Prenatal exposure to polycyclic aromatic hydrocarbons and executive functions at school age: Results from a combined cohort study

Yu Ni; Adam A Szpiro; Christine T Loftus; Tomomi Workman; Alexis Sullivan; Erin R Wallace; Anne M Riederer; Drew B Day; Laura E Murphy; Ruby H N Nguyen; Sheela Sathyanarayana; Emily S Barrett; Qi Zhao; Daniel A Enquobahrie; Christopher Simpson; Shaikh I Ahmad; Jessica A Arizaga; Brent R Collett; Karen J Derefinko; Kurunthachalam Kannan; Nicole R Bush; Kaja Z LeWinn; Catherine J Karr

doi:10.1016/j.ijheh.2024.114407

Prenatal exposure to polycyclic aromatic hydrocarbons and executive functions at school age: Results from a combined cohort study

Int J Hyg Environ Health. 2024 Jul:260:114407. doi: 10.1016/j.ijheh.2024.114407. Epub 2024 Jun 15.

Authors

Yu Ni¹, Adam A Szpiro², Christine T Loftus³, Tomomi Workman³, Alexis Sullivan⁴, Erin R Wallace³, Anne M Riederer³, Drew B Day⁵, Laura E Murphy⁶, Ruby H N Nguyen⁷, Sheela Sathyanarayana⁸, Emily S Barrett⁹, Qi Zhao¹⁰, Daniel A Enquobahrie¹¹, Christopher Simpson³, Shaikh I Ahmad⁴, Jessica A Arizaga⁴, Brent R Collett¹², Karen J Derefinko¹³, Kurunthachalam Kannan¹⁴, Nicole R Bush¹⁵, Kaja Z LeWinn⁴, Catherine J Karr¹⁶

Affiliations

¹ Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA; Division of Epidemiology and Biostatistics, School of Public Health, College of Health and Human Services, San Diego State University, San Diego, CA, USA. Electronic address: yni5@sdsu.edu.
² Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
³ Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.
⁴ Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
⁵ Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA, USA.
⁶ Department of Psychiatry, University of Tennessee Health Science Center, Memphis, TN, USA.
⁷ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minnesota, USA.
⁸ Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA; Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, School of Medicine, University of Washington, Seattle, WA, USA.
⁹ Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ, USA.
¹⁰ Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
¹¹ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
¹² Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
¹³ Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Pharmacology, Addiction Science, and Toxicology, University of Tennessee Health Science Center, Memphis, TN, USA.
¹⁴ Wadsworth Center, New York State Department of Health, Albany, NY, USA.
¹⁵ Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Pediatrics, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
¹⁶ Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA; Department of Pediatrics, School of Medicine, University of Washington, Seattle, WA, USA.

PMID: 38879913
DOI: 10.1016/j.ijheh.2024.114407

Abstract

Background: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited.

Methods: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture.

Results: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident.

Conclusion: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.

Keywords: Executive functions; Maternal psychosocial stress; Mixture analysis; Polycyclic aromatic hydrocarbons.

MeSH terms

Adult
Child
Cohort Studies
Environmental Pollutants / urine
Executive Function* / drug effects
Female
Humans
Male
Maternal Exposure
Memory, Short-Term / drug effects
Polycyclic Aromatic Hydrocarbons* / urine
Pregnancy
Prenatal Exposure Delayed Effects*

Substances

Polycyclic Aromatic Hydrocarbons
Environmental Pollutants