Sex-Specific Associations between Prenatal Exposure to Di(2-ethylhexyl) Phthalate, Epigenetic Age Acceleration, and Susceptibility to Early Childhood Upper Respiratory Infections
Sarah M. Merrill,
Nicole Letourneau,
Gerald F. Giesbrecht,
Karlie Edwards,
Julia L. MacIsaac,
Jonathan W. Martin,
Amy M. MacDonald,
David W. Kinniburgh,
Michael S. Kobor,
Deborah Dewey,
Gillian England-Mason,
The APrON Study Team
Affiliations
Sarah M. Merrill
Department of Psychiatry and Human Behavior, The Warren Alpert Medical School at Brown University, Providence, RI 02903, USA
Nicole Letourneau
Faculty of Nursing, University of Calgary, Calgary, AB T2N 1N4, Canada
Gerald F. Giesbrecht
Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Karlie Edwards
Department of Medical Genetics, British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Julia L. MacIsaac
Department of Medical Genetics, British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Jonathan W. Martin
Science for Life Laboratory, Department of Environmental Science, Stockholm University, 106 91 Stockholm, Sweden
Amy M. MacDonald
Alberta Centre for Toxicology, University of Calgary, Calgary, AB T2N 1N4, Canada
David W. Kinniburgh
Alberta Centre for Toxicology, University of Calgary, Calgary, AB T2N 1N4, Canada
Michael S. Kobor
Department of Medical Genetics, British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Deborah Dewey
Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Gillian England-Mason
Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
The APrON Study Team
University of Calgary, Calgary, AB T2N 1N4, Canada
Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer that can affect immune system development and susceptibility to infection. Aging processes (measured as epigenetic age acceleration (EAA)) may mediate the immune-related effects of prenatal exposure to DEHP. This study’s objective was to examine associations between prenatal DEHP exposure, EAA at three months of age, and the number of upper respiratory infections (URIs) from 12 to 18 months of age using a sample of 69 maternal–child pairs from a Canadian pregnancy cohort. Blood DNA methylation data were generated using the Infinium HumanMethylation450 BeadChip; EAA was estimated using Horvath’s pan-tissue clock. Robust regressions examined overall and sex-specific associations. Higher prenatal DEHP exposure (B = 6.52, 95% CI = 1.22, 11.81) and increased EAA (B = 2.98, 95% CI = 1.64, 4.32) independently predicted more URIs. In sex-specific analyses, some similar effects were noted for boys, and EAA mediated the association between prenatal DEHP exposure and URIs. In girls, higher prenatal DEHP exposure was associated with decreased EAA, and no mediation was noted. Higher prenatal DEHP exposure may be associated with increased susceptibility to early childhood URIs, particularly in boys, and aging biomarkers such as EAA may be a biological mechanism. Larger cohort studies examining the potential developmental immunotoxicity of phthalates are needed.
