August 20, 2010 — Exposure to organophosphate pesticides, especially prenatally, significantly increased susceptibility to attention-deficit/hyperactivity disorder (ADHD) in children born to Mexican American women in the Salinas Valley, an area of intensive agriculture and heavy pesticide use.

These latest findings support previous results from a study published in the June issue of Pediatrics and reported by Medscape Medical News at that time that showed US children with higher levels of organophosphate pesticide metabolites in their urine were more likely to have ADHD compared with their counterparts with lower levels.

In the current study, investigators found prenatal exposures had a greater association than did exposures after birth. A 10-fold increase in levels of urinary dialkyl phosphate (DAP) metabolites in the mother's urine during pregnancy correlated to a 500% increase in the diagnosis of attention disorders in 5-year-olds, according to the study of over 300 children.

Organophosphate pesticides work by disrupting neurotransmitters, particularly acetylcholine, which is critical for brain development in humans and helps to sustain attention and short-term memory. Exposure to these compounds may also disrupt DNA replication and the growth of nerve axons and dendrites.

Young children are more vulnerable to organophosphate exposure than adults because of lower levels of acetylcholinesterase, which detoxifies these pesticides, the study authors explained.

"Given that these compounds are designed to attack the nervous system of organisms, there is reason to be cautious, especially in situations where exposure may coincide with critical periods of fetal and child development," lead study author Amy Marks, MPH, who was an analyst at the University of California (UC) Berkeley's School of Public Health at the time of the study, said in a statement.

The study was published online August 19 in Environmental Health Perspectives.

Pesticide Metabolites Linked to Behavior

The mothers were recruited during pregnancy by the Center for the Health Assessment of Mothers and Children of Salinas, which is conducting a longitudinal examination of environmental exposures and reproductive health.

All were Mexican American women living in the Salinas Valley, an agricultural region where more than 235,000 kg of pesticides is applied annually.

Researchers analyzed 6 organophosphate metabolites in urine samples collected from the mothers during pregnancy and from their children from birth to the age of 5 years. The presence of these metabolites indicated exposure to pesticides, such as chlorpyrifos, diazinon, and oxydemeton-methyl, which are widely used.

Children's behavior was assessed at 3.5 years (n = 331) and 5 years (n = 323) using mothers' reports (Child Behavior Checklist) and standardized psychological tests (NEPSY-II visual attention subtest at the age of 3.5 years and Conners' Kiddie Continuous Performance Test [K-CPT] at the age of 5 years).

Psychometricians scored the 5-year-olds' behavior during testing using the Hillside Behavior Rating Scale (HBRS). The researchers controlled for potentially confounding factors, such as birthweight, lead exposure, and breastfeeding.

The study's key finding was the strong adverse association of DAP levels in utero with attention disorders in young children, a finding that was most robust in 5-year-old boys. Although a positive link between prenatal pesticide exposure and attention problems was seen for 3.5-year-olds, it was not statistically significant, which did not surprise the researchers.

"Symptoms of attention disorders are harder to recognize in toddlers," said Ms. Marks. "Diagnoses of ADHD often occur after a child enters school."

Thoroughly Wash Fruits and Vegetables

Prenatal DAPs were nonsignificantly associated with maternal reports of attention problems and ADHD at the age of 3.5 years but were significantly related at the age of 5 years (attention: β = 0.7; 95% confidence interval [CI], 0.2 – 1.2; ADHD: β = 1.3; 95% CI, 0.4 – 2.1). DAPs were associated with the K-CPT ADHD Confidence Index (odds ratio [OR], 5.1; 95% CI, 1.7 – 15.7) and nonsignificantly associated with HBRS ADHD (β = 0.4; 95% CI, −0.04 to 0.9). DAPs were also associated with a composite ADHD indicator of the various measures (OR, 3.6; 95% CI, 1.2 – 11.0).

Specifically, for each 10-fold increase in DAP concentrations, children were about 5 times more likely to be above 70% confidence on the ADHD index. Total DAP concentrations were associated with having ADHD symptoms using the composite indicator (ie, the 3 assessment methods).

"We found that higher concentrations of organophosphate metabolites in the urine of pregnant women was associated with increased odds of attention problems and poorer attention scores in their young children as assessed either by maternal report, psychometrician observation, or by direct assessment," the study authors write.

"These associations appeared to be more robust at age 5 than 3.5 years and stronger in boys than girls. Children's concurrent organophosphate metabolite levels at age 3.5 and 5 years were unrelated to attention outcomes....While results of this study are not conclusive, our findings suggest that prenatal exposure to organophosphate pesticides may affect young children's attention.

"High levels of the symptoms of ADHD by age 5 are a major contributor to learning and achievement problems in school, accidental injuries at home and in the neighborhood, and a host of problems in peer relationships and other essential competencies," said UC Berkeley psychology professor Stephen Hinshaw, PhD, an expert in ADHD who was not involved in the study. "Finding preventable risk factors is therefore a major public health concern."

Senior author of the article, Brenda Eskenazi, PhD, UC Berkeley professor of epidemiology and maternal and child health, cautioned, "We have not proved causality, but at least 3 studies now suggest there is an association between DAP exposure and attention disorders. The other caveat is that these children were not clinically diagnosed. We used maternal subjective measures of reporting, and though we used objecting testing as well, it was not necessarily DSM-IV criteria.

"Additionally, I doubt we are talking about a high proportion of children with ADHD being explained by organophosphate exposure, as ADHD is complex and multifactorial. But this is a potential factor."

She noted that steps can be taken to lessen the risks associated with prenatal exposure. "It's known that food is a significant source of pesticide exposure among the general population," she said. "I would recommend thoroughly washing fruits and vegetables before eating them, especially if you're pregnant."

The study authors have disclosed no relevant financial relationships.

Environ Health Perspect. Published online August 19, 2010.