The relationship between mothers' use of spray preparations and their children's renal and urinary abnormalities - National survey on children's health and the environment (Eco-Children's Survey)

A research team from the Department of Pediatrics and the Hyogo Eco-Children Survey Hyogo Unit Center at Hyogo Medical University College School of Medicine (Nishinomiya, Hyogo Prefecture; President: Keiichiro Suzuki) analyzed data from approximately 84,000 parent-child pairs from the National Survey on Children's Health and the Environment (hereafter referred to as the "Eco-Children Survey") to examine the relationship between pregnant women's use of household products containing organic solvents and spray preparations and the frequency of renal and urinary tract abnormalities discovered in children by the age of one.

The results showed that the use of spray preparations (waterproofing sprays, spray insecticides) during pregnancy was associated with a higher incidence of renal and urinary abnormalities detected by the time the child reached the age of one, but that there was no association with the use of organic solvents. These results suggest that there may be an association between maternal exposure to spray preparations during pregnancy and the occurrence of renal and urinary abnormalities in children.

However, there are limitations to this research, such as the types of ingredients in the spray formulation used being unclear and the exact time when the spray formulation was used not being known.

The results of this research were published in the International Journal of Urology, an academic journal in the field of urology published by the Japanese Department of Urology, on June 20, 2023.
*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.

- Using data from the Eco-Children Survey, we investigated the relationship between the use of organic solvents and spray preparations by pregnant women and the frequency of renal and urinary abnormalities detected in children by the time they reached the age of one.

- There was no correlation between maternal use of organic solvents and the frequency of renal and urinary abnormalities detected by the age of one.

-The results showed that when pregnant women used waterproof spray, the frequency of renal and urinary abnormalities discovered in male babies by the age of one was higher than in the group that did not use the spray.

- Results showed that when pregnant women used spray insecticides, the frequency of renal and urinary abnormalities discovered in girls by the age of one was higher than in the group that did not use insecticides.

-In the disease-specific analysis, the frequency of vesicoureteral reflux was higher in boys when pregnant women used waterproof spray compared to those who did not, and the frequency of hydronephrosis was higher in girls when pregnant women used spray insecticide.

The National 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 launched by the Ministry of the Environment in 2010 targeting approximately 100,000 parent-child pairs nationwide to clarify the impact of chemical exposure from the fetal to childhood period 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 Survey is being carried out in collaboration with the Ministry of the Environment and related organizations, 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 surveys in various regions of Japan.

Renal and urinary tract abnormalities, including various structural malformations characterized by abnormal renal development during fetal development, are the most common cause of end-stage renal disease in children, accounting for 62.2% of pediatric chronic kidney disease cases. Urinary tract abnormalities have been reported in 41.3% of children receiving renal replacement therapy (kidney transplantation, peritoneal dialysis, hemodialysis), highlighting the importance of early diagnosis and treatment. Several studies have examined the relationship between exposure to organic solvents during pregnancy and renal and urinary tract abnormalities in children, reporting a significantly higher incidence of external genital anomalies (cryptorchidism and hypospadias) in boys born to mothers exposed to organic solvents during pregnancy. However, no studies have examined the relationship between exposure to spray formulations and renal and urinary tract abnormalities in children. In this study, we investigated whether there is a relationship between the frequency of renal and urinary tract abnormalities detected between fetal development and age 1 year and maternal use of organic solvents and household products containing spray formulations during pregnancy.

This study included 84,237 individuals who provided valid responses to self-administered questionnaires from approximately 100,000 parent-child pairs enrolled in the Eco-Child Study, who completed the survey from early pregnancy through age one. Twins were excluded from the study. Of these, 799 children (0.95%) were diagnosed with renal and urinary tract abnormalities by age one. The association between maternal use of organic solvents, sprays (waterproof sprays, spray insecticides, insect repellents), and herbicides during pregnancy and renal and urinary tract abnormalities was analyzed using logistic regression analysis (*1), with maternal age, body mass index (BMI) at the time of pregnancy, gestational diabetes, history of kidney disease, smoking status, and preterm birth as covariates (*2). In a more detailed analysis, renal and urinary tract abnormalities were also classified as vesicoureteral reflux, hydronephrosis, and cryptorchidism.

The results showed no correlation between pregnant women's use of organic solvents or herbicides and the frequency of renal and urinary tract abnormalities discovered by the time a child turns one year old.Next, the group in which pregnant women used waterproof spray showed a higher frequency of renal and urinary tract abnormalities discovered by the time a child turns one year old in both boys and girls compared to the group in which they did not use it, with the frequency being significantly higher in boys.Furthermore, the group in which pregnant women used spray insecticide showed a higher frequency of renal and urinary tract abnormalities discovered by the time a child turns one year old in girls compared to the group in which they did not use it, but no difference was observed in boys.No correlation was found between the use of insect repellent spray and the frequency of renal and urinary tract abnormalities in either boys or girls.

A detailed analysis by disease showed that the frequency of vesicoureteral reflux discovered by the age of one was higher in boys who had used waterproof sprays during pregnancy than in those who had not. Furthermore, the frequency of hydronephrosis discovered by the age of one was higher in girls who had used insecticide sprays during pregnancy than in those who had not.

This study has several limitations. First, maternal use of spray preparations was assessed through responses to a questionnaire, which is considered to lack objectivity. Furthermore, the exact timing of spray preparation use could not be determined. Furthermore, although we were able to analyze the association with the experience of using spray preparations, we were unable to analyze the specific associations (e.g., the environment in which they were used, the ingredients they contained, etc.). Finally, we used data on renal and urinary malformations diagnosed within the first year of life, but it is possible that some cases were diagnosed after that age.

(Terminology)
*1 Covariates: Factors that are considered in statistical analysis because they are thought to affect the results.
*2 Logistic regression analysis: A statistical method for examining the difference in the probability of a specific event occurring when multiple factors are related.

In the future, research will be needed to determine what effects the use of spray formulations has, and if the ingredients in the spray formulations have an effect, what those ingredients are, the amount of exposure, and the timing of exposure.

It is expected that the Eco-Children Survey will continue to shed light on environmental factors, such as chemicals, that affect children's development and health.

・Magazines featured
"International Journal of Urology" DOI: 10.1111/iju.15229

・Thesis title
"Association between maternal use of spray formulations and offspring urological anomalies: The Japan Environment and Children's Study"

·author
Yohei TANIGUCHI*1, Hideki SHIMOMURA*1, Hideki HASUNUMA*2,3, Naoko TANIGUCHI*1,2, Tetsuro FUJINO*1, Takeshi UTSUNOMIYA*1, Masumi OKUDA*1, Masayuki SHIMA*2,3, Yasuhiro TAKESHIMA*1, the Japan Environment and Children's Study (JECS) Group*4

*1 Yohei Taniguchi, Hideki Shimomura, Naoko Taniguchi, Tetsuro Fujino, Tsuyoshi Utsunomiya, Masami Okuda, Yasuhiro Takeshima: Department of Pediatrics, Hyogo Medical University School of Medicine
*2 Naoko Taniguchi, Hideki Hasunuma, Masayuki Shima: Eco-Children Hyogo Unit Center
*3 Hideki Hasunuma, Masayuki Shima: Department of Public Health, Hyogo Medical University School of Medicine
*4 JECS Group: Consists of the Eco-Child Study Steering Committee Chairman (research representative), the Core Center Director, the Medical Support Center Representative, and each Unit Center.