Personalized Care for Prenatal Stress Reduction & Prevention of Preterm Birth (PTB) Disparities

This project addresses the major public health problem of preterm birth (PTB), delivery \<37 weeks, by deploying a novel, personalized, comprehensive 3-tier PTB prevention program \[University of North Carolina (UNC) PTBCARE+\]. PTB affects 1 in 10 infants born in the United States (US) and is the leading cause of neonatal morbidity and mortality; survivors are at high risk for lifelong adverse health sequelae. Stress is an established risk factor for both spontaneous PTB (sPTB) and medically indicated PTB miPTB). Of significant public health concern, Black patients have 49% higher rates of PTB, are more likely to have early PTB, and increased perceived stress in pregnancy compared to patients of other races. Stress may alter biology, including stress-related gene expression in maternal blood and allostatic load index. Evidence from other fields of medicine supports incorporation of both stress reduction programs and 'patient navigators' as effective approaches to improve health outcomes, and data in obstetrics supports improved outcomes with PTB specialty clinics. However, such programs are not routinely employed in obstetrics. The effect of a specialty prenatal care program targeting stress reduction as a strategy to reduce PTB and PTB disparities remains unknown, representing a critical knowledge gap. The central hypothesis of this project is that enrollment in a personalized, comprehensive PTB support program (UNC PTBCARE+) is associated with reduced perceived stress, stress-related gene expression, allostatic load, and lower rates of PTB \<35 weeks. This hypothesis is supported by published and preliminary data as follows: First, UNC pregnant patients at high risk for PTB have high rates of stress and life stressors (e.g., financial insecurity, racism). Second, biologic stress markers including gene transcript levels differ by PTB status in mid-pregnancy blood. Third, specialty PTB care reduces stress in a NC cohort. Building upon prior work and that of others, this exciting proposal evaluates the efficacy of the novel UNC PTBCARE+ program. The investigation focus on PTB \<35 weeks due to its relative frequency, higher association with neonatal morbidity and mortality as compared to later PTB, to include PTB in the 34th week of gestation (because the delivery gestational age considered 'standard of care' for delivery among individuals with stable but severe preeclampsia and preterm membrane rupture), and to align with multiple other published PTB RCTs. This study will recruit 1,350 pregnant patients between 8+0 and 19+6 weeks gestation with an elevated a priori risk of either medically-indicated preterm birth or spontaneous preterm birth. Subjects will be randomized 2:1 to receive UNC PTBCARE+ vs. usual care. Randomization will be stratified based on maternal race and ethnicity (individuals who identify only as White and non-Hispanic vs. individuals who identify as belonging to one or more other races and/or Hispanic ethnicity and (b) perceived stress scores (those with perceived stress scores ≥20 vs. those with lower perceived stress scores scores). All participants, regardless of randomization assignment, will have 2 study visits during pregnancy. * Visit 1 (V1) will occur at randomization, 8+0 - 19+6 weeks gestation. * Visit 2 (V2) will occur in mid pregnancy, between 22+0 and 29+6 weeks gestation. At both visits, patients will complete validated surveys evaluating a broad spectrum of stressors, discrimination, adverse childhood experiences, perceived social support, resiliency, medication barriers and adherence, care access and satisfaction,, intervention fidelity and sustainability, use of stress relief modalities, and have blood collected to measure biologic stress markers. The UNC PTBCARE+ program is personalized. All patients randomized to UNC PTBCARE+ receive a stress reduction toolkit and will work with a PTB Care Coordinator who will provide support, facilitate clinician-prescribed medical care, and serve as a patient-provider liaison. Additional benefits / support items and support elements are provided to some participants on an "as needed" basis, per study protocol, and are not included in the initial registration to preserve scientific integrity and protect the rights of research participants. This study registration will be updated with complete intervention details after the study is fully enrolled and all participants have delivered. Psychosocial and financial stressor screening results from V1 will determine UNC PTBCARE+ tier assignment. Thus, participants are randomized only after Visit 1 surveys are completed. This solutions-oriented RCT of UNC PTBCARE+ vs. usual care provides an ideal forum to test the primary hypothesis and study stress-related PTB pathophysiology through the following Aims: * Aim 1. Evaluate the effects of the UNC PTBCARE+ program on perceived stress and resilience in pregnant patients at high risk for PTB. Hypothesis: Patients randomized to UNC PTBCARE+ will have lower levels of perceived stress and higher levels of resilience at V2 vs. V1; those randomized to usual care will have no change. * Aim 2. Quantify the extent to which the UNC PTBCARE+ program is associated with improved biologic stress measures during pregnancy. Hypothesis: Patients randomized to UNC PTBCARE+ will have reduced stress-related gene expression and allostatic load scores in maternal blood at V2 vs. V1 compared to those randomized to usual care who will have no change, increasing insight into PTB pathophysiology. * Aim 3. Determine the effects of the UNC PTBCARE+ program on PTB \<35 weeks. Hypothesis: Patients randomized to UNC PTBCARE+ will have lower rates of early PTB compared to those randomized to usual care. This study provides tangible, personalized solutions to the major public health problem of PTB and carries enormous potential to provide generalizable, low-risk strategies to reduce PTB and related disparities.