities in preterm birth. We discovered that epithelial cells of the amniotic membrane surrounding the fetus develop persistent infection, producing inflammatory cytokines that cause preterm labor. To prevent preterm birth in congenital HCMV infection, we identified factors that enable persistent infection and demonstrated that interfering with one of these factors –production of the anti-cell death protein survivin – selectively eliminates persistently infected cells. We propose to identify molecular pathways in the amniotic epithelium that enable persistent infection and preterm labor (Aim 1) and drugs that reduce persistent infection (Aim 2). This work has potential to reduce the risk of preterm birth, especially in communities disproportionately affected by HCMV.

Clinical and metabolomic characteristics of pulmonary hypertension and respiratory distress syndrome in infants <34 weeks of gestation and their predictive effect on chronic lung disease

Martina Steurer Muller, MD | Pediatrics, UCSF School of Nursing

Race and ethnicity specific perinatal risk factors for respiratory distress syndrome (RDS) and pulmonary hypertension (PH) in preterm infants are largely unknown. There is evidence that specific metabolic markers differ in these infants compared to controls. RDS and PH are often associated with development of chronic lung disease (CLD), a major contributor to morbidity and mortality of prematurity. Our aim is to investigate race and ethnicity specific clinical and metabolic risk factors for RDS and PH in preterm infants. For this purpose, we will use the database maintained by the California Office of Statewide Health Planning and Development. It contains detailed information on infant characteristics derived from linked hospital discharge records and birth and death certificates of all live born infants in California born between 2007-2012. All of these newborns had routine metabolic screening performed through the California Newborn Screening program (including amino acid levels, carnitine profiles and hormone levels) using a heel-stick blood draw in the first week of life. We will perform multiple regression to identify clinical and metabolic risk factors in infants with RDS and PH, then stratify the results by race/ethnicity. Insight into race and ethnicity specific clinical and metabolomic risk factors for RDS and PH might allow primary prevention and identify subgroups that benefit from early interventions.

Race/ethnicity and sociodemographic variation in resuscitation and outcomes of extreme prematurity in a population-based cohort in California

Elizabeth Rogers, MD | Pediatrics, USCF School of Medicine , James Anderson, MD | Pediatrics, UCSF School of Medicine

Multiple studies have shown socioeconomic and racial-ethnic disparities in outcomes of prematurity. We will be zeroing in on rural, suburban, and areas of Fresno County to look at differences in the survival and major morbidity of infants born <36 weeks’ gestation, stratified by race/ethnicity and socioeconomic status. To do this we will be utilizing data collected by the California Office of Statewide Health Planning and Development (OSHPD). The OSHPD birth cohort database contains detailed information on maternal and infant characteristics derived from linked hospital discharge, birth certificate, and death records, including all records for the mother and infant from 1 year before birth to 1 year after birth. Major morbidity is captured using ICD-9-CM codes for grade III or IV intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity requiring surgery; all of which have been associated with neurodevelopmental impairment.

Stress, resilience and coping in Hispanic women in Fresno: The SOLARS study expansion

Monica McLemore, PhD, MPH, RN | Family Health Care Nursing, UCSF School of Nursing , Anu Manchikanti Gomez, PhD, MSc | School of Social Welfare, University of California, Berkeley

Previous studies of preterm birth in Hispanic women and other women of color are limited by their cross-sectional study design, in which data on stress are frequently collected at a single, retrospective time point. The SOLARS study is distinguished by a prospective repeated measures design, where assessments and biomarker sampling will be conducted several times across a single pregnancy. Additionally, this study will assess whether coping and resilience have an impact on preterm birth during pregnancy by measuring the types of resilience that are specific to the study population. The present study is based in Fresno and has the potential to provide crucial new insights into differences among and between Hispanic women, as well as identify potential interventions for stress reduction, support for coping and mechanisms of resilience. A companion study of Black women in Oakland has already launched and will be expanded to include Hispanic women.

Exploring the dual burden of severe maternal morbidity and preterm birth in California

Audrey Lyndon, PhD, RN | Family Health Care Nursing, UCSF School of Nursing

For most families experiencing preterm birth, the infant(s)’ vulnerable health status will be the primary focus as the family adapts to this unexpected outcome. However, for a subset of families experiencing preterm birth, the mother also faces serious to potentially life-threatening complications. For these families, the burden of prematurity is compounded by the burden of the mother’s physical and emotional recovery from serious complications, as well as the partner’s emotional recovery from experiencing a situation where the health and potentially the lives of both the mother and the baby were at risk. The consequences of dual burden of severe maternal morbidity and preterm birth on the life of a young family may be profound. The purpose of this study is to explore the prevalence of this dual burden on families in California and in PTBi-CA geographies, including San Francisco and Fresno Counties and the city of Oakland.

Cumulative risk for preterm birth by characteristics and biomarkers across pregnancies in African-American women

Laura Jelliffe-Pawlowski, PhD | Epidemiology and Biostatistics, UCSF School of Medicine , Kelli Ryckman, PhD | Epidemiology, University of Iowa

African Americans experience some of the highest rates of preterm birth and its recurrence (preterm birth occurring in two or more pregnancies), meaning that a disproportionate number of African American families are caring for and raising more than one child born preterm. Social, emotional, environmental and health exposures (poverty, discrimination and obesity) are strong contributors to these risk disparities, but traditional measures (income, education, emotional well-being) of these risks are difficult to obtain or quantify across multiple pregnancies. Additionally, there are likely biological markers measured during pregnancy that signal a response to these stressors. Our study will examine maternal characteristics as well as biological markers of stress in mid-pregnancy blood samples across multiple subsequent pregnancies in a subset of African American women. Combining cell-to-society risk factors is an essential first step for identifying better treatment and prevention strategies for preterm birth, and has the potential to substantially contribute to understanding one of the major health disparities in maternal-fetal medicine.

Visualization of individual and environmental risks and protectors for preterm birth in Fresno County

Marta Jankowska, PhD | Family and Preventive Medicine, Qualcomm Institute, University of California, San Diego , Christina Chambers, PhD | Pediatrics, University of California, San Diego

The causes of preterm birth (PTB) are complex, and better methods for amalgamating, visualizing, and performing exploratory analysis on risk factors for PTB are needed. In Fresno County, California, complex pathways to PTB are at play leading to the highest PTB rate in California, including demographics, existing health conditions, socioeconomic background, and environmental factors such as pollution. Data integration and visualization offers a field of research and developed tools for exploring patterns, identifying relationships, and synthesizing information in large, multiscale and multivariate datasets. Being able to visualize risks of PTB in Fresno will allow researchers, clinicians, community members, and public health professionals to understand linkages and generate new hypotheses about the risk factors of PTB. This pilot study will leverage existing cyberinfrastructure, and adapt it as needed to generate a data integration and visualization tool for the exploration and analysis of Fresno County PTB and risk factor data. Data will include: genetic, biological, health outcome, behavioral, social, policy, and environmental data from a variety of sources. Testing and refinement of the tool will include feedback from research collaborators, community partners, clinicians, and public health professionals.

San Francisco Preterm Fetal Infant Mortality Review (SF PFIMR)

Rebecca Jackson, MD | Obstetrics, Gynecology & Reproductive Science, UCSF School of Medicine

Our goal is to develop a surveillance system for preterm birth similar to the existing DPH system for monitoring fetal and infant death. The FIMR involves collection of vital statistics, detailed chart review, and patient interview by a public health nurse. The expanded surveillance system (PFIMR) will leverage biological data that are already routinely collected in the medical record, but not currently systematically abstracted and will fill gaps in monitoring about the social determinants of health and conditions of pregnant women in the hours immediately before the preterm birth. Surveillance results will be shared with the existing FIMR community advisory group, similar to the current FIMR process. Once piloted, PFIMR may be implemented citywide or statewide.

OMX, a novel oxygen carrying protein, for resuscitation in preterm delivery secondary to placental under-perfusion states

Jeffrey Fineman, MD | Pediatrics, UCSF School of Medicine , Emin Maltepe, MD, PhD | Pediatrics, UCSF School of Medicine

Ischemic placental diseases are implicated in >50% of iatrogenic preterm deliveries. Importantly, ischemic placental disease, and its associated preterm delivery, is a significant risk factor for perinatal death and long-term disability. Despite years of extensive research, prevention and treatment strategies are lacking. Clearly, the ability to improve placental oxygen delivery either acutely or chronically could have a dramatic impact on the incidence and outcomes of preterm births.

Our partner, Omniox, Inc., has developed a novel oxygen delivery biotherapeutic, OMX. OMX is a stable, and easily administered agent, which oxygenates hypoxic tissues without the toxicity associated with earlier oxygenation therapies; nitric oxide scavenging and increased oxidant stress.

We hypothesize that OMX administration during placental underperfusion states will augment placental oxygen delivery, decrease preterm birth rates, and improve outcomes. We will utilize a placental insufficiency lamb model induced by maternal (and subsequently, placental) hypoxia to determine the effect of OMX treatment on fetal-placental oxygen delivery, cardiopulmonary hemodynamics, and end-organ injury.

Qualifying risk: Exploring how life course stress experiences influence the risk of preterm birth among Black women

Leslie Dubbin, PhD, MPH, RN | Social & Behavioral Sciences, UCSF School of Nursing , Monica McLemore, PhD, MPH, RN | Family Health Care Nursing, UCSF School of Nursing

The purpose of this study is to qualitatively explore the intersections of socioeconomic status, social circumstances and experiences that may be potential mediators or protectors for the risk of preterm birth across a socioeconomically diverse sample of pregnant Black women. Our aim of this study is to better understand the chronic stressors and protective resources that may affect the instances of preterm birth and the health outcomes of pregnant Black women. Our research questions are: how do Black women from varying degrees of social advantage conceptualize and experience stress, and what tools of resilience and mechanisms of coping do they engage when experiencing stress during their pregnancy? This study will deeply explore a range of stress producing circumstances across different life domains and describe the resources and mechanisms Black women engage to mitigate its effects.

Is preterm birth associated with air pollution from oil and gas power plants in California? A natural experiment

Joan Casey, PhD, MA | Department of Psychiatry, UCSF School of Medicine

While the etiology of preterm birth remains unclear, some studies suggest that social (e.g., poverty) and environmental (e.g., air pollution) exposures are risk factors. We propose to study air pollution from oil and coal-fired power plants to evaluate (1) the association between air pollution and preterm birth and (2) effect modification by race/ethnicity and socioeconomic status. We will use a quasi-experimental design. Coal-fired power plant retirements in California from 2001-2013 represent a natural experiment, whereby the surrounding communities are exposed to emissions up to the point of retirement and unexposed after retirement. We will further consider how the change in air pollution impacts the pregnancies of important, vulnerable subgroups including mothers of different race/ethnicities, those with less education, and communities with higher rates of poverty. The results from our analysis will have important implications for future policy decisions regarding fuel source, power plant retirements, and environmental justice.

Interventions Research

Developing a digital health solution to support pregnant women at risk of preterm birth: a design thinking approach

Victoria Stenmark, MD, MPH | Highland Hospital, Oakland

Preterm birth disproportionately affects low-income and minority women. Women from these communities suggest additional information and support could be beneficial during pregnancy. Digital health solutions may improve knowledge, decision-making, and ultimately, clinical outcomes. While these solutions have shown promise in improving mental health, weight gain, smoking, and blood pressure monitoring during pregnancy, to our knowledge, developers have not comprehensively engaged low-income women to understand their needs and to ensure solutions are culturally and linguistically responsive. In partnership with Bay Area low-income minority women with lived experience, we will conduct a qualitative analysis of their resource and informational needs using a design thinking approach and then co-develop and prototype a digital health solution that will be evaluated for usability and acceptability.

Drug use and pregnancy policy study (D-APPS)

Sarah Roberts, DrPH | Advancing New Standards in Reproductive Health (ANSIRH), UCSF Bixby Center for Global Reproductive Health

Most states have enacted one or more policies targeting drug use during pregnancy. These include punitive policies, e.g. allowing civil commitment of pregnant women for drug use and mandating reporting to Child Protective Services (CPS). They have also enacted supportive policies, e.g. giving pregnant women priority in entering substance abuse treatment. These policies continue to be enacted at the state-level; some components are included in federal legislation. These policies could influence preterm birth. Punitive policies could also have unintended consequences, such as deterring women from prenatal care. If women are deterred from prenatal care, there are fewer opportunities to provide other health-promoting interventions, such as prenatal care-based interventions to prevent preterm birth. The primary purpose of this project is to assess effects of state-level policies targeting drug use during pregnancy on preterm birth and prenatal care utilization and whether effects vary by race/ethnicity.

Milk, Growth and Microbiota: An RCT of Donor Milk vs. Formula to Supplement Breastfeeding Late Preterm Newborns

Valerie Flaherman, MD, MPH | Pediatrics, UCSF School of Medicine

Among U.S. births, 8% occur in the late preterm period, between 34 0/7 and 36 6/7 weeks gestation. Breastfeeding helps establish healthy intestinal bacteria (microbiota) for late preterm infants, but their mothers may not initially make enough milk to allow them to grow. Formula supplementation may be needed to initiate growth but can alter intestinal microbiota. Donor milk could be used instead of formula but has not been studied in late preterm infants. The aim of this proposal is to study the effects of donor milk on growth and on intestinal microbiota among late preterm breastfeeding newborns. We propose a randomized, controlled trial enrolling late preterm newborns and randomly assigning them either to breastfeed with additional formula, or to breastfeed with additional donor milk. Our outcomes will be growth and intestinal microbiota. If donor milk supports growth and healthy intestinal microbiota, it might be an important therapeutic option.

EatSF: Fruit and Vegetable Vouchers to Support Pregnant Mothers in San Francisco with Food Security and Healthy Dietary Intake

Hilary Seligman, MD, MAS | Departments of Medicine, and Epidemiology & Biostatistics, UCSF School of Medicine, Feeding America

Women in low-income households frequently report challenges affording the healthy foods they prefer to eat, particularly fruits and vegetables. The tension between what a limited food budget allows and the desire to eat a healthier diet is often strongest during pregnancy. EatSF allows participants to exchange vouchers for fruits and vegetables of their choice at one of our 15 EatSF corner stores, grocery stores, or farmers markets. Since April 2015, we have distributed $5-10 of vouchers to more than 1000 households every week for 6-12 months (totaling more than $350,000 of produce). In February 2017, EatSF will expand to pregnant mothers. This expansion presents a unique opportunity to examine the program’s impact. This grant allows us to determine the extent to which weekly $10 EatSF vouchers supports healthy dietary intake, reduces food insecurity, and lowers pre-term birth rates among low-income, pregnant mothers in San Francisco.

Using community health workers for preterm birth prevention

Melanie Thomas, MD, MS | Psychiatry, UCSF School of Medicine , Laura Gottlieb, MD, MPH | Family and Community Medicine, UCSF School of Medicine

Our project, “Using Community Health Workers for Preterm Birth (PTB) Prevention,” will examine the effects of embedding a Community Health Worker (CHW) program in prenatal care clinics at Zuckerberg San Francisco General (ZSFG). CHWs trained by the San Francisco Homeless Prenatal Program, all of whom experienced significant social risk while pregnant themselves, will ask ZSFG pregnant patients about social and mental health needs they may have. The CHWs will then help these patients connect with hospital and community resources.

Previous studies have shown that having a lot of stress can be connected with PTB. The goal of our project is to give pregnant women supports that can reduce stress, decrease social challenges, and ultimately reduce the chance that babies come too early. We anticipate that trained, community-based CHWs will better understand the priorities of ZSFG pregnant patients and can help these women identify and meet their own goals for care.

Perceptions and availability of postpartum contraception among women and health care providers following preterm birth

Heike Thiel de Bocanegra, PhD | Obstetrics, Gynecology & Reproductive Science, UCSF School of Medicine

Rapid repeat pregnancy, occurring less than 6 months after delivery, puts women at increased risk of preterm birth. Access to high-efficacy postpartum contraception can help women to prevent extremely short inter-pregnancy intervals. We do not yet know, however, what the women who experience preterm birth think about postpartum contraception. In this project, we will conduct 30 in-depth interviews with women who had preterm births in three geographies (San Francisco, Oakland, and Fresno) to explore their preferences and attitudes about postpartum contraception. We will ask them what they think about education on postpartum contraception and how and when they want to learn about contraceptive choices. Additionally, we will conduct 30 clinician interviews and review hospital birth data to assess provider and system factors in contraceptive provision in maternity wards. Findings will inform the development of patient-centered interventions to improve counseling and provision of contraception.

Periviable GOALS: Formative research to create a decision support tool for periviable decision-making

Miriam Kuppermann, PhD, MPH | Obstetrics, Gynecology & Reproductive Science, UCSF School of Medicine

This project is part of a larger collaborative effort focused on patient informed, shared decision making in the context of threatened periviable delivery. We will conduct formative research among Spanish-speaking Latina and low income English-speaking women and their providers, as the initial step in developing a decision support intervention to facilitate informed, shared decision making about neonatal resuscitation among women who present to labor and delivery at periviable gestations and their health care providers. We will conduct design sessions targeting three populations (women who have delivered infants at 22-25 weeks gestation, pregnant women who are between 22 and 25 weeks gestation, and health care providers involved in the care of these women) to help us gain an understanding of periviable birth issues and decision support needs from multiple perspectives. The knowledge gained from this formative work will be used in designing the decision tool.

Social determinants of health, adversity and resilience (SOAR) Factors

Danielle Hessler, PhD | Family and Community Medicine, UCSF School of Medicine , Dayna Long, MD | UCSF Benioff Children’s Hospital Oakland

A growing body of evidence highlights the importance of addressing social and psychological stressors to prevent preterm birth and improve the quality of care for prenatal patients and their families. These stressors can be viewed collectively under the umbrella of “SOAR,” which includes social determinants of health, adversity, mental health and resilience. Pregnancy related care settings are uniquely positioned to address and integrate discussion of SOAR factors with patients, however, providers are often faced with limited time and competing priorities in health care encounters, particularly in low-income areas. To address these gaps, our qualitative study aims to explore providers’ current practices, barriers and preferences towards screening and addressing SOAR factors for women who are at risk for preterm birth in the Oakland area. Findings from the study will inform the design and implementation of future programs to screen and address SOAR factors within prenatal care settings.

Clinical accuracy of a new method to wirelessly monitor skin temperature in preterm neonates using adhesive-embedded sensors

Linda Franck, PhD, RN | Department of Family Health Care Nursing, School of Nursing , Todd Coleman, PhD | Institute of Engineering and Medicine, University of California, San Diego

Thermal stress — including hypothermia, hyperthermia and thermal instability — are major causes of neonatal mortality and morbidity in preterm infants. Technology for monitoring temperature in the Neonatal Intensive Care Unit (NICU) has not changed since the 1990s. Although an essential part of life-saving NICU care, temperature monitoring is a major source of daily stress for vulnerable preterm infants. With recent advances in adhesive-integrated flexible electronic systems (AIFES), human physiological signals can now be monitored wirelessly. The AIFES ultra-thin, high resolution sensors and circuitry designed for conformal lamination onto the skin can now be inexpensively fabricated and imbedded in medical adhesives used routinely in the NICU. The purpose of this pilot study is to generate preliminary data on the accuracy and feasibility of the new AIFES temperature sensor compared with the ‘gold standard’ digital thermometer in preterm infants 28 to 37 weeks gestational age. If the findings from this pilot and subsequent studies demonstrate accuracy and feasibility, the AIFES technology could revolutionize temperature monitoring for preterm infants and eliminate a major source of NICU stress.

Informing model articulation by eliciting the family experience: a pilot study of the Special Start neonatal follow up program

Laura Frame, PhD | UCSF Benioff Children’s Hospital Oakland

Infants born prematurely face a host of challenges during the time of hospitalization, through the transition process from hospital to home, and then once stabilized at home. Caring for a premature baby at home can be further complicated for parents grappling with poverty, violence, migration and other stressors. UCSF Benioff Children’s Hospital Oakland operates a specialized relationship-based, multidisciplinary program, Special Start, offering weekly home visits to families of premature babies at high social risk. This project builds a comprehensive evaluation strategy for Special Start by articulating its theory of change and key components of the intervention model, incorporating the subjective experience of families who have received the program’s services. Interviews with parents and focus groups with providers will inform a program manual and evaluation plan. This project is an important step in evaluating a longstanding intervention to reduce the burden of preterm birth in PTBi’s target geography of Oakland, California.

Defining the interrelationship between preconception and preterm birth through a community-engaged process

Christine Dehlendorf, MD, MAS | Family and Community Medicine, UCSF School of Medicine

Poor use of contraceptives in the postpartum period can contribute to high rates of and disparities in unintended pregnancy and short interpregnancy intervals, a risk factor for preterm birth. Given San Francisco’s significant disparities in preterm birth rates, the research team plans to engage community stakeholders and conduct formative work around women of color’s attitudes and preferences for perinatal family planning care and contraceptive counseling. Through engagement with the target audience and with reproductive justice advocates, the project will also take into account contextual factors related to reproductive health experiences and preferences of women of color. The research team has previously developed a tablet-based contraceptive decision support tool designed to facilitate shared decision making between patients and providers, and hopes to use the results from the formative work to create a clinic-based intervention designed to improve the family planning experiences of peripartum women at risk for preterm birth.