Ethnoracial Disparities in Nitrogen Dioxide Pollution in the United States: Comparing Data Sets from Satellites, Models, and Monitors.

In the United States (U.S.), studies on nitrogen dioxide (NO2) trends and pollution-attributable health effects have historically used measurements from in situ monitors, which have limited geographical coverage and leave 66% of urban areas unmonitored. Novel tools, including remotely sensed NO2 measurements and estimates of NO2 estimates from land-use regression and photochemical models, can aid in assessing NO2 exposure gradients, leveraging their complete spatial coverage. Using these data sets, we find that Black, Hispanic, Asian, and multiracial populations experience NO2 levels 15-50% higher than the national average in 2019, whereas the non-Hispanic White population is consistently exposed to levels that are 5-15% lower than the national average. By contrast, the in situ monitoring network indicates more moderate ethnoracial NO2 disparities and different rankings of the least- to most-exposed ethnoracial population subgroup. Validating these spatially complete data sets against in situ observations reveals similar performance, indicating that all these data sets can be used to understand spatial variations in NO2. Integrating in situ monitoring, satellite data, statistical models, and photochemical models can provide a semiobservational record, complete geospatial coverage, and increasingly high spatial resolution, enhancing future efforts to characterize, map, and track exposure and inequality for highly spatially heterogeneous pollutants like NO2.

Insights from Application of a Hierarchical Spatio-Temporal Model to an Intensive Urban Black Carbon Monitoring Dataset.

Existing regulatory pollutant monitoring networks rely on a small number of centrally located measurement sites that are purposefully sited away from major emission sources. While informative of general air quality trends regionally, these networks often do not fully capture the local variability of air pollution exposure within a community. Recent technological advancements have reduced the cost of sensors, allowing air quality monitoring campaigns with high spatial resolution. The 100×100 black carbon (BC) monitoring network deployed 100 low-cost BC sensors across the 15 km2 West Oakland, CA community for 100 days in the summer of 2017, producing a nearly continuous site-specific time series of BC concentrations which we aggregated to one-hour averages. Leveraging this dataset, we employed a hierarchical spatio-temporal model to accurately predict local spatio-temporal concentration patterns throughout West Oakland, at locations without monitors (average cross-validated hourly temporal R 2=0.60). Using our model, we identified spatially varying temporal pollution patterns associated with small-scale geographic features and proximity to local sources. In a sub-sampling analysis, we demonstrated that fine scale predictions of nearly comparable accuracy can be obtained with our modeling approach by using ~30% of the 100×100 BC network supplemented by a shorter-term high-density campaign.

Prenatal and childhood exposure to per- and polyfluoroalkyl substances (PFAS) and child executive function and behavioral problems.

Early life exposure to per- and polyfluoroalkyl substances (PFAS) may adversely impact neurodevelopment, but epidemiological findings are inconsistent. In the Project Viva pre-birth cohort, we examined associations of prenatal and childhood PFAS plasma concentrations with parent and teacher assessments of children's behavior problems [Strengths and Difficulties Questionnaire (SDQ)] and executive function abilities [Behavior Rating Inventory of Executive Function (BRIEF)] at age 6-10 years (sample sizes 485-933). PFAS concentrations in pregnant Project Viva mothers (in 1999-2002) and children at ages 6-10 (in 2007-10) were similar to concentrations at similar time points in women and children in the nationally representative U.S. National Health and Nutrition Examination Survey. We observed no consistent associations of prenatal PFAS concentrations with behavior or executive function. Childhood concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) were associated with higher parent-rated SDQ Total Difficulties scores (mean = 6.7, standard deviation (SD) = 4.9), suggesting greater behavioral problems (top (Q4) versus bottom (Q1) quartile PFOA: 1.5, 95% confidence interval (CI): 0.3, 2.7; PFOS: 1.4, 95% CI: 0.3, 2.5; PFHxS: 1.2, 95% CI: 0.1, 2.3; PFNA: 1.2, 95% CI: 0.1, 2.2; PFDA: 1.1, 95% CI: 0.0, 1.1); teacher-rated SDQ scores did not show associations. Higher childhood PFOS was associated with higher (indicating more problems) parent-rated BRIEF General Executive Composite (GEC) scores (standardized to mean = 50, SD = 10) (Q4 vs. Q1: 2.4, 95% CI: 0.2, 4.6), while teacher BRIEF GEC scores indicated more problems among children with higher PFHxS (Q4 vs. Q1: 3.5, 95% CI: -0.8, 6.3). There were no consistent patterns of sexual dimorphism in associations. In a cohort of U.S. children, we observed cross-sectional associations of childhood PFAS concentrations with greater behavioral and executive function problems, but no consistent associations with prenatal PFAS.

[Evaluation of aspects of mental health in health personnel in the context of the COVID-19 pandemic]. / Evaluación de aspectos de la salud mental en trabajadores hospitalarios en el contexto de la pandemia de COVID-19.

In the global and national context of the COVID 19 pandemic, early detection and prevention of mental illnesses in exposed populations is relevant in situations of extreme demand. In this context, hospital workers are a highly demanded population being a clear risk group. This work shows the partial results of an investigation that is being carried out by the Mental Health Service of the General Hospital "B. Rivadavia", of the Autonomous City of Buenos Aires (CABA), which aims to evaluate some aspects of the mental health of its staff. A survey is underway that was proposed by the members of the Mental Health Service to the different sectors of the Hospital and sent electronically. The survey includes indicators of the following aspects: symptoms of stress, the depressive and anxious series and consumption of psychoactive substances. Partial results show clear involvement of health personnel in different areas evaluated.

Predictors of Per- and Polyfluoroalkyl Substance (PFAS) Plasma Concentrations in 6-10 Year Old American Children.

Certain per- and polyfluoroalkyl substances (PFASs) are suspected developmental toxicants, but data on PFAS concentrations and exposure routes in children are limited. We measured plasma PFASs in children aged 6-10 years from the Boston-area Project Viva prebirth cohort, and used multivariable linear regression to estimate associations with sociodemographic, behavioral, and health-related factors, and maternal PFASs measured during pregnancy. PFAS concentrations in Project Viva children (sampled 2007-2010) were similar to concentrations among youth participants (aged 12-19 years) in the 2007-8 and 2009-10 National Health and Nutrition Examination Survey (NHANES); mean concentrations of most PFASs declined from 2007 to 2010 in Project Viva and NHANES. In mutually adjusted models, predictors of higher PFAS concentrations included older child age, lower adiposity, carpeting or a rug in the child's bedroom, higher maternal education, and higher neighborhood income. Concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexanesulfonate (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH) were 26-36% lower in children of black mothers compared to children of white mothers and increased 12-21% per interquartile range increase in maternal pregnancy PFASs. Breastfeeding duration did not predict childhood PFAS concentrations in adjusted multivariable models. Together, the studied predictors explained the observed variability in PFAS concentrations to only a modest degree.

Sociodemographic and Perinatal Predictors of Early Pregnancy Per- and Polyfluoroalkyl Substance (PFAS) Concentrations.

Per- and polyfluoroalkyl substances (PFASs), used in food packaging and stain-resistant coatings, are suspected developmental toxicants that are ubiquitous and persistent in the environment. We measured plasma PFAS concentrations during early pregnancy (median = 9.7 weeks gestation) among 1645 women in the Boston-area Project Viva cohort, recruited during 1999-2002. We used multivariable linear regression to estimate associations of sociodemographic and perinatal predictors, including measures of pregnancy physiology (albumin, glomerular filtration rate (GFR)), with log-transformed plasma PFAS concentrations. Geometric mean concentrations for the four main PFASs, perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexanesulfonate (PFHxS) and perfluorononanoate (PFNA) were 25.4, 5.7, 2.5, and 0.6 ng/mL, respectively, comparable with general U.S. population concentrations during those years. Higher early pregnancy PFAS concentrations were associated with younger age (except PFNA), less educational attainment, nulliparity, no history of breastfeeding and higher prepregnancy body mass index in adjusted models. In addition, lower GFR was associated with 3-4% higher PFAS concentrations and higher albumin was associated with 4-6% higher PFAS concentrations. Our results show associations consistent (parity and breastfeeding) and less consistent (age and education) with previous studies. We also report associations with GFR and albumin, which were strongly related to PFAS concentrations and thus could confound estimates of PFAS-outcome associations in epidemiologic studies.

Effects of fine particulate matter and its constituents on low birth weight among full-term infants in California.

Relationships between prenatal exposure to fine particles (PM2.5) and birth weight have been observed previously. Few studies have investigated specific constituents of PM2.5, which may identify sources and major contributors of risk. We examined the effects of trimester and full gestational prenatal exposures to PM2.5 mass and 23 PM2.5 constituents on birth weight among 646,296 term births in California between 2000 and 2006. We used linear and logistic regression models to assess associations between exposures and birth weight and risk of low birth weight (LBW; <2500g), respectively. Models were adjusted for individual demographic characteristics, apparent temperature, month and year of birth, region, and socioeconomic indicators. Higher full gestational exposures to PM2.5 mass and several PM2.5 constituents were significantly associated with reductions in term birth weight. The largest reductions in birth weight were associated with exposure to vanadium, sulfur, sulfate, iron, elemental carbon, titanium, manganese, bromine, ammonium, zinc, and copper. Several of these PM2.5 constituents were associated with increased risk of term LBW. Reductions in birth weight were generally larger among younger mothers and varied by race/ethnicity. Exposure to specific constituents of PM2.5, especially traffic-related particles, sulfur constituents, and metals, were associated with decreased birth weight in California.

Satellite data for environmental justice: a scoping review of the literature in the United States.

In support of the environmental justice (EJ) movement, researchers, activists, and policymakers often use environmental data to document evidence of the unequal distribution of environmental burdens and benefits along lines of race, class, and other socioeconomic characteristics. Numerous limitations, such as spatial or temporal discontinuities, exist with commonly used data measurement techniques, which include ground monitoring and federal screening tools. Satellite data is well poised to address these gaps in EJ measurement and monitoring; however, little is known about how satellite data has advanced findings in EJ or can help to promote EJ through interventions. Thus, this scoping review aims to (1) explore trends in study design, topics, geographic scope, and satellite datasets used to research EJ, (2) synthesize findings from studies that use satellite data to characterize disparities and inequities across socio-demographic groups for various environmental categories, and (3) capture how satellite data are relevant to policy and real-world impact. Following PRISMA extension guidelines for scoping reviews, we retrieved 81 articles that applied satellite data for EJ research in the United States from 2000 to 2022. The majority of the studies leveraged the technical advantages of satellite data to identify socio-demographic disparities in exposure to environmental risk factors, such as air pollution, and access to environmental benefits, such as green space, at wider coverage and with greater precision than previously possible. These disparities in exposure and access are associated with health outcomes such as increased cardiovascular and respiratory diseases, mental illness, and mortality. Research using satellite data to illuminate EJ concerns can contribute to efforts to mitigate environmental inequalities and reduce health disparities. Satellite data for EJ research can therefore support targeted interventions or influence planning and policy changes, but significant work remains to facilitate the application of satellite data for policy and community impact.

Plasma concentrations of per- and polyfluoroalkyl substances in pregnancy and breastfeeding duration in Project Viva.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) may disrupt mammary gland development and function; thereby inhibiting milk supply and breastfeeding duration. However, conclusions on the potential effects of PFAS and breastfeeding duration are limited by prior epidemiologic studies that inconsistently adjusted for past cumulative breastfeeding duration and by a lack of examination of the joint effects of PFAS mixtures. METHODS: In Project Viva, a longitudinal cohort that enrolled pregnant participants from 1999 to 2002 in the greater Boston, MA area, we studied 1079 women who ever attempted to lactate. We investigated associations of plasma concentrations of select PFAS in early pregnancy (mean: 10.1 weeks gestation) with breastfeeding termination by 9 months, after which women typically cite self-weaning as the reason for terminating breastfeeding. We used Cox regression for single-PFAS models and quantile g-computation for mixture models, adjusting for sociodemographics, prior breastfeeding duration, and weeks of gestation at the time of blood draw. RESULTS: We detected 6 PFAS [perfluorooctane sulfonate; perfluorooctanoate (PFOA); perfluorohexane sulfonate; perfluorononanoate; 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA); 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA)] in >98 % of samples. Sixty percent of lactating women terminated breastfeeding by 9 months postpartum. Women with higher plasma concentrations of PFOA, EtFOSAA, and MeFOSAA had a greater hazard of terminating breastfeeding in the first 9 months postpartum [HR (95 % CI) per doubling concentration: 1.20 (1.04, 1.38) for PFOA; 1.10 (1.01, 1.20) for EtFOSAA; 1.18 (1.08, 1.30) for MeFOSAA]. In the quantile g-computation model, simultaneously increasing all PFAS in the mixture by one quartile was associated with 1.17 (95 % CI: 1.05, 1.31) greater hazard of terminating breastfeeding in the first 9 months. CONCLUSION: Our findings suggest that exposure to PFAS may be associated with reduced breastfeeding duration and draw further attention to environmental chemicals that may dysregulate human lactation.

State-of-the-Science Data and Methods Need to Guide Place-Based Efforts to Reduce Air Pollution Inequity.

BACKGROUND: Recently enacted environmental justice policies in the United States at the state and federal level emphasize addressing place-based inequities, including persistent disparities in air pollution exposure and associated health impacts. Advances in air quality measurement, models, and analytic methods have demonstrated the importance of finer-scale data and analysis in accurately quantifying the extent of inequity in intraurban pollution exposure, although the necessary degree of spatial resolution remains a complex and context-dependent question. OBJECTIVE: The objectives of this commentary were to a) discuss ways to maximize and evaluate the effectiveness of efforts to reduce air pollution disparities, and b) argue that environmental regulators must employ improved methods to project, measure, and track the distributional impacts of new policies at finer geographic and temporal scales. DISCUSSION: The historic federal investments from the Inflation Reduction Act, the Infrastructure Investment and Jobs Act, and the Biden Administration's commitment to Justice40 present an unprecedented opportunity to advance climate and energy policies that deliver real reductions in pollution-related health inequities. In our opinion, scientists, advocates, policymakers, and implementing agencies must work together to harness critical advances in air quality measurements, models, and analytic methods to ensure success. https://doi.org/10.1289/EHP13063.

Challenges and opportunities for overcoming dog use in agrochemical evaluation and registration.

Progress in developing new tools, assays, and approaches to assess human hazard and health risk provides an opportunity to re-evaluate the necessity of dog studies for the safety evaluation of agrochemicals. A workshop was held where partic­ipants discussed the strengths and limitations of past use of dogs for pesticide evaluations and registrations. Opportunities were identified to support alternative approaches to answer human safety questions without performing the required 90-day dog study. Development of a decision tree for determining when the dog study might not be necessary to inform pesticide safety and risk assessment was proposed. Such a process will require global regulatory authority participation to lead to its acceptance. The identification of unique effects in dogs that are not identified in rodents will need further evaluation and determination of their relevance to humans. The establishment of in vitro and in silico approaches that can provide critical data on relative species sensitivity and human relevance will be an important tool to advance the decision process. Promising novel tools including in vitro comparative metabolism studies, in silico models, and high-throughput assays able to identify metabolites and mechanisms of action leading to development of adverse outcome pathways will need further development. To replace or eliminate the 90-day dog study, a collaborative, multidisciplinary, international effort that transcends organi­zations and regulatory agencies will be needed in order to develop guidance on when the study would not be necessary for human safety and risk assessment.

National and Intraurban Air Pollution Exposure Disparity Estimates in the United States: Impact of Data-Aggregation Spatial Scale.

Air pollution exposure disparities by race/ethnicity and socioeconomic status have been analyzed using data aggregated at various spatial scales. Our research question is this: To what extent does the spatial scale of data aggregation impact the estimated exposure disparities? We compared disparities calculated using data spatially aggregated at five administrative scales (state, county, census tract, census block group, census block) in the contiguous United States in 2010. Specifically, for each of the five spatial scales, we calculated national and intraurban disparities in exposure to fine particles (PM2.5) and nitrogen dioxide (NO2) by race/ethnicity and socioeconomic characteristics using census demographic data and an empirical statistical air pollution model aggregated at that scale. We found, for both pollutants, that national disparity estimates based on state and county scale data often substantially underestimated those estimated using tract and finer scales; in contrast, national disparity estimates were generally consistent using tract, block group, and block scale data. Similarly, intraurban disparity estimates based on tract and finer scale data were generally well correlated for both pollutants across urban areas, although in some cases intraurban disparity estimates were substantially different, with tract scale data more frequently leading to underestimates of disparities compared to finer scale analyses.

Assessing the Distribution of Air Pollution Health Risks within Cities: A Neighborhood-Scale Analysis Leveraging High-Resolution Data Sets in the Bay Area, California.

BACKGROUND: Air pollution-attributable disease burdens reported at global, country, state, or county levels mask potential smaller-scale geographic heterogeneity driven by variation in pollution levels and disease rates. Capturing within-city variation in air pollution health impacts is now possible with high-resolution pollutant concentrations. OBJECTIVES: We quantified neighborhood-level variation in air pollution health risks, comparing results from highly spatially resolved pollutant and disease rate data sets available for the Bay Area, California. METHODS: We estimated mortality and morbidity attributable to nitrogen dioxide (NO2), black carbon (BC), and fine particulate matter [PM ≤2.5µm in aerodynamic diameter (PM2.5)] using epidemiologically derived health impact functions. We compared geographic distributions of pollution-attributable risk estimates using concentrations from a) mobile monitoring of NO2 and BC; and b) models predicting annual NO2, BC and PM2.5 concentrations from land-use variables and satellite observations. We also compared results using county vs. census block group (CBG) disease rates. RESULTS: Estimated pollution-attributable deaths per 100,000 people at the 100-m grid-cell level ranged across the Bay Area by a factor of 38, 4, and 5 for NO2 [mean=30 (95% CI: 9, 50)], BC [mean=2 (95% CI: 1, 2)], and PM2.5, [mean=49 (95% CI: 33, 64)]. Applying concentrations from mobile monitoring and land-use regression (LUR) models in Oakland neighborhoods yielded similar spatial patterns of estimated grid-cell-level NO2-attributable mortality rates. Mobile monitoring concentrations captured more heterogeneity [mobile monitoring mean=64 (95% CI: 19, 107) deaths per 100,000 people; LUR mean=101 (95% CI: 30, 167)]. Using CBG-level disease rates instead of county-level disease rates resulted in 15% larger attributable mortality rates for both NO2 and PM2.5, with more spatial heterogeneity at the grid-cell-level [NO2 CBG mean=41 deaths per 100,000 people (95% CI: 12, 68); NO2 county mean=38 (95% CI: 11, 64); PM2.5 CBG mean=59 (95% CI: 40, 77); and PM2.5 county mean=55 (95% CI: 37, 71)]. DISCUSSION: Air pollutant-attributable health burdens varied substantially between neighborhoods, driven by spatial variation in pollutant concentrations and disease rates. https://doi.org/10.1289/EHP7679.

Prenatal Organophosphate Pesticide Exposure and Traits Related to Autism Spectrum Disorders in a Population Living in Proximity to Agriculture.

BACKGROUND: Prenatal exposure to organophosphate (OP) pesticides has been linked with poorer neurodevelopment and behaviors related to autism spectrum disorders (ASD) in previous studies, including in the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a birth cohort living in the agricultural Salinas Valley in California. OBJECTIVES: To investigate the association of prenatal exposure to OP pesticides with traits related to ASD, in childhood and adolescents in CHAMACOS. METHODS: We assessed OP exposure during pregnancy with measurements of dialkyl phosphates (DAP) metabolites in urine, and residential proximity to OP use during pregnancy using California's Pesticide Use Reporting (PUR) data and estimated associations with ASD-related traits using linear regression models. We measured traits reported by parents and teachers as well as the child's performance on tests that evaluate the ability to use facial expressions to recognize the mental state of others at 7, 101/2, and 14 years of age. RESULTS: Prenatal DAPs were associated with poorer parent and teacher reported social behavior [e.g., a 10-fold DAP increase was associated with a 2.7-point increase (95% confidence interval (CI): 0.9, 4.5) in parent-reported Social Responsiveness Scale, Version 2, T-scores at age 14]. We did not find clear evidence of associations between residential proximity to OP use during pregnancy and ASD-related traits. CONCLUSIONS: These findings contribute mixed evidence linking OP pesticide exposures with traits related to developmental disorders like ASD. Subtle pesticide-related effects on ASD-related traits among a population with ubiquitous exposure could result in a rise in cases of clinically diagnosed disorders like ASD. https://doi.org/10.1289/EHP2580.

Prenatal and childhood exposure to per- and polyfluoroalkyl substances (PFASs) and child cognition.

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are suspected developmental toxicants, but epidemiological evidence on neurodevelopmental effects of PFAS exposure is inconsistent. We examined associations of prenatal and childhood PFAS exposure with performance on assessments of cognition in children. METHODS: We included mother-child pairs from Project Viva, a longitudinal Boston-area birth cohort enrolled during 1999-2002. We quantified concentrations of eight PFASs, including perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexane sulfonate (PFHxS), in plasma collected from women during pregnancy (median 9.7 weeks gestation) and from children at a visit in mid-childhood (median age 7.7 years). In early childhood (median age 3.2 years) we administered standardized assessments of visual motor skills and vocabulary comprehension, and in mid-childhood we assessed visual motor skills, visual memory, and verbal and non-verbal intelligence. Using multivariable regression, we estimated associations of prenatal and childhood PFAS plasma concentrations with children's cognitive assessment scores, adjusted for relevant covariates including breastfeeding, maternal intelligence, parental education, and household income. Samples sizes ranged from 631 to 971, depending on analysis. RESULTS: Prenatal PFAS concentrations were associated with both better and worse cognitive performance; children with top quartile prenatal concentrations of some PFASs had better visual motor abilities in early childhood and non-verbal IQ and visual memory in mid-childhood, while children with upper quartile prenatal PFOA and PFOS had lower mid-childhood visual-motor scores. In cross-sectional analyses of mid-childhood PFAS concentrations and cognitive assessments, visual-motor scores on the Wide Range Assessment of Visual Motor Abilities (WRAVMA) (standardized mean = 100, standard deviation = 15) were lower among children with higher PFHxS (fourth quartile (Q4) vs. Q1: -5.0, 95% confidence interval (CI): -9.1, -0.8). Upper quartiles of childhood PFOA and PFOS were also associated with somewhat lower childhood WRAVMA scores, but childhood PFASs were not associated with verbal or non-verbal IQ or visual memory. CONCLUSIONS: We present evidence suggesting associations of prenatal and childhood PFAS exposure with lower childhood visual motor abilities. Other results were inconsistent, with higher prenatal PFASs associated in some cases with better cognitive outcomes.

Erratum: "Prenatal Organophosphate Pesticide Exposure and Traits Related to Autism Spectrum Disorders in a Population Living in Proximity to Agriculture".

[This corrects the article DOI: 10.1289/EHP2580.].

Residential Proximity to Major Roadways at Birth, DNA Methylation at Birth and Midchildhood, and Childhood Cognitive Test Scores: Project Viva(Massachusetts, USA).

BACKGROUND: Epigenetic variability is hypothesized as a regulatory pathway through which prenatal exposures may influence child development and health. OBJECTIVE: We sought to examine the associations of residential proximity to roadways at birth and epigenome-wide DNA methylation. We also assessed associations of differential methylation with child cognitive outcomes. METHODS: We estimated residential proximity to roadways at birth using a geographic information system (GIS) and cord blood methylation using Illumina's HumanMethylation450-array in 482 mother-child pairs in Project Viva. We identified individual CpGs associated with residential-proximity-to-roadways at birth using robust linear regression [[Formula: see text]]. We also estimated association between proximity-to-roadways at birth and methylation of the same sites in blood samples collected at age 7-11 y ([Formula: see text]). We ran the same analyses in the Generation R Study for replication ([Formula: see text]). In Project Viva, we investigated associations of differential methylation at birth with midchildhood cognition using linear regression. RESULTS: Living closer to major roadways at birth was associated with higher cord blood (and-more weakly-midchildhood blood) methylation of four sites in LAMB2. For each halving of residential-proximity-to-major-roadways, we observed a 0.82% increase in DNA methylation at cg05654765 [95% confidence interval (CI): (0.54%, 1.10%)], 0.88% at cg14099457 [95% CI: (0.56%, 1.19%)], 0.19% at cg03732535 [95% CI: (0.11%, 0.28)], and 1.08% at cg02954987 [95% CI: (0.65%, 1.51%)]. Higher cord blood methylation of these sites was associated with lower midchildhood nonverbal cognitive scores. Our results did not replicate in the Generation R Study. CONCLUSIONS: Our discovery results must be interpreted with caution, given that they were not replicated in a separate cohort. However, living close to major roadways at birth was associated with cord blood methylation of sites in LAMB2-a gene known to be linked to axonal development-in our U.S. cohort. Higher methylation of these sites associated with lower nonverbal cognitive scores at age 7-11 y in the same children. https://doi.org/10.1289/EHP2034.

Generation and characterization of ABBV642, a dual variable domain immunoglobulin molecule (DVD-Ig) that potently neutralizes VEGF and PDGF-BB and is designed for the treatment of exudative age-related macular degeneration.

Exudative age-related macular degeneration (AMD) is the most common cause of moderate and severe vision loss in developed countries. Intraocular injections of vascular endothelial growth factor (VEGF or VEGF-A)-neutralizing proteins provide substantial benefit, but frequent, long-term injections are needed. In addition, many patients experience initial visual gains that are ultimately lost due to subretinal fibrosis. Preclinical studies and early phase clinical trials suggest that combined suppression of VEGF and platelet-derived growth factor-BB (PDGF-BB) provides better outcomes than suppression of VEGF alone, due to more frequent regression of neovascularization (NV) and suppression of subretinal fibrosis. We generated a dual variable domain immunoglobulin molecule, ABBV642 that specifically and potently binds and neutralizes VEGF and PDGF-BB. ABBV642 has been optimized for treatment of exudative AMD based on the following design characteristics: 1) high affinity binding to all VEGF-A isoforms and both soluble and extracellular matrix (ECM)-associated PDGF-BB; 2) potential for extended residence time in the vitreous cavity to decrease the frequency of intraocular injections; 3) rapid clearance from systemic circulation compared with molecules with wild type Fc region for normal FcRn binding, which may reduce the risk of systemic complications; and 4) low risk of potential effector function. The bispecificity of ABBV642 allows for a single injection of a single therapeutic agent, and thus a more streamlined development and regulatory path compared with combination products. In a mouse model of exudative AMD, ABBV642 was observed to be more effective than aflibercept. ABBV642 has potential to improve efficacy with reduced injection frequency in patients with exudative AMD, thereby reducing the enormous disease burden for patients and society.

Infant Breastfeeding Duration and Mid-Childhood Executive Function, Behavior, and Social-Emotional Development.

OBJECTIVE: The authors aim was to examine associations of breastfeeding duration and exclusivity in infancy with executive function, behavior, and social-emotional development in mid-childhood. METHODS: The authors studied 1037 participants in Project Viva, a prebirth cohort that enrolled pregnant mothers from 1999 to 2002 and followed children for 7 to 10 years. Main exposures were: (1) duration of any breastfeeding in the first 12 months and (2) duration of exclusive breastfeeding in the first 6 months. Main outcomes were child executive function, behavior, and social-emotional development, assessed by (1) the Behavior Rating Inventory of Executive Function (BRIEF) and (2) the Strengths and Difficulties Questionnaire (SDQ), completed independently by parents and teachers. Higher scores indicate greater problems. RESULTS: In linear regression models adjusted for sociodemographics, maternal intelligence, home environment, early child care, and maternal depression, longer breastfeeding duration was not associated with substantially better executive function, behavior, or social-emotional development. For example, for each additional month of any breastfeeding, the BRIEF Global Executive Composite score (parent) was 0.10 points higher (95% confidence interval, -0.01 to 0.22) and the SDQ total difficulties score was 0.06 points higher (-0.01, 0.12). Breastfeeding duration was also not associated with BRIEF or SDQ subscales, nor was exclusive breastfeeding duration associated with any of the outcomes analyzed. CONCLUSION: Despite beneficial effects on general intelligence, longer duration of any breastfeeding or of exclusive breastfeeding was not associated with better executive function, behavior, or social-emotional development in mid-childhood.