Pesticides are among the increasingly well-documented hazardous exposures among children in agricultural settings. Unintentional ingestion from improperly stored acutely toxic pesticide products, as well as inhalation and skin contact from drift or spills, has the potential for immediate, devastating, and sometime lethal consequences for farm children.^13–16 Fortunately, such severe acute toxicity is rare in US farm children. Not rare in agricultural settings is the proximity of housing, schools, and play areas to agricultural fields or livestock production where regular pesticide application occurs.

The opportunity for “take home” exposure, where parents serve as “vectors” for residues transferred from occupational activities via their skin, clothing, and footwear into family vehicles and residences is now well established.^17–20 Pesticides may contaminate rural drinking water supplies. Wells that rely on shallow groundwater sources are at highest risk; approximately 61% of shallow groundwater samples from agricultural areas contain at least one detectable pesticide according to the National Water Quality Assessment Program.²¹ Very few (1.2%) of the pesticides detected exceed their individual benchmark levels that are intended to be protective of the general population. However, detection of more than one pesticide contaminant is common and health-based benchmarks are not available for combined exposures. The use of biological markers of pesticide exposure such as urinary metabolites have clearly demonstrated uptake in farm children and pregnant women that exceeds levels observed in reference populations.^17,22,23

Characterizing the scope of the problem is impossible due to lacking data systems for comprehensive tracking and surveillance. Although 12 states maintain a National Institute for Occupational Safety and Health (NIOSH)-sponsored Sentinel Event Notification System for Occupational Risks (SENSOR) that collects medical provider reports of pesticide-related illness or injury, these are focused primarily on occupationally related exposures. In rare instances, these have included some pediatric relevant outcomes such as a SENSOR-prompted birth defect cluster analysis among migrant workers²⁴ and the use of SENSOR data to review poisoning events associated with schools, which included spray drift onto school grounds from neighboring farmland.¹⁵ Although the Poison Control Centers Toxic Exposure Surveillance System (TESS) publishes annual summaries of self-reported calls to the centers from the public and medical community and include pesticide incidents, these represent acute exposure concerns, are subject to reporting bias and selection bias, and do not provide information specific to the agricultural setting.¹⁴

Underreporting in existing systems is highly problematic given the poor recognition of pediatric pesticide exposure among health care providers.^25,26 This reflects the limited attention in current medical education to topics in children’s environmental health.^27–30 Also, clinical presentations in children may be more subtle and less specific than in adults.^26,31 This is aggravated by the lack of diagnostic tools to confirm that a pesticide overexposure occurred.^32,33 Furthermore, long waits at some rural health clinics or limited access to health care may preclude farmworkers and their children from presenting to medical care for suspected pesticide illness.³⁴

Agricultural pesticide chemicals include neurotoxicants, mutagens, carcinogens, immunotoxicants, and endocrine disruptors based on experimental toxicology data. These provide biological plausibility for an expanding and relatively consistent epidemiological evidence base that supports a link between pesticide exposure in early life with some of the most prevalent and severe chronic health conditions in US children.

Pesticide exposures in fetal life and early childhood are associated with risk of behaviors seen in ADHD, autism, as well as cognitive effects, adverse birth outcomes including low birth weight and birth defects, and pediatric cancer. Fewer epidemiological studies designed to address immune dysfunction, asthma, or reproductive system development and health have been conducted, although several studies in adult workers have linked pesticides to respiratory health outcomes including wheeze.^35,36 Toxicological mechanisms of pesticide active ingredients support the need for better characterization of these health endpoints.

Research emphasis in the last decade on the widely used organophosphate class of insecticides has revealed much about the unique vulnerability of the developing central nervous system, including elucidation of toxicological mechanisms, genetic vulnerabilities, and risk of clinically relevant outcomes in observational epidemiological studies. Similar to observations of chronic sequelae of OP poisoning in adult workers, children who experienced an early life acute OP poisoning (age <3 years) demonstrate subtle but identifiable ongoing neurobehavioral deficits at school age.³⁷

Of even greater public health concern are the findings from three recent and ongoing well-designed prospective birth cohort studies in US children, including one in a Mexican American agricultural farmworker community (the Center for the Health Assessment of Mothers and Children of Salinas or CHAMACOS). These studies demonstrate relative consistency of poorer cognitive and behavioral outcomes based on validated assessment tools in infants, toddlers, preschoolers, and early-school-aged children with increased prenatal exposure to organophosphate pesticides.^38–44 In addition, several studies have implicated early life (prenatal and/or postnatal) OP exposure with symptoms and/or diagnosis of ADHD or symptoms of pervasive developmental delay (autism).^40,41,45,46 Whereas the birth cohort studies have identified cognitive impacts associated with prenatal exposure but not postnatal exposure, others have reported associations of measures of postnatal OP exposures with adverse effects on measures of neurobehavioral function, including short-term memory, executive function, reaction time, and motor skills.^26,47,48

There has also been high attention to pediatric cancer. Several review articles describe multiple ecologic and case-control studies exploring parental exposures or pesticide use in the home with childhood brain tumors, leukemias and lymphomas, and a number of other tumor types.^49–52 Reliance on retrospective, nonspecific exposure assessment as well as limited sample size are common limitations in this literature. These reviews, along with a recent meta-analysis of two cohorts and 38 case-control studies, demonstrate a body of evidence with strongest links to leukemia and brain cancer.⁵³ The associations for leukemia appear greatest for maternal exposure through household use or occupational exposures preconceptionally and prenatally. Incidence of brain cancer appears to be influenced more by paternal exposure and has been linked to occupational exposure before conception through birth.

The chronic exposure patterns and health implications of non-organophosphate agricultural pesticides or the influence of mixtures have received much less focused study. The use of pyrethroid insecticides has been increasing in agriculture and toxicological data for active ingredients in this group raise concern for neurodevelopmental toxicity and carcinogenicity.⁵⁴ Preliminary recent findings in an urban setting are suggestive that pyrethroid-containing products may have adverse neurodevelopmental effects, but confirmatory studies from well-designed epidemiological studies in agricultural settings are lacking.⁵⁵

Recognizing the concern for children’s routine exposure to pesticides from multiple sources, the American Academy of Pediatrics Council on Environmental Health is developing a new technical report and policy statement that reviews the evidence for pediatric harm, the data gaps, and policy recommendations (personal communication, American Academy of Pediatric Executive Council on Environmental Health).

Organic methods of agricultural production represent an approach to growing crops and raising livestock that avoids synthetic chemicals such as pesticides as well as hormones, antibiotics, genetic engineering, and irradiation. Organic produce contains lower levels of pesticide residue and experimental studies of children demonstrate that a diet of organic produce can reduce exposure levels in children.^56,57 There are no studies that directly examine exposure to pesticides from conventionally grown foods and the development of adverse health outcomes. However, the exposure to organophosphate measured in the cohort studies described above have found adverse neurodevelopmental effects in populations exposed in ranges comparable to those observed among children consuming conventional diets.⁵⁷

Organic agriculture may also benefit the growing problem of antimicrobial-resistant organisms. Studies demonstrate that antimicrobials applications in food production promotes the development and subsequent dissemination to humans of resistant organisms.⁵⁸ Although the proportion of the problem attributed to nontherapeutic livestock use is not well understood, the largest use of antimicrobial agents outside human medicine is in food animals.⁵⁹

Animal feed handling, movement of animals on manure, and the storage and removal of their manure produce a complex mixture of air contaminants. The type and extent released reflect animal type, management practices, and facility type and size. Known respiratory irritants and proinflammatory components, including ammonia, hydrogen sulfide, volatile organic compounds, and particulate matter and bioaerosols (glucans, endotoxin), are of primary concern.⁶⁰ Perception of odors has been linked to respiratory complaints and reduced measures of quality of life. An immunosuppressive effect of odor on mucosal immunity has also been hypothesized.⁶¹

Livestock production in the United States has sharply transformed in recent decades, from small family operations to an industry dominated by large and concentrated production processes.⁶² The impact of these facilities on community air quality and child health is of high concern to communities but available data are largely limited to occupational exposures and investigation of adult health outcomes.^63,64

Respiratory health consequences among workers in high-density animal production are well documented.^65,66 Effects include mucous membrane irritation, bronchitis, asthma, chronic obstructive pulmonary disease, and interstitial lung disease. Health impacts on adults from environmental exposures assessed as proximity to animal operations have also been demonstrated, including deficits in lung function (forced expiratory volume in 1 second [FEV₁]) and asthma symptoms.⁶⁷ A systematic review of research on the association between animal feeding operations (AFOs) and the health of individuals living nearby notes the strong limitations of the evidence base. Among nine relevant studies examined, the authors conclude that existing data provide inconsistent evidence of a weak association between self-reported adverse health outcomes, particularly among individuals with allergies or family history of allergic disease.⁶⁸

Data on child exposures are particularly scarce. Limited surveys suggest exposure to large-scale animal production is associated with increases in asthma prevalence and asthma symptoms among US children.^69–71 This area of research is critical, given that asthma is the most prevalent chronic disease among US children, affecting roughly 10% and rates have been increasing over the last two decades.⁷²

Exposure characterization for child residents in areas with large animal feeding operations is needed. Longitudinal studies that can decipher impacts of these exposures across life stages of children on mechanistically and clinically relevant endpoints associated with allergic disease, immune function, lung function, and lung function growth will be most informative.

This is underscored by ongoing investigations of a role for early life exposure to endotoxin or other microbiological factors associated with animals or farm life (e.g., raw milk consumption) decreasing risk of the development of asthma or other allergic disease.⁷³ These observations are derived from studies largely conducted in nonindustrial farm settings in Europe. This effect has been less evident in the US context.^70,74

Nitrate is a common contaminant in rural well water. Important sources are nitrogen-containing fertilizer use and/or high-volume manure waste. The most recently available survey data from the United States Geological Survey indicate that 20% of US agricultural area wells exceed the nitrate maximum contaminant level (MCL) set by the United States Environmental Protection Agency (US EPA).⁷⁵ The MCL is set to protect infants from the development of methemoglobinemia or “blue baby” syndrome. This severe syndrome of inadequate oxygenation of tissues can be fatal. Among the reported cases of methemoglobinemia in US infants, most have been attributed to the use of contaminated well water for preparation of infant formula.⁷⁶

Infants are physiologically vulnerable to the development of methemoglobinemia due to several factors. Their higher gastric pH favors nitrate-reducing bacteria that convert ingested nitrate into methemoglobin-producing nitrite. In addition, fetal hemoglobin, the predominant form in infants up to 3 months of age, is oxidized more readily to methemoglobin by nitrite than is adult hemoglobin. Lastly, the activity of the red blood cell enzyme systems that reduce methemoglobin back to normal hemoglobin is reduced by about half in infants compared with adults. Prompt recognition is vital to ensuring delivery of potentially lifesaving treatment.

Less well-established child health consequences are under investigation. Findings linking maternal exposure to nitrate in pregnancy with subsequent birth defects are suggestive but equivocal.^77–80 Studies of nitrate in drinking water and development of type I diabetes support a hypothesized linkage but are ecological in design. Results from case-control studies, which have all been done outside the United States, are inconsistent.⁸¹

Whereas large suppliers of public water sources are required to monitor nitrate concentrations regularly, private wells are not. Few rural wells are routinely tested for nitrates.⁸² Well water recommendations targeted to pediatric care providers have recently become available.⁸³ Effective dissemination of these recommendations, improved surveillance of agricultural drinking water, and well-designed epidemiological investigations of developmental and chronic health outcomes in higher risk communities are needed.

Noise exposure related to agricultural equipment is a well-recognized hazard with high exposure levels experienced by farmworkers and families.⁸⁴ Impacts of early life exposure in the farm environment on the function of the developing ear have not been studied, although it has been hypothesized that the developing child’s vulnerability to acoustic trauma and strain on the middle and inner ear is qualitatively different.⁸⁵ Existing studies suggest that hearing impairment among agricultural workers develops early in life.⁸⁶ The limited studies assessing hearing loss in farm youth have documented increased risk compared to national samples or nonrural counterparts and increased risk associated with active involvement in farm work.^87,88 Longitudinal studies in children that address noise as well as exposures to potentially synergistic ototoxic chemical exposures on the farm, including solvents and pesticides, are needed.⁸⁵

Sun exposure is the major environmental risk factor associated with nonmelanomatous skin cancer (basal cell carcinoma, squamous cell carcinoma).⁸⁹ Review of epidemiologic studies is also suggestive that sunlight exposure and sunburn during childhood and adolescence increases the risk of melanoma.⁸⁹ In addition, reviews and meta-analyses of cancer epidemiological studies are suggestive of increased risk of skin cancers for adult agricultural workers that may reflect higher sun exposure as well as other environmental factors such as pesticides.⁹⁰ In the large cancer incidence study of pesticide applicators enrolled in the Agricultural Health Study, spouses of applicators were observed to have a significant excess of melanoma (standardized incidence ratio [SIR] 1.64, 95% confidence interval [CI] 1.27–2.09), although the effect was not observed among the applicators themselves.⁹¹ In a study of risk factors for squamous cell carcinoma in Saskatchewan, a largely rural agricultural Canadian province, agricultural occupation was a significant factor 1.49 (95 % CI 1.22–1.82).⁹²

Skin cancer is rare in children, although the risk of melanoma increases considerably in the adolescent years. Few studies address risk in this age group. One study done in a high-exposure setting (Australia) found that among the more well-established risk factors (propensity to develop nevi and freckles, red hair, blue eyes, inability to tan, and a family history of the disease), adolescents who had lived or currently lived on a farm had a significantly increased risk (odds ratio [OR] = 1.9, 95% CI = 1.1–3.3).⁹³ Reported exposures to sunlight, pesticides, fertilizers, or aerial spraying were not significant predictors in this study.

These observations raise concern given that rural children may spend more time outdoors compared to their urban counterparts.⁹⁴ A survey of 11- to 18-year-old US youth demonstrates that among factors influencing risk of sunburn is the number of hours spent outside.⁹⁵

Several case and outbreak reports of zoonotic disease transmission to children who work or live on or near farm animal operations have been described. Transmission routes include oral, respiratory, direct, and indirect contacts with infected animals or contaminated soil and water.^4,96,97 Outbreaks in communities downwind of infected animals have been reported.⁹⁸ The zoonotic diseases found in agricultural settings for which young children or the developing fetus may be at increased risk include campylobacteriosis, coxiellosis, cryptosporidiosis, enterohemmorhagic Escherichia coli (EHEC), listeriosis, salmonellosis, toxoplasmosis, and yersinosis.⁴

The developing immune system of very young children, particularly infants, places them at greater risk for acquiring serious infections and developing infections of antibiotic-resistant organisms connected to the agricultural use of antimicrobials.⁹⁹ For example, whereas most strains of E. coli are harmless and commensal in healthy mammals, E. coli 0157:H7 produces a powerful toxin and can cause severe hemorrhagic enterocolitis. Children under the age of 5 years are at risk of hemolytic uremia syndrome as a complication.¹⁰⁰

As with pesticide illness or nitrate excesses in private wells, there are no systematic surveillance data on transmission of infections related to farm animals. Although health care providers are trained in the diagnosis and prevention of zoonoses, the nonspecific clinical presentation in children (e.g., diarrheal disease) requires an index of suspicion for animal reservoirs and farm-related transmission. The true prevalence of zoonoses among agricultural community residents is unknown. Seroprevalence studies may help identify high-exposure subgroups as well as specific animal and child behavior risk factors that influence exposure.¹⁰¹ Effective surveillance efforts will require coordination and education of the veterinary, medical, and public health community.⁴

Provide opportunities for training and improved capacity of clinicians and public health professionals who serve agricultural families on identification and reduction of environmental health risks of children.

Such programs could encompass development of data-gathering approaches in communities to define factors that influence exposure, prevalence of health conditions associated with agricultural hazards, and improvements associated with intervention strategies. Programs that foster collaborations of medical, public health, agricultural science, and veterinary health sectors should be prioritized. This should be done at the local, state, and federal level.

Develop programs for education of agricultural communities on reduction of environmental health risks for children in their homes, schools, and public areas. Engage local youth in environmental health programs and provide exposure to environmental health careers.

Provide empirical data on exposure levels children experience in agricultural settings to key known environmental hazards—noise, animal operation–related air contaminants, agricultural chemicals including pesticides, drinking water contaminants particularly nitrates, and zoonotic infectious agents. Examine the variability in these exposures in relationship to lifestage and agricultural production factors. Consider all pathways and combined exposures in air, water, dietary, soil, and house dust.

Support epidemiological research that evaluates the impact of nonacute agricultural chemical exposures and important chronic pediatric morbidities or suspected toxicities such as autism, ADHD, asthma, allergic rhinitis, skin disease, diabetes, low birth weight, premature birth, birth defects, obesity, cancer, and hearing loss. Promote approaches that evaluate multiagent effects and timing of exposures.

Establish a comprehensive national surveillance program for identification and tracking of important environmental hazards in agricultural communities, including pesticide-related incidents, drinking water contaminants, and zoonoses. Data system applications that can integrate and incorporate existing relevant data such as outcomes in electronic medical records and exposures collected from regulatory authorities (e.g., pesticide applications) should be advanced. Surveillance activities should establish strong linkages among the medical, veterinary, and public health communities that serve agricultural communities.

Developmental toxicity endpoints including but not limited to neurodevelopment, reproductive health, and endocrine disruption should be a priority requirement when evaluating the health impacts of agricultural contaminants, including new agricultural chemicals for licensing, regulatory decisions, or re-registration of existing products. If evidence supports reasonable concern for developmental health consequences rather than demonstrated negative health effects, regulatory authorities including US EPA and USDA should adapt policy approaches to limit childhood and pregnancy exposure.

Include overall hazardous exposure reduction for children as a goal in agricultural chemical use and agricultural production policies and require assessment of alternatives where child health concern exists. For example, enhance promotion of integrated pest management and organic methods of agriculture, require assessment of alternatives, increase well water monitoring, and promote effective farm waste management strategies and zoning to reduce exposures to children their homes, daycares, and schools from contaminants.