child urinary DAPs and attention-related performance errors on the Wisconsin Card Sorting Test; however the population was small (n = 48) (Lizardi et al. 2008). In the present study, associations between attention measures and prenatal DAPs are stronger than those with child DAP concentrations. Furthermore, results with child DAPs must be viewed with caution, because they reflect con- current exposures, the temporal relation with the outcome is unclear, and exposure may not be independent of childhood behavior. We find some evidence of effect modifica- tion by sex of the child. The clinical presenta- tion of attention deficit disorder may vary by the child’s sex, with girls reportedly display- ing more inattentive-type problems and boys displaying more hyperactive and impulsive behaviors (Biederman et al. 2002; Staller and Faraone 2006). Studies of other substances have found marked differences in neurotoxic susceptibility by sex. For example, one study found that 6-year-old boys prenatally exposed to cocaine displayed more problem behaviors (hyperactivity) than controls but observed no such differences among girls (Delaney- Black et al. 2004). A recent meta-analysis reported that differences in brain morphology between youth with ADHD and controls var- ied by child sex (Hutchinson et al. 2008), and a functional imaging study found that men with ADHD displayed different neural activ- ity patterns than controls, but women did not (Valera et al. 2010). The mechanisms by which OPs could cause attentional problems and/or impulsiv- ity can be only speculated, as ADHD is a complex disorder and the precise causes are unknown. However, there is consider- able evidence that neurotransmitters includ- ing dopamine, noradrenaline, and serotonin, the primary target of ADHD pharmacologic treatments, are involved. Less is known about the role of the cholinergic system. Although OP pesticides at high doses will inhibit acetyl- cholinesterase, experimental evidence in ani- mals suggests that even OP doses that cause no or little cholinesterase inhibition may produce biochemical and behavioral effects (Costa 2006), including adverse effects on sustained attention and an increase in impul- sivity in rodents (Middlemore-Risher et al. 2010). In addition, there is a growing body of evidence that OPs may operate through a variety of noncholinergic mechanisms, such as by disruption of various cellular processes such as DNA replication and axonal and dendritic growth (Howard et al. 2005) and by oxidative stress in the developing brain (Slotkin and Seidler 2009). Our study has many strengths. We were able to assess prenatal OP exposure and follow the children longitudinally. Our findings are generally consistent whether we use creatinine or non-creatinine-adjusted DAP metabolite concentrations. Although DAP concentra- tions were not associated with all outcomes, we found evidence for an association across various assessment methods, including mater- nal report, child testing, and subjective obser- vation by evaluators blinded to exposure. This study has some limitations. Notably, the assessment of exposure to OPs is challeng- ing because of the rapid metabolism of OP pesticides (Needham 2005) and the lack of a measure of long-term exposure; however, because the prenatal measures are an average of two measurements, they may better reflect ongoing exposure during the pregnancy. Also, the prenatal maternal urinary DAP concen- trations in our study are higher than in a nationally representative sample of women of childbearing age (109.0 vs. 82.3 nmol/L) (Bradman et al. 2005; CDC 2004) and there- fore may not be generalizable to less-exposed populations. Another limitation is that some of the measures we used to assess behavior in these Organophosphate pesticides and attention Mexican-American children were standardized for the general U.S. population. Therefore, the percentage of children identified as hav- ing a problem may not be comparable with that expected for the general U.S. population. Nevertheless, this limitation should not affect the examination of the relative associations of DAPs and outcomes within our own homo- geneous study population. Future studies should evaluate whether associations of OP exposure and attention disorders persist in older children and in chil- dren in different populations. ADHD is often not diagnosed until children are of school age, and screening instruments may identify attention problems more accurately in older children than in preschoolers. In addition, future investigations should consider whether children with certain genetic polymorphisms (e.g., paraoxonase 1) may be more likely to show attention problems in relation to OP exposure. Approximately 8–9% of school-age children are estimated to have ADHD (Pastor and Reuben 2008); given that attention Table 7. Adjusteda logistic regression model for attention-related outcomes at ages 3.5 and 5 years per 10-fold increase in child urinary DAP concentrations [OR (95% CI)]. Model noutcome/n Total DAPs DMs DEs 3.5 Years CBCL Attention problems 17/289 1.6 (0.8–3.5) 1.6 (0.8–3.3) 1.9 (0.9–3.9) ADHD 17/288 1.4 (0.7–3.1) 1.4 (0.7–3.0) 1.0 (0.5–2.2) 5 Years CBCL Attention problems 13/319 1.0 (0.4–2.4) 0.9 (0.4–2.1) 1.8 (0.8–3.9) ADHD 22/319 0.6 (0.3–1.2) 0.5 (0.3–1.1)* 0.9 (0.5–1.7) K-CPT Markedly atypical Percent omissions 58/309 1.0 (0.6–1.6) 0.9 (0.6–1.5) 1.5 (1.0–2.2)* Percent commissions 53/309 1.1 (0.7–1.7) 1.1 (0.7–1.8) 0.9 (0.6–1.4) Hit reaction time 19/308 1.1 (0.5–2.3) 1.0 (0.5–2.0) 1.3 (0.7–2.4) ADHD Confidence Index > 70th percentile 24/294 1.3 (0.7–2.5) 1.2 (0.7–2.3) 1.5 (0.8–2.8) Hillside Behavioral Rating Scale Attention ≥ 7 of 12 23/319 1.4 (0.7–2.8) 1.1 (0.6–2.1) 1.4 (0.8–2.6) Composite ADHD indicator ADHD indicator 25/316 1.0 (0.5–2.0) 0.8 (0.4–1.5) 2.0 (1.1–3.6)** aAdjusted for maternal total DAPs, psychometrician, age at assessment, sex, maternal education, depressive symptoms, PPVT, child care, and breast-feeding, as well as maternal urinary DAPs. *p < 0.10. **p < 0.05. Table 8. Adjusteda linear regression models for attention-related outcomes at ages 3.5 and 5 years per 10-fold increase in child urinary DAP concentrations [β (95% CI)]. Model n Total DAPs DMs DEs 3.5 Years CBCL Attention problems 289 0.1 (–0.2 to 0.4) 0.1 (–0.2 to 0.3) 0.2 (0.0 to 0.5)* ADHD 288 0.1 (–0.3 to 0.6) 0.1 (–0.3 to 0.6) 0.2 (–0.3 to 0.7) NEPSY Visual attention 277 –0.1 (–0.5 to 0.3) –0.1 (–0.5 to 0.3) –0.1 (–0.5 to 0.3) 5 Years CBCL Attention problems 319 0.0 (–0.3 to 0.2) –0.1 (–0.3 to 0.2) 0.0 (–0.2 to 0.3) ADHD 319 0.0 (–0.5 to 0.5) 0.0 (–0.5 to 0.4) 0.1 (–0.3 to 0.6) K-CPT ADHD Confidence Index 294 –0.7 (–3.8 to 2.3) –1.0 (–3.9 to 1.9) 2.2 (–0.5 to 5.0) aAdjusted for maternal total DAPs, psychometrician, age at assessment, sex, maternal education, depressive symptoms, PPVT, child care, and breast-feeding, as well as maternal urinary DAPs. *p < 0.10. Environmental Health Perspectives • volume 118 | number 12 | December 2010 1773