Pesticide Regions Linked to Autism
This is a reformatted version of an article from The Sacramento Bee and the original scientific study
STUDY: HIGHER RISK SEEN FOR PREGNANCIES THERE
By Edward Ortiz
Monday, June 23, 2014 | The Sacramento Bee
Pregnant women who live near areas where agricultural pesticides are applied experience a higher risk of delivering children with autism or other developmental delays, a UC Davis study has found.
The study, published today in the periodical Environmental Health Perspectives, found that mothers who lived within roughly one mile of where pesticides were applied were found to have a 60 percent higher risk of having children with any of the spectrum of autism disorders, such as Asperger's syndrome.
The study is the latest in a growing body of research exploring links between the environment and the development of autism.
The results are no small matter for the Central Valley, which receives most of the 200 million pounds of agricultural pesticides applied annually in California.
In Sacramento County, roughly 3,100 public school students have been diagnosed as autistic. The diagnosed autistic population in the county has risen sevenfold since 2000, according to the California Department of Education.
The study, conducted by a team of researchers at UC Davis' MIND Institute, is unique for its use of a large state case group of children confirmed as having autism spectrum disorder and developmental delays, said lead researcher Janie Shelton.
The subjects were part of research called the Childhood Autism Risks from Genetics and Environment study. A total of 970 participants were used in the study – with the emphasis on whether proximity to pesticide applications affected children before birth.
The study explored the geographic location of families that now have children between 2 and 5 years old who were diagnosed with autism or developmental delay. Children who have normal development also were included.
To do the study, researchers culled the addresses of the 970 mothers from preconception to full-term pregnancy and compared those to data from the California Pesticide Use Report.
A majority of the mothers in the study resided within two hours of Sacramento during their pregnancies.
Four pesticide groups were included in the study. The most commonly applied group involved 21 pesticides called organophosphates.
The pesticides are used widely in agriculture because of the way they block certain nerve function in insects. The chemicals can also curtail certain nerve function in humans.
"It's concerning that we found an association with these chemicals and autism spectrum disorder because they are in such widespread use," Shelton said.
Chlorpyrifos was the most commonly applied pesticide in the study.
"The chlorpyrifos applied over the course of pregnancy had the greatest association with an elevated risk of autism spectrum disorder in the second trimester," Shelton said.
The Environmental Protection Agency phased out home use of chlorpyrifos in 2000 because of its potential to trigger neurological effects.
EPA research has shown that unborn children and the young are more susceptible than adults to adverse effects from exposure to chlorpyrifos.
The second most common pesticide applied in the study area involved pyrethroids, synthetic chemicals linked to respiratory ailments, heart palpitations and nausea in farmworkers. Pyrethroids have been identified as an endocrine disruptor in lab animals.
The study provides new evidence of a link between pyrethroids and autism disorders, Shelton said.
In the study, pyrethroids were most strongly linked to autism disorders during two periods among women in the study - immediately prior to conception and in the third trimester of pregnancy. Shelton said it is not yet understood why the third trimester shows the greatest exposure risk during a pregnancy.
"It does appear that later in the pregnancy is a more vulnerable period," said Irva Hertz-Picciotto, co-author of the study and professor of environmental epidemiology at UC Davis.
The pesticides identified in the study are seen as predictors for developmental delays since exposure to them before birth may affect development of the brain when it is getting neurally organized, Hertz-Picciotto said.
"Among the different kinds of environmental chemicals we're interested in - pesticides are different because they're designed to kill," Hertz-Picciotto said. "This makes them more suspect as toxins."
The issue of a child's proximity to where pesticides are being applied has become a recent concern in other studies. Recently, the California Department of Health looked at 2,511 schools in 15 counties that had the highest overall farm pesticide use.
It found that 30 schools in Sacramento County and 18 in Yolo County were within a quarter-mile of where pesticides are applied.
Call The Bee's Edward Ortiz, (916) 327-1071. Follow him on Twitter @edwardortiz.
Original Study Information
Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study
Authors: Janie F. Shelton, Estella M. Geraghty, Daniel J. Tancredi, Lora D. Delwiche, Rebecca J. Schmidt, Beate Ritz, Robin L. Hansen, and Irva Hertz-Picciotto
Publication: Environmental Health Perspectives http://dx.doi.org/10.1289/ehp.1307044
Received: May 4, 2013
Accepted: June 3, 2014
Advance Publication: June 23, 2014
Abstract
Background: Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism.
Objectives: To evaluate whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) Study.
Methods: The CHARGE study is a population-based case-control study of ASD, developmental delay (DD), and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997-2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25km, 1.5km, and 1.75km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316).
Results: Approximately one-third of CHARGE Study mothers lived, during pregnancy, within 1.5km (just under one mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for 3rd trimester exposures [OR = 2.0, 95% confidence interval (CI) = (1.1, 3.6)], and 2nd trimester chlorpyrifos applications: OR = 3.3 [95% CI = (1.5, 7.4)]. Children of mothers residing near pyrethroid insecticide applications just prior to conception or during 3rd trimester were at greater risk for both ASD and DD, with OR's ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified.
Conclusions: This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, and particularly, organophosphates and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates.
Introduction
California is the top agricultural producing state in the nation, grossing 38 billion dollars in revenue from farm crops in 2010. Each year approximately 200 million pounds of active pesticide ingredients are applied throughout the state. While pesticides are critical for the modern agricultural industry, certain commonly used pesticides have been associated with abnormal and impaired neurodevelopment in children.
Developmental delay (DD) refers to young children who experience significant delays reaching milestones in relation to cognitive or adaptive development. Adaptive skills include communication, self-care, social relationships, and/or motor skills. In the U.S., DD affects approximately 3.9% of all children ages 3-10 years, and is approximately 1.7 times more common among boys than girls.
Autism is a developmental disorder with symptoms appearing by age three. Specific deficits occur in domains of social interaction and language, and individuals show restricted and repetitive behaviors, activities, or movements. The autism spectrum disorders (ASDs) represent lower severity, usually with regard to language ability. ASDs affect boys 4-5 times more than girls and the Centers for Disease Control and Prevention recently estimated a prevalence of 1.1% among children 8 years of age, a 78% increase since their 2007 estimate. Available evidence suggests that causes of both ASD and DD are heterogeneous, and that environmental factors can contribute strongly to risk.
The majority of pesticides sold in the U.S. are neurotoxic and operate through one of three primary mechanisms:
- Inhibition of acetylcholinesterase (AChE)
- Voltage-gated sodium channel disruption
- Inhibition of gamma-Aminobutyric acid (GABA)
AChE primarily functions as an inhibitory neurotransmitter, but also has critical roles in the development of learning, cognition, and memory. GABA is also an inhibitory neurotransmitter, and necessary for development and maintenance of neuronal transmission.
Though limited research has assessed in utero exposures to pesticides, animal models (rats) of early exposure to organophosphates showed more severe neurodevelopmental effects for males than females. Based on previously published epidemiology or mechanistic considerations, we selected the following pesticide families to investigate for this analysis: organophosphates, carbamates, organochlorines, and pyrethroids.
The aim of this paper is to explore the relationship between agricultural pesticide applications and neurodevelopmental outcomes by:
- Assessing the gestational exposure during pregnancy to CHARGE study mothers
- Testing the hypothesis that children with ASD or DD had higher risk of exposure in utero than typically developing children
- Evaluating specific windows of vulnerability during gestation
Study Design
The Childhood Autism Risks from Genes and Environment (CHARGE) study is an ongoing California population-based case-control study which aims to uncover a broad array of factors contributing to autism and developmental delay. Since 2003, the CHARGE study has enrolled over 1,600 participants whose parents answer extensive questionnaires regarding environmental exposures including their place of residence during pregnancy.
Cases are recruited from children diagnosed with full syndrome ASD or DD in one of the regional centers of the California Department of Developmental Services (DDS). Eligibility in the DDS system does not depend on citizenship or financial status, and is widely used across socioeconomic levels and racial/ethnic groups. It is estimated that 75-80% of the total population of children with an autism diagnosis are enrolled in the system.
The referents are recruited from the general population (GP) identified through California birth records, and are frequency matched to the autism case population on gender, age, and the catchment area for the regional they would have gone to, had they been a case. Children are eligible if they are aged 2-5 years, born in California, live with a biological parent who speaks either English or Spanish, and reside in the study catchment area.
Key Findings
Study Population Characteristics
The study examined 970 participants:
- ASD cases: 486
- DD cases: 168
- Typically developing controls: 316
Approximately one-third of CHARGE Study mothers lived, during pregnancy, within 1.5km (just under one mile) of an agricultural pesticide application.
Table 1. Characteristics [n (%) or mean ± SD] of the CHARGE study population (n=970).
| Characteristic | ASD | Delayed | Typical | P-value: ASD vs. TD | P-value: DD vs. TD |
|---|---|---|---|---|---|
| Total | 486 | 168 | 316 | ||
| Male | 414 (85.2) | 115 (68.5) | 262 (82.9) | 0.39 | 0.0003 |
| Child's age at enrollment in months (mean ± SD) | 36.7 ± 9.7 | 38.3 ± 8.9 | 36.9 ± 8.9 | 0.73 | 0.11 |
| Child's race/ethnicity | 0.12 | <0.0001 | |||
| White | 246 (50.6) | 66 (39.3) | 165 (52.2) | ||
| Hispanic | 130 (26.8) | 60 (35.7) | 73 (23.1) | ||
| Other | 110 (22.6) | 41 (24.4) | 78 (24.7) | ||
| Mother's age (mean ±SD) | 31.3 ± 5.5 | 30.8 ± 6.6 | 31.1 ± 5.7 | 0.69 | 0.57 |
| Father's age (mean ±SD) | 33.9 (6.4) | 33.1 (7.8) | 33.5 (7.0) | 0.49 | 0.52 |
| Mother's Education | 0.12 | <0.0001 | |||
| High school or less | 67 (13.8) | 51 (30.4) | 46 (14.6) | ||
| Some college | 197 (40.5) | 68 (40.5) | 100 (31.7) | ||
| College or professional | 222 (45.7) | 49 (29.2) | 170 (53.8) | ||
| Father's Education | 0.58 | <0.0001 | |||
| High school or less | 106 (21.8) | 74 (44.1) | 81 (25.6) | ||
| Some college | 153 (31.5) | 47 (27.9) | 91 (28.8) | ||
| College or professional | 225 (46.3) | 44 (26.2) | 144 (45.6) | ||
| Regional Center/Region | <0.0001 | 0.01 | |||
| Alta | 174 (35.8) | 82 (48.8) | a131 (41.5) | ||
| North Bay | 64 (13.2) | 19 (11.3) | 53 (16.8) | ||
| East Bay | 81 (16.7) | 17 (10.1) | 65 (20.6) | ||
| Valley Mountain | 85 (17.5) | 38 (22.6) | 49 (15.5) | ||
| Southern California | 82 (16.9) | 12 (7.1) | 18 (5.7) | ||
| Maternal Birth Place | 0.07 | 0.0003 | |||
| In the US | 367 (75.5) | 127 (75.60 | 259 (82.0) | ||
| In Mexico | 38 (7.8) | 28 (16.7) | 22 (7.0) | ||
| Outside US or Mexico | 81 (16.7) | 13 (7.7) | 35 (11.1) | ||
| Year of Birth | 0.0003 | 0.49 | |||
| 1999-2003 | 348(71.6) | 94 (56.0) | 187 (59.2) | ||
| 2004-2008 | 138 (28.4) | 74 (44.1) | 129 (40.8) | ||
| Homeowner | 320 (65.8) | 100 (59.5) | 242 (76.6) | 0.001 | <0.0001 |
| Private health insurance | 402 (82.7) | 118 (70.2) | 270 (85.4) | 0.31 | <0.0001 |
| Peri-conceptional prenatal vitamin | 252 (52.0) | 79 (53.0) | 189 (59.8) | 0.003 | 0.01 |
| Known chromosomal abnormality | 11 (2.3) | 50 (32.7) | 0 (0.0) |
Table 2. Exposure to pesticide applications (any versus none) within 1.5km of the home during the three months prior to conception through delivery according to outcome (ASD n = 486, DD n = 168, TD n = 316).
| Exposure | ASD:N | ASD: unweighted % | ASD: weighted % | DD:N | DD: unweighted % | DD: weighted % | TD: N | TD: unweighted % | TD: weighted % |
|---|---|---|---|---|---|---|---|---|---|
| No agriculturally applied pesticides | 342 | 70.4 | 70.1 | 124 | 73.8 | 66.9 | 219 | 69.3 | 72.2 |
| Any agriculturally applied pesticides | 144 | 29.6 | 29.9 | 44 | 26.2 | 33.0 | 97 | 30.7 | 27.8 |
| Organophosphates | 125 | 25.7 | 26.6 | 32 | 19.1 | 25.2 | 84 | 26.6 | 24.9 |
| Chlorpyrifos | 61 | 12.6 | 14.4 | 20 | 11.9 | 18.4 | 45 | 14.2 | 12.4 |
| Pyrethroids | 106 | 21.8 | 22.5 | 36 | 21.4 | 28.3 | 67 | 21.2 | 20.1 |
| Type 1 pyrethroids | 49 | 10.1 | 10.4 | 17 | 10.1 | 16.3 | 29 | 9.2 | 7.9 |
| Type 2 pyrethroids | 100 | 20.6 | 20.9 | 34 | 20.2 | 26.9 | 63 | 19.9 | 19.1 |
| Carbamates | 54 | 11.1 | 11.0 | 13 | 7.7 | 11.1 | 30 | 9.5 | 7.3 |
| Organochlorines | 24 | 4.9 | 4.9 | 4 | 2.4 | 3.9 | 10 | 3.2 | 3.3 |
Table 3. Adjusted odds ratios and 95% confidence intervals for autism spectrum disorder (ASD) and residential proximity to agricultural pesticide applications (any versus none) within pre-specified buffers, by time period.
| Pesticide, buffer radius (km) | Pregnancy | Pre-conception | 1st trimester | 2nd trimester | 3rd trimester |
|---|---|---|---|---|---|
| Organophosphates | |||||
| 1.25 | 1.60 (1.02, 2.51) | 1.37 (0.76, 2.50) | 1.53 (0.87, 2.68) | 1.57 (0.87, 2.83) | 1.99 (1.11, 3.56) |
| 1.5 | 1.54 (1.00, 2.38) | 1.38 (0.82, 2.31) | 1.45 (0.88, 2.41) | 1.85 (1.08, 3.15) | 2.07 (1.23, 3.50) |
| 1.75 | 1.26 (0.83, 1.92) | 1.30 (0.80, 2.13) | 1.02 (0.63, 1.65) | 1.54 (0.93, 2.55) | 1.99 (1.20, 3.30) |
| Chlorpyrifos | |||||
| 1.25 | 1.57 (0.82, 3.00) | 1.07 (0.40, 2.89) | 1.26 (0.52, 3.06) | 2.55 (0.95, 6.84) | 1.83 (0.72, 4.65) |
| 1.5 | 1.66 (0.94, 2.93) | 1.07 (0.46, 2.48) | 1.32 (0.65, 2.70) | 3.31 (1.48, 7.42) | 1.78 (0.82, 3.87) |
| 1.75 | 1.78 (1.05, 3.02) | 1.25 (0.59, 2.65) | 1.12 (0.58, 2.16) | 2.63 (1.28, 5.41) | 2.15 (1.04, 4.41) |
| Pyrethroids | |||||
| 1.25 | 1.34 (0.82, 2.20) | 1.82 (0.92, 3.60) | 1.59 (0.86, 2.96) | 1.56 (0.83, 2.94) | 1.64 (0.84, 3.19) |
| 1.5 | 1.41 (0.89, 2.25) | 1.82 (1.00, 3.31) | 1.53 (0.88, 2.67) | 1.69 (0.93, 3.06) | 1.87 (1.02, 3.43) |
| 1.75 | 1.27 (0.83, 1.96) | 1.69 (0.97, 2.95) | 1.14 (0.67, 1.91) | 1.49 (0.87, 2.58) | 1.83 (1.04, 3.23) |
| Type 2 | |||||
| 1.25 | 1.40 (0.83, 2.34) | 2.01 (0.97, 4.16) | 1.64 (0.85, 3.17) | 1.29 (0.65, 2.56) | 1.51 (0.75, 3.05) |
| 1.5 | 1.53 (0.94, 2.51) | 1.98 (1.06, 3.71) | 1.85 (1.01, 3.38) | 1.45 (0.78, 2.73) | 1.67 (0.87, 3.21) |
| 1.75 | 1.30 (0.82, 2.05) | 1.64 (0.92, 2.94) | 1.32 (0.76, 2.29) | 1.33 (0.75, 2.38) | 1.56 (0.86, 2.84) |
| Carbamates | |||||
| 1.25 | 1.37 (0.66, 2.84) | - | - | - | - |
| 1.5 | 1.80 (0.81, 3.08) | - | - | - | - |
| 1.75 | 1.43 (0.78, 2.62) | - | - | - | - |
Table 4. Adjusted odds ratios and 95% confidence intervals for developmental delay (DD) and residential proximity to agricultural pesticide applications (any versus none) within pre-specified buffers, by time period.
| Pesticide, buffer radius (km) | Pregnancy | Pre-conception | 1st trimester | 2nd trimester | 3rd trimester |
|---|---|---|---|---|---|
| Organophosphates | |||||
| 1.25 | 1.23 (0.65, 2.31) | 1.20 (0.54, 2.65) | 1.29 (0.60, 2.79) | 1.62 (0.75, 3.48) | 1.10 (0.46, 2.67) |
| 1.5 | 1.07 (0.60, 1.92) | 0.94 (0.45, 1.97) | 1.00 (0.50, 1.99) | 1.46 (0.72, 2.96) | 0.92 (0.40, 2.13) |
| 1.75 | 1.01 (0.59, 1.73) | 1.30 (0.69, 2.46) | 0.98 (0.54, 1.80) | 1.52 (0.81, 2.85) | 1.21 (0.60, 2.46) |
| Chlorpyrifos | |||||
| 1.25 | 1.62 (0.68, 3.85) | 1.73 (0.58, 5.17) | 1.61 (0.53, 4.87) | 1.73 (0.48, 6.19) | 1.04 (0.25, 4.28) |
| 1.5 | 1.31 (0.61, 2.82) | 1.11 (0.41, 3.00) | 1.27 (0.48, 3.36) | 1.43 (0.46, 4.44) | 0.73 (0.21, 2.48) |
| 1.75 | 1.63 (0.84, 3.16) | 1.34 (0.55, 3.25) | 1.40 (0.62, 3.17) | 1.63 (0.61, 4.39) | 1.34 (0.50, 3.60) |
| Pyrethroids | |||||
| 1.25 | 1.53 (0.81, 2.90) | 1.96 (0.90, 4.29) | 1.70 (0.80, 3.61) | 1.63 (0.72, 3.68) | 1.69 (0.74, 3.88) |
| 1.5 | 1.37 (0.76, 2.47) | 1.44 (0.69, 3.03) | 1.41 (0.72, 2.76) | 1.27 (0.58, 2.79) | 1.75 (0.81, 3.78) |
| 1.75 | 1.19 (0.68, 2.08) | 1.88 (0.98, 3.60) | 1.36 (0.73, 2.51) | 1.42 (0.72, 2.80) | 2.34 (1.18, 4.67) |
| Type 2 | |||||
| 1.25 | 1.56 (0.81, 2.90) | 1.43 (0.61, 3.33) | 1.60 (0.72, 3.59) | 1.78 (0.78, 4.08) | 1.80 (0.77, 4.18) |
| 1.5 | 1.46 (0.79, 2.70) | 1.09 (0.48, 2.46) | 1.49 (0.71, 3.12) | 1.41 (0.64, 3.13) | 1.87 (0.85, 4.11) |
| 1.75 | 1.34 (0.76, 2.37) | 1.18 (0.57, 2.43) | 1.37 (0.71, 2.64) | 1.66 (0.84, 3.28) | 2.31 (1.15, 4.66) |
| Carbamates | |||||
| 1.25 | 2.48 (1.04, 5.91) | - | - | - | - |
| 1.5 | 1.65 (0.70, 3.89) | - | - | - | - |
| 1.75 | 1.32 (0.60, 2.88) | - | - | - | - |
Summary of Key Findings
Organophosphates:
- Proximity during gestation was associated with a 60% increased risk for ASD
- Highest risk for 3rd trimester exposures (OR = 2.0)
- For chlorpyrifos specifically, 2nd trimester applications showed OR = 3.3
Pyrethroids:
- Children of mothers residing near pyrethroid insecticide applications just prior to conception or during 3rd trimester were at greater risk for both ASD and DD
- OR's ranged from 1.7 to 2.3
Carbamates:
- Risk for DD was increased in those near carbamate applications
- No specific vulnerable period was identified
Discussion
Applications of two of the most common agricultural pesticides (organophosphates and pyrethroids) nearby the home may increase the prevalence of ASD. The findings relating agricultural pesticides to DD were less robust, but were suggestive of an association with applications of carbamates during pregnancy nearby the home.
These findings support the results of two previous studies linking ASD to gestational agricultural pesticide exposure.
While organophosphate use drastically increased between the 1960's through the late 1990's, over the past-decade, use has been declining. For indoor use, chlorpyrifos has largely been replaced with pyrethroids, but research indicates pyrethroids may not necessarily be safer.
Conclusions
Children of mothers who live near agricultural areas, or who are otherwise exposed to organophosphate, pyrethroid, or carbamate pesticides during gestation may be at increased risk for neurodevelopmental disorders. Further research on gene-by-environment interactions may reveal vulnerable sub-populations.
Source: Environmental Health Perspectives
