describes the characteristics of the sample, stratified according to level of prenatal chlorpyrifos exposure. Chlorpyrifos levels ranged from undetectable to 63 pg/g, and 20.6% of the sample was classified as having high chlorpyrifos exposure. There were significant race/ethnicity differences in the distribution of chlorpyrifos exposure, in that 24.2% of black women and 14.9% of Dominican women had high exposure. Cotinine levels ranged from 0.01 ng/mL to 8.79 ng/mL, and 37% of the sample was classified as being exposed to ETS during pregnancy. Women who were highly exposed to chlorpyrifos were significantly more likely to have residential exposure to ETS during pregnancy, compared with women with lower chlorpyrifos exposure. The sample was largely at term, because of the timing of air monitoring later in pregnancy and the exclusion of high-risk pregnancies, as defined above (only 4% of the pregnancies were <37 weeks).
Characteristics of the Study Population According to Prenatal Chlorpyrifos Exposure Level (N = 254)
shows the unadjusted means and SDs for continuous BSID-II scores and proportions delayed for the 2 exposure groups at 12, 24, and 36 months of age. The 36-month average PDI score was significantly lower among children exposed to high levels of chlorpyrifos, compared with those exposed to lower levels (P = .01). At 36 months, significantly greater proportions of children with cognitive (P = .05) and psychomotor (P = .002) delays were observed among children exposed prenatally to high levels of chlorpyrifos. Although none of the other differences reached statistical significance in these bivariate tests, children exposed to high levels of chlorpyrifos scored lower, on average, on 5 of the 6 age-specific tests than did children exposed to lower levels. Similarly, the percentage of children experiencing developmental delay was higher among children exposed to high chlorpyrifos levels than among children with low exposure for 5 of the 6 age-specific tests.
BSID-II Means and Proportion Delayed at 12, 24, and 36 Months According to Chlorpyrifos Exposure Level (N = 254)
Five behavioral domains were assessed with the CBCL at 36 months of age. shows the proportions of children scoring in the problem range on each of these scales for the 2 exposure groups. A greater proportion of children with high chlorpyrifos exposure were in the clinical problem range on all 5 of the scales; the difference reached statistical significance in bivariate tests for both attention problems (P = .03) and attention-deficit/hyperactivity disorder (ADHD) problems (P = .03).
Proportions Scoring in the Clinical Problem Range on the CBCL at 36 Months According to Prenatal Chlorpyrifos Exposure Level (N = 228)
shows the results of multivariate regression analyses estimating the age-specific effects of prenatal chlorpyrifos exposure on MDI scores, after adjustment for gender, ethnicity, gestational age at birth, home environment, prenatal ETS exposure, maternal education, and maternal intelligence. The adverse effect of prenatal chlorpyrifos exposure on MDI scores (−3.3 points) was marginally significant at 36 months of age (P = .06). Longer gestation was protective, despite the restricted range of gestational ages. Mother’s lack of a high school degree was associated with a statistically significant 3-point deficit in MDI scores. Black children outscored Dominican children consistently, and these effects seemed to increase with child age through 36 months (ranging from 0.2 points at 12 months to 6.3 points at 36 months). Female subjects scored, on average, significantly higher than male subjects (3.0 –3.8 points). In addition, children who lived in homes with higher HOME scores (both stimulation and interaction) scored higher scores at 36 months of age. Children exposed to ETS during the prenatal period showed a 3-point decrease in MDI scores at 24 months (P = .06), but this effect was no longer apparent at 36 months. Interaction terms for the interaction of chlorpyrifos exposure with the other exposure and sociodemographic variables were tested in the full model, and none was significant. Together, exposures and sociodemographic covariates accounted for 25% of the variance in MDI scores at 36 months.
Multivariate Linear Regression Models Testing Main and Interactive Effects of Prenatal Chlorpyrifos Exposure on 12-, 24-, and 36-Month MDI Scores, Adjusted for Race, Gender, Maternal Education, Maternal IQ, Gestational Age, and Prenatal ETS Exposure
shows the results of multivariate regression analyses estimating the age-specific effects of prenatal chlorpyrifos exposure on PDI scores, after adjustment for gender, ethnicity, gestational age at birth, home environment, prenatal exposure to ETS, maternal education, and maternal intelligence. A significant negative chlorpyrifos effect was seen at 36 months, in that children exposed to high prenatal levels scored, on average, 6.5 points lower on the PDI, compared with those with low levels (P
= .003). Of the covariates, only race (P
= .03) and gestational age (P
= .03) had statistically significant effects on motor development at 36 months, consistent with the findings that maternal education and other socioeconomic status proxies have little impact on motor development in the early years.47
All interaction terms for the interaction of chlorpyrifos exposure with the other exposure and sociodemographic variables were tested in the full model, and none was significant. In particular, the lack of a significant interaction between chlorpyrifos exposure levels and HOME scores for MDI or PDI scores suggests that, although the quality of the home environment may have a significant independent effect on MDI scores (P
< .001) and a marginal effect on PDI scores (P
= .06), it neither protects against nor exacerbates the adverse impact of prenatal chlorpyrifos exposure on mental or motor development at 36 months of age.
Multivariate Linear Regression Models Testing Main and Interactive Effects of Prenatal Chlorpyrifos Exposure on 12-, 24-, and 36-Month PDI Scores, Adjusted for Race, Gender, Maternal Education, Maternal IQ, Gestational Age, and Prenatal ETS Exposure
Because there was a significant effect of race/ethnicity on BSID-II scores in most models, and because of the risk of possible uncontrolled confounding by other unmeasured race-associated exposures, we conducted race-specific analyses at 36 months. The adverse chlorpyrifos effect on PDI scores was significant at the .05 level in both race/ethnicity groups. Specifically, among black children with high versus low exposure, the deficit was ~7 points (97.07 points vs 104.22 points). Among Dominican children with high versus low exposure, the deficit was ~6 points (93.95 points vs 99.13 points). The chlorpyrifos effect on MDI scores was significant (P < .05) for black children, with a deficit of ~6 points (88.47 points vs 94.81 points), but was not significant for Dominican children, for whom the deficit was slightly less than 2 points (85.17 points vs 86.87 points). These findings were consistent with the overall chlorpyrifos results, which were stronger for the PDI than the MDI at 36 months.
and show the results of logistic regression analyses estimating the adjusted risks of delays (MDI and PDI) as a function of prenatal chlorpyrifos exposure, after adjustment for gestational age, gender, ethnicity, maternal education, maternal intelligence, and home environment. Before 36 months of age, highly exposed children were no more likely to exhibit mental or motor delays than were those with lower exposure. At 36 months of age, the odds of highly exposed children having mental delays were 2.4 times as great (95% CI: 1.12–5.08; P = .02) and the odds of motor delays were 4.9 times as great (95% CI: 1.78–13.72; P = .002), compared with children with lower prenatal exposures.
Logistic Regression Models Testing Effects of Chlorpyrifos on the Odds of Mental Delay at 12, 24, and 36 Months, Adjusted for Race, Gender, Gestational Age, Maternal Education, Maternal IQ, ETS Exposure, and Home Environment
Logistic Regression Models Testing Effects of Chlorpyrifos on the Odds of Psychomotor Delay at 12, 24, and 36 Months, Adjusted for Race, Gender, Gestational Age, Maternal Education, Maternal IQ, ETS Exposure, and Home Environment
After examination of the age-specific results for the MDI and the PDI, GLM was conducted to explore developmental trajectories. In addition to the test of main effects, GLM tested the interaction of each independent variable with age, to obtain estimates of effects over time. Covariates were included if they were significant predictors in any age-specific model; for the MDI, these were ethnicity, maternal education, gender, gestational age, HOME scores, and ETS exposure. Covariates for the PDI were ethnicity, gender, gestational age, HOME scores, and ETS exposure. Results of the GLM analysis (n = 189) were consistent with the age-specific findings with respect to the effects of chlorpyrifos, race, and HOME scores. In addition, GLM analyses provided estimates of within-subject effects (change over time) and within-subject contrasts, indicating at exactly which age the effects occurred. Preliminary analyses indicated no significant interactions of chlorpyrifos exposure with any of the covariates, including ETS exposure and race (P > .05). Therefore, all interactions terms were excluded from the final models.
shows the estimated means for MDI scores over time according to prenatal chlorpyrifos exposure level, adjusted for the effects of covariates. Both high-exposure and lower-exposure groups demonstrated decreases in scores, as reported frequently for low-income populations during the toddler years, followed by increases in the later preschool period. The recovery by 3 years of age was slightly greater for children with low exposure, compared with children with high exposure, but the chlorpyrifos within-subject effect (change over time) was not significant (P = .23). The GLM analysis did indicate significant within-subject effects of both race (P = .001) and HOME scores (P = .03) on MDI scores, consistent with results at the individual time points. A second GLM analysis, including only 1 independent variable and using tests of within-subject contrasts, showed that the ethnicity effect on MDI scores emerged between 12 and 24 months (P = .001).
FIGURE 1 Estimated effects of prenatal chlorpyrifos exposure on MDI scores for children 12 to 36 months of age according to race/ethnicity by using GLM repeated-measures analysis of variance. The models were adjusted for race/ethnicity, gender, gestational age, (more ...)
The results of the GLM analysis for PDI scores revealed a significant within-subject effect (change over time) of prenatal chlorpyrifos exposure (P = .01), with an estimated deficit of >7 points at 36 months of age among children exposed to high levels of chlorpyrifos (). There was also a significant change over time in the effect of ethnicity, in that the difference between the mean PDI scores of the 2 groups increased over time, with Dominican children having lower mean scores regardless of exposure level (P = .001). A second GLM analysis, including only these 2 independent variables and using tests of within-subject contrasts, showed that the ethnicity effect on PDI scores emerged between 12 and 24 months (P = .001) and the chlorpyrifos effect emerged between 24 and 36 months (P = .003).
FIGURE 2 Estimated effects of prenatal chlorpyrifos exposure on PDI scores for children 12 to 36 months of age according to race/ethnicity by using GLM repeated-measures analysis of variance. The models were adjusted for race/ethnicity, gender, gestational age, (more ...)
shows the results of logistic regression analyses estimating the adjusted risk of behavior problems as a function of chlorpyrifos exposure. Significant chlorpyrifos effects were found for attention problems, ADHD problems, and pervasive developmental disorder (PDD) problems. In addition, children with prenatal ETS exposure were significantly more likely to score in the clinical range for ADHD problems. Despite the significant associations between chlorpyrifos exposure and these subscales, only 3.9% to 4.9% of the sample scored in the clinical range, which resulted in large CIs. There was no evidence of interaction between ETS exposure and chlorpyrifos exposure for these behavior problems, but small numbers limited our ability to test these effects.
Logistic Regression Models Testing Effects of Chlorpyrifos on the Odds of Behavioral Disorder at 36 Months, Adjusted for Race, Gender, Gestational Age, Maternal Education, Maternal IQ, ETS Exposure, and Home Environment (N = 228)
Because the EPA ban occurred during the study period, we examined its overall effect on chlorpyrifos levels and BSID-II scores over time. The ban was actually a phase-out, beginning with announcements of the impending regulation and some early removal of products from retail stores. After the ban, it was possible that some families continued to use pesticide products purchased before the ban. It was therefore difficult to determine with precision the date when exposure stopped; however, it was possible to classify the births in the present sample into the preban period (before January 2000), the midban or phase-out period (January 2000 to December 2000), and the postban period (January 2001 and later). One-way analysis of variance of ban effects on mean logarithmically transformed chlorpyrifos levels showed significant decreases in mean chlorpyrifos blood levels at delivery in this sample across the preban (0.92 pg/g), midban (0.81 pg/g), and postban periods (0.90 pg/g) (F = 49.81; P < .001). There were significant increases in 36-month BSID-II MDI scores from the preban period (average score: 87.13 points) to the midban period (average score: 91.69 points) (F = 3.88; P = .02) and in PDI scores from the preban period (average score: 97.31 points) to the midban period (average score: 101.79 points) (F = 2.91; P = .056), but there were slight nonsignificant decreases in scores after full implementation of the ban (MDI average score: 89.48 points; PDI average score: 99.40 points). The initial decrease in chlorpyrifos levels from the preban period to the midban period corresponded to the largest increase in BSID-II scores, but larger epidemiologic studies will be needed to assess the full impact of the ban, including the longer-term effects of possible substitute pesticides.