'Safe' Insecticides Tied to Neurobehavioral Problems in Kids

Batya Swift Yasgur, MA, LSW

March 06, 2017

Prenatal and childhood exposure to pyrethroid insecticides may adversely affect neurobehavioral development in children up to age 6 years, new research shows.

A group of French researchers led by Jean-François Viel, MD, PhD, and Prof Andreas G. Franke, MD, both of the University of Mainz, Germany, investigated the associations between exposure to pyrethroid insecticides and behavioral skills in 6-year-olds.

Pyrethroids are synthetic chemicals that are widely used in agricultural settings. They are also found in an array of products, including mosquito repellents and treatments for head lice, scabies, and fleas. The general population is exposed to pyrethroids via diet and indoor residential uses (ie, through ingestion and dermal and inhalational pathways).

Using a longitudinal design, the researchers assessed pyrethroid exposure in children prenatally and at age 6 years. They found that in 6-year-old children, increased prenatal concentrations of the cis-dimethylcyclopropane carbolic acid metabolite were associated with internalizing difficulties. A positive association was also found between the presence of childhood 3-phenoxybenzoic acid (3-PBA) and externalizing difficulties.

"The current study suggests that exposure to certain pyrethroids at the low environmental doses encountered by the general public may be associated with internalizing and externalizing behavioral disorders in children," Dr Viel told Medscape Medical News.

"Internalizing behaviors are inhibited and overcontrolled in nature, while children with externalizing behaviors suffer from challenging conditions such as attention deficit, hyperactivity, and oppositionality," he explained.

The study was published online March 1 in Occupational and Environmental Medicine.


Recent research pointing to adverse health consequences of exposure to organophosphate insecticides has led to increased use of pyrethroid insecticides, which have been considered a safer alternative. However, pyrethroids are neurotoxicants in insects, and animal studies suggest the potential for neurodevelopmental toxicity in human beings.

Previous research has shown an association between increased urinary levels of pyrethroid metabolites in children and disorders such as autism or attention-deficit/hyperactivity disorder, but exposure to pyrethroid insecticides both prenatally and during childhood has not been investigated.

"There has been little attention to potential neurotoxicity of pyrethroids in human beings, which is why we decided to conduct this study," Dr Viel recounted.

The researchers used a longitudinal design to assess the relationship between prenatal and childhood pyrethroid concentrations, using data from the French PELAGIE mother-child study. That study enrolled 3421 pregnant women from Brittany, France, between 2002 and 2006. Of this cohort, 287 randomly selected mothers agreed to participate in neuropsychological follow-up.

Mothers enrolled in their first prenatal visit before the nineteenth week of gestation and completed a questionnaire about family, social, and demographic characteristics, as well as diet and lifestyle.

Medical staff at the maternity units provided information about the pregnancy, delivery, birth weight, and neonatal health of the women and their newborns. When their children were 6 years old, the mothers completed a questionnaire to provide information regarding sociodemographic characteristics and lifestyle factors, as well as information about their child's behavior, health, and environmental exposures.

Psychologists who were blinded to pyrethroid exposure levels in the study participants conducted neurodevelopmental assessments and maternal interviews to assess the home environment. They also collected children's urine samples as well as dust samples.

The researchers assessed or adjusted for numerous risk factors, including known predictors of neurodevelopmental problems, and considered information about additional environmental neurotoxic exposures from substances such as organophosphate insecticides and tobacco smoke.

Children's behaviors were assessed using three subscales (prosocial behavior, internalizing disorders, and externalizing disorders) of the Strengths and Difficulties Questionnaire, which is a brief screening device used in epidemiologic research to identify children at high risk for mental health disorders.

Levels of five pyrethroid metabolites (trans-dimethylcyclopropane carboxylic acid [DCCA], cis-DCCA, cis-3-(2,2-dibromovinyl)-2,2-DCCA [cis-DBCA], 3-phenoxybenzoic acid [3-PBA], and 4-fluoro-3-PBA [ 4-F-3-PBA]) were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age.

The researchers found an association between increased prenatal cis-DCCA concentrations and internalizing difficulties (Cox P value = .05).

They also found a positive association between 3-PBA concentrations and externalizing difficulties (Cox P value = .04). Moreover, high odds ratios (ORs) were found for abnormal or borderline social behavior (OR, 2.93; 95% confidence interval [CI], 1.27 - 6.78; and OR, 1.91; 95% CI, 0.80 - 4.57 for the intermediate and highest metabolite categories, respectively).

One of the study limitations is that "assessing pyrethroid exposures in urine samples is challenging because they are cleared from the body in just a few days, with substantial within-child variability," the researchers note.

The study had important strengths, including its longitudinal design, "which looks at the association between pyrethroid exposure and childhood behavioral difficulties at two time points — during the first trimester of pregnancy and at age 6," Dr Viel commented.

"We are being cautious because this is an observational study, so we cannot draw firm conclusions based simply on an association," he added. Nevertheless, "we think general practitioners should be aware of these findings."

"Important Contribution"

"I think this is a good study, and its methods are sound," commented Kimberly Yolton, PhD, professor of pediatrics, University of Cincintti College of Medicine and the Division of General and Community Pediatrics, Cincinnati Children's Hospital Medical Center, Ohio, who was not involved with the study.

"The investigators measured many covariates that others do not take into consideration, such as home environment and maternal IQ," she told Medscape Medical News.

However, she noted that the researchers "did not fully clarify the potential impact of tobacco smoke, which was present in 41% of home environments and in close to 25% of mothers when they were assessed during pregnancy."

The study nevertheless "makes an important contribution" because "it allows us to look at both prenatal exposures and those that occur during childhood, which enables us to understand more about the impact of these chemicals."

She emphasized that pyrethroids are becoming more common and require more research.

Dr Viel agreed. "We are aware that our study should be confirmed by other studies, and we need that now more than ever," he said.

He noted that the study is ongoing and will reassess the children at approximately 11 to 12 years of age.

"This issue has just come to attention, so we believe other studies working on other mother-child cohorts should concentrate on these pesticides," he stated.

This study was supported by the French National Research Agency, the French Pfizer Foundation, and the French Research Institute for Public Health. The study authors and Dr Yolton have disclosed no relevant financial relationships.

Occup Environ Med. Published online March 1, 2017. Full text


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