Faculty Bibliography

IMPORTANCE:Preeclampsia, gestational hypertension, and gestational diabetes, the most common pregnancy complications, are associated with substantial morbidity and mortality in mothers and children. Little is known about the biological processes that link the occurrence of these pregnancy complications with adverse child outcomes; altered biological aging of the growing fetus up to birth is one molecular pathway of increasing interest. OBJECTIVE:To evaluate whether exposure to each of these 3 pregnancy complications (gestational diabetes, gestational hypertension, and preeclampsia) is associated with accelerated or decelerated gestational biological age in children at birth. DESIGN, SETTING, AND PARTICIPANTS:Children included in these analyses were born between 1998 and 2018 and spanned multiple geographic areas of the US. Pregnancy complication information was obtained from maternal self-report and/or medical record data. DNA methylation measures were obtained from blood biospecimens collected from offspring at birth. The study used data from the national Environmental Influences on Child Health Outcomes (ECHO) multisite cohort study collected and recorded as of the August 31, 2021, data lock date. Data analysis was performed from September 2021 to December 2022. EXPOSURES:Three pregnancy conditions were examined: gestational hypertension, preeclampsia, and gestational diabetes. MAIN OUTCOMES AND MEASURES:Accelerated or decelerated biological gestational age at birth, estimated using existing epigenetic gestational age clock algorithms. RESULTS:A total of 1801 child participants (880 male [48.9%]; median [range] chronological gestational age at birth, 39 [30-43] weeks) from 12 ECHO cohorts met the analytic inclusion criteria. Reported races included Asian (49 participants [2.7%]), Black (390 participants [21.7%]), White (1026 participants [57.0%]), and other races (92 participants [5.1%]) (ie, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, multiple races, and other race not specified). In total, 524 participants (29.0%) reported Hispanic ethnicity. Maternal ages ranged from 16 to 45 years of age with a median of 29 in the analytic sample. A range of maternal education levels, from less than high school (260 participants [14.4%]) to Bachelor's degree and above (629 participants [34.9%]), were reported. In adjusted regression models, prenatal exposure to maternal gestational diabetes (β, -0.423; 95% CI, -0.709 to -0.138) and preeclampsia (β, -0.513; 95% CI, -0.857 to -0.170), but not gestational hypertension (β, 0.003; 95% CI, -0.338 to 0.344), were associated with decelerated epigenetic aging among exposed neonates vs those who were unexposed. Modification of these associations, by sex, was observed with exposure to preeclampsia (β, -0.700; 95% CI, -1.189 to -0.210) and gestational diabetes (β, -0.636; 95% CI, -1.070 to -0.200), with associations observed among female but not male participants. CONCLUSIONS AND RELEVANCE:This US cohort study of neonate biological changes related to exposure to maternal pregnancy conditions found evidence that preeclampsia and gestational diabetes delay biological maturity, especially in female offspring.

BACKGROUND:The within-person and between-sensor variability of metrics from different interstitial continuous glucose monitoring (CGM) sensors in adults with type 2 diabetes not taking insulin is unclear. METHODS:Secondary analysis of data from 172 participants from the Hyperglycemic Profiles in Obstructive Sleep Apnea randomized clinical trial. Participants simultaneously wore Dexcom G4 and Abbott Libre Pro CGM sensors for up to 2 weeks at baseline and again at the 3-month follow-up visit. RESULTS:At baseline (up to 2 weeks of CGM), mean glucose for both the Abbott and Dexcom sensors was approximately 150 mg/dL (8.3 mmol/L) and time in range (70-180 mg/dL [3.9-10.0 mmol/L]) was just below 80%. When comparing the same sensor at 2 different time points (two 2-week periods, 3 months apart), the within-person coefficient of variation (CVw) in mean glucose was 17.4% (Abbott) and 14.2% (Dexcom). CVw for percent time in range: 20.1% (Abbott) and 18.6% (Dexcom). At baseline, the Pearson correlation of mean glucose from the 2 sensors worn simultaneously was r = 0.86, root mean squared error (RMSE), 13 mg/dL (0.7 mmol/L); for time in range, r = 0.88, RMSE, 8 percentage points. CONCLUSIONS:Substantial variation was observed within sensors over time and across 2 different sensors worn simultaneously on the same individuals. Clinicians should be aware of this variability when using CGM technology to make clinical decisions. ClinicalTrials.gov Identifier: NCT02454153.

This study aims to assess the relationship between county-level fatal crash injuries and road environmental characteristics at all times of the day and during the rush and non-rush hour periods. We merged eleven-year (2010 - 2020) data from the Fatality Analysis Reporting System. The outcome variable was the county-level fatal crash injury counts. The predictor variables were measures of road types, junction types and work zone, and weather types. We tested the predictiveness of two nested negative binomial models and adjudged that a nested spatial negative binomial regression model outperformed the non-spatial negative binomial model. The median county crash mortality rates at all times of the day and during the rush and non-rush hour periods were 18.4, 7.7, and 10.4 per 100,000 population, respectively. Fatal crash injury rate ratios were significantly elevated on interstates and highways at all times of the day - rush and non-rush hour periods inclusive. Intersections, driveways, and ramps on highways were associated with elevated fatal crash injury rate ratios. Clusters of high fatal crash injury rates were observed in counties located in Montana, Nevada, Colorado, Kansas, New Mexico, Oklahoma, Texas, Arkansas, Mississippi, Alabama, Georgia, and Nevada. The built and natural road environment factors are associated with county-level fatal crash injuries during the rush and non-rush hour periods. Understanding the association of road environment characteristics and the cluster distribution of fatal crash injuries may inform areas in need of focused intervention.

Compared with non-Hispanic White women, Latina women are less likely to receive genetic counseling (GC) and testing (GT) following BC diagnosis. This study used secondary data analysis to explore beliefs about GC among Latina BC survivors in and outside the US mainland. GC/GT-naïve, high-risk, Spanish-preferring Latina BC survivors (n = 52) in FL and PR completed the Behavioral Beliefs about GC scale. Participants reported high positive beliefs about GC (M = 4.19, SD = 0.92); the majority agreed that GC was beneficial to understand cancer risk (90%) and promote discussion (87%) in their family. Participants reported low-to-moderate scores for barriers (Ms = 1.53-3.40; SDs = 0.59-0.90). The most frequently endorsed barriers were desire for additional GC information (M = 3.44; SD = 0.90), and GC logistic concerns (M = 2.71; SD = 0.80). No statistically significant differences for barriers and benefits scales were identified by place of residence (all ps ≥ 0.12). These findings highlight the importance of delivering culturally sensitive GC information to high-risk Latina BC survivors.

AIMS:To estimate recent trends in cigarette use and health insurance coverage for United States adults with and without mental health and substance use disorders (MH/SUD). DESIGN:Event study analysis of smoking and insurance coverage trends among US adults with and without MH/SUD using 2008-19 public use data from the National Survey on Drug Use and Health, an annual, cross-sectional survey. SETTING:USA. PARTICIPANTS:A nationally representative sample of non-institutionalized respondents aged 18-64 years (n = 448 762). MEASUREMENTS:Outcome variables were three measures of recent cigarette use and one measure of past-year health insurance coverage. We compared outcomes between people with and without MH/SUD (MH disorder: past-year mental illness, predicted from Kessler-6 and the World Health Organization-Disability Assessment Schedule impairment scale; SUD: met survey-based DSM-IV criteria for past-year alcohol, cannabis, cocaine or heroin use disorder) and over time. FINDINGS:Comparing pooled data from 2008 to 2009 and from 2018 to 2019, current smoking rates of adults with MH/SUD decreased from 37.9 to 27.9% while current smoking rates of adults without MH/SUD decreased from 21.4 to 16.3%, a significant difference in decrease of 4.9 percentage points (pts) [95% confidence interval (CI) = 3.3-6.6 pts]. Daily smoking followed similar patterns (difference in decrease of 3.9 pts (95% CI = 2.3-5.4 pts). Recent smoking abstinence rates for adults with MH/SUD increased from 7.4 to 10.9%, while recent smoking abstinence rates for adults without MH/SUD increased from 9.6 to 12.0%, a difference in increase of 1.0 pts (95% CI = -3.0 to 0.9 pts). In 2018-19, 11% of net reductions in current smoking, 12% of net reductions in daily smoking and 12% of net increases in recent smoking abstinence coincided with greater gains in insurance coverage for adults with MH/SUD compared to those without MH/SUD. CONCLUSIONS:Improvements in smoking and abstinence outcomes for US adults with mental health and substance use disorders appear to be associated with increases in health insurance coverage.

Climate change may affect mental health. We conducted an umbrella review of meta-analyses examining the association between mental health and climate events related to climate change, pollution and green spaces. We searched major bibliographic databases and included meta-analyses with at least five primary studies. Results were summarized narratively. We included 24 meta-analyses on mental health and climate events (n = 13), pollution (n = 11), and green spaces (n = 2) (two meta-analyses provided data on two categories). The quality was suboptimal. According to AMSTAR-2, the overall confidence in the results was high for none of the studies, for three it was moderate, and for the other studies the confidence was low to critically low. The meta-analyses on climate events suggested an increased prevalence of symptoms of post-traumatic stress, depression, and anxiety associated with the exposure to various types of climate events, although the effect sizes differed considerably across study and not all were significant. The meta-analyses on pollution suggested that there may be a small but significant association between PM_2.5, PM₁₀, NO₂, SO₂, CO and mental health, especially depression and suicide, as well as autism spectrum disorders after exposure during pregnancy, but the resulting effect sizes varied considerably. Serious methodological flaws make it difficult to draw credible conclusions. We found reasonable evidence for an association between climate events and mental health and some evidence for an association between pollution and mental disorders. More high-quality research is needed to verify these associations.

Peer-driven interventions can be effective in reducing HIV injection risk behaviors among people who inject drugs (PWID). We employed a causal mediation framework to examine the mediating role of recall of intervention knowledge in the relationship between a peer-driven intervention and subsequent self-reported HIV injection-related risk behavior among PWID in the HIV Prevention Trials Network (HPTN) 037 study. For each intervention network, the index participant received training at baseline to become a peer educator, while non-index participants and all participants in the control networks received only HIV testing and counseling; recall of intervention knowledge was measured at the 6-month visit for each participant, and each participant was followed to ascertain HIV injection-related risk behaviors at the 12-month visit. We used inverse probability weighting to fit marginal structural models to estimate the total effect (TE) and controlled direct effect (CDE) of the intervention on the outcome. The proportion eliminated (PE) by intervening to remove mediation by the recall of intervention knowledge was computed. There were 385 participants (47% in intervention networks) included in the analysis. The TE and CDE risk ratios for the intervention were 0.47 [95% confidence interval (CI): 0.28, 0.78] and 0.73 (95% CI: 0.26, 2.06) and the PE was 49%. Compared to participants in the control networks, the peer-driven intervention reduced the risk of HIV injection-related risk behavior by 53%. The mediating role of recall of intervention knowledge accounted for less than 50% of the total effect of the intervention, suggesting that other potential causal pathways between the intervention and the outcome, such as motivation and skill, self-efficacy, social norms and behavior modeling, should be considered in future studies.

RATIONALE & OBJECTIVE/OBJECTIVE:Anemia is common in chronic kidney disease (CKD); although anemia is associated with adverse outcomes, the available treatments are not ideal. We characterized the burden, risk factors for, and risks associated with anemia by estimated glomerular filtration rate (eGFR) and hemoglobin level. STUDY DESIGN/METHODS:Cross-sectional and prospective cohort study. SETTING & PARTICIPANTS/METHODS:Outpatient data from 5,004,957 individuals across 57 health care centers in the United States from 2016 to 2019, extracted from the Optum Labs Data Warehouse. EXPOSURE/METHODS:Severity of anemia, presence of low iron test results, eGFR. OUTCOME/RESULTS:Incident kidney failure with replacement therapy, cardiovascular disease, coronary heart disease, stroke, heart failure, death. ANALYTICAL APPROACH/METHODS:deficiency, and erythropoiesis-stimulating agent (ESA) use, stratified by sex and eGFR, were characterized. Polychotomous logistic regression was used to estimate the adjusted odds ratios of different hemoglobin levels across eGFR. Cox proportional hazards regression was used to calculate adjusted hazard ratios for adverse outcomes across hemoglobin level. RESULTS:The mean age was 54 years, and 42% were male. Lower eGFR was very strongly associated with increased prevalence of anemia, even after adjustment. Although iron studies were checked infrequently in patients with anemia, low iron test results were highly prevalent in those tested: 60.4% and 81.3% of men and women, respectively. ESA use was uncommon, with a prevalence of use of<4%. Lower hemoglobin was independently associated with increased risk of incident kidney failure with replacement therapy, cardiovascular disease, coronary heart disease, stroke, heart failure, and death. LIMITATIONS/CONCLUSIONS:Reliance on ICD codes for medical diagnoses, death information obtained from claims data, observational study. CONCLUSIONS:Severe anemia was common and strongly associated with lower eGFR and multiple adverse outcomes. Low-iron test results were highly prevalent in those tested despite iron studies being checked infrequently. ESA use in nondialysis CKD patients was uncommon.