The association between prenatal per-and polyfluoroalkyl substance levels and Kawasaki disease among children of up to 4 years of age: A prospective birth cohort of the Japan Environment and Children's study

Hiroyoshi Iwata; Sumitaka Kobayashi; Mariko Itoh; Sachiko Itoh; Rahel Mesfin Ketema; Naomi Tamura; Chihiro Miyashita; Takeshi Yamaguchi; Keiko Yamazaki; Hideyuki Masuda; Yu Ait Bamai; Yasuaki Saijo; Yoshiya Ito; Shoji F Nakayama; Michihiro Kamijima; Reiko Kishi; Japan Environment, Children's Study JECS Group

doi:10.1016/j.envint.2023.108321

The association between prenatal per-and polyfluoroalkyl substance levels and Kawasaki disease among children of up to 4 years of age: A prospective birth cohort of the Japan Environment and Children's study

Environ Int. 2024 Jan:183:108321. doi: 10.1016/j.envint.2023.108321. Epub 2023 Nov 11.

Authors

Hiroyoshi Iwata¹, Sumitaka Kobayashi², Mariko Itoh¹, Sachiko Itoh¹, Rahel Mesfin Ketema³, Naomi Tamura¹, Chihiro Miyashita¹, Takeshi Yamaguchi¹, Keiko Yamazaki¹, Hideyuki Masuda⁴, Yu Ait Bamai⁵, Yasuaki Saijo⁶, Yoshiya Ito⁷, Shoji F Nakayama⁸, Michihiro Kamijima⁹, Reiko Kishi¹⁰; Japan Environment, Children's Study JECS Group

Affiliations

¹ Center for Environmental and Health Sciences, Hokkaido University, North-12, West-7, Kita-ku, Sapporo 060-0812, Japan.
² Center for Environmental and Health Sciences, Hokkaido University, North-12, West-7, Kita-ku, Sapporo 060-0812, Japan; Division of Epidemiological Research for Chemical Disorders, Research Center for Chemical Information and Management, National Institute of Occupational Safety and Health, 6-21-1, Nagao, Tama-ku, Kawasaki 214-8585, Japan.
³ Center for Environmental and Health Sciences, Hokkaido University, North-12, West-7, Kita-ku, Sapporo 060-0812, Japan; Faculty of Health Sciences, Hokkaido University, North-12, West-5, Kita-ku, Sapporo 060-0812, Japan.
⁴ Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo, Tokyo 202-8585, Japan.
⁵ Center for Environmental and Health Sciences, Hokkaido University, North-12, West-7, Kita-ku, Sapporo 060-0812, Japan; Department of Pharmaceutical Sciences, University of Antwerp, University Square 1, 2610 Wilrijk, Belgium.
⁶ Division of Public Health and Epidemiology, Department of Social Medicine, Asahikawa Medical University, 1-1-1 Midorigaoka-higashi-2-jo, Asahikawa 078-8510, Japan.
⁷ Faculty of Nursing, Japanese Red Cross Hokkaido College of Nursing, 664-1 Akebono-cho, Kitami 090-0011, Japan.
⁸ Japan Environment and Children's Study Programme Office, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan.
⁹ Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.
¹⁰ Center for Environmental and Health Sciences, Hokkaido University, North-12, West-7, Kita-ku, Sapporo 060-0812, Japan. Electronic address: rkishi@med.hokudai.ac.jp.

PMID: 38061246
DOI: 10.1016/j.envint.2023.108321

Abstract

Kawasaki disease (KD) is common among pediatric patients and is associated with an increased risk of later cardiovascular complications, though the precise pathophysiology of KD remains unknown. Per- and polyfluoroalkyl substances (PFAS) have gathered notoriety as the causal pathogens of numerous diseases as well as for their immunosuppressive effects. The present epidemiological study aims to assess whether PFAS may affect KD risk. We evaluated research participants included in the ongoing prospective nationwide birth cohort of the Japan Environment and Children's Study (JECS). Among the over 100,000 pregnant women enrolled in the JECS study, 28 types of PFAS were measured in pregnancy in a subset of participants (N = 25,040). The JECS followed their children born between 2011 and 2014 (n total infants = 25,256; n Kawasaki disease infants = 271), up to age four. Among the 28 types of PFAS, those which were detected in >60 % of participants at levels above the method reporting limit (MRL) were eligible for analyses. Multivariable logistic regressions were implemented on the seven eligible PFAS, adjusting for multiple comparison effects. Finally, we conducted Weighted Quantile Sum (WQS) and Bayesian kernel machine regression (BKMR) to assess the effects of the PFAS mixture on KD. Therefore, we ran the BKMR model using kernel mechanical regression equations to examine PFAS exposure and the outcomes of KD. Upon analysis, the adjusted multivariable regression results did not reach statistical significance for the seven eligible substances on KD, while odds ratios were all under 1.0. WQS regression was used to estimate the mixture effect of the seven eligible PFAS, revealing a negative correlation with KD incidence; similarly, BKMR implied an inverse association between the PFAS mixture effect and KD incidence. In conclusion, PFAS exposure was not associated with increased KD incidence.

Keywords: Japan Environment and Children’s Study; Kawasaki disease; Per- and polyfluoroalkyl substances.

MeSH terms

Alkanesulfonic Acids*
Bayes Theorem
Birth Cohort
Child, Preschool
Environmental Pollutants*
Female
Fluorocarbons* / toxicity
Humans
Infant
Infant, Newborn
Japan
Mucocutaneous Lymph Node Syndrome* / chemically induced
Pregnancy
Prospective Studies
Vitamins

Substances

Alkanesulfonic Acids
Environmental Pollutants
Fluorocarbons
Vitamins