LatinX harm reduction capital, medication for opioid use disorder, and nonfatal overdose: A structural equation model analysis among people who use drugs in Massachusetts.

BACKGROUND: We introduce the concept of harm reduction capital (HRCap) as the combination of knowledge, resources, and skills related to substance use risk reduction, which we hypothesize to predict MOUD use and opioid overdose. In this study, we explored the interrelationships between ethnicity, HRCap, nonfatal overdose, and MOUD use among PWUD. METHODS: Between 2017 and 2019, people who currently or in the past used opioids and who lived in Massachusetts completed a one-time survey on substance use history, treatment experiences, and use of harm reduction services. We fit first-order measurement constructs for positive and negative HRCap (facilitators and barriers). We used generalized structural equation models to examine the inter-relationships of the latent constructs with LatinX self-identification, past year overdose, and current use of MOUD. RESULTS: HRCap barriers were positively associated with past-year overdose (b=2.6, p<0.05), and LatinX self-identification was inversely associated with HRCap facilitators (b=-0.49, p<0.05). There was no association between overdose in the past year and the current use of MOUD. LatinX self-identification was positively associated with last year methadone treatment (b=0.89, p<0.05) but negatively associated with last year buprenorphine treatment (b=-0.68, p<0.07). Latinx PWUD reported lower positive HRCap than white non-LatinX PWUD and had differential utilization of MOUD. CONCLUSION: Our findings indicate that a recent overdose was not associated with the current use of MOUD, highlighting a severe gap in treatment utilization among individuals at the highest risk. The concept of HRCap and its use in the model highlight substance use treatment differences, opportunities for intervention, and empowerment.

Psychosocial Stressors and Postpartum Depressive Symptoms Are Linked to Postpartum Contraceptive Use.

Background: Postpartum contraception plays a critical role in reducing the occurrence of rapid subsequent pregnancy, offering individuals reproductive choice, and promoting overall reproductive planning and well-being. In this study, we investigated the relationship between psychosocial stress during pregnancy, postpartum depressive symptoms (PDS), and postpartum contraceptive use. Materials and Methods: We analyzed data from the Pregnancy Risk Assessment Monitoring System (2012-2019), which included comprehensive information about maternal experiences, views, and needs before, during, and after pregnancy from four states and a large city, with a total sample size of N = 36,356. We conducted descriptive analyses as well as adjusted multivariable logistic regression models. Main Findings: Our findings demonstrate significant negative associations between partner-related (adjusted odds ratio [aOR] = 0.82, 95% confidence interval [95% CI]: 0.76-0.89, p ≤ 0.001) and trauma-related (aOR = 0.83, 95% CI: 0.75-0.92, p ≤ 0.001) stressors and postpartum contraceptive use. Additionally, we observed a negative association between PDS and postpartum contraceptive use (OR = 0.88, 95% CI: 0.80-0.97, p ≤ 0.01), indicating that individuals experiencing PDS are less likely to utilize contraception after giving birth. Furthermore, our study highlights racial/ethnic, socioeconomic, and parity postpartum contraceptive use disparities. Conclusions: Our findings emphasize the importance of incorporating psychosocial stressors and mental health into the promotion of effective postpartum contraception practices. These results have valuable implications for health care providers, policymakers, and researchers as they can guide the development of targeted interventions and support systems to contribute to improved reproductive health outcomes.

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.

Applied risk mapping and spatial analysis of address-level decedent data to inform opioid overdose interventions: The Massachusetts HEALing Communities Study.

BACKGROUND: Death certificate data provide powerful and sobering records of the opioid overdose crisis. In Massachusetts, where address-level decedent data are publicly available upon request, mapping and spatial analysis of fatal overdoses can provide valuable insights to inform prevention interventions. We describe how we used this approach to support a community-level intervention to reduce opioid-involved overdose mortality. METHODS: We developed a method to clean and geocode decedent data that substituted injury locations (the likely location of fatal overdoses) for deaths recorded in hospitals. After geomasking for greater privacy protection, we created maps to visualize the spatial distribution of decedent residence addresses, alone and juxtaposed with drive and walk-time distances to opioid treatment programs (OTPs), and place of death by overdose address. We used spatial statistical analyses to identify locations with significant clusters of overdoses. RESULTS: In the 8 intervention communities, 785 individuals died from opioid-involved overdoses between 2017 and 2020. We found that 19.7% of fatal overdoses were recorded in hospitals, 50.2% occurred at the decedent's residence, and 30.1% at another location. We identified overdose hotspots in study communities. By juxtaposing decedent residence data with drive- and walk-time analyses, we highlighted actionable spatial gaps in access to OTP treatment. CONCLUSION: To better understand local fatal opioid overdose risk environments and inform the development of community-level prevention interventions, we used publicly available address-level decedent data to conduct nuanced spatial analyses. Our approach can be replicated in other jurisdictions to inform overdose prevention responses.

Trends and correlates of abscess history among people who inject drugs in Massachusetts: A mixed methods exploration of experiences amidst a rapidly evolving drug supply.

Background: Injection drug use poses significant risk for skin and soft tissue infections, such as abscesses. In places with endemic fentanyl and an increasingly contaminated drug supply, injecting and injection-related harms may be increasing, yet are understudied. We aimed to explore abscess prevalence, experiences, and themes among people who inject drugs (PWID) in the context of an evolving drug supply. Methods: Between 2019 and 2022, we surveyed and interviewed Massachusetts- based PWID about current drug use behaviors and abscess experiences. Chi-square tests explored correlates of abscess history and trends for past-year abscess percentages over time. Transcribed interview data were analyzed to identify themes related to abscess risk and opportunities for intervention. Results: Of the 297 PWID surveyed, 65.3% reported having an abscess at the injection site in their lifetime; 67.5% of these instances occurred within the last year. Reported past-year abscesses increased from 36.7% to 75.6% between 2019 and 2022. Correlates of past-year abscesses included frequent injection; methamphetamine, crack, or fentanyl use; and injection into the neck or calf. Methadone treatment was associated with significantly fewer recent abscesses. Interview data (n=151) confirmed the identified abscess risks, including syringe sharing and lack of hygienic supplies. Qualitative interviews provided additional data regarding healthcare provider stigma contributing to healthcare avoidance and the self-treatment of abscesses with adverse results. Conclusions: Abscesses are an increasing concern among PWID residing in areas of high fentanyl prevalence and a contaminated drug supply. Community drug checking, overdose prevention sites, injection hygiene interventions, and improved access to care are indicated.

Investigating Maternal Stress, Depression, and Breastfeeding: A Pregnancy Risk Assessment Monitoring System (2016-2019) Analysis.

Breastfeeding is invaluable for postpartum physical healing and mental wellbeing, but psychosocial stress and depression impede such recovery processes. To inform future interventions and policies, associations between breastfeeding, maternal stress, and depression were examined. Data from the Pregnancy Risk Assessment Monitoring System (PRAMS) were analyzed (2016-2019). Logistic regression models were used to calculate adjusted odds ratios with 95% confidence intervals. Of the total sample (n = 95,820), approximately 88% of participants attempted breastfeeding. Our findings indicate that participants who experienced any form of stress had a slightly higher likelihood of breastfeeding compared to those without stress. Specifically, partner-related and financial-related stressors were significantly associated with increased odds of breastfeeding. However, no significant associations were observed trauma-related or emotional-related stressors and breastfeeding. Additionally, no significant association was found between depression at different stages (preconception, prenatal, and postpartum) and breastfeeding. A significant interaction effect was noted between having experienced any of the 13 stressors and Black race/ethnicity on breastfeeding odds. Similarly, significant interaction effects were observed between partner-related, trauma, financial, or emotional stressors and Black race/ethnicity. These findings emphasize the importance of considering various factors when promoting breastfeeding in diverse populations, and screening for psychosocial stress during postpartum visits. Our study recommends tailoring breastfeeding interventions to address the needs of Black mothers which could significantly improve maternal health and breastfeeding outcomes.

Spatial access to buprenorphine-waivered prescribers in the HEALing communities study: Enhanced 2-step floating catchment area analyses in Massachusetts, Ohio, and Kentucky.

INTRODUCTION: The opioid overdose epidemic continues to impact a large swath of the population in the US. Medications for opioid use disorders (MOUD) are an effective resource to combat the epidemic; however, there is limited research on MOUD treatment access that accounts for both supply of and demand for services. We aimed to examine access to buprenorphine prescribers in the HEALing Communities Study (HCS) Wave 2 communities in Massachusetts, Ohio, and Kentucky during 2021, and the association between buprenorphine access and opioid-related incidents, specifically fatal overdoses and opioid-related responses by emergency medical services (EMS). METHODS: We calculated Enhanced 2-Step Floating Catchment Area (E2SFCA) accessibility indices for each state, as well as Wave 2 communities in each state, based on the location of providers (buprenorphine-waivered clinicians from the US Drug Enforcement Agency Active Registrants database), population-weighted centroids at the census block group level, and catchment areas defined by the state or community's average commute time. In advance of intervention initiation, we quantified the opioid-related risk environment of communities. We assessed gaps in services by using bivariate Local Moran's I analysis, incorporating accessibility indices and opioid-related incident data. RESULTS: Massachusetts Wave 2 HCS communities had the highest rates of buprenorphine prescribers per 1000 patients (median: 165.8) compared to Kentucky (38.8) and Ohio (40.1). While urban centers in all three states had higher E2SFCA index scores compared to rural communities, we observed that suburban communities often had limited access. Through bivariate Local Moran's I analysis, we identified numerous locations with low buprenorphine access surrounded by high opioid-related incidents, particularly in communities that surrounded Boston, Massachusetts; Columbus, Ohio; and Louisville, Kentucky. CONCLUSION: Rural communities demonstrated a great need for additional access to buprenorphine prescribers. However, policymakers should also direct attention toward suburban communities that have experienced significant increases in opioid-related incidents.

Methods for jurisdictional vulnerability assessment of opioid-related outcomes.

In 2020, an estimated 2.7 million people in the US had opioid use disorder, increasing their risk of opioid-related morbidity and mortality. While jurisdictional vulnerability assessments (JVA) of opioid-related outcomes have been conducted previously in the US, there has been no unifying methodological framework. Between 2019 and 2021, we prepared ten JVAs, in collaboration with the Council of State and Territorial Epidemiologists, the Centers for Disease Control and Prevention, and state public health agencies, to evaluate the risk for opioid-involved overdose (OOD) fatalities and related consequences. Our aim is to share the framework we developed for these ten JVAs, based on our study of the work of Van Handel et al. from 2016, as well as a summary of 18 publicly available assessments of OOD or associated hepatitis C virus infection vulnerability. We developed a three-tiered framework that can be applied by jurisdictions based on the number of units of analysis (e.g., counties, ZIP Codes, census tracts): under 10 (Tier 1), 10 to <50 (Tier 2), and 50 or more (Tier 3). We calculated OOD vulnerability indices based on variable ranks, weighted variable ranks, or multivariable regressions, respectively, for the three tiers. We developed thematic maps, conducted spatial analyses, and visualized service provider locations, drive-time service areas, and service accessibility relative to OOD risk. The methodological framework and examples of our findings from several jurisdictions can be used as a foundation for future assessments and help inform policies to mitigate the impact of the opioid overdose crisis.

Medical mistrust, discrimination, and COVID-19 vaccine behaviors among a national sample U.S. adults.

Background: COVID-19 vaccine uptake has been suboptimal and disparities in uptake have exacerbated health inequities. It has been postulated that mistrust in the healthcare system and experiences of discrimination or unfair treatment in other settings may be barriers to uptake of the COVID-19 vaccine, although few studies to date have investigated medical mistrust and perceived discrimination together. Method: We conducted a cross-sectional online survey between April 23-May 3, 2021, among a national sample of U.S. adults ages 18 years and older. We assessed receipt of and intention to be vaccinated for COVID-19 and associations with the validated Medical Mistrust Index and Everyday Discrimination Scale. Results: 1449 individuals responded, of whom 70.2% either had ≥1 dose of COVID-19 vaccine or reported that they were 'very' or 'somewhat' likely to be vaccinated in the future. In bivariate analyses, vaccination status was significantly associated with age, race/ethnicity, education, income, employment, marital status, health insurance, and political party affiliation. In multivariable analyses comparing those who had ≥1 vaccine dose or were likely to get vaccinated in the future with those who had not had any vaccine doses or did not intend to be vaccinated, each additional point in the Medical Mistrust Index was independently associated with a 16% decrease in the odds of vaccination (adjusted odds ratio = 0.84; 95% confidence interval = 0.81, 0.86). Discriminatory experiences were not associated with vaccination behavior or intention in bivariate or multivariable analyses. Conclusions: Medical mistrust is significantly associated with vaccination status and intentions. Increasing uptake of COVID-19 vaccines will likely require substantive efforts on the part of public health and healthcare officials to build trust with those who are not yet fully vaccinated. We recommend that these efforts focus on building the 'trustworthiness' of these entities, an approach that will require a paradigm shift away from a focus on correcting individual beliefs and knowledge, to acknowledging and addressing the root causes underlying mistrust.

Opioid-Involved Overdose Vulnerability in Wyoming: Measuring Risk in a Rural Environment.

BACKGROUND: Between 2009 and 2019 opioid-involved fatal overdose rates increased by 45% and the average opioid dispensing rate in Wyoming was higher than the national average. The opioid crisis is shaped by a complex set of socioeconomic, geopolitical, and health-related variables. We conducted a vulnerability assessment to identify Wyoming counties at higher risk of opioid-related harm, factors associated with this risk, and areas in need of overdose treatment access to inform priority responses. METHODS: We compiled 2016 to 2018 county-level aggregated and de-identified data. We created risk maps and ran spatial analyses in a geographic information system to depict the spatial distribution of overdose-related measures. We used addresses of opioid treatment programs and buprenorphine providers to develop drive-time maps and ran 2-step floating catchment area analyses to measure accessibility to treatment. We used a straightforward and replicable weighted ranks approach to calculate final county vulnerability scores and rankings from most to least vulnerable. FINDINGS: We found Hot Springs, Carbon, Natrona, Fremont, and Sweetwater Counties to be most vulnerable to opioid-involved overdose fatalities. Opioid prescribing rates were highest in Hot Springs County (97 per 100 persons), almost two times the national average (51 per 100 persons). Statewide, there were over 90 buprenorphine-waivered providers, however accessibility to these clinicians was limited to urban centers. Most individuals lived further than a four-hour round-trip drive to the nearest methadone treatment program. CONCLUSIONS: Identifying Wyoming counties with high opioid overdose vulnerabilities and limited access to overdose treatment can inform public health and harm reduction responses.

Spatial epidemiology: An empirical framework for syndemics research.

Syndemics framework describes two or more co-occurring epidemics that synergistically interact with each other and the complex structural social forces that sustain them leading to excess disease burden. The term syndemic was first used to describe the interaction between substance abuse, violence, and AIDS by Merrill Singer. A broader range of syndemic studies has since emerged describing the framework's applicability to other public health scenarios. With syndemic theory garnering significant attention, the focus is shifting towards developing robust empirical analytical approaches. Unfortunately, the complex nature of the disease-disease interactions nested within several social contexts complicates empirical analyses. In answering the call to analyze syndemics at the population level, we propose the use of spatial epidemiology as an empirical framework for syndemics research. Spatial epidemiology, which typically relies on geographic information systems (GIS) and statistics, is a discipline that studies spatial variations to understand the geographic landscape and the risk environment within which disease epidemics occur. GIS maps provide visualization aids to investigate the spatial distribution of disease outcomes, the associated social factors, and environmental exposures. Analytical inference, such as estimation of disease risks and identification of spatial disease clusters, can provide a detailed statistical view of spatial distributions of diseases. Spatial and spatiotemporal models can help us to understand, measure, and analyze disease syndemics as well as the social, biological, and structural factors associated with them in space and time. In this paper, we present a background on syndemics and spatial epidemiological theory and practice. We then present a case study focused on the HIV and HCV syndemic in West Virginia to provide an example of the use of GIS and spatial analytical methods. The concepts described in this paper can be considered to enhance understanding and analysis of other syndemics for which space-time data are available.

Prevalence and correlates of non-fatal overdose among people who use drugs: findings from rapid assessments in Massachusetts, 2017-2019.

BACKGROUND: People who experience non-fatal overdose (NFOD) are at high risk of subsequent overdose. With unprecedented increases in fentanyl in the US drug supply, many Massachusetts (MA) communities have seen a surge in opioid-related overdoses. The objective of this study was to determine factors associated with lifetime and past year NFOD in at-risk MA communities. METHODS: We conducted multiple rapid assessments among people who use drugs (PWUD) in eight MA communities using non-probability sampling (purposive, chain referral, respondent-driven) methods. We collected sociodemographic, substance use, overdose history, substance use treatment, and harm reduction services utilization data. We examined the prevalence of NFOD (lifetime and past year) and identified factors associated with NFOD through multivariable logistic regression analyses in a subset of 469 study participants between 2017 and 2019. RESULTS: The prevalence of lifetime and last year non-fatal opioid overdose was 62.5% and 36.9%, respectively. Many of the study participants reported heroin (64%) and fentanyl (45%) use during the 30 days preceding the survey. Nonprescription buprenorphine and fentanyl use were independently associated with higher odds of lifetime NFOD, while marijuana use was associated with lower odds of lifetime NFOD (p < 0.05). Injection as the route of administration, benzodiazepine, nonprescription buprenorphine, heroin, and fentanyl use were independently associated with higher odds, while methadone use was associated with lower odds of past year NFOD (p < 0.05). CONCLUSION: We documented a high prevalence of past year and lifetime NFOD among PWUD in MA. Our findings provide indicators that can help inform interventions to prevent overdoses among PWUD, including overdose prevention, medication treatment, and naloxone distribution.

Post-discharge healthcare utilization in infants with neonatal opioid withdrawal syndrome.

The opioid epidemic in the United States has led to a significant increase in the incidence of neonatal opioid withdrawal syndrome (NOWS); however, the understanding of long-term consequences of NOWS is limited. The objective of this study was to evaluate post-discharge healthcare utilization in infants with NOWS and examine the association between NOWS severity and healthcare utilization. A retrospective cohort design was used to ascertain healthcare utilization in the first year after birth-related discharge using the CERNER Health Facts® database. ICD-9/ICD-10 diagnostic codes were used to identify live births and to classify infants into two study groups: NOWS and uncomplicated births (a 25% random sample). Evaluated outcomes included rehospitalization, emergency department (ED) visits within 30-days and one-year after discharge, and a composite one-year utilization event (either hospitalization or emergency department visit during that year). NOWS severity was operationalized as pharmacologic treatment, length of hospitalization, and medical conditions often associated with NOWS. In 3,526 infants with NOWS (restricted to gestational age ≥ 33 weeks), NOWS severity was associated with an increase in composite one-year utilization (OR: 1.1; 95% CI: 1.04-1.2) after adjusting for prematurity, sepsis, jaundice, use of antibiotics, infant sex, insurance status, race, hospital bed size, year of birth, and census division. In a subset of full-term infants (3008 with NOWS and 88,452 uncomplicated births), having a NOWS diagnosis was associated with higher odds of a 30-day (OR: 1.6; 95% CI: 1.03-2.4) and one-year rehospitalization (OR: 1.6; 95% CI: 1.1-2.4) after adjusting for infant sex, race, type of medical insurance, hospital location, census division, year of primary encounter, hospital bed size, and medical conditions. This study found higher healthcare utilization during the first year of life in infants diagnosed with NOWS, especially those with severe NOWS. Findings suggest a need for closer post-discharge follow-up and management of infants with NOWS.

Characterizing opioid-involved overdose risk in local communities: An opioid overdose vulnerability assessment across Indiana, 2017.

The objective of this initiative was to conduct a comprehensive opioid overdose vulnerability assessment in Indiana and evaluate spatial accessibility to opioid use disorder treatment, harm reduction services, and opioid response programs. We compiled 2017 county-level (n = 92) data on opioid-related and socioeconomic indicators from publicly available state and federal sources. First, we assessed the spatial distribution of opioid-related indicators in a geographic information system (GIS). Next, we used a novel regression-weighted ranking approach with mean standardized covariates and an opioid-involved overdose mortality outcome to calculate county-level vulnerability scores. Finally, we examined accessibility to opioid use disorder treatment services and opioid response programs at the census tract-level (n = 1511) using two-step floating catchment area analysis. Opioid-related emergency department visit rate, opioid-related arrest rate, chronic hepatitis C virus infection rate, opioid prescription rate, unemployment rate, and percent of female-led households were independently and positively associated with opioid-involved overdose mortality (p < 0.05). We identified high-risk counties across the rural-urban continuum and primarily in east central Indiana. We found that only one of the 19 most vulnerable counties was in the top quintile for treatment services and had naloxone provider accessibility in all of its census tracts. Findings from our vulnerability assessment provide local-level context and evidence to support and inform future public health policies and targeted interventions in Indiana in areas with high opioid overdose vulnerability and low service accessibility. Our approach can be replicated in other state and local public health jurisdictions to assess opioid-involved public health vulnerabilities.

Self-regulation and emotional reactivity in infants with prenatal exposure to opioids and alcohol.

BACKGROUND: Infants with prenatal substance exposure are at increased risk for developmental problems, with self-regulatory challenges being some of the most pronounced. The current study aimed to investigate the extent to which prenatal substance exposure (alcohol, opioids) impacts infant self-regulation during a relational stressor and the association between self-regulation and infant affect. METHODS: Participants were 100 mother-child dyads recruited prenatally (Mean = 23.8 gestational weeks) and completed the Still Face Paradigm (SFP) when infants were 5 to 8 months of age (Mean = 6.9 months) as part of an ENRICH prospective birth cohort study. Based on prospective repeated assessment of maternal substance use in pregnancy, infants were grouped into: 1) Unexposed controls; 2) Alcohol-exposed; 3) Opioid-exposed due to maternal use of medications for opioid use disorder (MOUD) with or without other opioids; 4) MOUD and alcohol. Infant stress reactivity (negative affect) and self-regulation were assessed during the validated 5-episode SFP. Mixed effects linear models were used to analyze differences in the percent of self-regulation and percent of negative affect among the study groups across SFP episodes, as well as the group-by-self-regulation interaction with respect to infant negative affect. RESULTS: The MOUD+Alcohol group demonstrated significantly lower self-regulation at baseline compared to controls (p < 0.05). There was a significant group-by-self-regulation interaction (p = 0.028). Higher self-regulation was associated with lower negative affect across SFP episodes in the MOUD+Alcohol group (p = 0.025) but not other groups. CONCLUSION: Self-regulation skills are particularly important for emotional modulation in infants with prenatal polysubstance exposure, highlighting the development of these skills as a promising intervention target.

The association between prenatal alcohol exposure and protein expression in human placenta.

BACKGROUND: The need for earlier recognition of children at risk for neurobehavioral problems associated with prenatal ethanol exposure (PAE) has prompted investigations of biomarkers prognostic for altered fetal development. Here, we examined whether PAE alters the expression of angiogenesis-related proteins and cytokines in human placenta in subjects from an Ethanol, Neurodevelopment, Infant and Child Health prospective cohort. METHODS: PAE was ascertained by screening questionnaires, Time-line Follow-back interviews and a panel of ethanol biomarkers at two study visits. After delivery, placental tissue samples were collected for protein analysis. RESULTS: No significant differences in the prevalence of substance use, demographic or medical characteristics were observed between the No PAE and PAE groups. PAE was associated with significant reductions in placental expression of VEGFR2 and annexin-A4, while the levels of VEGFR1 and CCM-3 trended downward. A trend toward higher expression of the cytokines TNF-α and IL-13 was also observed in the PAE group. Receiver operating characteristic analyses of the data demonstrated a moderate-to-high degree of diagnostic accuracy for individual placental proteins. Combinations of proteins substantially increased their ability to differentiate between PAE and No PAE subjects. CONCLUSIONS: These results establish the feasibility of harvesting placental tissue for protein analyses of PAE in a prospective manner. In addition, given the importance of vascular remodeling in both placenta and developing brain, the role of angiogenic and cytokine proteins in this process warrants further investigation for their utility for predicting alterations in brain development, as well as their mechanistic role in PAE-induced pathology.

Association between prenatal opioid exposure, neonatal opioid withdrawal syndrome, and neurodevelopmental and behavioral outcomes at 5-8 months of age.

BACKGROUND: While use of prescription opioids and medication assisted therapy (MAT) for opioid use disorder in pregnancy, as well as the incidence of neonatal opioid withdrawal syndrome (NOWS) continue to rise, little is known about outcomes for children with NOWS beyond the newborn period. METHODS: We examined 1) prenatal MAT exposure vs. unexposed healthy controls [HC]; and 2) treatment for NOWS and NOWS severity on infant neurodevelopmental and behavioral outcomes at 5-8 months of age in 78 maternal-infant pairs from the ENRICH prospective cohort study. Data were obtained from 3 study visits: prenatal, delivery, and neurodevelopmental evaluation at 5-8 months of age. Neurodevelopmental outcomes included the Bayley Scales of Infant Development [BSID-III], caregiver questionnaires (Parenting Stress Index [PSI-SF], Infant Behavior Questionnaire [IBQ-R], Sensory Profile), and the experimental Still-Face Paradigm (SFP). RESULTS: No differences in the BSID-III, PSI-SF, or IBQ-R scores were observed between MAT and HC groups; however, MAT-exposed and HC infants differed with respect to SFP self-regulation (ß = -18.9; p = 0.01) and Sensory Profile sensation seeking (OR = 4.87; 95% CI: 1.55; 15.30) after adjusting for covariates. No significant differences between Treated-for-NOWS vs. not-Treated-for-NOWS were observed. Shorter timing to NOWS treatment initiation was associated with higher Total Stress (ß = -9.08; p = 0.035), while longer hospitalization was associated with higher Parent-child dysfunctional interaction (p = 0.018) on PSI-SF. CONCLUSIONS: Our results provide additional evidence of little-to-no effect of MAT and pharmacological treatment of NOWS on infant neurodevelopmental and behavioral outcomes at 5-8 months of age. However, prolonged hospitalization might increase family psychosocial stress and requires further examination.

Prevalence of alcohol use in pregnant women with substance use disorder.

BACKGROUND: Prenatal care programs for women with opioid use disorder (OUD) often focus treatment/counseling plans around illicit substances, while concurrent use of alcohol might present an equal or greater risk to the fetus. METHODS: This study evaluated self-reported prevalence of alcohol use in patients participating in a comprehensive prenatal care program for women with substance use disorder (SUD; n = 295), of which 95% are treated for OUD, and pregnant women being served through general obstetrical clinics at the University of New Mexico (n = 365). During the screening phase of a prospective study, patients were asked to report alcohol use in the periconceptional period, and between the last menstrual period and pregnancy recognition. RESULTS: The screening interview was conducted at 22.3 (median = 22; Q1 = 16; Q3 = 29) gestational weeks. Among patients screened at the SUD clinic, 28.8% and 24.1% reported at least one binge drinking episode in the periconceptional period and in early pregnancy, respectively. The prevalence of binge drinking was similar in the general obstetrics population (24.7% and 24.4%, respectively). Among those who reported drinking in early pregnancy, median number of binge drinking episodes was higher among patients screened at the SUD clinic (median = 3; Q1 = 1; Q3 = 10) compared to the general obstetrics group (median = 1; Q1 = 1; Q3 = 3; p < 0.001). CONCLUSIONS: This study demonstrates a high prevalence of prenatal alcohol use in early pregnancy in both groups, while patients with SUD/OUD consume more alcohol. These findings underscore the need for targeted screening and intervention for alcohol use in all pregnant women, especially those with SUD/OUD.

Challenges of diagnosing fetal alcohol spectrum disorders in foster and adopted children.

Fetal Alcohol Spectrum Disorders (FASD) might be 10-15 times more prevalent among foster/adopted children compared to the general population; however, many of these children remain undiagnosed or misdiagnosed. The lack of confirmed prenatal alcohol exposure (PAE) may be a key barrier to diagnosis. Our sample included 681 patients evaluated for FASD, according to the University of Washington 4-Digit Diagnostic Code, at a pediatric specialty clinic. Guardianship status and other patient characteristics were evaluated by multinomial logistic regression as potential predictors of being classified into one of the following FASD groups: 1) full or partial Fetal Alcohol Syndrome (FAS/pFAS; n = 97); 2) Static Encephalopathy/Alcohol-Exposed (SE/AE) or Neurobehavioral Disorder/Alcohol-Exposed (ND/AE) (n = 135); and 3) some features of FASD (equivalent to pFAS, SE/AE or ND/AE phenotypes) but unknown PAE (n = 449). Median age at assessment was 7.0 years, non-Hispanic White constituted the predominant racial/ethnic group (49.5%), and the majority (81.8%) lacked involvement from a biological parent/relative. Many patients (66.0%) had some features of FASD but lacked reliable PAE information. Children classified into the 'some features/unknown PAE' group had higher median age of assessment (8 years) compared to other groups (6 years; p < 0.001). No association was observed between race/ethnicity or child's sex and FASD outcomes (p > 0.05). Adopted/foster children were 2.8 times as likely (95% CI: 1.6; 4.8) to be classified into the 'some features/unknown PAE' group compared to children living with a parent/relative after adjusting for covariates. This study's findings indicate that adopted/foster children are more likely to have unknown PAE and not receive a FASD diagnosis, potentially denying them access to specialized services, treatment, and rehabilitation.