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1. Combined Exposure to Folate and Lead during Pregnancy and Autistic-Like Behaviors among Canadian Children from the MIREC Pregnancy and Birth Cohort

Author

Alampi, Joshua D., Lanphear, Bruce P., MacFarlane, Amanda J., Oulhote, Youssef, Braun, Joseph M., Muckle, Gina, Arbuckle, Tye E., Ashley-Martin, Jillian, Hu, Janice M.Y., Chen, Aimin, and McCandless, Lawrence C.

Subjects
Statistics, Risk factors, Health aspects, Lead (Metal) -- Health aspects -- Statistics, Autism -- Statistics -- Risk factors, Preschool children -- Statistics -- Health aspects, Prenatal influences -- Statistics -- Health aspects, Folic acid -- Health aspects -- Statistics, Lead -- Health aspects -- Statistics
Abstract

Introduction Lead exposure has a detrimental effect on child neurodevelopment. (1-3) Although exposure is decreasing, no safe level or threshold has been identified. (3) Moreover, lead exposure is higher among [...], BACKGROUND: Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead. OBJECTIVES: We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. METHODS: We used data from the Maternal--Infant Research on Environmental Chemicals study (2008-2011), a Canadian pregnancy and birth cohort study. Childhood autistic-like behaviors were documented in 601 children 3-4 y of age with the Social Responsiveness Scale-2 (SRS-2), where higher scores denote more autistic-like behaviors. We measured BLLs and plasma total folate concentrations during the first and third trimesters of pregnancy. We also estimated gestational FA supplementation via surveys and genotyped the maternal MTHFR 677C>T single nucleotide polymorphism (SNP). We estimated the confounder-adjusted associations between [log.sub.2]-transformed BLLs and SRS-2 scores by two indicators of folate exposure and maternal MTHFR 677C>T genotype using linear regression. RESULTS: Third-trimester BLLs were associated with increased SRS-2 scores [[[beta].sub.adj] = 3:3; 95% confidence interval (CI): 1.1, 5.5] among participants with low (T SNP ([[beta].sub.adj] = 0:9; 95% CI: -1:2, 3.1) than those without the T allele ([[beta].sub.adj] = -0:3; 95% CI: -1:3, 0.7), but the difference was not statistically significant (p-interaction = 0:28). DISCUSSION: Folate may modify the associations between gestational lead exposure and childhood autistic-like behaviors, suggesting that it mitigates the neurotoxic effects of prenatal lead exposure. https://doi.org/10.1289/EHP14479

Published
2024
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4. Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns

Author

Puvvula, Jagadeesh, Song, Lucie C., Zalewska, Klaudia J., Alexander, Ariel, Manz, Kathrine E., Braun, Joseph M., Pennell, Kurt D., DeFranco, Emily A., Ho, Shuk-Mei, Leung, Yuet-Kin, Huang, Shouxiong, Vuong, Ann M., Kim, Stephani S., Percy, Zana, Bhashyam, Priyanka, Lee, Raymund, Jones, Dean P., Tran, Vilinh, Kim, Dasom V., Calafat, Antonia M., Botelho, Julianne C., and Chen, Aimin

Published
2025
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11. Gestational exposure to environmental chemical mixtures and cognitive abilities in children: A pooled analysis of two North American birth cohorts

Author

Puvvula, Jagadeesh, Hwang, Wei-Ting, McCandless, Lawrence, Xie, Changchun, Braun, Joseph M., Vuong, Ann M., Oulhote, Youssef, Schisterman, Enrique F., Shinohara, Russell T., Booij, Linda, Bouchard, Maryse F., Linn, Kristin, Borghese, Michael M., Seguin, Jean R., Zidek, Angelika, Till, Christine, Fraser, William, Yolton, Kimberly, Cecil, Kim M., Ashley-Martin, Jillian, Arbuckle, Tye E., Lanphear, Bruce, and Chen, Aimin

Published
2025
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24. Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study

Author

Liu, Yun, Eliot, Melissa N, Papandonatos, George D, Kelsey, Karl T, Fore, Ruby, Langevin, Scott, Buckley, Jessie, Chen, Aimin, Lanphear, Bruce P, Cecil, Kim M, Yolton, Kimberly, Hivert, Marie-France, Sagiv, Sharon K, Baccarelli, Andrea A, Oken, Emily, and Braun, Joseph M

Subjects
Biomedical and Clinical Sciences, Health Sciences, Pediatric, Clinical Research, Genetics, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Aetiology, Good Health and Well Being, Adolescent, Alkanesulfonic Acids, Child, DNA Methylation, Environmental Pollutants, Epigenome, Female, Fluorocarbons, Humans, Infant, Newborn, Longitudinal Studies, Pregnancy, Environmental Sciences, Medical and Health Sciences, Toxicology, Biomedical and clinical sciences, Environmental sciences, Health sciences
Abstract

BackgroundDNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation.ObjectivesWe examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006; Cincinnati, Ohio).MethodsWe quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (n=266) and peripheral leukocytes at 12 years of age (n=160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children's age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999-2002; Boston, Massachusetts) to replicate significant associations.ResultsAfter adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, q

Published
2022

25. Maternal and newborn metabolomic changes associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations at delivery: an untargeted approach

Author

Puvvula, Jagadeesh, Manz, Kathrine E., Braun, Joseph M., Pennell, Kurt D., DeFranco, Emily A., Ho, Shuk-Mei, Leung, Yuet-Kin, Huang, Shouxiong, Vuong, Ann M., Kim, Stephani S., Percy, Zana P., Bhashyam, Priyanka, Lee, Raymund, Jones, Dean P., Tran, Vilinh, Kim, Dasom V., and Chen, Aimin

Published
2024
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29. Gestational Exposure to Phthalates and Social Responsiveness Scores in Children Using Quantile Regression: The EARLI and HOME Studies

Author

Patti, Marisa A, Newschaffer, Craig, Eliot, Melissa, Hamra, Ghassan B, Chen, Aimin, Croen, Lisa A, Fallin, M Daniele, Hertz-Picciotto, Irva, Kalloo, Geetika, Khoury, Jane C, Lanphear, Bruce P, Lyall, Kristen, Yolton, Kimberly, and Braun, Joseph M

Subjects
Pediatric, Mental Health, Prevention, Autism, Intellectual and Developmental Disabilities (IDD), Behavioral and Social Science, Brain Disorders, Clinical Research, Autism Spectrum Disorder, Autistic Disorder, Child, Child, Preschool, Cohort Studies, Environmental Exposure, Environmental Pollutants, Female, Humans, Phthalic Acids, Pregnancy, phthalates, prenatal, endocrine-disrupting chemicals, neurodevelopment, Toxicology
Abstract

Linear regression is often used to estimate associations between chemical exposures and neurodevelopment at the mean of the outcome. However, the potential effect of chemicals may be greater among individuals at the 'tails' of outcome distributions. Here, we investigated distributional effects on the associations between gestational phthalate exposure and child Autism Spectrum Disorder (ASD)-related behaviors using quantile regression. We harmonized data from the Early Autism Risk Longitudinal Investigation (EARLI) (n = 140) Study, an enriched-risk cohort of mothers who had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study (n = 276), a general population cohort. We measured concentrations of 9 phthalate metabolites in urine samples collected twice during pregnancy. Caregivers reported children's ASD-related behaviors using the Social Responsiveness Scale (SRS) at age 3-8 years; higher scores indicate more ASD-related behaviors. In EARLI, associations between phthalate concentrations and SRS scores were predominately inverse or null across SRS score quantiles. In HOME, positive associations of mono-n-butyl phthalate, monobenzyl phthalate, mono-isobutyl phthalate, and di-2-ethylhexyl phthalate concentrations with SRS scores increased in strength from the median to 95th percentile of SRS scores. These results suggest associations between phthalate concentrations and SRS scores may be stronger in individuals with higher SRS scores.

Published
2021

30. Association between self-reported caffeine intake during pregnancy and social responsiveness scores in childhood: The EARLI and HOME studies

Author

Patti, Marisa A, Li, Nan, Eliot, Melissa, Newschaffer, Craig, Yolton, Kimberly, Khoury, Jane, Chen, Aimin, Lanphear, Bruce P, Lyall, Kristen, Hertz-Picciotto, Irva, Fallin, Margaret Daniele, Croen, Lisa A, and Braun, Joseph M

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Health Sciences, Basic Behavioral and Social Science, Brain Disorders, Nutrition, Clinical Research, Autism, Behavioral and Social Science, Mental Health, Pediatric Research Initiative, Prevention, Pediatric, Intellectual and Developmental Disabilities (IDD), Aetiology, 2.3 Psychological, social and economic factors, Reproductive health and childbirth, Adult, Autism Spectrum Disorder, Body Mass Index, Caffeine, Child, Child, Preschool, Databases, Factual, Female, Humans, Male, Maternal Exposure, Pregnancy, Self Report, Young Adult, General Science & Technology
Abstract

Maternal nutrition during gestation has been investigated for its role in child neurodevelopment. However, little is known about the potential impact of gestational caffeine exposure on child autistic behaviors. Here, we assess the relation between maternal caffeine intake during pregnancy and children's behavioral traits related to Autism Spectrum Disorder (ASD). We harmonized data from two pregnancy cohorts, Early Autism Risk Longitudinal Investigation (EARLI) (n = 120), an enriched-risk cohort of mothers who previously had a child with ASD, from Pennsylvania, Maryland, and Northern California (2009-2012), and the Health Outcomes and Measures of the Environment (HOME) Study (n = 269), a general population cohort from Cincinnati, Ohio (2003-2006). Mothers self-reported caffeine intake twice during pregnancy. Caregivers reported child behavioral traits related to ASD using the Social Responsiveness Scale (SRS) when children were aged 3-8 years. Higher scores indicate more ASD-related behaviors. We estimated covariate-adjusted differences in continuous SRS T-scores per interquartile range increase in caffeine intake. Self-reported caffeine intake during pregnancy was positively associated with SRS T-scores among children in EARLI (β: 2.0; 95% CI -0.1, 4.0), but to a lesser extent in HOME (β: 0.6; 95% CI -0.5, 1.6). In HOME, pre-pregnancy body mass index (BMI) modified the association between caffeine intake and SRS T-scores, where more positive associations were observed among women with higher BMIs. Our findings suggest gestational caffeine intake may represent a marker of vulnerability to childhood ASD-related behaviors. Additional studies are warranted to extend these findings.

Published
2021

41. Balanced implicit Patankar–Euler methods for positive solutions of stochastic differential equations of biological regulatory systems.

Author

Chen, Aimin, Ren, Quanwei, Zhou, Tianshou, Burrage, Pamela, Tian, Tianhai, and Burrage, Kevin

Subjects
*STOCHASTIC differential equations, *EULER method, *BIOLOGICAL systems
Abstract

Stochastic differential equations (SDEs) are a powerful tool to model fluctuations and uncertainty in complex systems. Although numerical methods have been designed to simulate SDEs effectively, it is still problematic when numerical solutions may be negative, but application problems require positive simulations. To address this issue, we propose balanced implicit Patankar–Euler methods to ensure positive simulations of SDEs. Instead of considering the addition of balanced terms to explicit methods in existing balanced methods, we attempt the deletion of possible negative terms from the explicit methods to maintain positivity of numerical simulations. The designed balanced terms include negative-valued drift terms and potential negative diffusion terms. The proposed method successfully addresses the issue of divisions with very small denominators in our recently designed stochastic Patankar method. Stability analysis shows that the balanced implicit Patankar–Euler method has much better stability properties than our recently designed composite Patankar–Euler method. Four SDE systems are used to examine the effectiveness, accuracy, and convergence properties of balanced implicit Patankar–Euler methods. Numerical results suggest that the proposed balanced implicit Patankar–Euler method is an effective and efficient approach to ensure positive simulations when any appropriate stepsize is used in simulating SDEs of biological regulatory systems. [ABSTRACT FROM AUTHOR]

Published
2024
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