The relationship between maternal use of organic solvents at work and the onset of West syndrome in children

A research team from the Department of Pediatrics and the Hyogo Eco-Child Survey Hyogo Unit Center at Hyogo Medical University School of Medicine (Nishinomiya, Hyogo Prefecture, President: Keiichiro Suzuki) analyzed the relationship between the frequency of use of items containing volatile organic solvents used at work for more than half a day during pregnancy and the onset of West syndrome, a type of intractable epilepsy, in children, based on data from approximately 100,000 parent-child pairs from the National Survey on Children's Health and the Environment (hereinafter referred to as the "Eco-Child Survey"). The results showed that the more frequently oil-based markers were used, the higher the percentage of children who developed the condition. This suggests that there may be a relationship between the frequency with which mothers used oil-based markers at work for more than half a day during pregnancy and the onset of West syndrome. Note that this study does not show a causal relationship. In addition, there are limitations such as the type of oil-based marker being unclear, it being unclear whether the substances contained in the oil-based markers were the cause, and the effects of other substances not being fully considered. The results of this study were published in the comprehensive science journal "Scientific Reports" published by Springer Nature on December 28, 2024.
*The contents of this study are the opinions of the authors and do not necessarily represent the views of the Ministry of the Environment or the National Institute for Environmental Studies.

Association between maternal usage of volatile organic compounds and West syndrome, The Japan Environment and Children's Study

Hideki Shimomura(1), Naoko Taniguchi(1)(2), Tetsuro Fujino(1)(2), Sachi Tokunaga(1), Yohei Taniguchi(1), Takafumi Nishioka(1), Narumi Tokuda(2), Masumi Okuda(1), Masayuki Shima(2)(3), Yasuhiro Takeshima(1), and the Japan Environment and Children's Study Group(4)

1H. Shimomura, N. Taniguchi, T. Fujino, S. Tokunaga, Y. Taniguchi, T. Nishioka, M. Okuda, and Y. Takeshima: Department of Pediatrics, Hyogo Medical University School of Medicine
2. Naoko Taniguchi, Tetsuro Fujino, Narumi Tokuda, Masayuki Shima: Eco-Children Hyogo Unit Center
3. Masayuki Shima: Department of Public Health, Hyogo Medical University School of Medicine

(Affiliation at the time of paper submission)

The Nationwide Survey on Children's Health and the Environment (hereafter referred to as the "ECO-CHILD Study") is a large-scale, long-term birth cohort study that was launched by the Ministry of the Environment in 2010 and targets approximately 100,000 parent-child pairs nationwide in order to clarify the impact of exposure to chemicals from the fetal to childhood stage on children's health. Biological samples such as umbilical cord blood, blood, urine, breast milk, and milk teeth are collected, preserved, and analyzed, and follow-up surveys are conducted to clarify the relationship between children's health and environmental factors such as chemicals.
The Eco-Children Study is being carried out in collaboration with the Ministry of the Environment, with a Core Center at the National Institute for Environmental Studies as the central research institution, a Medical Support Center at the National Center for Child Health and Development to provide medical support, and Unit Centers as regional survey bases at 15 universities and other institutions selected through a public application process to conduct the study in various regions of Japan.
West syndrome is a type of intractable epilepsy that develops in infancy due to various causes. The main causes are perinatal and congenital abnormalities, but there are cases where no clear cause is found. In recent years, advances in Department of Genetics testing methods have revealed that some patients with no known cause have genetic abnormalities. Genetic abnormalities are influenced by various factors, so it is difficult to determine a specific factor as the cause. Animal experiments and other studies have reported that some organic solvents may induce genetic changes in the human body. Therefore, we investigated whether products containing organic solvents during pregnancy and the frequency of use of such products are related to the onset of West syndrome in children.

This study targeted 88,280 people who provided valid responses to a self-administered questionnaire out of approximately 100,000 parent-child pairs who were registered in the Eco-Child Study and whose data was obtained from early pregnancy until the child's second birthday. The analysis looked at the association between the frequency of use of products thought to contain organic solvents at work during pregnancy, or organic solvents themselves (kerosene, petroleum, benzine, gasoline, oil-based markers, water-based paints, inkjet printers, organic solvents) for more than half a day (not used, 1-3 times a month, or more than once a week) and the onset of West Syndrome in children up to the age of two.
Statistical analysis was performed using logistic regression analysis*2 with the mother's occupation, mother's age, number of weeks at birth, and child's sex as covariates*1. We also analyzed the association with the frequency of permanent marker use.
As a result, it was found that the risk of developing West Syndrome increased in those who used oil-based markers or water-based paints/inkjet printers more than once a month (more than half a day each time). None of the mothers of children who developed West Syndrome exclusively used water-based paints/inkjet printers, so it was not possible to analyze the frequency of use of water-based paints/inkjet printers and the onset of West Syndrome. Regarding the frequency of use of oil-based markers and the onset of West Syndrome, it was found that the risk of developing West Syndrome increased in the following order: not using oil-based markers, 1-3 times a month, and once a week or more.

In the future, we believe it will be necessary to investigate the impact of the use of oil-based markers on the onset of West Syndrome. It is expected that the Eco-Children Study will continue to shed light on environmental factors such as chemicals that affect children's development and health.
This study has several limitations. First, because the study used questionnaires to collect information on the use of products that are thought to contain organic solvents or the products themselves, it was not possible to accurately examine the effects of exposure to the substances. Second, because information was collected using questionnaires, it was not possible to examine the effects of sources other than the type, amount, and concentration of the organic solvent, or the products used. Third, it was not possible to examine other substances to which the women were exposed during pregnancy, or substances to which the children were exposed after birth. Finally, it was not possible to examine whether it was the substances to which the women were exposed or other workplace conditions that influenced the onset of West syndrome.

*1 Covariates: Factors that affect the outcome
*2 Logistic regression analysis: A statistical method for examining the probability of a specific event occurring when multiple factors are related.
*3 West syndrome: A type of intractable epilepsy that develops in infancy and requires prompt treatment. In many cases, the cause is unknown.

Scientific Reports