Reducing perceived barriers to scaling up overdose education and naloxone distribution and medications for opioid use disorder in the United States in the HEALing (helping end addiction long-term®) communities study.

BACKGROUND: Scaling up overdose education and naloxone distribution (OEND) and medications for opioid use disorder (MOUD) is needed to reduce opioid overdose deaths, but barriers are pervasive. This study examines whether the Communities That HEAL (CTH) intervention reduced perceived barriers to expanding OEND and MOUD in healthcare/behavioral health, criminal-legal, and other/non-traditional venues. METHODS: The HEALing (Helping End Addiction Long-Term®) Communities Study is a parallel, wait-list, cluster randomized trial testing the CTH intervention in 67 communities in the United States. Surveys administered to coalition members and key stakeholders measured the magnitude of perceived barriers to scaling up OEND and MOUD in November 2019-January 2020, May-June 2021, and May-June 2022. Multilevel linear mixed models compared Wave 1 (intervention) and Wave 2 (wait-list control) respondents. Interactions by rural/urban status and research site were tested. RESULTS: Wave 1 respondents reported significantly greater reductions in mean scores for three outcomes: perceived barriers to scaling up OEND in Healthcare/Behavioral Health Venues (-0.26, 95% confidence interval, CI: -0.48, -0.05, p = 0.015), OEND in Other/Non-traditional Venues (-0.53, 95% CI: - 0.84, -0.22, p = 0.001) and MOUD in Other/Non-traditional Venues (-0.34, 95% CI: -0.62, -0.05, p = 0.020). There were significant interactions by research site for perceived barriers to scaling up OEND and MOUD in Criminal-Legal Venues. There were no significant interactions by rural/urban status. DISCUSSION: The CTH Intervention reduced perceived barriers to scaling up OEND and MOUD in certain venues, with no difference in effectiveness between rural and urban communities. More research is needed to understand facilitators and barriers in different venues.

Effects of the Communities that Heal (CTH) intervention on perceived opioid-related community stigma in the HEALing Communities Study: results of a multi-site, community-level, cluster-randomized trial.

Background: Community stigma against people with opioid use disorder (OUD) and intervention stigma (e.g., toward naloxone) exacerbate the opioid overdose crisis. We examined the effects of the Communities that HEAL (CTH) intervention on perceived opioid-related community stigma by stakeholders in the HEALing Communities Study (HCS). Methods: We collected three surveys from community coalition members in 66 communities across four states participating in HCS. Communities were randomized into Intervention (Wave 1) or Wait-list Control (Wave 2) arms. We conducted multilevel linear mixed models to compare changes in primary outcomes of community stigma toward people treated for OUD, naloxone, and medication for opioid use disorder (MOUD) by arm from time 1 (before the start of the intervention) to time 3 (end of the intervention period in the Intervention arm). Findings: Intervention stakeholders reported a larger decrease in perceived community stigma toward people treated for OUD (adjusted mean change (AMC) -3.20 [95% C.I. -4.43, -1.98]) and toward MOUD (AMC -0.33 [95% C.I. -0.56, -0.09]) than stakeholders in Wait-list Control communities (AMC -0.18 [95% C.I. -1.38, 1.02], p = 0.0007 and AMC 0.11 [95% C.I. -0.09, 0.31], p = 0.0066). The relationship between intervention status and change in stigma toward MOUD was moderated by rural-urban status (urban AMC -0.59 [95% CI, -0.87, -0.32], rural AMC not sig.) and state. The difference in stigma toward naloxone between Intervention and Wait-list Control stakeholders was not statistically significant (p = 0.18). Interpretation: The CTH intervention decreased stakeholder perceptions of community stigma toward people treated for OUD and stigma toward MOUD. Implementing the CTH intervention in other communities could decrease OUD stigma across diverse settings nationally. Funding: US National Institute on Drug Abuse.

Impact of the Communities That HEAL Intervention on Buprenorphine-Waivered Practitioners and Buprenorphine Prescribing: A Prespecified Secondary Analysis of the HCS Randomized Clinical Trial.

Importance: Buprenorphine significantly reduces opioid-related overdose mortality. From 2002 to 2022, the Drug Addiction Treatment Act of 2000 (DATA 2000) required qualified practitioners to receive a waiver from the Drug Enforcement Agency to prescribe buprenorphine for treatment of opioid use disorder. During this period, waiver uptake among practitioners was modest; subsequent changes need to be examined. Objective: To determine whether the Communities That HEAL (CTH) intervention increased the rate of practitioners with DATA 2000 waivers and buprenorphine prescribing. Design, Setting, and Participants: This prespecified secondary analysis of the HEALing Communities Study, a multisite, 2-arm, parallel, community-level, cluster randomized, open, wait-list-controlled comparison clinical trial was designed to assess the effectiveness of the CTH intervention and was conducted between January 1, 2020, to December 31, 2023, in 67 communities in Kentucky, Massachusetts, New York, and Ohio, accounting for approximately 8.2 million adults. The participants in this trial were communities consisting of counties (n = 48) and municipalities (n = 19). Trial arm randomization was conducted using a covariate constrained randomization procedure stratified by state. Each state was balanced by community characteristics including urban/rural classification, fatal opioid overdose rate, and community population. Thirty-four communities were randomized to the intervention and 33 to wait-list control arms. Data analysis was conducted between March 20 and September 29, 2023, with a focus on the comparison period from July 1, 2021, to June 30, 2022. Intervention: Waiver trainings and other educational trainings were offered or supported by the HEALing Communities Study research sites in each state to help build practitioner capacity. Main Outcomes and Measures: The rate of practitioners with a DATA 2000 waiver (overall, and stratified by 30-, 100-, and 275-patient limits) per 100 000 adult residents aged 18 years or older during July 1, 2021, to June 30, 2022, were compared between the intervention and wait-list control communities. The rate of buprenorphine prescribing among those waivered practitioners was also compared between the intervention and wait-list control communities. Intention-to-treat and per-protocol analyses were performed. Results: A total of 8 166 963 individuals aged 18 years or older were residents of the 67 communities studied. There was no evidence of an effect of the CTH intervention on the adjusted rate of practitioners with a DATA 2000 waiver (adjusted relative rate [ARR], 1.04; 95% CI, 0.94-1.14) or the adjusted rate of practitioners with a DATA 2000 waiver who actively prescribed buprenorphine (ARR, 0.97; 95% CI, 0.86-1.10). Conclusions and Relevance: In this randomized clinical trial, the CTH intervention was not associated with increases in the rate of practitioners with a DATA 2000 waiver or buprenorphine prescribing among those waivered practitioners. Supporting practitioners to prescribe buprenorphine remains a critical yet challenging step in the continuum of care to treat opioid use disorder. Trial Registration: ClinicalTrials.gov Identifier: NCT04111939.

A Qualitative Study of Health Equity's Role in Community Coalition Development.

Opioid overdose deaths are dramatically increasing in the United States and disproportionately affecting minority communities, with the increasing presence of fentanyl exacerbating this crisis. Developing community coalitions is a long-standing strategy used to address public health issues. However, there is a limited understanding of how coalitions operate amid a serious public health crisis. To address this gap, we leveraged data from the HEALing Communities Study (HCS)-a multisite implementation study aiming to reduce opioid overdose deaths in 67 communities. Researchers analyzed transcripts of 321 qualitative interviews conducted with members of 56 coalitions in the four states participating in the HCS. There were no a priori interests in themes, and emergent themes were identified through inductive thematic analysis and then mapped to the constructs of the Community Coalition Action Theory (CCAT). Themes emerged related to coalition development and highlighted the role of health equity in the inner workings of coalitions addressing the opioid epidemic. Coalition members reported seeing the lack of racial and ethnic diversity within their coalitions as a barrier to their work. However, when coalitions focused on health equity, they noted that their effectiveness and ability to tailor their initiatives to their communities' needs were strengthened. Based on our findings, we suggest two additions to enhance the CCAT: (a) incorporating health equity as an overarching construct that affects all stages of development, and (b) ensuring that data about individuals served are included within the pooled resource construct to enable monitoring of health equity.

Public Health Surveillance of Behavioral Health Emergencies through Emergency Medical Services Data.

Objective: To identify the demographic, clinical and EMS characteristics of events documented as behavioral health emergencies (BHE) by EMS. Methods: This was a cross-sectional study using the 2018 National Emergency Medical Services Information System (NEMSIS) Version 3 dataset. All events that had patient care provided with a documented impression (field diagnosis) of ICD-10 codes F01-F99 (i.e., mental, behavioral, and neurodevelopmental disorders) were labeled a BHE and included. Descriptive statistics were calculated. Results: A total of 1,594,821 (7.3%) EMS calls had a BHE impression. The most common was mental and behavioral disorders due to psychoactive substance use (42.3%). More males than females had BHEs (54.6% vs. 45.4%), and most patients were ages 18-34 (31.5%). Most BHE occurred in urban settings (89.6%). Almost half (47.9%) were dispatched with a complaint unrelated to behavioral health. Conclusion: BHEs were noted in 7.3% of NEMSIS events, and the majority were associated with substance use disorders. EMS professionals need comprehensive training on best practices for BHE. Stakeholders should have information on prevalence of BHEs to ensure proper educational standards, training practices, and resource allocation.

Co-occurring risk and protective factors and regulatory behavior of infants living in low-income homes.

Early self-regulation is a foundation for lifelong wellness and can be shaped by the interplay among several vital exposures. In this study, we examined the emergence of reliable profiles based upon exposure to risk and protective factors in infancy, determined if sociodemographic resources predict profile membership, and determined if these profiles predict early regulatory behaviors in a sample of infants reared in low-income homes. Data were collected from a sample of primarily Black or White mother-infant dyads living in low-income homes in the Midwest (n = 222) during the infants' first year of life (mean maternal age at enrollment: 26.29 years; range 18-43 years). Exposures included mother-infant interactions; father support; maternal depression, stress, and self-efficacy; home environment; food security; and breastfeeding duration. Sociodemographic resources included poverty status; economic hardship; maternal education, employment, and age; parental marital status; and infant race and sex. Infant regulatory behaviors were measured with the Infant Behavior Questionnaire-Revised Very Short Form effortful control subscale (mean age 11 months; range 8.5-14.3 months). Latent profile analysis was used to profile infants by risk and protective exposures. Regression was used to differentiate profiles by sociodemographic resources and to predict infant regulatory behavior from profiles. Three profiles emerged: low father support, good maternal mental health, and poor maternal mental health. A married mother, less economic hardship, and working mothers predicted infant exposure to good maternal mental health. Infant regulatory behavior was best when the infant was exposed to the good maternal mental health profile. Implications for future research are discussed.

Community engagement to implement evidence-based practices in the HEALing communities study.

BACKGROUND: The implementation of evidence-based practices to reduce opioid overdose deaths within communities remains suboptimal. Community engagement can improve the uptake and sustainability of evidence-based practices. The HEALing Communities Study (HCS) aims to reduce opioid overdose deaths through the Communities That HEAL (CTH) intervention, a community-engaged, data-driven planning process that will be implemented in 67 communities across four states. METHODS: An iterative process was used in the development of the community engagement component of the CTH. The resulting community engagement process uses phased planning steeped in the principles of community based participatory research. Phases include: 0) Preparation, 1) Getting Started, 2) Getting Organized, 3) Community Profiles and Data Dashboards, 4) Community Action Planning, 5) Implementation and Monitoring, and 6) Sustainability Planning. DISCUSSION: The CTH protocol provides a common structure across the four states for the community-engaged intervention and allows for tailored approaches that meet the unique needs or sociocultural context of each community. Challenges inherent to community engagement work emerged early in the process are discussed. CONCLUSION: HCS will show how community engagement can support the implementation of evidence-based practices for addressing the opioid crisis in highly impacted communities. Findings from this study have the potential to provide communities across the country with an evidence-based approach to address their local opioid crisis; advance community engaged research; and contribute to the implementation, sustainability, and adoption of evidence-based practices. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04111939).

Hair sampling for cortisol analysis with mother-toddler dyads living in low-income homes.

BACKGROUND: A first step to advance stress science research in young children is understanding the relationship between chronic stress in a mother and chronic stress in her child. One non-invasive measure of chronic stress is hair cortisol. However, little is known about strategies for hair sampling in mother-toddler dyads living in low-income homes in the U.S. To address prior limitations, the purpose of this study was to understand the feasibility of sampling hair for cortisol analysis in mother-toddler dyads living in low-income homes in the U.S. We examined feasibility related to participation, eligibility, and gathering an adequate hair sample weight. METHODS: We approached 142 low-income, racially diverse, urban-dwelling mothers who were participating in an ongoing longitudinal birth cohort study for informed consent to cut approximately 150 hairs from the posterior vertex of their scalp and their toddlers' (20-24 months) scalp. We demonstrated the process of sampling hair with a hairstyling doll during home visits to the mother and toddler using rounded-end thinning shears. RESULTS: Overall, 94 of 142 mother-toddler dyads (66 %) participated in hair sampling. The most common reason for participation refusal was related to hairstyle. All but three hair samples were of adequate weight for cortisol extraction. DISCUSSION: The findings from this study can help researchers address sampling feasibility concerns in hair for cortisol analysis research in mother-toddler dyads living in low-income homes in the U.S.

Structural and Social Determinants of Health Factors Associated with County-Level Variation in Non-Adherence to Antihypertensive Medication Treatment.

BACKGROUND: Non-adherence to antihypertensive medication treatment (AHM) is a complex health behavior with determinants that extend beyond the individual patient. The structural and social determinants of health (SDH) that predispose populations to ill health and unhealthy behaviors could be potential barriers to long-term adherence to AHM. However, the role of SDH in AHM non-adherence has been understudied. Therefore, we aimed to define and identify the SDH factors associated with non-adherence to AHM and to quantify the variation in county-level non-adherence to AHM explained by these factors. METHODS: Two cross-sectional datasets, the Centers for Disease Control and Prevention (CDC) Atlas of Heart Disease and Stroke (2014-2016 cycle) and the 2016 County Health Rankings (CHR), were linked to create an analytic dataset. Contextual SDH variables were extracted from the CDC-CHR linked dataset. County-level prevalence of AHM non-adherence, based on Medicare fee-for-service beneficiaries' claims data, was extracted from the CDC Atlas dataset. The CDC measured AHM non-adherence as the proportion of days covered (PDC) with AHM during a 365 day period for Medicare Part D beneficiaries and aggregated these measures at the county level. We applied confirmatory factor analysis (CFA) to identify the constructs of social determinants of AHM non-adherence. AHM non-adherence variation and its social determinants were measured with structural equation models. RESULTS: Among 3000 counties in the U.S., the weighted mean prevalence of AHM non-adherence (PDC < 80%) in 2015 was 25.0%, with a standard deviation (SD) of 18.8%. AHM non-adherence was directly associated with poverty/food insecurity (ß = 0.31, P-value < 0.001) and weak social supports (ß = 0.27, P-value < 0.001), but inversely with healthy built environment (ß = -0.10, P-value = 0.02). These three constructs explained one-third (R2 = 30.0%) of the variation in county-level AHM non-adherence. CONCLUSION: AHM non-adherence varies by geographical location, one-third of which is explained by contextual SDH factors including poverty/food insecurity, weak social supports and healthy built environments.

Geovisualization and Spatial Analysis of Infant Mortality and Preterm Birth in Ohio, 2008-2015: Opportunities to Enhance Spatial Thinking.

OBJECTIVES: Geovisualization and spatial analysis are valuable tools for exploring and evaluating the complex social, economic, and environmental interactions that lead to spatial inequalities in health. The objective of this study was to describe spatial patterns of infant mortality and preterm birth in Ohio by using interactive mapping and spatial analysis. METHODS: We conducted a retrospective cohort study using Ohio vital statistics records from 2008-2015. We geocoded live births and infant deaths by using residential address at birth. We used multivariable logistic regression to adjust spatial and space-time cluster analyses that examined the geographic clustering of infant mortality and preterm birth and changes in spatial distribution over time. RESULTS: The overall infant mortality rate in Ohio during the study period was 6.55 per 1000 births; of 1 097 507 births, 10.3% (n = 112 552) were preterm. We found significant geographic clustering of both infant mortality and preterm birth centered on large urban areas. However, when known demographic risk factors were taken into account, urban clusters disappeared and, for preterm birth, new rural clusters appeared. CONCLUSIONS: Although many public health agencies have the capacity to create maps of health outcomes, complex spatial analysis and geovisualization techniques are still challenging for public health practitioners to use and understand. We found that actively engaging policymakers in reviewing results of the cluster analysis improved understanding of the processes driving spatial patterns of birth outcomes in the state.

Food Insecurity and Depression among Economically Disadvantaged Mothers: Does Maternal Efficacy Matter?

BACKGROUND: Nearly 13 million American children experience food insecurity. Research suggests that maternal depression is associated with food insecurity, such that mothers who experience depression are more likely to be food insecure. Maternal self-efficacy may be an important protective factor against depression during the postpartum year, interrupting the link between depression and food insecurity. We extend prior research by examining food insecurity in households with infants and investigating the potential for maternal efficacy to moderate the relation between depression and food insecurity. METHODS: Data were drawn from the Kids in Columbus Study, a longitudinal study of diverse, economically disadvantaged mothers and their young children in Columbus, Ohio (N = 219). Data for this study were drawn from data collected between July 2014 and June 2016. RESULTS: Over one-third of families experienced food insecurity. Further, depression was positively and significantly related to household food insecurity; this relationship, however, was dependent on maternal efficacy. When maternal efficacy was high, the relationship between depression and food insecurity was nonsignificant; when maternal efficacy was low, there was a significant, positive association between depression and food insecurity. CONCLUSIONS: Increasing maternal self-efficacy during the postpartum period may reduce food insecurity in low-income mothers who are experiencing depression.

Relations of Maternal Depression and Parenting Self-Efficacy to the Self-Regulation of Infants in Low-Income Homes.

There is increasing recognition that young children's self-regulation provides a foundation for overall wellness later in life. Yet, infants reared in poverty may exhibit less-developed self-regulation compared to their more advantaged peers. Factors associated with poverty that may influence early self-regulation include maternal depression and parenting self-efficacy. However, few researchers have examined how both parenting self-efficacy and maternal depression may affect young children's self-regulation. The purpose of this study was to investigate the associations among maternal depression, parenting self-efficacy, and infant self-regulation for a racially diverse sample of 142 mother-infant dyads living in low-income households in the United States. Maternal depressive symptomatology was determined with the Edinburgh Postnatal Depressive Scale. Parenting self-efficacy was determined with a self-report measure, reflecting caregivers' mindset or feelings reflecting competency as a parent of an infant. Infant self-regulation was measured by parental report of the Infant Behavior Questionnaire Short Form Effortful Control subscale. While maternal depressive symptomatology and self-efficacy were directly and significantly correlated with infant self-regulation, results of a mediation model suggested that parenting self-efficacy mediated the relationship between maternal depressive symptomatology and infant self-regulation. Lower maternal depressive symptomatology predicted better parenting self-efficacy, in turn predicting better infant self-regulation. This study increases our understanding of how early factors shape the self-regulation of infants reared in low-income homes - highlighting the potential role of targeting parenting self-efficacy for parenting interventions for mothers experiencing depressive symptoms.

Conditions of Poverty, Parent-Child Interactions, and Toddlers' Early Language Skills in Low-Income Families.

Objectives The study examined the relations between parent-child interaction in the first year of life to toddlers' language skills at age 2 years for a sample of children reared in poverty; of specific interest was testing the Family Stress Model, which proposes that the conditions of poverty influence children's language skills through caregiver well-being (e.g., distress, depression) and interaction dysregulation. Methods Participants were from the Kids in Columbus Study, a birth-cohort study of children born to urban families experiencing material hardship. Caregiver questionnaires were collected when the child was 4-7 months to document poverty conditions (maternal hardship, institutional resources), caregiver well-being (depression, distress), and dysregulation in parent-child interactions. The Bayley-III assessed receptive and expressive language skills when the children were 2 years. Results On average, receptive language skills were nearly 1 SD below the normative mean. Path models showed a significant effect of caregiver-child dysregulated interactions on toddlers' language skills, and an indirect effect of maternal distress on parent-child interactions and, in turn, toddlers' language skills. Conclusions for Practice This study confirmed the theoretical Family Stress Model as a viable representation of the effects of poverty on the language skills of toddlers reared in homes experiencing socioeconomic disadvantage.

Leveraging health care reform to accelerate nurse practitioner full practice authority.

BACKGROUND AND PURPOSE: Since development of the nurse practitioner (NP) role, NPs have been advocating for policy allowing them to practice to the full extent of their training. The aim of this research was to determine whether passage of the Affordable Care Act (ACA) had an impact on expansion of NPs' scope of practice. METHODS: This was a retrospective descriptive study of NPs' scope of practice legislation from 1994 to 2016 using regulatory theory. Data sources included annual reports on NP legislation and state-level legislative and media coverage. CONCLUSIONS: Eight states adopted full practice authority (FPA) from 2011 to 2016, representing a two-fold increase compared with the previous 10 years. Seven states adopted Medicaid expansion. Nursing interest groups and politicians shaped their argument in favor of FPA around the increasingly insured population because of the ACA, provider shortages, and rural health care access issues. IMPLICATIONS FOR PRACTICE: Shaping the discourse of FPA beyond the benefits to the NP profession makes way for broader political interest and participation. Although the future of the ACA is unknown, as the 28 states without FPA continue to advocate for legislative change, they could benefit from the strategies of these newly adapted FPA states.

An Exploration of Contributing Factors to Patient Safety.

One in 3 patients is estimated to experience health care-related harm during hospitalization. This descriptive, cross-sectional study used the Safety Attitudes Questionnaire to measure interprofessional staff perceptions of safety and teamwork climate and a retrospective, modified Global Trigger Tool chart review methodology to measure unit-level patient outcomes. Safety climate and teamwork did not have a statistically significant relationship with the frequency of adverse events identified by the Global Trigger Tool. Researchers may consider the Global Trigger Tool for detecting unit-level adverse events.

Measuring Stress in Young Children Using Hair Cortisol: The State of the Science.

Extensive literature suggests that adverse experiences in early childhood may deleteriously impact later health. These effects are thought to be related to the impact of persistent or chronic stress on various biological processes, mediated by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and ultimately irregularities in cortisol levels. Ameliorating persistent stress in young children requires accurately measuring the chronicity of physiologic stress, which is difficult in young children because of unreliable self-report and the burden and inaccuracy associated with using invasive acute-stress biomeasures. A better way to approximate persistent stress in young children is measuring hair cortisol concentration (HCC), as it only requires one noninvasive collection to measure months of HPA-axis activity or experienced stress. However, few studies measure HCC in young children despite wide use in adult stress research. This article reviews and synthesizes research that uses HCC to approximate persistent stress in healthy children, 12-60 months of age. Reviewed studies indicate that HCC is elevated in young children who are experiencing forms of persistent stress such as low socioeconomic status and maternal distress. Hair cortisol is thus a promising measure of early childhood persistent stress, but due to the limited use of HCC in this population, much research is still needed. Specifically, nurse researchers may need to measure several factors associated with early childhood persistent stress and HCC to identify which children are at risk for stress-related disease.

Childhood stress and birth timing among African American women: Cortisol as biological mediator.

Preterm birth (PTB) occurs among 1:11U.S. white women and 1:7.5 African American women and is a significant driver of racial disparities in infant mortality. Maternal stress is the most common clinical phenotype underlying spontaneous PTB. Specific patterns of stress and biological mediators driving PTB remain unclear. We examined the effect of childhood stress on birth timing among African American women and evaluated maternal cortisol elevation as a biological mediator. A prospective observational design was employed, with a single study visit at 28-32 weeks gestation and medical record review. The Stress and Adversity Inventory was administered, which provides a comprehensive estimate of childhood stress, stress in adulthood, and five core characteristic subscales (interpersonal loss, physical danger, humiliation, entrapment, role disruption). Venipuncture was performed between 11:00am and 4:00pm and plasma cortisol quantified by ELISA. Analyses controlled for stress in adulthood. Among a final sample of 89, cumulative childhood stress predicted birth timing (p=0.01). The association was driven by stress related to interpersonal loss and physical danger, with support for maternal cortisol as a biological mediator (ab=0.02, 95% CI [0.001, 0.045]; ab=0.02, 95% CI [0.001, 0.043], respectively). Results were similar, overall, in sub-group analyses among spontaneously laboring women (n=53); however, role disruption arose as an additional predictor, as mediated by cortisol elevations (ab=0.03, 95% CI [0.005, 0.074]). Of note, cortisol was no longer supported as a mediator linking physical danger to birth timing after adjusting for sleep quality and hours awake prior to venipuncture (ab=0.02, 95% CI [-0.0001, 0.046]). We provide preliminary evidence that, independent of stress in adulthood, childhood stress of specific core characteristics may shape birth timing, with cortisol elevation as a biological mediator. Further investigation is warranted and may bolster the development of biologically-informed screening tools for the prediction and targeted prevention of stress-related PTB.

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing: Pathway Analysis Among African American Women.

BACKGROUND: Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking. OBJECTIVES: We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1ß production. METHODS: A candidate gene study using a prospective cohort design was used. We collected blood samples at 28-32 weeks of gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN single-nucleotide polymorphism (SNP) rs2637988 was genotyped, and lipopolysaccharide-stimulated IL-1Ra and IL-1ß production was quantified. Medical record review determined timing of birth. RESULTS: Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = .21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]). Women with GG genotype showed less inhibition of IL-1ß production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = .93, p = .03). Greater IL-1ß production at 28-32 weeks of pregnancy was marginally associated with earlier birth (b* = .21, p = .05). DISCUSSION: Women with GG genotype may be at risk for earlier birth because of diminished IL-1ß inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.