Occupational pesticide exposure in early pregnancy associated with sex-specific neurobehavioral deficits in the children at school age

doi:10.1016/j.ntt.2014.10.006

Neurotoxicology and Teratology

Volume 47, January–February 2015, Pages 1-9

https://doi.org/10.1016/j.ntt.2014.10.006 Get rights and content

Abstract

Prenatal exposure to pesticides may affect neurodevelopment, while the impact of modern pesticides is unclear. From 1997–2001, women working in greenhouse horticultures were recruited at the beginning of their pregnancy. Based on detailed interview of the women and their employers, those categorized as occupationally exposed to pesticides were moved to unexposed work functions or went on paid leave, while women without any exposure were considered unexposed controls. Of the resulting birth cohort of 203 children, 133 (65%) were examined at age 6 to 11 years together with 44 newly recruited children of same age whose mothers were not occupationally exposed to pesticides in pregnancy. All children underwent a standardized examination including a battery of neurodevelopmental tests. Maternal occupational pesticide exposure in early pregnancy was associated with prolonged brainstem auditory evoked potential latencies in the children as a whole and with impaired neuropsychological function in girls, while no effect was apparent in boys. In girls, language and motor speed functions were significantly inversely associated with prenatal exposure, and a non-significant tendency toward decreased function was also seen for other neuropsychological outcomes. A structural equation model that combined all these test results showed an overall impaired neuropsychological function in girls prenatally exposed to pesticides. Thus, our findings suggest an adverse effect of maternal occupational pesticide exposure on their children's neurodevelopment, despite the fact that the exposures occurred solely during early pregnancy and under well regulated working conditions, where special measures to protect pregnant women were applied.

Section snippets

Background

Prenatal exposures to neurotoxic or neuroendocrine disrupting chemicals are thought to contribute to impaired neurodevelopment and related disorders (Frye et al., 2012, Grandjean and Landrigan, 2014). Many pesticides possess neurotoxic and endocrine disrupting properties (Andersen et al., 2002, Bjorling-Poulsen et al., 2008). Experimental and epidemiological research suggests that low-dose prenatal and early postnatal pesticide exposure may adversely affect neurodevelopment (Bjorling-Poulsen et

Study population and design

This study is a part of an ongoing prospective study on the effects of pesticide exposure in early pregnancy on the growth and development in these children. From 1996 to 2000, we recruited pregnant women working in greenhouses and referred to the Department of Occupational Health at Odense University Hospital in Denmark for risk assessment of their working conditions and guidance for safe work practices during pregnancy. Following childbirth, their children were first examined at three months

Results

A higher fraction of the unexposed children was from social classes 1–3 (Table 1), mainly because 24 (54.4%) of the newly recruited controls were from social classes 1–3 compared to only 9.5% of the previously recruited unexposed children and 20.5% of the exposed children from the original cohort. More unexposed children had a history of concussion. None of the other characteristics deviated significantly between prenatally pesticide-exposed and unexposed children.

Due to technical problems,

Discussion

In this study, maternal occupational pesticide exposure in early pregnancy was associated with prolonged BAEP latencies in the children and, in the girls, with impaired neurobehavioral function. The results indicate an adverse effect on general intellectual development in girls, with most pronounced effects in domains of language function and to a lesser extent in motor speed and short-term memory functions. No exposure-related effect on neuropsychological function was apparent in the boys.

Transparency Document

Transparency document.

Acknowledgments

The study was supported by grants from the Danish Environmental Protection Agency (Grant numbers 669-00102 and 660-00103). We are grateful to the children and families for their participation in the study. We thank Lene Barfod and Mariann Bøllund and the study team for the skilled help with child examinations and the database.

References (54)

S. Araki et al.
Neurophysiological methods in occupational and environmental health: methodology and recent findings
Environ Res
(1997)
A.G. Atanasov et al.
Inhibition of 11 beta-hydroxysteroid dehydrogenase type 2 by dithiocarbamates
Biochem Biophys Res Commun
(2003)
S.T. Brookes et al.
Subgroup analyses in randomized trials: risks of subgroup-specific analyses; power and sample size for the interaction test
J Clin Epidemiol
(2004)
F. Debes et al.
Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years
Neurotoxicol Teratol
(2006)
P. Grandjean et al.
Neurobehavioural effects of developmental toxicity
Lancet Neurol
(2014)
P. Grandjean et al.
Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury
Neurotoxicol Teratol
(1997)
P. Grandjean et al.
Cardiac autonomic activity in methylmercury neurotoxicity: 14-year follow-up of a Faroese birth cohort
J Pediatr
(2004)
M.K. Horton et al.
Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory?
Neurotoxicol Teratol
(2012)
P.R. Jacobsen et al.
Persistent developmental toxicity in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides
Reprod Toxicol
(2012)
A. Lafuente et al.
Neurotoxic effects induced by endosulfan exposure during pregnancy and lactation in female and male rat striatum
Toxicology
(2013)

E.D. Levin et al.

Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations

Neurotoxicol Teratol

(2002)

E.D. Levin et al.

Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging

Behav Brain Res

(2010)

S. Llop et al.

Prenatal and postnatal insecticide use and infant neuropsychological development in a multicenter birth cohort study

Environ Int

(2013)

K. Murata et al.

Delayed brainstem auditory evoked potential latencies in 14-year-old children exposed to methylmercury

J Pediatr

(2004)

T.A. Slotkin

Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates

Toxicol Appl Pharmacol

(2004)

S. Valerius et al.

Consistent g- as well as consistent verbal-, numerical- and figural-factors in nested factor models? Confirmatory factor analyses using three test batteries

Intelligence

(2014)

A. Venerosi et al.

Sex dimorphic behaviors as markers of neuroendocrine disruption by environmental chemicals: the case of chlorpyrifos

Neurotoxicology

(2012)

B. Weiss

Same sex, no sex, and unaware sex in neurotoxicology

Neurotoxicology

(2011)

J.E. Aldridge et al.

Developmental exposure to chlorpyrifos elicits sex-selective alterations of serotonergic synaptic function in adulthood: critical periods and regional selectivity for effects on the serotonin transporter, receptor subtypes, and cell signaling

Environ Health Perspect

(2004)

H.R. Andersen et al.

Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro

Toxicol Appl Pharmacol

(2002)

H.R. Andersen et al.

Impaired reproductive development in sons of women occupationally exposed to pesticides during pregnancy

Environ Health Perspect

(2008)

H.R. Andersen et al.

Paraoxonase 1 polymorphism and prenatal pesticide exposure associated with adverse cardiovascular risk profiles at school age

PLoS One

(2012)

J. Bakker et al.

Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development

J Neuroendocrinol

(2010)

E.S. Bisenius et al.

Sex differences and the development of the rabbit brain: effects of vinclozolin

Biol Reprod

(2006)

M. Bjorling-Poulsen et al.

Potential developmental neurotoxicity of pesticides used in Europe

Environ Health

(2008)

M.F. Bouchard et al.

Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children

Environ Health Perspect

(2011)

J.M. Braun et al.

Prenatal bisphenol A exposure and early childhood behavior

Environ Health Perspect

(2009)

Cited by (45)

The impact of unfavorable and toxic environmental conditions on autonomic tone modulations while wearing N95 face masks
2024, Case Studies in Chemical and Environmental Engineering
The wearing of respirators has significantly increased over the last years mainly due to the COVID-19 pandemic. The prolonged wearing of respirators may have impacted the Heart Rate Variability (HRV) of the consumer. The scientific community has been attempting to understand the possible influential factors behind it. Unfavorable environmental factors may play a significant role in influencing the HRV for prolonged wearing of the respirators, mainly due to air pollution, and high concentrations of toxic metals and organochlorine compounds in the blood. Hence, this study aims to investigate the influence of unfavorable environmental conditions on the HRV parameters for prolonged wearing of N95 respirators. The study cohort was selected from the young volunteers living in the Aral Sea region, which is infamous for unfavorable environmental conditions due to dust storms with toxic particles, soil salinity, and high usage of pesticides. The study cohort consisted of 1110 male volunteers aged 19–22 and divided into two groups, inhabitants from unfavorable environment (North group) and inhabitants from unaffected environmental conditions (South group). HRV parameters of RMSSD, SDNN, pNN50, HF, LF/HF, SI, SBP, DBP, and SpO2 were measured and statistically compared in two stages, without wearing N95 respirators and while wearing an N95 mask for a 30–40 min period. Our analysis showed a significant increase in RMSSD, SDNN, pNN50 %, and HF parameters while wearing an N95 mask for a 30–40 min period in both groups. SI and LF/HF ratio shows a significant increase while wearing N95 in the «North » group and SI and LF/HF ratio decreased in the «South » group. The prevalence of distribution of subjects having SI more than 150 conv. units while wearing N95 marks in the «North » group were significantly higher compared to the «South » group. Autonomic tone reactivity to the N95 respirators was found in the «North » group in the form of an increase in sympathetic activity. We can conclude that the features of autonomic tone reactivity to wearing N95 respirators were found in the subjects from the environmentally unfavorable regions in the form of measuring the autonomic nervous system imbalance in favor of the increase in SNS activity. This observation is possibly related to the effects of organochlorine pesticides and heavy metals on the human nervous system in the participants living in unfavorable regions of the Aral ecological disaster.
Early and transitory hypoactivity and olfactory alterations after chronic atrazine exposure in female Sprague-Dawley rats
2024, NeuroToxicology
Several studies have shown that chronic exposure to the herbicide atrazine (ATR) causes alterations in locomotor activity and markers of the dopaminergic systems of male rats. However, few studies have evaluated the sex-dependent effects of atrazine exposure. The aim of the present study was to evaluate whether chronic ATR exposure causes alterations in behavioral performance and dopaminergic systems of female rats. At weaning, two groups of rats were exposed to 1 or 10 mg ATR/kg body weight daily thorough the food, while the control group received food without ATR for 14 months. Spontaneous locomotor activity was evaluated monthly for 12 months, while anxiety, egocentric and spatial memory, motor coordination, and olfactory function tasks were evaluated between 13 and 14 months of ATR exposure. Tyrosine hydroxylase (TH) and monoamine content in brain tissue were assessed at the end of ATR treatment. Female rats treated with 1 or 10 mg ATR showed vertical hypoactivity compared to the control group only in the first month of ATR exposure. Impairments in olfactory functions were found due to ATR exposure. Nevertheless, no alterations in anxiety, spatial and egocentric memory, or motor coordination tasks were observed, while the levels of TH and dopamine and its metabolites in brain tissue were similar among groups. These results suggest that female rats could present greater sensitivity to the neurotoxic effects of ATR on spontaneous locomotor activity in the early stages of development. However, they are unaffected by chronic ATR exposure later in life compared to male rats. More studies are necessary to unravel the sex-related differences observed after chronic ATR exposure.
Prenatal exposure to pyrethroid and organophosphate insecticides and language development at age 20–36 months among children in the Odense Child Cohort
2021, International Journal of Hygiene and Environmental Health
Citation Excerpt :
The developing brain is particularly vulnerable to neurotoxicants, and major windows of vulnerability occur in utero and during early postnatal life (Grandjean and Landrigan, 2014; Rice and Barone, 2000). Several birth cohort studies have reported associations between prenatal exposure to organophosphate and pyrethroid insecticides and impaired childhood neurodevelopment, i.e., cognitive and/or behavioural deficits, although mainly in populations with elevated exposure from occupational or indoor use or from residence in proximity to pesticide-treated agricultural areas (Andersen et al., 2015; Bouchard et al., 2011; Eskenazi et al., 2018; Gunier et al., 2017; Liu et al., 2016; Llop et al., 2013; Rauh et al., 2006; Shelton et al., 2014). A few studies have investigated neurodevelopmental outcomes associated with prenatal organophosphate and pyrethroid exposure in populations considered to be mainly exposed through ingestion of residues in foods (Cartier et al., 2016; Dalsager et al., 2019; Donauer et al., 2016; Jusko et al., 2019; Nkinsa et al., 2020; Tanner et al., 2020; Viel et al., 2015, 2017; Yolton et al., 2013), and the results have been equivocal perhaps in part due to differences in study design.
Prenatal exposure to organophosphate and pyrethroid insecticides has been associated with impaired neurodevelopment. Few longitudinal studies have investigated associations with early language development in populations with mainly low dietary exposure.
To investigate associations between biomarkers of maternal gestational exposure to organophosphate and pyrethroid insecticides and the child's language development at age 20–36 months in the prospective Odense Child Cohort.
Metabolites of organophosphate and pyrethroid insecticides were measured in maternal urine samples collected at gestational week 28. Language development was assessed among 755 singletons at age 20–36 months using the Vocabulary and Complexity scores of the MacArthur-Bates Communicative Development Inventories, standardized into age and sex specific percentile scores according to a Danish reference study. Multiple logistic regression models were used to estimate the odds of scoring below the 15th percentile scores in relation to maternal urinary insecticide metabolite concentrations after adjustment for confounders.
The generic pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA) and the chlorpyrifos metabolite 3,5,6-trichloro-2-pyridinol (TCPY) were detectable in more than 90% of the urine samples analyzed. Likewise, 82.2% had detectable concentrations of diethyl phosphates (DE) and 58.4% of dimethyl phosphates (DM), both of which are common metabolites of organophosphate insecticides. None of the metabolites was associated with higher odds of delayed results below the 15th percentile language scores. In contrast, reduced probability for scoring below the 15th percentile Vocabulary score was seen for the highest tertile of 3-PBA in boys and for the upper tertile of TCPY and DE in girls.
In this prospective cohort, with predominantly dietary insecticide exposure, we found no evidence that gestational exposure to organophosphate or pyrethroid insecticides adversely affected early language development in the children. The observed indication of a positive effect of insecticides on language development may be explained by residual and unmeasured confounding from socioeconomic factors and dietary habits. Follow-up of these children should include assessment of more complex cognitive functions in later childhood, as well as associations with their own postnatal insecticide exposure.
Heart rate variation and human body burdens of environmental mixtures in the Cree First Nation communities of Eeyou Istchee, Canada
2021, Environment International
Heart rate variability (HRV) is a measure of cardiac autonomic regulation that examines the variation in beat-to-beat fluctuations in heart rate. While many exposure-based studies have examined the effects of single or similar groups of contaminants on HRV parameters, none have examined the association between complex environmental mixtures, including organic and elemental contaminants, and HRV.
Using data collected from the Multi-Community Environment-and-Health Study in Eeyou Istchee (Quebec, Canada), we assessed HRV in two time domain measures: root mean square of successive differences (RMSSD) and standard deviation of the N-N (RR) intervals (SDNN); and in three frequency domains: high frequency (HF), low-frequency (LF), and very-low frequency (VLF) in 443 participants. We first examined mixture effects of nineteen organic and metal contaminants in blood using principal component analysis (PCA) and a multivariable general linear regression on HRV responses, adjusting for age, sex, body mass index, smoking status, and kidney disease covariates. We subsequently assessed HRV outcome response variables using Bayesian kernel machine regression (BKMR) to further examine individual contaminant contribution and overall mixture effects.
In the PCA, a significant positive association was observed between RMSSD and principal component (PC) axis 2, which was highly positively-loaded for nickel and moderately negatively-loaded for mercury. A negative association between SDNN and PC-1, which was highly positively-loaded for all PCBs (polychlorinated biphenyls) and organochlorines and moderately positively-loaded for mercury, was observed. Additionally, a significant and positive association was observed between PC-2 and SDNN and a significant and negative association between PC-3 (negatively loaded for cadmium) and LF. Associations with contaminants were not observed for HF or VLF. BKMR results suggest that trans-nonachlor and cis-nonachlor are primarily responsible for reductions in HRV; however, their contributions to HRV deficits was non-significant when examined as a complete mixture.
While PCA results suggested that organochlorines, mercury, nickel, and cadmium may all play a role in altering various HRV, subsequent BKMR analysis illustrated the individual components driving these effects may be trans- and cis-nonachlor and nickel and likely not mercury or cadmium. However, other contaminants appear to temper this effect when the entire mixture of chemicals is assessed as a whole. This study expands our knowledge of the effects of environmental contaminant mixtures on HRV, which is especially important in exposed populations such as those in the Eeyou Istchee territory, whilst utilizing novel statistical methods such as PCA and BKMR to examine co-exposures concurrently.
A framework for assessing the impact of chemical exposures on neurodevelopment in ECHO: Opportunities and challenges
2020, Environmental Research
Citation Excerpt :
In addition to performance on neuropsychological tests, neuroanatomical and neurophysiological differences have been reported in those exposed prenatally to OPs. For, example, one study found that prenatal exposure to OPs was associated with prolonged brainstem auditory evoked potential latencies in girls, suggesting that some of these outcomes may have a sex-specific pattern (Andersen et al., 2015). Chlorpyrifos concentrations in umbilical cord blood were associated with cortical thinning and region-specific cortical deformations measured with neuroanatomic imaging data acquired at 5.9–11.2 years of age (Rauh et al., 2012).
The Environmental influences on Child Health Outcomes (ECHO) Program is a research initiative funded by the National Institutes of Health that capitalizes on existing cohort studies to investigate the impact of early life environmental factors on child health and development from infancy through adolescence. In the initial stage of the program, extant data from 70 existing cohort studies are being uploaded to a database that will be publicly available to researchers. This new database will represent an unprecedented opportunity for researchers to combine data across existing cohorts to address associations between prenatal chemical exposures and child neurodevelopment. Data elements collected by ECHO cohorts were determined via a series of surveys administered by the ECHO Data Analysis Center. The most common chemical classes quantified in multiple cohorts include organophosphate pesticides, polychlorinated biphenyls, polybrominated diphenyl ethers, environmental phenols (including bisphenol A), phthalates, and metals. For each of these chemicals, at least four ECHO cohorts also collected behavioral data during infancy/early childhood using the Child Behavior Checklist. For these chemicals and this neurodevelopmental assessment (as an example), existing data from multiple ECHO cohorts could be pooled to address research questions requiring larger sample sizes than previously available. In addition to summarizing the data that will be available, the article also describes some of the challenges inherent in combining existing data across cohorts, as well as the gaps that could be filled by the additional data collection in the ECHO Program going forward.
Exposure to Environmental Pesticides and the Risk of Autism Spectrum Disorders: A Population-Based Case-Control Study
2024, Medicina (Lithuania)

View all citing articles on Scopus

View full text

Occupational pesticide exposure in early pregnancy associated with sex-specific neurobehavioral deficits in the children at school age

Abstract

Section snippets

Background

Study population and design

Results

Discussion

Transparency Document

Acknowledgments

Environ Res

Biochem Biophys Res Commun

J Clin Epidemiol

Neurotoxicol Teratol

Lancet Neurol

Neurotoxicol Teratol

J Pediatr

Neurotoxicol Teratol

Reprod Toxicol

Toxicology

Neurotoxicol Teratol

Behav Brain Res

Environ Int

J Pediatr

Toxicol Appl Pharmacol

Intelligence

Neurotoxicology

Neurotoxicology

Developmental exposure to chlorpyrifos elicits sex-selective alterations of serotonergic synaptic function in adulthood: critical periods and regional selectivity for effects on the serotonin transporter, receptor subtypes, and cell signaling

Environ Health Perspect

Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro

Toxicol Appl Pharmacol

Impaired reproductive development in sons of women occupationally exposed to pesticides during pregnancy

Environ Health Perspect

Paraoxonase 1 polymorphism and prenatal pesticide exposure associated with adverse cardiovascular risk profiles at school age

PLoS One

Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development

J Neuroendocrinol

Sex differences and the development of the rabbit brain: effects of vinclozolin

Biol Reprod

Potential developmental neurotoxicity of pesticides used in Europe

Environ Health

Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children

Environ Health Perspect

Prenatal bisphenol A exposure and early childhood behavior

Environ Health Perspect