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The association of preconception and prenatal cannabis and tobacco exposure with autism symptoms in offspring: A population-based longitudinal study

Cajachagua-Torres, Kim N; Boer, Olga D; Louwerse, Anneke; Ghassabian, Akhgar; Reiss, Irwin K M; Jaddoe, Vincent W V; El Marroun, Hanan
Prenatal cannabis and tobacco exposure is associated with attention and behavior problems in children, while associations with autism symptoms remain unclear. We prospectively examined whether parental cannabis and tobacco use during pregnancy were associated with childhood autism symptoms. Information on parental cannabis and tobacco use was assessed using questionnaires, and maternal cannabis metabolites were detected via urinalysis. We measured autistic symptoms using two mother-reported instruments: Child Behavior Checklist (CBCL) at ages 1.5, 3, and 6; and Social Responsiveness Scale (SRS) at 6 years (n = 4380). Linear mixed models were used to examine the association between parental cannabis and tobacco use and CBCL autism symptoms across childhood. Linear regression was used for SRS autism symptoms. Maternal cannabis use before, but not during, pregnancy was associated with higher CBCL autism symptoms across childhood (β: 0.33, 95 % CI: 0.02, 0.63). Paternal cannabis use was linked to higher CBCL autism symptoms across childhood (β: 0.27, 95 % CI: 0.05, 0.50), explained by maternal psychopathology; no association was found with SRS autism symptoms. Excluding cannabis users, children whose mothers used tobacco throughout pregnancy had more SRS autism symptoms (β: 0.03, 95 % CI: 0.003, 0.05), not CBCL; no association was found with paternal tobacco use. Our results suggest that maternal and paternal cannabis use is not associated with offspring autism symptoms, although preconception use is associated with autism symptoms across childhood. In contrast, maternal continued tobacco use during pregnancy was associated with autism symptoms, but not paternal use, suggesting possible intrauterine programming rather than family-based factors.
PMID: 41016606
ISSN: 1872-9738
CID: 5974372

Prenatal Exposure to Organophosphate Ester Flame Retardants and Child Cognition: Findings from the Environmental influences on Child Health Outcomes Cohort

Ghassabian, Akhgar; Etzel, Taylor; Ames, Jennifer L; O'Connor, Thomas G; Buckley, Jessie P; Shahin, Sarvenaz; Herbstman, Julie B; Barrett, Emily S; Liang, Donghai; Croen, Lisa A; Schmidt, Rebecca J; Quirós-Alcalá, Lesliam; Schantz, Susan L; Lyall, Kristen; Choi, Giehae; Carignan, Courtney C; Woodruff, Tracey J; Morello-Frosch, Rachel; Shin, Hyeong-Moo; Buss, Claudia; Li, Zhongmin; Kannan, Kurunthachalam; Bennett, Deborah H; ,
Experimental evidence shows that organophosphate esters (OPEs), common flame retardants and plasticizers, can cause developmental neurotoxicity. We investigated the extent to which prenatal OPE exposure was associated with child cognition. Participants were 831 mother-child pairs from 3 sites in the Environmental influences on Child Health Outcomes (ECHO) Cohort with data on urinary levels of 9 OPE analytes during gestation (2009-2019) and child cognition. Based on detection frequencies, analytes were modeled continuously (adjusted for urinary dilution and log2-transformed), categorically (high/low/non-detect), or dichotomously (detect/non-detect). Children's cognition was measured using the Wechsler Preschool and Primary Scale of Intelligence or Wechsler Intelligence Scale for Children at mean age 5.7 years (SD=0.7). We examined associations of OPE analyte with age- and sex-standardized cognition scores using linear regression with generalized estimating equations to account for clustering within sites. We also tested for effect measure modification by sex. The analyte with the highest detection frequency (96.4%) was diphenyl phosphate (DPHP), a primary metabolite of triphenyl phosphate (TPHP). Higher concentrations of DPHP were associated with lower cognition scores ( per doubling of concentrations=-0.46, 95%CI: -0.90, -0.02). Bis(butoxyethyl) phosphate (BBOEP), bis(1-chloro-2-propyl) phosphate (BCPP), and bis(2-methylphenyl) phosphate (BMPP) above the detection limit (vs. below) were associated with higher cognition scores mainly in boys; but, sex interaction with BMPP was not significant. Prenatal exposure to DPHP, a widely detected OPE, was associated with lower cognitive functioning, though the effect size was small. Given widespread exposure, findings related to this and other OPEs should be further examined in mechanistic studies.
PMID: 41317781
ISSN: 1873-6424
CID: 5968962

Prenatal exposure to environmental phenolic compounds and their association with childhood atopic dermatitis, asthma, and allergic rhinitis in the ECHO cohort

Miller, Rachel L; Wang, Yuyan; Aalborg, Jenny; Alshawabkeh, Akram N; Braun, Joseph M; Breton, Carrie V; Carignan, Courtney C; Dabelea, Dana; Dunlop, Anne L; Ferrara, Assiamira; Gao, Griffith; Gaylord, Abigail; Geiger, Sarah D; Gold, Diane R; Abul, Mehtap Haktanir; Hartert, Tina V; Herbstman, Julie; Hoepner, Lori A; Karagas, Margaret R; Karr, Catherine J; Kelly, Rachel S; Khatchikian, Camilo E; Liu, Mengling; Lyall, Kristen; Meeker, John D; Morello-Frosch, Rachel; O'Connor, Thomas G; Oh, Jiwon; Sathyanarayana, Sheela; Sordillo, Joanne E; Trasande, Leonardo; Woodruff, Tracey J; ,
Phenolic compounds may be harmful to the developing fetus, but many have not been studied in-depth for adverse childhood allergic and respiratory health effects. We hypothesized that higher levels of phenolic compounds in prenatal spot urine would be associated with greater odds of childhood atopic dermatitis, allergic rhinitis, and asthma, and that child sex may modify these associations. 3198 mother-child paired cases were enrolled from 16 cohorts in the U.S. ECHO consortium. Fifteen phenols (e.g. benzophenones, parabens, bisphenols, triclosans) were measured from mother's urine during pregnancy using a multi-class chemical panel. Childhood outcomes included parent-reported atopic dermatitis (1466 mother-child pairs) between ages 0-3 years, and allergic rhinitis (901 mother-child pairs) and asthma (1662 mother-child pairs) between ages 5-9 years. Prenatal parabens were associated with increased odds of atopic dermatitis (odds ratio (OR) 1.13, 95 % confidence intervals (CI) 1.02, 1.26). Benzophenones were associated with lower odds of asthma (OR 0.77, CI 0.66, 0.90). Compared to boys, girls demonstrated higher odds of parabens (1.21, CI 1.04, 1.42), benzophenones (1.18, CI 1.00, 1.38) and bisphenol S (1.21, CI 1.03, 1.43) being associated with atopic dermatitis, and of the benzophenones (1.46, CI 1.11, 1.93) being associated with allergic rhinitis. An association of benzophenones (0.66, CI 0.53, 0.83) with lower odds of asthma was stronger among boys. These findings suggest that prenatal paraben and other phenol exposures may adversely affect early-life allergic and respiratory outcomes, with sex-specific vulnerability. Novel, multi-modality approaches to reduce maternal phenol exposure during pregnancy are urgently needed to protect children's health.
PMID: 41161078
ISSN: 1873-6750
CID: 5961392

Reproductive toxicity of micro- and nanoplastics: Insights from experimental and human studies

Wehrli, Lydia; Martin, Olwenn V; Trasande, Leonardo; Damdimopoulou, Pauliina
The exponential rise in plastic production has driven widespread contamination by micro- and nanoplastics (MNPs) in the environment. These plastic particles and their chemical additives have been detected in water sources, human bodily fluids, and reproductive tissues. With global fertility rates declining, their role as potential contributors is under investigation. This scoping review compares findings from in vitro experiments, in vivo studies across animal models, and epidemiological data to assess potential reproductive hazards associated with MNP exposure. Forty original studies published within the last decade were identified. MNPs have been detected in human breast milk, placenta, endometrium, ovaries, testis, semen, follicular fluid, blood, and urine samples. Humans are estimated to absorb 74,000-121,000 particles annually through inhalation, ingestion, skin contact, and use of plastic materials, including medical devices. Experimental evidence demonstrates that MNPs can cross biological barriers, interact with cells, and disrupt cellular pathways, including steroidogenesis, energy metabolism, inflammatory pathways, and oxidative stress. Thirty in vivo animal studies have associated MNPs with altered reproductive endpoints in both males (i.e., altered semen quality and spermatogenesis) and females (i.e., altered folliculogenesis, depleted ovarian reserve, and reduced litter sizes), with possible transgenerational effects. In conclusion, current evidence suggests MNPs may represent a reproductive health hazard to humans and animals. The relative contributions of particle toxicity and their chemical additives remain difficult to disentangle. Overall, plastics and their associated chemicals represent a serious health and environmental concern, which continues to grow in the absence of restrictions and international agreements.
PMID: 41164869
ISSN: 1365-2796
CID: 5961502

Prenatal Organophosphate Pesticide Exposure and Targeted Maternal Pregnancy Metabolomic Profiles in the NYU CHES Cohort

Cavalier, Haleigh; Ghassabian, Akhgar; Long, Sara E; Afanasyeva, Yelena; Sumner, Susan; McRitchie, Susan; Coble, Rachel; Chen, Yu; Kannan, Kurunthachalam; Li, Zhongmin; Liu, Mengling; Trasande, Leonardo
Prior research links prenatal exposure to organophosphate (OP) pesticides to adverse health outcomes via molecular mechanisms, such as oxidative stress, neurotransmitter disruption, and mitochondrial dysfunction. This study investigates such mechanisms by assessing the relationships between prenatal OP pesticide exposure and targeted urinary maternal metabolomic profiles using data from the New York University Children's Health and Environment Study (NYU CHES) cohort (n = 890). Urine samples were collected at three time points during pregnancy (T
PMID: 41071016
ISSN: 1520-5851
CID: 5952342

The effects of plastic exposures on children's health and urgent opportunities for prevention

Trasande, Leonardo; Đorđević, Aleksandra Buha; Fernandez, Marina Olga
Children face an urgent threat in the form of hazards posed by plastics in the environment. Despite robust and rapidly accumulating evidence on the effects of plastic on children's health, plastic presents a paradox for child health providers: while plastic is a vehicle for so many interventions, robust evidence from laboratory and human studies show that chemicals used to produce plastics contribute to chronic conditions in multiple organ systems and disrupt hormone function, and exposure to plastic-derived toxins is associated with adverse birth outcomes, metabolic conditions, neurodevelopmental disease and disability, and reproductive conditions. Evidence-based, safe, simple, and low-cost steps exist for child health providers in primary care to help families limit children's exposure to plastic-derived toxins. Health-care providers also have a crucial opportunity to protect the health and wellbeing of future generations of children by supporting local and global campaigns for governments, industries, and the general public to reduce the accumulation of plastics in the environment and minimise the use of plastics within health-care systems.
PMID: 40992383
ISSN: 2352-4650
CID: 5951372

COVID-19 Pandemic Exposure and Toddler Behavioral Health in the ECHO Program

Akbaryan, Anahid; Churchill, Marie L; McGrath, Monica; Alshawabkeh, Akram; Enlow, Michelle Bosquet; Brennan, Patricia A; Collazo Vargas, Julianna; Costello, Lauren A; D'Sa, Viren; Dunlop, Anne; Elliott, Amy J; Firestein, Morgan; Ghassabian, Akhgar; Hofheimer, Julie A; Koinis-Mitchell, Daphne; Margolis, Amy; Morales, Santiago; Morello-Frosch, Rachel; Nozadi, Sara S; O'Connor, Thomas G; Schantz, Susan L; Woodruff, Tracey; Wright, Rosalind J; Shuffrey, Lauren C; ,
IMPORTANCE/UNASSIGNED:Studies suggest developmental concerns for infants born during the COVID-19 pandemic, but evidence on its impact on toddler behavioral and emotional well-being remains limited. OBJECTIVE/UNASSIGNED:To assess whether birth timing relative to the COVID-19 pandemic is associated with toddler internalizing and externalizing problems. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study utilized Environmental Influences on Child Health Outcomes (ECHO) cohort data collected between September 27, 2009, and July 21, 2023. Children were divided into 3 groups: the prepandemic group, who were born and assessed before March 13, 2020; the pandemic-assessed group, who were born before March 13, 2020, but assessed after that date; and the pandemic-born group, who were born and assessed on or after March 13, 2020. Data were collected from 9 ECHO cohort sites across the United States and Puerto Rico. EXPOSURE/UNASSIGNED:The COVID-19 pandemic, designated as starting on March 13, 2020. MAIN OUTCOME AND MEASURE/UNASSIGNED:Parent-reported internalizing and externalizing symptoms on the Preschool Child Behavior Checklist (CBCL 1½-5) at age 18 to 39 months. RESULTS/UNASSIGNED:The 3438 children (mean [SD] age, 2.33 years [5.38 months]; 1770 [51.5%] male; 537 [16.2%] Black, 1722 [50.1%] Hispanic; and 1538 [44.7%] White) were divided into 3 groups: 1323 in the prepandemic group (mean [SD] age, 2.41 years [5.66 months]); 1690 in the pandemic-assessed group (mean [SD] age, 2.32 years [5.16 months]); and 425 in the pandemic-born group (mean [SD] age, 2.14 years [4.47 months]). Both the pandemic-assessed group (unadjusted β = -1.51; 95% CI, -2.27 to -0.75; adjusted β = -1.73; 95% CI, -2.48 to -0.99) and the pandemic-born group (unadjusted β = -2.03; 95% CI, -3.13 to -0.93; adjusted β = -1.90; 95% CI, -2.99 to -0.80) had lower levels of internalizing problems compared with the prepandemic (ie, historical) group. Similarly, both the pandemic-assessed (unadjusted β = -1.74; 95% CI, -2.46 to -1.02; adjusted β = -1.81; 95% CI, -2.53 to -1.09) and the pandemic-born group (unadjusted β = -3.16; 95% CI, -4.20 to -2.12; adjusted β = -3.17; 95% CI, -4.22 to -2.12) each had lower levels of externalizing problems compared with the prepandemic group. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, toddlers with prenatal and postnatal as well as those with only postnatal COVID-19 pandemic exposure showed fewer internalizing and externalizing problems than those born and assessed prior to the onset of the pandemic. These findings underscore the need for further research to identify protective factors that may buffer the impact of the pandemic on child behavior.
PMID: 40900589
ISSN: 2574-3805
CID: 5936292

Effects of a federal smoke-free housing policy on adverse birth outcomes among NYC public-housing residents

Eisenberg-Guyot, Jerzy; Baker, Melanie; Titus, Andrea R; Anastasiou Pesante, Elle; Kim, Byoungjun; Ghassabian, Akhgar; Thorpe, Lorna E
INTRODUCTION/BACKGROUND:Identifying strategies to mitigate the effects of secondhand smoke exposure is crucial for public health. Thus, we estimated the effect of a 2018 federal smoke-free housing (SFH) policy on adverse birth outcomes among New York City (NYC) public-housing residents. METHODS:We obtained data on all live births to NYC residents in NYC from 2013 to 2022, using the borough-block-lot of the birthing person's address to identify births to public-housing residents. We then estimated the effect of the SFH policy on risk of preterm birth or low birth weight among births to NYC public-housing residents using a linear-probability difference-in-differences estimator, weighted by inverse probability weights to increase the plausibility of the parallel-trends assumption. RESULTS:Our sample included 44 455 births to public-housing residents and 803 648 births to non-public-housing residents. Difference-in-difference analyses suggested the SFH policy did not affect risk of preterm birth (risk difference (RD) per 100: 0.1; 95% CI -0.6 to 0.9) or low birth weight (RD per 100: 0.3, 95% CI -0.4 to 1.0). Event-study analyses supported these findings and lent credibility to the parallel-trends assumption. CONCLUSIONS:We estimated no initial effects of a federal SFH policy on risk of preterm birth or low birth weight among births to NYC public-housing residents.
PMID: 40850782
ISSN: 1468-3318
CID: 5909862

Stability of cytokine and immunoglobulin concentrations in the general population: prepandemic basal concentrations and intraindividual changes until the COVID-19 pandemic

Gasull, Magda; Pumarega, José; Aguilar, Ruth; Campi, Laura; Prieto-Merino, David; Villar-García, Judit; Rius, Cristina; Bolúmar, Francisco; Trasande, Leonardo; Dobaño, Carlota; Moncunill, Gemma; Porta, Miquel
BACKGROUND/UNASSIGNED:While there is wide evidence on concentrations of cytokines in patients attending health care facilities, evidence is scant on physiological, basal concentrations of cytokines in the general population and across sociodemographic groups, as well as on their potential stability over time. Furthermore, from a public health perspective it is remarkable that no studies have analyzed intraindividual changes in such concentrations from before the COVID-19 pandemic until its outbreak. OBJECTIVES/UNASSIGNED:To investigate: (a) prepandemic concentrations of cytokines and immunoglobulins to viral exposures in a general, non-institutionalized population, and their associated sociodemographic variables; (b) the intraindividual change in such concentrations between a prepandemic period (2016-17) and the initial pandemic period (2020-21); and (c) whether such change was similar in participants who in 2020-21 were SARS-CoV-2 seronegative and seropositive, and between participants who did and did not develop COVID-19. METHODS/UNASSIGNED:We conducted a prospective cohort study in 240 individuals from the general population of Barcelona, Spain. Thirty cytokines and 31 immunoglobulins were measured in paired serum samples collected in 2016-17 and 2020-21 in the same individuals. RESULTS/UNASSIGNED:The median value of the relative intraindividual change in cytokine concentrations between 2016 and 2020 was <15% for 29 of the 30 cytokines. A substantial number of participants had an intraindividual increase or decrease ≥15% in some cytokines. No major differences in intraindividual changes of cytokine and immunoglobulin levels between 2016 and 2020 were observed between participants who did and did not develop COVID-19. CONCLUSION/UNASSIGNED:We provide novel information on physiological, basal ex-vivo concentrations of cytokines and immunoglobulins in a general population, which should be relevant for clinical practice and public health. Intraindividual changes in cytokines and immunoglobulins during the 4 years from 2016-17 to 2020-21 were moderate, and they did not differ between participants who in 2020-21 were SARS-CoV-2 seropositive and seronegative, nor between participants who did and did not develop COVID-19 disease. These findings are also novel and relevant for medicine and public health. In particular, the stability in the biomarkers is relevant to assess the role of the immunological and inflammatory state (measured through baseline levels of cytokines and immunoglobulins) in the development of SARS-CoV-2 seropositivity and COVID-19 disease, as well as in the susceptibility to other infections and pathologies.
PMCID:12263939
PMID: 40672932
ISSN: 2296-2565
CID: 5906472

Key sociodemographic factors and food packaging attributes associated with poor diet quality among rural Americans: a cross-sectional survey study

Koziatek, Christian A; Motola, Haley L; Holden, Karen S; Hubert-Simon, Jill; Wise, Nathan; Prabu, Anirudh; Doran, Kelly M; Thorpe, Lorna E; Trasande, Leonardo; Lee, David C
OBJECTIVES/OBJECTIVE:Rural residents face unique challenges that contribute to poor diet quality and health. The objective of this study was to assess diet quality using the Alternative Healthy Eating Index (aHEI) among residents of a rural New York county with poor health outcomes, and identify geographic and individual-level factors associated with lower diet quality. DESIGN/METHODS:We performed a cross-sectional study using survey data and multivariable linear regression analyses, supplemented by geographic distribution assessment of aHEI scores. SETTING/METHODS:Sullivan County, New York, a rural county with poor health outcomes. PARTICIPANTS/METHODS:Households in Sullivan County who responded to a dietary and sociodemographic health survey in 2021-2022. OUTCOME MEASURES/METHODS:The primary outcome was the aHEI score and its dietary subscores. Secondary measures included sociodemographic characteristics, receipt of income assistance, financial hardship, food and housing insecurity, primary food store type, distance to food store and frequency of canned or plastic-wrapped food consumption. RESULTS:The overall survey response rate was 42.5%. The mean aHEI score was 56.5 (SD: 11.9), normally distributed across respondents. Lower aHEI scores were associated with not completing high school (10.0 points lower vs college graduates, p<0.01), reporting a disability (3.5 points lower, p<0.01), experiencing food insecurity (3.0 points lower, p<0.01) and frequent consumption of canned foods (6.2 points lower compared with those who never consumed canned foods, p<0.01). Geographic analysis revealed clustering of predictors but no substantial geographic clustering of aHEI scores. CONCLUSIONS:Poor diet quality in rural areas is associated with education level, disability, food insecurity and canned food consumption. These findings highlight potentially modifiable risk factors and support the need for targeted interventions to improve diet quality and reduce health disparities in rural populations.
PMCID:12314980
PMID: 40744514
ISSN: 2044-6055
CID: 5903722