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Prenatal exposure to common plasticizers: a longitudinal study on phthalates, brain volumetric measures, and IQ in youth

Ghassabian, Akhgar; van den Dries, Michiel; Trasande, Leonardo; Lamballais, Sander; Spaan, Suzanne; Martinez-Moral, Maria-Pilar; Kannan, Kurunthachalam; Jaddoe, Vincent W V; Engel, Stephanie M; Pronk, Anjoeka; White, Tonya; Tiemeier, Henning; Guxens, Mònica
Exposure to phthalates, used as plasticizers and solvents in consumer products, is ubiquitous. Despite growing concerns regarding their neurotoxicity, brain differences associated with gestational exposure to phthalates are understudied. We included 775 mother-child pairs from Generation R, a population-based pediatric neuroimaging study with prenatal recruitment, who had data on maternal gestational phthalate levels and T1-weighted magnetic resonance imaging in children at age 10 years. Maternal urinary concentrations of phthalate metabolites were measured at early, mid-, and late pregnancy. Child IQ was assessed at age 14 years. We investigated the extent to which prenatal exposure to phthalates is associated with brain volumetric measures and whether brain structural measures mediate the association of prenatal phthalate exposure with IQ. We found that higher maternal concentrations of monoethyl phthalate (mEP, averaged across pregnancy) were associated with smaller total gray matter volumes in offspring at age 10 years (β per log10 increase in creatinine adjusted mEP = -10.7, 95%CI: -18.12, -3.28). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (β for mediated path =-0.31, 95%CI: -0.62, 0.01, p = 0.05, proportion mediated = 18%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. Our findings suggest the global impact of prenatal phthalate exposure on brain volumetric measures that extends into adolescence and underlies less optimal cognitive development.
PMID: 37644173
ISSN: 1476-5578
CID: 5618482

Prenatal Air Pollution Exposure and Autism Spectrum Disorder in the ECHO Consortium

Ghassabian, Akhgar; Dickerson, Aisha S; Wang, Yuyan; Braun, Joseph M; Bennett, Deborah H; Croen, Lisa A; LeWinn, Kaja Z; Burris, Heather H; Habre, Rima; Lyall, Kristen; Frazier, Jean A; Glass, Hannah C; Hooper, Stephen R; Joseph, Robert M; Karr, Catherine J; Schmidt, Rebecca J; Friedman, Chloe; Karagas, Margaret R; Stroustrup, Annemarie; Straughen, Jennifer K; Dunlop, Anne L; Ganiban, Jody M; Leve, Leslie D; Wright, Rosalind J; McEvoy, Cindy T; Hipwell, Alison E; Giardino, Angelo P; Santos, Hudson P; Krause, Hannah; Oken, Emily; Camargo, Carlos A; Oh, Jiwon; Loftus, Christine; O'Shea, T Michael; O'Connor, Thomas G; Szpiro, Adam; Volk, Heather E; ,
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.
PMID: 40498638
ISSN: 1552-9924
CID: 5869322

Exposure to Endocrine Disruptors in Early life and Neuroimaging Findings in Childhood and Adolescence: a Scoping Review

Cajachagua-Torres, Kim N; Quezada-Pinedo, Hugo G; Wu, Tong; Trasande, Leonardo; Ghassabian, Akhgar
PURPOSE OF REVIEW: Evidence suggests neurotoxicity of endocrine disrupting chemicals (EDCs) during sensitive periods of development. We present an overview of pediatric population neuroimaging studies that examined brain influences of EDC exposure during prenatal period and childhood. RECENT FINDINGS: We found 46 studies that used magnetic resonance imaging (MRI) to examine brain influences of EDCs. These studies showed associations of prenatal exposure to phthalates, organophosphate pesticides (OPs), polyaromatic hydrocarbons and persistent organic pollutants with global and regional brain structural alterations. Few studies suggested alteration in functional MRI associated with prenatal OP exposure. However, studies on other groups of EDCs, such as bisphenols, and those that examined childhood exposure were less conclusive. These findings underscore the potential profound and lasting effects of prenatal EDC exposure on brain development, emphasizing the need for better regulation and strategies to reduce exposure and mitigate impacts. More studies are needed to examine the influence of postnatal exposure to EDC on brain imaging.
PMCID:11324673
PMID: 39078539
ISSN: 2196-5412
CID: 5696332

Semiparametric distributed lag quantile regression for modeling time-dependent exposure mixtures

Wang, Yuyan; Ghassabian, Akhgar; Gu, Bo; Afanasyeva, Yelena; Li, Yiwei; Trasande, Leonardo; Liu, Mengling
Studying time-dependent exposure mixtures has gained increasing attentions in environmental health research. When a scalar outcome is of interest, distributed lag (DL) models have been employed to characterize the exposures effects distributed over time on the mean of final outcome. However, there is a methodological gap on investigating time-dependent exposure mixtures with different quantiles of outcome. In this article, we introduce semiparametric partial-linear single-index (PLSI) DL quantile regression, which can describe the DL effects of time-dependent exposure mixtures on different quantiles of outcome and identify susceptible periods of exposures. We consider two time-dependent exposure settings: discrete and functional, when exposures are measured in a small number of time points and at dense time grids, respectively. Spline techniques are used to approximate the nonparametric DL function and single-index link function, and a profile estimation algorithm is proposed. Through extensive simulations, we demonstrate the performance and value of our proposed models and inference procedures. We further apply the proposed methods to study the effects of maternal exposures to ambient air pollutants of fine particulate and nitrogen dioxide on birth weight in New York University Children's Health and Environment Study (NYU CHES). This article is protected by copyright. All rights reserved.
PMID: 35612351
ISSN: 1541-0420
CID: 5230212

Beyond traffic jam alleviation: evaluating the health and health equity impacts of New York City's congestion pricing plan

Ghassabian, Akhgar; Titus, Andrea R; Conderino, Sarah; Azan, Alexander; Weinberger, Rachel; Thorpe, Lorna E
New York City (NYC) is slated to be the first jurisdiction in the USA to implement a cordon-based congestion tax, which will be levied on vehicles entering its Central Business District. Several cities around the world, for example, London and Stockholm, have had similar cordon-based pricing programmes, defined as road pricing that charges drivers a fee for entering a specified area (typically a congested urban centre). In addition to reducing congestion and creating revenue, projections suggest the NYC congestion pricing plan may yield meaningful traffic-related air quality improvements that could result in health benefits. NYC is a large city with high air pollution and substantial racial/ethnic and socioeconomic health inequities. The distinct geography and meteorological conditions of the city also suggest that the policy's impact on air quality may extend beyond the NYC metropolitan area. As such, the potential breadth, directionality and magnitude of health impacts on communities who might be heavily affected by the nation's first congestion pricing plan should be empirically investigated. We briefly review evaluation studies of other cordon-based congestion pricing policies and argue that implementation of this policy provides an excellent opportunity to employ a quasi-experimental study design to evaluate the policy's impacts on air quality and health outcomes across population subgroups using a health equity lens. We discuss why real-time evaluations of the NYC congestion pricing plan can potentially help optimise benefits for communities historically negatively affected by traffic-related air pollution. Assessing intended and unintended impacts on health equity is key to achieving these goals.
PMID: 38195634
ISSN: 1470-2738
CID: 5624072

Prenatal phthalate exposure and anogenital distance in infants at 12 months

Cajachagua-Torres, Kim N; Salvi, Nicole B; Seok, Eunsil; Wang, Yuyan; Liu, Mengling; Kannan, Kurunthachalam; Kahn, Linda G; Trasande, Leonardo; Ghassabian, Akhgar
OBJECTIVE:Anogenital distance (AGD) is a postnatal marker of in utero exposure to androgens and anti-androgens, and a predictor of reproductive health. We examined the association between gestational exposure to phthalates and AGD in male and female infants. METHODS:In 506 mother-infant pairs (276 males, 230 females), we measured urinary concentrations of phthalate metabolites at < 18 and 18-25 weeks of gestation and AGD at child age 12.9 months (95 % range 11.4-21.1). Phthalate metabolite concentrations were adjusted for urinary dilution, averaged, and natural log-transformed. We measured anus-clitoris distance (AGDac) and anus-fourchette distance (AGDaf) in females, and anus-scrotum distance, anus-penis distance, and penile width in males. We used linear regression and partial-linear single-index (PLSI) models to examine associations between phthalates and AGD as single pollutants and in mixture. RESULTS:Fifty-eight percent of mothers were Hispanic, followed by 27 % non-Hispanic White. Higher exposures to ∑di-isononyl(phthalate) (∑DiNP) was associated with longer AGDaf [1.28 mm (95 % confidence interval [CI]: 0.52, 2.03) and 0.97 mm (95 %CI: 0.25, 1.69), respectively]. Higher exposures to ∑di(2-ethylhexyl)phthalate (∑DEHP) was associated with longer AGDac [2.80 mm (95 %CI: 1.17, 4.44), and 1.90 mm (95 %CI: 0.76, 3.04), respectively]. No association was observed between phthalate metabolites and AGD in males after multiple testing correction. In mixture analyses, ∑DiNP and ∑DEHP were the main contributors to longer AGD in females. We also detected an interaction between ∑DiNP and ∑DEHP in association with AGD in females. CONCLUSION/CONCLUSIONS:Early pregnancy phthalate exposure was associated with longer AGD in female infants. Biological mechanisms underlying these associations should be further investigated.
PMID: 40262489
ISSN: 1873-6750
CID: 5830162

Pre- and postnatal exposure to PM2.5 and NO2 and blood pressure in children: Results from the ECHO Cohort

Ni, Yu; Law, Andrew; Gao, Xingyu; Szpiro, Adam A; Loftus, Christine T; Jones, Miranda; Dearborn, Logan C; Hazlehurst, Marnie F; Sherris, Allison R; Ilango, Sindana; LeWinn, Kaja Z; Bush, Nicole R; Zhao, Qi; Trasande, Leonardo; Flynn, Joseph T; Enquobahrie, Daniel A; Nguyen, Ruby H N; O'Connor, Tom; Vyas, Arpita K; Zhang, Mingyu; Mirzakhani, Hooman; Hipwell, Alison; Starling, Anne; Peterson, Alicia K; Ghassabian, Akhgar; Ferrara, Assiamira; Aschner, Judy; Collingwood, Scott; Karagas, Margaret R; Katzow, Michelle; Stroustrup, Annemarie; Haktnair, Mehtap; Hartert, Tina V; Snyder, Brittney M; Jan, Sophia; Singh, Anne Marie; Dabelea, Dana; Malek, Angela M; Straughen, Jennifer K; Camargo, Carlos A; Buxton, Miatta A; Wright, Rosalind; Carroll, Kecia; Sanderson, Keia; Mitchell, Daphne Koinis; D'Sa, Viren; Hockett, Christine; Dunlop, Anne L; Farzen, Shohreh F; Mumford, Sunni L; Alshawabkeh, Akram N; Santos, Hudson P; Zhang, Xueying; Niu, Zhongzheng; Ji, Nan; Breton, Carrie; Liang, Donghai; Karr, Catherine J; ,
BACKGROUND:There is growing interest in understanding the link between early life exposures to ambient air pollution and childhood blood pressure; however, existing findings, largely from single site/cohort studies, are inconclusive. METHODS:(per 10-ppb) exposures with blood pressure outcomes were estimated using linear and Poisson regressions adjusted for sociodemographic, lifestyle, temporal, and spatial confounders. RESULTS:with both SBP (β: -2.42, 95 %CI: -4.70, -0.14) and DBP (β: -1.94, 95 %CI: -3.81, -0.08) percentiles were suggested. CONCLUSION/CONCLUSIONS:and blood pressure was counterintuitive and warrants further investigation.
PMID: 41448419
ISSN: 1096-0953
CID: 5987972

Residential Mobility During Pregnancy and Birth Outcomes in the United States: The Environmental influences on Child Health Outcomes (ECHO) Cohort (2010-2019)

D'Adamo, Angela; Kress, Amii M; Habre, Rima; Towe-Goodman, Nissa; Desjardins, Michael R; Alshawabkeh, Akram; Aris, Izzuddin M; Camargo, Carlos A; Carroll, Kecia N; Cassidy-Bushrow, Andrea E; Chu, Su H; Civil, Yolaine; Craft, Alexandrea L; Croen, Lisa A; Deoni, Sean; Dsa, Viren; Dunlop, Anne L; Elliot, Amy J; Ferrara, Assiamira; Ganiban, Jody M; Ghassabian, Akhgar; Hartert, Tina; Watts, Delma-Jean; Karagas, Margaret R; Karr, Catherine J; Koinis-Mitchell, Daphne; Kramer, Michael; McEvoy, Cindy T; Mirzakhani, Hooman; O'Connor, Thomas G; Perng, Wei; Schmidt, Rebecca J; Shah, Uzma; Tung, Irene; Wright, Rosalind J; Knapp, Emily A
PURPOSE/OBJECTIVE:To examine factors associated with moving during pregnancy and impacts of assigning nSES at enrollment, delivery, or a time-weighted average on birth outcomes (birthweight, birthweight-for-gestational-age z-score, low birthweight, gestational age, small-for-gestational age, preterm birth). METHODS:We used data from the Environmental influences on Child Health Outcomes (ECHO) Cohort Study (2010-2019) with nSES data from the American Community Survey (ACS) matched by time and location to monthly residential histories. We used multivariable logistic models with Generalized Estimating Equations to identify factors associated with moving and quantify exposure misclassification in model estimates. RESULTS:Approximately 7% of 15,376 participants moved at least once during pregnancy. Maternal age (OR: 0.97, 95% CI: 0.95, 0.98) and other race vs. White (OR: 0.39, 95% CI: 0.20, 0.80) were associated with lower odds of moving; lower neighborhood-level education (OR: 1.34, 95% CI: 1.11, 1.62) and living in urban neighborhoods (OR: 3.03, 95% CI: 1.39, 6.59) were associated with higher odds. Among movers, estimates between nSES and birth outcomes changed ≥16% by address assignment; birthweight-for-gestational-age z-score was significant only when using nSES at delivery. CONCLUSION/CONCLUSIONS:Sociodemographic and nSES characteristics are associated with moving during pregnancy; movers may experience exposure misclassification and underestimated effects on birth outcomes.
PMID: 41554464
ISSN: 1873-2585
CID: 5988172

Considerations When Accounting for Race and Ethnicity in Studies of Poverty and Neurodevelopment

Semanaz, Clementine; Ghassabian, Akhgar; Delaney, Scott; Fang, Fang; Williams, David R; Tiemeier, Henning
OBJECTIVE:Poverty and systemic racism within rare intertwined. Children of marginalized racial and ethnic identities experience higher levels of poverty and adverse psychiatric outcomes. Thus, in models of poverty and neurodevelopment, race and ethnicity-as proxies for exposure to systemic disadvantage-are regularly considered confounders. Recently, however, some researchers claimed that using race and ethnicity as confounders is statistically dubious, and potentially socially damaging. Instead, they argue for the use of variables measuring other social determinants of health (SDoH). We explore this approach. METHOD/METHODS:Data are from 7,836 10-year-olds in the Adolescent Brain and Cognitive Development study. We fit mixed regression models for the association of household poverty measures with psychiatric symptoms, magnetic resonance imaging-derived (MRI) cortical measures, and cognition with and without (1) race and ethnicity adjustment; (2); poverty-by-race and ethnicity interaction terms and (3) alternative SDoH variables. Propensity-based weights were used to calibrate the sample to key US demographics. RESULTS:For psychiatric and cognitive outcomes, poverty-outcome relationships differed across racial and ethnic groups (poverty-by-race-and-ethnicity interaction p<0.05). For MRI outcomes, adjusting for race and ethnicity changed the estimate of poverty's impact. Alternative SDoH adjustment could not fully account for the impact of race and ethnicity on the associations explored. CONCLUSION/CONCLUSIONS:Poverty and race and ethnicity combine to influence neurodevelopment. Results suggest effects of poverty are generally inconsistent across race and ethnicity, which supports prior research demonstrating the non-equivalence of SDoH indicators by race and ethnicity. Studies exploring these relationships should assess interaction between poverty and race and ethnicity and/or stratify when appropriate. Replacing race and ethnicity with alternative SDoH may induce bias.
PMID: 40120644
ISSN: 1527-5418
CID: 5814542

Racial and ethnic disparities in environmental chemical exposures and hypertensive disorders of pregnancy: The ECHO-wide cohort study

Liu, Hongxiu; Kress, Amii M; Yu, Emma X; Ning, Xuejuan; Ghassabian, Akhgar; Kahn, Linda G; Mehta-Lee, Shilpi; Brubaker, Sara; Alshawabkeh, Akram; Meeker, John; Camargo, Carlos A; Suglia, Shakira F; Elliott, Amy J; Ferrara, Assiamira; Zhu, Yeyi; Gern, James E; Bendixsen, Casper; Gold, Diane R; Cassidy-Bushrow, Andrea E; Singh, Anne Marie; Farzan, Shohreh F; Niu, Zhongzheng; Hipwell, Alison E; Karagas, Margaret R; Mirzakhani, Hooman; O'Connor, Thomas G; Simhan, Hyagriv; Oken, Emily; Sanderson, Keia; Petriello, Michael; Geiger, Sarah Dee; Carroll, Kecia N; Lawrence, Grace N; Dunlop, Anne L; Dabelea, Dana; Norman, Gwendolyn; Carignan, Courtney; Zhao, Qi; Trasande, Leonardo; ,; ,; ,
Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and infant mortality and morbidity worldwide. This prospective cohort study investigated the association of racial and ethnic disparities in HDP and explored the potential mediation effect of environmental chemical exposures on excess HDP risk among non-Hispanic Black pregnant people. A total of 3,279 pregnant people were included from 11 cohorts across the United States in the Environmental influences on Child Health Outcomes (ECHO) Program. We analyzed 20 environmental chemicals detected in over 70 % of biospecimens collected during pregnancy. Among Hispanic, non-Hispanic White, and non-Hispanic Black participants, 11.8 %, 10.8 %, and 16.6 % were diagnosed with HDP, respectively. Compared with non-Hispanic White participants, non-Hispanic Black participants had a higher risk of HDP (aRR = 1.48; 95 % CI 1.13-1.94) and higher levels of traditional phthalate metabolites, but lower levels of phthalate alternative metabolites and perfluorooctanoic acid. Hispanic participants had a lower risk of gestational hypertension (aRR = 0.62; 95 % CI 0.40-0.98) and lower levels of perfluoroalkyl substances than non-Hispanic White participants. Critically, despite these race/ethnicity-specific exposure patterns, individual chemical exposures did not mediate the association between racial/ethnic group and HDP. These findings highlight the need to investigate cumulative chemical mixtures and non-chemical environmental and social determinants as potential drivers of HDP disparities.
PMID: 41344632
ISSN: 1873-6424
CID: 5975142