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Maternal exposure to legacy PFAS compounds PFOA and PFOS is associated with disrupted cytokine homeostasis in neonates: The Upstate KIDS study (2008-2010)

Jones, Laura E; Ghassabian, Akhgar; Yeung, Edwina; Mendola, Pauline; Kannan, Kurunthachalam; Bell, Erin M
There is growing concern that exposure to per/polyfluoroalkyl substances (PFAS), persistent chemicals used widely to make consumer products water- or grease-proof, may alter immune function, leading to reduced vaccine response or greater susceptibility to infections. We investigated associations between two legacy PFAS (PFOA and PFOS) and infant cytokine levels measured in newborn dried bloodspots (NDBS) from a large population-based birth cohort in Upstate New York, to determine whether exposure to legacy PFAS is associated with variability in cytokine profiles in newborns. We performed adjusted mixed effects regressions for each cytokine against PFOS and PFOA followed by exploratory factor analysis (EFA) on specific cytokine subsets selected via the prior regressions. Among 3448 neonates (2280 singletons and 1168 twins), significant cytokines were dominated by cytokines negatively associated with the given PFAS. Adjusted single-pollutant models with continuous log-transformed PFOA showed significant negative associations with IL-16 (-0.07, 95% CI: -0.3, -0.1), IL-5 (-0.05, 95%CI: -0.09, -0.02), IL-6 (-0.06, 95%CI: -0.1, -0.02), 6-Ckine (0.06, 95% CI: -0.10, -0.02) and significant positive associations with IL-1α (0.066, 95%CI: 0.03, 0.11), MCP-1 (0.06, 95%CI: 0.03, 0.10). Estimates for PFOS were slightly larger than estimates for PFOA but only significant for 6-Ckine (-0.21, 95%CI: -0.09, -0.33) after correction for multiplicity. Our data consistently suggest that legacy PFAS exposures are associated with disrupted, typically reduced, cytokine levels in neonates, with PFOA exposure resulting in more significant differences in individual cytokines and cytokine groupings than PFOS. Regression by PFAS quartile shows evidence of nonlinear dose-response relationships for most cytokines and cytokine groupings.
PMID: 39848095
ISSN: 1873-6750
CID: 5802472

Thyroid disrupting chemicals during pregnancy: an invitation to collaborate in the consortium on thyroid and pregnancy [Letter]

Derakhshan, Arash; Ghassabian, Akhgar; Trasande, Leonardo; Korevaar, Tim I M
This is an invitation letter for the principal investigators and cohort studies to join the Consortium on Thyroid and Pregnancy. The inclusion criteria are population-based cohorts with data on maternal thyroid function during pregnancy and any measurement of known groups of endocrine disrupting chemicals.
PMCID:11760081
PMID: 39856777
ISSN: 1756-6614
CID: 5782102

The Exposome and Human Health [Editorial]

Gago-Ferrero, Pablo; Cousins, Ian; Ghassabian, Akhgar; Lamoree, Marja; Schlenk, Daniel; Toms, Leisa-Maree; Wang, Bin; Zimmerman, Julie
PMID: 39834261
ISSN: 1520-5851
CID: 5802132

Neighborhood opportunity and residential instability: associations with mental health in middle childhood

Putnick, Diane L; Tyris, Jordan; McAdam, Jordan; Ghassabian, Akhgar; Mendola, Pauline; Sundaram, Rajeshwari; Yeung, Edwina
BACKGROUND:Neighborhood quality may contribute to child mental health, but families with young children often move, and residential instability has also been tied to adverse mental health. This study's primary goal was to disentangle the effects of neighborhood quality from those of residential instability on mental health in middle childhood. METHODS:1,946 children from 1,652 families in the Upstate KIDS cohort from New York state, US, were followed prospectively from birth to age 10. Residential addresses were linked at the census tract level to the Child Opportunity Index 2.0, a multidimensional indicator of neighborhood quality. The number of different addresses reported from birth to age 10 was counted to indicate residential instability, and the change in COI quintile indicated social mobility. Parents completed three assessments of attention-deficit/hyperactivity disorder, problematic behavior, and internalizing psychopathology symptoms at ages 7, 8, and 10. Child and family covariates were selected a priori to adjust sample characteristics, increase estimate precision, and account for potential confounding. RESULTS:In unadjusted models, higher neighborhood quality at birth was associated with fewer psychopathology symptoms in middle childhood, but associations were largely mediated by residential instability. In adjusted models, residential instability was associated with more psychopathology symptoms, even accounting for social mobility. Neighborhood quality at birth had indirect effects on child mental health symptoms through residential instability. CONCLUSIONS:Children born into lower-quality neighborhoods moved more, and moving more was associated with higher psychopathology symptoms. Findings were similar across different timings of residential moves, for girls and boys, and for children who did not experience a major life event. Additional research is needed to better understand which aspects of moving are most disruptive to young children.
PMID: 39835418
ISSN: 1469-7610
CID: 5802162

Co-occurring Psychopathology in Children With and Without Autism Spectrum Disorder (ASD): Differences by Sex in the ECHO Cohorts

Volk, Heather E; Fortes, Diogo; Musci, Rashelle; Kim, Amanda; Bastain, Theresa M; Camargo, Carlos A; Croen, Lisa A; Dabelea, Dana; Duarte, Cristiane S; Dunlop, Anne L; Gachigi, Kennedy; Ghassabian, Akhgar; Hertz-Picciotto, Irva; Huddleston, Kathi C; Joseph, Robert M; Keating, Daniel; Kelly, Rachel S; Kim, Young Shin; Landa, Rebecca J; Leve, Leslie D; Lyall, Kristen; Northrup, Jessie B; O'Connor, Thomas; Ozonoff, Sally; Ross, Anna; Schmidt, Rebecca J; Schweitzer, Julie B; Shuffrey, Lauren C; Shuster, Coral; Vance, Emily; Weiss, Scott T; Wilkening, Greta; Wright, Robert O
PURPOSE/OBJECTIVE:Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems. METHODS: Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.5-18 years by surveys. We examined mean differences in CBCL Total Problems and DSM-oriented subscale scores by autism diagnosis and by child sex. Analyses using logistic regression were conducted to examine whether autism was associated with higher CBCL scores. We further examined if these relationships differed by child age category (< 6 years, 6-11 years, 12 + years). The relationships between SRS score and CBCL total and subscale scores were examined using quantile regression models, with analyses adjusted for child sex and age. RESULTS: In ECHO, 553 youth were reported by a parent to have a clinician diagnosis of autism spectrum disorder (ASD) (432 [78%] boys and 121 [22%] girls). Youth on the spectrum had higher mean CBCL raw scores on Total Problems and all DSM-oriented subscales compared to those not on the spectrum (all p < 0.0001). Analyses adjusted for sex and stratified by age group indicated that higher odds of autism diagnosis were associated with total, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scales in the top 30% of the CBCL score distribution. Autistic girls were more likely to have parent-reported depression and anxiety compared to autistic boys. In quantile regression analyses, we observed evidence of stronger associations between SRS and CBCL for those in higher quantiles of CBCL total problems scale score (beta representing 1-unit change in SRS associated with 1-unit increase in CBCL total problems scale score), among children in the 70-90th percentile (β = 1.60, p < 0.01), or top 10th percentile (β = 2.43, p < 0.01) of the CBCL total problems scale score distribution. Similar findings were seen for the DSM-oriented depression, anxiety, and ADHD subscales. CONCLUSION/CONCLUSIONS: Results from this large national sample suggest increased behavioral and emotional problems among autistic children compared to non-autistic children throughout early life. Among children on the spectrum this may warrant increased monitoring for co-occurring behavioral and emotional problems.
PMID: 39762643
ISSN: 1573-3432
CID: 5804942

Prenatal polycyclic aromatic hydrocarbons exposure and child growth and adiposity: A longitudinal study

Shahin, Sarvenaz; Ghassabian, Akhgar; Blaauwendraad, Sophia M; Duh-Leong, Carol; Kannan, Kurunthachalam; Long, Sara E; Herrera, Teresa; Seok, Eunsil; Pierce, Kristyn A; Liu, Mengling; Trasande, Leonardo
BACKGROUND:Exposure to polycyclic aromatic hydrocarbons (PAHs) during childhood has been associated with altered growth and adiposity in children. The effects of prenatal exposure to PAHs on developmental programming of growth and adiposity are still unknown. OBJECTIVE:To study the association of prenatal exposure to PAHs with early childhood growth and adiposity measures. METHODS:In NYU Children's Health and Environment Study (2016-2019), we studied 880 mother-child pairs for maternal urinary PAH metabolites in early, mid, and late pregnancy and measured child weight, length/height, triceps, and subscapular skinfold thicknesses at 1, 2, 3, and 4 years. We used linear mixed models to investigate associations between average pregnancy exposure to PAHs and the z-scores of child repeated measures. The models were adjusted for sociodemographic and health-related factors. RESULTS:Children prenatally exposed to higher levels of PAHs had greater weight and length/height z scores. We found an interaction with time-point of child assessment, showing stronger associations at later ages. For instance, PAH exposure was associated with higher weight z-scores at 3 years: coefficient per Ln-unit increase in 2-NAP=0.25 (95%CI: 0.13, 0.37), 2-PHEN=0.25 (95%CI: 0.11, 0.39), 1-PYR=0.13 (95%CI: 0.02, 0.24), and 4-PHEN=0.09 (95%CI: 0.02, 0.15). Higher concentrations of 2-NAP (coefficient=0.21, 95%CI: 0.11, 0.31), 2-PHEN (coefficient=0.24, 95%CI: 0.12, 0.35), 3-PHEN (coefficient=0.13, 95%CI: 0.02, 0.24]), 4-PHEN (coefficient=0.09, 95%CI: 0.04, 0.15), and 1-PYR (coefficient=0.11, 95%CI: 0.02, 0.21) were associated with higher weight z-score at 4 years. CONCLUSION/CONCLUSIONS:Prenatal PAH exposure may contribute to the developmental programming of growth in childhood.
PMID: 39756778
ISSN: 1096-0953
CID: 5782092

Redlining in New York City: impacts on particulate matter exposure during pregnancy and birth outcomes

Herrera, Teresa; Seok, Eunsil; Cowell, Whitney; Brown, Eric; Magzamen, Sheryl; Ako, Ako Adams; Wright, Rosalind J; Trasande, Leonardo; Ortiz, Robin; Stroustrup, Annemarie; Ghassabian, Akhgar
BACKGROUND:Evidence suggests historical redlining shaped the built environment and health outcomes in urban areas. Only a handful of studies have examined redlining's association with air pollution and adverse birth outcomes in New York City (NYC). Additionally, no NYC-specific studies have examined the impact of redlining on birth weight. METHODS:) exposure during pregnancy using multivariable regression models. Additionally, we examined how maternal residence in a historically redlined neighbourhood during pregnancy influenced birth weight z-score, preterm birth and low birth weight. RESULTS:in our models assessing the relationship between redlining grade and birth outcome, our results did not change. DISCUSSION/CONCLUSIONS:levels today.
PMID: 39242189
ISSN: 1470-2738
CID: 5688422

Prenatal exposure to residential greenness, fetal growth, and birth outcomes: a cohort study in New York City

Heo, Seulkee; Afanasyeva, Yelena; Liu, Mengling; Mehta-Lee, Shilpi; Yang, Wenqing; Trasande, Leonardo; Bell, Michelle L; Ghassabian, Akhgar
Findings for greenspace's impacts on birth outcomes are largely dependent on vegetation indexes. Examinations are needed for various greenspace indicators given varying pathways for fetal development. This prospective cohort study assessed the impacts of prenatal greenspace exposure on preterm birth (PTB), term low birthweight (TLBW), birthweight, and estimated fetal weight (EFW) for pregnant women in the New York City area, 2016-2023 (n=2765). Longitudinal greenspace exposure was measured for residential histories during pregnancy using the Enhanced Vegetation Index (EVI) for 1000m buffers and four park metrics, namely, the total number, sum of area, and the accessibility of parks within residential buffers (500 m) and the distance to the closest park. Multivariable regression models were used to estimate the associations for quartiles of exposure (with the first quartile [Q1] as reference). Greenspace exposure was not associated with TLBW, birthweight, or EFW. Odds ratios of PTB for the Q2, Q3, and Q4 EVI exposure groups compared to the Q1 group were 0.65 (95% CI: 0.43-0.98), 0.51 (0.32-0.80), and 0.56 (0.35-0.90), respectively. PTB risks decreased in higher exposure groups (Q2-Q4) of the total park number. Results indicate the benefits of prenatal greenspace exposure for fetal maturity and neonatal outcomes.
PMID: 39562151
ISSN: 1476-6256
CID: 5758462

Sociodemographic and dietary determinants of glyphosate exposure in a NYC-based pregnancy cohort

Mellor, Ellison; Trasande, Leonardo; Albergamo, Vittorio; Kannan, Kurunthachalam; Li, Zhongmin; Ghassabian, Akhgar; Afanasyeva, Yelena; Liu, Mengling; Cowell, Whitney
Previous studies have provided evidence for associations between glyphosate and aminomethylphosphonic acid (AMPA) exposure and adverse birth outcomes. However, few pregnancy cohort studies have investigated dietary and other determinants of glyphosate and AMPA exposure. We aimed to identify dietary and sociodemographic factors that predict glyphosate and AMPA exposure in a contemporary, urban pregnancy cohort in the US. The study included 725 pregnant participants from the New York University Children's Health and Environment Study (NYU CHES) in New York City. Urinary concentrations of glyphosate and AMPA, determined by high-performance liquid chromatography and tandem mass spectrometry, were analyzed in urine collected from NYU CHES participants across three prenatal time points. The Diet Health Questionnaire II was completed to capture dietary intake during the prenatal period. Descriptive statistics and bivariate linear models were used to assess determinants of urinary glyphosate and AMPA concentrations. Median urinary glyphosate and AMPA levels were 0.36 ng/mL and 0.37 ng/mL, respectively. Lower glyphosate levels were associated with younger age, obesity, public insurance, being single, and lower educational attainment. Nuts, seeds and whole grain intake was associated with increased urinary glyphosate concentrations. Urinary glyphosate concentrations were lower in summer than in winter. The study findings highlight widespread exposure to glyphosate and AMPA in this pregnancy cohort, with nuts/seeds and whole grains identified as possible dietary sources of exposure. High detection rates in the study population necessitate further research on dietary exposure patterns and perinatal outcomes to inform targeted interventions and reduce exposure in vulnerable populations.
PMID: 39374760
ISSN: 1873-6424
CID: 5730122

Do small effects matter more in vulnerable populations? an investigation using Environmental influences on Child Health Outcomes (ECHO) cohorts

Peacock, Janet L; Coto, Susana Diaz; Rees, Judy R; Sauzet, Odile; Jensen, Elizabeth T; Fichorova, Raina; Dunlop, Anne L; Paneth, Nigel; Padula, Amy; Woodruff, Tracey; Morello-Frosch, Rachel; Trowbridge, Jessica; Goin, Dana; Maldonado, Luis E; Niu, Zhongzheng; Ghassabian, Akhgar; Transande, Leonardo; Ferrara, Assiamira; Croen, Lisa A; Alexeeff, Stacey; Breton, Carrie; Litonjua, Augusto; O'Connor, Thomas G; Lyall, Kristen; Volk, Heather; Alshawabkeh, Akram; Manjourides, Justin; Camargo, Carlos A; Dabelea, Dana; Hockett, Christine W; Bendixsen, Casper G; Hertz-Picciotto, Irva; Schmidt, Rebecca J; Hipwell, Alison E; Keenan, Kate; Karr, Catherine; LeWinn, Kaja Z; Lester, Barry; Camerota, Marie; Ganiban, Jody; McEvoy, Cynthia; Elliott, Michael R; Sathyanarayana, Sheela; Ji, Nan; Braun, Joseph M; Karagas, Margaret R; ,
BACKGROUND:A major challenge in epidemiology is knowing when an exposure effect is large enough to be clinically important, in particular how to interpret a difference in mean outcome in unexposed/exposed groups. Where it can be calculated, the proportion/percentage beyond a suitable cut-point is useful in defining individuals at high risk to give a more meaningful outcome. In this simulation study we compute differences in outcome means and proportions that arise from hypothetical small effects in vulnerable sub-populations. METHODS:Data from over 28,000 mother/child pairs belonging to the Environmental influences on Child Health Outcomes Program were used to examine the impact of hypothetical environmental exposures on mean birthweight, and low birthweight (LBW) (birthweight < 2500g). We computed mean birthweight in unexposed/exposed groups by sociodemographic categories (maternal education, health insurance, race, ethnicity) using a range of hypothetical exposure effect sizes. We compared the difference in mean birthweight and the percentage LBW, calculated using a distributional approach. RESULTS:When the hypothetical mean exposure effect was fixed (at 50, 125, 167 or 250g), the absolute difference in % LBW (risk difference) was not constant but varied by socioeconomic categories. The risk differences were greater in sub-populations with the highest baseline percentages LBW: ranging from 3.1-5.3 percentage points for exposure effect of 125g. Similar patterns were seen for other mean exposure sizes simulated. CONCLUSIONS:Vulnerable sub-populations with greater baseline percentages at high risk fare worse when exposed to a small insult compared to the general population. This illustrates another facet of health disparity in vulnerable individuals.
PMCID:11438038
PMID: 39342237
ISSN: 1471-2458
CID: 5714152