Faculty Bibliography

BACKGROUND/UNASSIGNED:The relationship between prenatal exposure to low-level air pollution and child autism spectrum disorder (ASD) is unclear. OBJECTIVE/UNASSIGNED:To examine associations of prenatal air pollution exposure with autism. METHODS/UNASSIGNED:quantiles) using quantile regression and with ASD diagnosis using logistic regression. Models were run within census divisions, and coefficients were pooled in a meta-analysis. RESULTS/UNASSIGNED:also was associated with ASD. DISCUSSION/UNASSIGNED:Associations with ASD outcomes were present even at low levels of air pollutants. https://doi.org/10.1289/EHP16675.

BACKGROUND:concentrations over 1998-2022 across the USA. METHODS:components with diameters below 1 μm were constrained by observations for four major components and from established scientific understanding for the other components. FINDINGS/RESULTS:ratio experienced simultaneous decrease (-0·0013 per year, p<0·0001). INTERPRETATION/CONCLUSIONS:. FUNDING/BACKGROUND:National Institute of Environmental Health Sciences, National Institutes of Health.

INTRODUCTION/BACKGROUND:Fentanyl-related deaths involving stimulants have increased in the US, but little is known about nonfatal overdoses involving use. We examined national trends in nonfatal fentanyl-related exposures involving co-use of cocaine or methamphetamine. METHODS:In this cross-sectional analysis, data from US poison centers were used to estimate annual trends in reported exposures involving fentanyl and stimulant use from 2015 to 2023. Cases included patients aged ≥13 with exposures involving intentional misuse or "abuse" of fentanyl where nonfatal adverse effects occurred (n=13,173). Co-exposure trends were examined, and multivariable logistic regression models were used to estimate how region and medical outcome severity were associated with (1) fentanyl-cocaine use (vs. fentanyl, no cocaine use) and (2) fentanyl-methamphetamine use (vs. fentanyl, no methamphetamine use). RESULTS:Between 2015 and 2023, among fentanyl-related exposures, cocaine use increased from 1.3% to 10.0% (669.2% increase, p<.001) and methamphetamine use increased from 1.5% to 10.8% (620.0% increase, p<.001). Exposures in the Northeast were associated with higher odds of cocaine co-use, while exposures in the Midwest, South, and West were associated with higher odds of methamphetamine co-use. Compared to those with less severe effects, those with a major (life-threatening) effect had higher odds of cocaine co-use, but lower odds of methamphetamine co-use. CONCLUSIONS:Similar to drug-related mortality trends, nonfatal fentanyl poisonings involving co-use of cocaine or methamphetamine increased in recent years and became increasingly widespread. Differences in experience of life-threatening adverse effects linked to different stimulants suggests varying risk according to which stimulant is involved.

IMPORTANCE/UNASSIGNED:In the context of the US opioid crisis, factors associated with the prevalence of opioid use disorder (OUD) must be identified to aid prevention and treatment. State medical cannabis laws (MCL) and recreational cannabis laws (RCL) are potential factors associated with OUD prevalence. OBJECTIVE/UNASSIGNED:To examine changes in OUD prevalence associated with MCL and RCL enactment among veterans treated at the Veterans Health Administration (VHA) and whether associations differed by age or chronic pain. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Using VHA electronic health records from January 2005 to December 2022, adjusted yearly prevalences of OUD were calculated, controlling for sociodemographic characteristics, receipt of prescription opioids, other substance use disorders, and time-varying state covariates. Staggered-adoption difference-in-difference analyses were used for estimates and 95% CIs for the relationship between MCL and RCL enactment and OUD prevalence. The study included VHA patients aged 18 to 75 years. The data were analyzed in December 2023. MAIN OUTCOME AND MEASURES/UNASSIGNED:International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) OUD diagnoses. RESULTS/UNASSIGNED:From 2005 to 2022, most patients were male (86.7.%-95.0%) and non-Hispanic White (70.3%-78.7%); the yearly mean age was 61.9 to 63.6 years (approximately 3.2 to 4.5 million patients per year). During the study period, OUD decreased from 1.12% to 1.06% in states without cannabis laws, increased from 1.13% to 1.19% in states that enacted MCL, and remained stable in states that also enacted RCL. OUD prevalence increased significantly by 0.06% (95% CI, 0.05%-0.06%) following MCL enactment and 0.07% (95% CI, 0.06%-0.08%) after RCL enactment. In patients aged 35 to 64 years and 65 to 75 years, MCL and RCL enactment was associated with increased OUD, with the greatest increase after RCL enactment among older adults (0.12%; 95% CI, 0.11%-0.13%). Patients with chronic pain had even larger increases in OUD following MCL (0.08%; 95% CI, 0.07%-0.09%) and RCL enactment (0.13%; 95% CI, 0.12%-0.15%). Consistent with overall findings, the largest increases in OUD occurred among patients with chronic pain aged 35 to 64 years following the enactment of MCL and RCL (0.09%; 95% CI, 0.07%-0.11%) and adults aged 65 to 75 years following RCL enactment (0.23%; 95% CI, 0.21%-0.25%). CONCLUSIONS AND RELEVANCE/UNASSIGNED:The results of this cohort study suggest that MCL and RCL enactment was associated with greater OUD prevalence in VHA patients over time, with the greatest increases among middle-aged and older patients and those with chronic pain. The findings did not support state cannabis legalization as a means of reducing the burden of OUD during the ongoing opioid epidemic.

BACKGROUND/UNASSIGNED:Organophosphate ester flame retardants and plasticizers (OPEs) have myriad uses in industry and consumer products. Increasing human exposure to OPEs has raised concerns about their potential effects on child neurodevelopment during pregnancy. OBJECTIVE/UNASSIGNED:We investigated whether OPE urinary concentrations during pregnancy were associated with child autism-related outcomes. METHODS/UNASSIGNED:We included 4159 mother-child pairs from 15 cohorts in the NIH Environmental influences on Child Health Outcomes (ECHO) Consortium, with children born from 2006-2020 (median age [interquartile range]: 6 [4,10] years). Nine OPE biomarkers were measured in urine samples collected mid- to late pregnancy. Dilution-adjusted biomarkers were modeled continuously, categorically (high [> median], moderate [≤ median], non-detect), or as detect/non-detect depending on their detection frequency. We assessed child autism-related traits via a) parent report on the Social Responsiveness Scale (SRS) and b) clinical autism diagnosis. We examined associations of OPEs with child outcomes, including modification by child sex, using generalized estimating equations to account for clustering by ECHO cohort. RESULTS/UNASSIGNED:Compared with non-detectable concentrations, high exposure to bis(butoxyethyl) phosphate (BBOEP) was associated with higher autistic trait scores (adj-β 0.97, 95% confidence interval [CI]: 0.42, 1.52) and greater odds of autism diagnosis (adjusted odds ratio [adj-OR]: 1.27, 95% CI: 1.07, 1.50). Bis(1-chloro-2-propyl) phosphate (BCPP) showed associations with autistic trait scores (BCPP adj-β for high exposure vs. non-detect: 0.34, 95% CI: -0.46, 1.13; BCPP adj-β for moderate exposure vs. non-detect: 0.72, 95% CI: 0.24, 1.20). High exposure to bis(2-chloroethyl) phosphate (BCETP) was associated with lower odds of autism diagnosis (adj-OR: 0.76, 95% CI: 0.60, 0.95). Other OPEs showed no associations in adjusted models. Associations between BBOEP and higher autistic trait scores were stronger in males than females. DISCUSSION/UNASSIGNED:Prenatal exposure to OPEs, specifically BCPP and BBOEP, may be associated with higher risk of autism diagnosis and related traits in childhood. https://doi.org/10.1289/EHP16177.

The objective of this study was to explore the buffering effect of support on the association between stress and postpartum depression (PPD) among immigrant women. We surveyed 223 Chinese pregnant or postpartum (within one year post-delivery) immigrant women in New York City. Surveys were conducted in English, Simplified Chinese or Mandarin, March-June 2021. PPD was measured with the Edinburgh PPD scale (EPDS); scores of 13 or higher indicate probable depression. Perceived stress was measured with one question, "How often did you feel stressed in the past week?"; responses were collapsed into a binary measure: Never/Rarely and Sometimes/Often/Always. Support was assessed with a general question about perception of receiving needed support and the Patient-Reported Outcomes Measurement Information System (PROMIS) V2.0 Short Form Informational, Instrumental, and Emotional Support measures. Bivariate and multivariable general linear regression models assessed the relationship among stress, support, and PPD. The EPDS mean score was 11.9 (95%CI:11.1-12.7) and 50% (95%CI: 42-57%) had EPDS scores ≥ 13, indicative of serious symptoms; 56% felt stressed in the past week and 37% reported getting needed support. Among women without perceived needed support, mean EPDS scores were higher among women who were stressed compared with women who were not (adjusted mean difference (aMD) 5.4; 95%CI:3.3-7.5); the association between stress and EPDS score was attenuated among women with needed support (aMD 1.1; 95%CI:-1.0, 3.1). Similar patterns held for emotional and instrumental support. Perceived and social support attenuated the association between perceived stress and depression symptoms among Chinese immigrant women. Enhancing support may be effective in countering the impact of stressors on PPD.

PurposeTo evaluate the association between demographic characteristics and weight-loss in response to financial incentives designed using behavioral economics.DesignRetrospective analysis of randomized clinical trial (RCT).SettingFIReWoRk RCT (NCT03157713), which found that financial incentives were more effective than provision of weight-management resources only for weight-loss.Subjects668 adults with obesity (221 in resources-only group, 447 in incentive groups) living in low-income neighborhoods.MeasuresDemographic characteristics and weight-loss.AnalysisLinear mixed-effects models with interaction terms to examine effect of incentives on weight-loss in different demographic groups.ResultsMean age of participants was 47.69 years, 81.0% were women, 72.6% were Hispanic, and mean BMI was 37.95 kg/m². Financial incentives increased percent weight loss at 6 months (difference in percent weight loss between financial incentive and resources-only group = -2.41%; 95% CI -3.23% to -1.58%). In fully adjusted models, participants who were Black lost less weight than participants who were White (difference in percent weight loss = 2.12%; 95% CI 0.25% to 3.99%). Differences in percent weight loss by sex, age, education and neighborhood income were absent. Models that tested for interactions between group assignment and percent weight loss did not demonstrate evidence of a heterogenous effect of incentives in sociodemographic subgroups.ConclusionBlack participants in the FIReWoRk intervention lost less weight than White participants, but effectiveness of financial incentives generally did not vary significantly by sociodemographic characteristics. However, it remains important to evaluate potential impacts of financial incentive programs on health disparities.

BACKGROUND:Maternal infections are linked to neurodevelopmental impairments, highlighting the need to investigate SARS-CoV-2-induced immune activation. OBJECTIVE:This study aimed to evaluate the impact of maternal infection on neurodevelopment and investigate whether cytokine and chemokine profiles predict delays at 24 months. METHODS:Conducted in Brazil (January 2021-March 2022), this follow-up study included 18 SARS-CoV-2 positive pregnant women at 35-37 weeks' gestation, 15 umbilical cord blood samples, and blood samples from 15 children at 6 months and 14 at 24 months. Developmental delay was defined using the Bayley Scales of Infant and Toddler Development, Third Edition, with scores below 90 in cognitive, communication, or motor domains. RESULTS:At 6 months, 33.3% of infants exhibited cognitive delays, 20% communication delays, and 40% motor delays, increasing to 35.71%, 64.29%, and 57.14% at 24 months, respectively. Elevated interferon-gamma and tumor necrosis factor-alpha in cord blood correlated with cognitive delays, while interleukin (IL)-6, IL-8, IL-17, and IL-1β were associated with motor delays. Increased C-X-C motif chemokine ligand 10 and other cytokines were associated with communication delays. CONCLUSION/CONCLUSIONS:Maternal SARS-CoV-2 may impact infant neurodevelopment, as early cytokine elevations correlate with delays, highlighting the importance of early monitoring and interventions to reduce long-term effects. IMPACT/CONCLUSIONS:Prenatal SARS-COV-2 infection in pregnant women is linked to developmental delays in toddlers, with cytokine and chemokine changes associated with neurodevelopmental outcomes at 24 months. This study shows the long-term impact of maternal SARS-COV-2 infection on child development, highlighting inflammatory markers like IFN-γ, TNFα, IL-6, IL-8, IL-17, IL-1β, and CXCL10. Identifying specific cytokines correlating with cognitive, communication, and motor delays suggests potential biomarkers for early intervention. Conducted in Fortaleza, Brazil, the study emphasizes understanding local epidemiological impacts on child development, especially in regions with high infection rates. Graphical depiction of the SARS-CoV-2-induced maternal immune activation and its impact on the child's neurological development. Maternal immune activation from SARS-CoV-2 infection can affect a baby's neurological development, leading to motor, communication, and cognitive delays, assessed at 6 and 24 months old. Alterations in cytokine and chemokine levels in cord blood at six months may help predict these adverse outcomes observed at 24 months.

Effective mild cognitive impairment (MCI) screening requires accessible testing. This study compared two tests for distinguishing MCI patients from controls: Rapid Automatized Naming (RAN) for naming speed and Low Contrast Letter Acuity (LCLA) for sensitivity to low contrast letters. Two RAN tasks were used: the Mobile Universal Lexicon Evaluation System (MULES, picture naming) and Staggered Uneven Number test (SUN, number naming). Both RAN tasks were administered on a tablet and in a paper/pencil format. The tablet format was administered using the Mobile Integrated Cognitive Kit (MICK) application. LCLA was tested at 2.5% and 1.25% contrast. Sixty-four participants (31 MCI, 34 controls; mean age 73.2 ± 6.8 years) were included. MCI patients were slower than controls for paper/pencil (75.0 vs. 53.6 sec, p < 0.001), and tablet MULES (69.0 sec vs. 50.2 sec, p = 0.01). The paper/pencil SUN showed no significant difference (MCI: 59.5 sec vs. controls: 59.9 sec, p = 0.07), nor did tablet SUN (MCI: 59.3 sec vs. controls: 55.7 sec, p = 0.36). MCI patients had worse performance on LCLA testing at 2.5% contrast (33 letters vs. 36, p = 0.04*) and 1.25% (0 letters vs. 14. letters, p < 0.001). Receiver operating characteristic (ROC) analysis showed similar performance of paper/pencil and tablet MULES in distinguishing MCI from controls (AUC = 0.77), outperforming both SUN (AUC = 0.63 paper, 0.59 tablet) and LCLA (2.5% contrast: AUC = 0.65, 1.25% contrast: AUC = 0.72). The MULES, in both formats, may be a valuable screening tool for MCI.

BACKGROUND:Our understanding of traditional atherosclerotic risk factors is based predominantly on one-time measurements and associations with adverse cardiovascular outcomes. OBJECTIVES/OBJECTIVE:The aim of this study was to evaluate the contribution of mid- to late-life cumulative risk factor exposure to healthy arterial aging, represented by a persistent coronary artery calcium (CAC) score of zero. METHODS:Among 2,044 community-dwelling, participants free of coronary heart disease from the ARIC (Atherosclerosis Risk in Communities) study, the associations of ∼30-year time-weighted average mid- to late-life (starting at a median age of 49 years in 1987-1989) traditional atherosclerotic risk factors (cholesterol, systolic blood pressure, fasting glucose, and smoking) with late-life (median age 80 years in 2018-2019) CAC 0 were evaluated. RESULTS:A total of 204 participants (10.0%) had CAC 0, and they tended to have more favorable mid- to late-life average risk factor profiles than those with CAC: lower total cholesterol, especially <160 mg/dL; lower systolic blood pressure, especially <125 mm Hg; and higher high-density lipoprotein cholesterol, especially >45 mg/dL. The association was less evident for fasting glucose, with no increased probability of CAC 0 at <95 mg/dL. Never smoking was associated with a 5.7 (95% CI: 2.3-16.7) times greater odds of CAC 0 vs smoking throughout mid- to late-life. Within sex-race groups, average modifiable risk factors predicted substantial differences in CAC 0 probability (eg, for a Black woman, 53% vs 0.4% for a low vs high risk factor profile, respectively). CONCLUSIONS:Favorable average risk factor profiles at mid- to late-life were associated with a greater probability of CAC 0 at older age. These results highlight the importance of maintaining a healthy risk factor profile from mid- to late-life, with implications for public health promotion and policy.