The association between prenatal perfluoroalkyl substance exposure and symptoms of attention-deficit/hyperactivity disorder in 8-year-old children and the mediating role of thyroid hormones in the Hokkaido study

Sachiko Itoh; Keiko Yamazaki; Satoshi Suyama; Atsuko Ikeda-Araki; Chihiro Miyashita; Yu Ait Bamai; Sumitaka Kobayashi; Hideyuki Masuda; Takeshi Yamaguchi; Houman Goudarzi; Emiko Okada; Ikuko Kashino; Takuya Saito; Reiko Kishi

doi:10.1016/j.envint.2021.107026

The association between prenatal perfluoroalkyl substance exposure and symptoms of attention-deficit/hyperactivity disorder in 8-year-old children and the mediating role of thyroid hormones in the Hokkaido study

Environ Int. 2022 Jan 15:159:107026. doi: 10.1016/j.envint.2021.107026. Epub 2021 Dec 7.

Affiliations

¹ Center for Environmental Health and Sciences, Hokkaido University, Sapporo, Japan.
² Funded Research Division of Child and Adolescent Psychiatry, Hokkaido University Hospital, Sapporo, Japan.
³ Center for Environmental Health and Sciences, Hokkaido University, Sapporo, Japan; Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
⁴ Center for Environmental Health and Sciences, Hokkaido University, Sapporo, Japan; Center for Medical Education and International Relations, Hokkaido University, Sapporo, Japan.
⁵ National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
⁶ Center for Environmental Health and Sciences, Hokkaido University, Sapporo, Japan. Electronic address: rkishi@med.hokudai.ac.jp.

PMID: 34890903
DOI: 10.1016/j.envint.2021.107026

Abstract

Background: Disruption of thyroid hormone (TH) levels during pregnancy contributes to attention deficit hyperactivity disorder (ADHD). Exposure to perfluoroalkyl substances (PFAS) during gestation may affect levels of maternal and neonatal TH; however, little is known about the effect of PFAS on ADHD mediated by TH.

Objectives: We investigated the impact of maternal PFAS exposure on children's ADHD symptoms with the mediating effect of TH.

Methods: In a prospective birth cohort (the Hokkaido study), we included 770 mother-child pairs recruited between 2002 and 2005 for whom both prenatal maternal and cord blood samples were available. Eleven PFAS were measured in maternal serum obtained at 28-32 weeks of gestation using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. TH and thyroid antibody, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured in maternal blood during early pregnancy (median 11 gestational weeks) and in cord blood at birth. ADHD symptoms in the children at 8 years of age were rated by their parents using the ADHD-Rating Scale (ADHD-RS). The cut-off value was set at the 80th percentile for each sex.

Results: Significant inverse associations were found between some PFAS in maternal serum and ADHD symptoms among first-born children. Assuming causality, we found only one significant association: maternal FT4 mediated 17.6% of the estimated effect of perfluoroundecanoic acid exposure on hyperactivity-impulsivity among first-born children.

Discussion: Higher PFAS levels in maternal serum during pregnancy were associated with lower risks of ADHD symptoms at 8 years of age. The association was stronger among first-born children in relation to hyperactivity-impulsivity than with regard to inattention. There was little mediating role of TH during pregnancy in the association between maternal exposure to PFAS and reduced ADHD symptoms at 8 years of age.

Keywords: Birth cohort; Mediation analysis; Neurodevelopment; Perfluoroalkyl substances; Thyroid hormone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Attention Deficit Disorder with Hyperactivity* / etiology
Child
Female
Fluorocarbons* / adverse effects
Humans
Infant, Newborn
Maternal Exposure / adverse effects
Pregnancy
Prospective Studies
Thyroid Hormones

Substances

Fluorocarbons
Thyroid Hormones