Environmental Health Perspectives • volume 117 | number 8 | August 2009 1309

Research | Children’s Health

Because the U.S. Centers for Disease Control 

and Prevention (CDC) lowered its level of concern for childhood blood lead concentration 

(BPb) from 25 to 10 μg/dL in 1991 (CDC 

1991), several individual cohort studies and 

meta-analyses have focused on cognitive developmental effects (psychometric intelligence or 

IQ) of BPb concentrations < 10 μg/dL. Two 

meta-analyses that included both cross-sectional and longitudinal studies concluded that 

there was no evidence of a threshold at 10 μg/

dL for effects on childhood IQ, but they did 

not examine the effects among children who 

had a maximum BPb concentration < 10 μg/

dL (Pocock et al. 1994; Schwartz 1994). An 

analysis of the Rochester Longitudinal Study 

(Canfield et al. 2003) reported a decrement 

of 7.4 points in IQ at 5 years of age associated 

with an increase in mean childhood BPb levels 

from 1 to 10 μg/dL for children who had a 

peak BPb concentration that never exceeded 

10 μg/dL. A more recent update of the 

Rochester cohort (Jusko et al. 2008) found that 

6-year-old subjects with a mean childhood BPb

concentration < 5 μg/dL scored 4.9 IQ points 

higher than children with mean childhood 

BPb between 5 and 9.9 μg/dL. An updated 

analysis of the Boston cohort found similar 

results among children with maximum BPb

levels < 10 μg/dL (Bellinger and Needleman 

2003). Although the weight of evidence suggests that adverse effects on cognitive development are associated with BPb concentrations 

< 10 μg/dL, the age of greatest vulnerability 

has not been clearly indicated.

In a pooled analysis of seven cohorts, 

Lanphear et al. (2005) examined four different BPb metrics in relationship to child IQ: 

mean BPb levels from 6 months to the age 

closest to the IQ test, early childhood mean 

BPb levels from 6 to 24 months of age, peak 

BPb levels measured anytime before the IQ 

test, and concurrent BPb defined as BPb levels measured closest to the IQ test. That study

found the measure of concurrent BPb levels to 

have the strongest relationship to IQ, but early 

childhood average, lifetime childhood average, 

and peak BPb levels were all significantly and 

inversely related to IQ. No attempt was made 

in that study to determine the age of greatest association with IQ across the spectrum of 

all annual BPb measurements. In an analysis 

of data from a clinical trial of succimer treatment in children with BPb levels between 20

and 44 μg/dL, Chen et al. (2005) attempted to 

determine whether BPb levels measured at early 

or late childhood were more strongly related to 

IQ scores. Their approach was to include both 

prior and concurrent BPb levels in each model 

of IQ scores. They concluded that BPb levels 

measured at 7 years of age was more strongly 

related to IQ measured at 7 years than the 

higher BPb levels measured at 2 years of age. 

That analysis had two important limitations: 

First, as the authors noted, analysis of both 

prior and concurrent BPb concentrations in 

the same model introduced the problem of collinearity between these two measures. Second, 

all children in this study had high BPb levels by 

contemporary standards (20–44 μg/dL), thus 

making generalization to a population with 

more typical levels somewhat problematic.

A study of the effects of lead on IQ by 

Wasserman et al. (2000) also addressed the 

problem of serial correlation of BPb measurements. They examined postnatal BPb relative to 

prenatal lead exposure in a Yugoslavian cohort 

of lead-exposed children. To reduce problems 

with tracking of prospective measurements, 

they created a categorical variable that characterized early and late postnatal measurements 

by whether they increased or decreased in relation to prenatal BPb levels. After adjustment for 

social factors and prenatal BPb, they found that 

early childhood BPb levels were most strongly 

related to decrements in IQ, but elevated BPb

levels in late childhood were also associated 

with IQ decrements.

Although recent research has provided a 

new understanding of the adverse effects of 

childhood lead exposure at BPb levels < 10 μg/

dL, the age of greatest susceptibility is still in 

question. Recent studies (Chen et al. 2005; 

Lanphear et al. 2005) suggest that lead exposure 

beyond 2 years of age, when BPb levels generally peak, may be more strongly associated with 

cognitive development. However, the strong 

correlation, or tracking, of BPb levels from 

infancy to school age makes the determination 

of the age of greatest susceptibility a difficult 

task. Brubaker (2008) examined the association 

of serial BPb measures and reduction in gray 

matter from magnetic resonance brain imaging 

of 157 young adults in the Cincinnati Lead 

Study and found that BPb concentrations at 

5 and 6 years of age were more highly associated with gray matter volume reductions in the 

prefrontal cortex than were BPb levels measured at earlier ages. They made no attempt to 

examine the effects of multiple BPb measures 

in the same model, so that analysis also does 

not directly address the problem of separating 

early and late childhood lead exposures.

Address correspondence to R.W. Hornung, 

Cincinnati Children’s Hospital Medical Center, 3333 

Burnet Ave., MLC 7035, Cincinnati, OH 45229-

3039 USA. Telephone: (513) 636-1948. Fax: (513) 

636-4402. E-mail: richard.hornung@cchmc.org

The authors declare they have no competing 

financial interests.

Received 25 November 2008; accepted 7 May 2009.

Age of Greatest Susceptibility to Childhood Lead Exposure: 

A New Statistical Approach

Richard W. Hornung,1,2 Bruce P. Lanphear,1,2,3 and Kim N. Dietrich1,2

1Cincinnati Children’s Environmental Health Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; 2Department 

of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA; 3Faculty of Health Sciences, Simon Fraser 

University and Child and Family Research Institute, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada

Background: Susceptibility to lead toxicity is often assumed to be greatest during early childhood 

(e.g., 2 years of age), but recent studies suggest that blood lead concentrations (BPb) taken at 5–7 years 

of age are more strongly associated with IQ.

Objective: We aimed to determine the age of greatest susceptibility to lead exposure using an innovative statistical approach that avoids the problem of correlated serial BPb measurements.

Methods: We analyzed two cohorts of children that were followed from infancy to 6 years of age 

in Rochester, New York (n = 211), and Cincinnati, Ohio (n = 251). Serial BPb levels were measured 

and IQ tests were done when children were 6 years of age. After adjustment for relevant covariates, 

the ratio of 6-year BPb to 2-year BPb was added to the multiple regression model to test whether 

the pattern of BPb profiles during childhood had additional effect on IQ.

Results: The ratio of BPb at 6 years to the BPb at 2 years showed a strong effect on IQ (p < 0.001) 

when added to the multiple regression model that included the average childhood BPb. IQ decreased by 

7.0 points for children whose BPb at 6 years of age was 50% greater than that at 2 years compared with 

children whose 6-year BPb was 50% less than their 2-year BPb. Similarly, criminal arrest rates were a 

factor of 3.35 higher for those subjects whose 6-year BPb was 50% higher than their 2-year BPb.

Conclusions: We conclude that 6-year BPb is more strongly associated with cognitive and 

behavioral development than is BPb measured in early childhood.

Key words: age effects, blood lead, collinearity, temporal pattern. Environ Health Perspect 

117:1309–1312 (2009). doi:10.1289/ehp.0800426 available via http://dx.doi.org/ [Online 7 May 2009]
Hornung et al.

1310 volume 117 | number 8 | August 2009 • Environmental Health Perspectives

To determine the age of greatest susceptibility, we introduce a new statistical approach 

to examine the relationship between temporal 

patterns in childhood BPb levels and subsequent cognitive and behavioral development. 

Our objective is to estimate the age most highly 

related to decrements in IQ while reducing or 

eliminating the bias that may be associated with 

strong correlation of serial BPb measurements.

Methods

To address the issue of age of greatest susceptibility, it is necessary to use data from studies that 

measured BPb serially from infancy through at 

least 6 years of age. Our primary analysis uses 

data from the Cincinnati Lead Study and the 

Rochester Longitudinal Study. The Cincinnati 

study contained data on 251 children enrolled 

during 1979–1984 (Dietrich et al. 1993). 

The Wechsler Intelligence Scale for Children–

Revised (Wechsler 1989) IQ test was administered to these children at approximately 6 years 

of age. The Rochester study included 211 children enrolled during 1994–1995 (Lanphear 

et al. 1999). The Wechsler Preschool and 

Primary Scale of Intelligence–Revised (Wechsler 

1974) IQ test was administered to these children 

at approximately 6 years of age. The combined 

cohort contained 462 children whose BPb concentrations were measured at least annually from 

infancy to 6 years of age. In both studies, the IQ 

measured at approximately 6 years of age is considered more stable than IQ tests at earlier ages, 

and also follows the strategy used in the international pooled analysis (Lanphear et al. 2005).

BPb concentration. In addition to yearly 

BPb measurements made annually from 1 

through 6 years of age, other BPb metrics were 

also available. We calculated the childhood 

average as the mean of all BPb measurements 

from 6 months through 6 years of age. The peak 

childhood BPb was defined as the maximum of 

all BPb measurements during the same period.

Statistical analysis. We used multiple 

regression models to investigate the relationship between BPb and IQ scores measured at 

6 years of age. In the analysis of the Cincinnati 

and Rochester cohorts, we included the five 

covariates identified in the international 

pooled analysis (Lanphear et al. 2005): site, 

Home Observation for Measurement of the 

Environment (HOME) score, birth weight, 

maternal IQ, and maternal education. The 

HOME score is an index reflecting the quality and quantity of emotional and cognitive 

stimulation in the home environment (Bradley 

and Caldwell 1979). We defined maternal education as the highest grade completed by the 

subject’s mother.

Our new approach was to examine the 

temporal pattern of the available longitudinal BPb data while controlling for the overall exposure to lead throughout childhood. 

Although children’s BPb levels generally peak 

at approximately 2 years of age and then slowly 

decline, this is not universally true. This would 

be the usual scenario if the child’s lead exposure 

environment was relatively stable from infancy 

to 6 years of age, primarily due to mouthing 

behavior. However, the temporal pattern of 

lead contamination in a child’s environment 

may change during childhood because of a 

move by the child’s family to a new location 

or because of home renovation. The newly 

occupied or renovated house could contain 

higher lead contamination that might result in 

a child’s BPb peaking beyond 2 years of age.

To address the impact of changes in the 

usual temporal pattern of childhood BPb, we 

created a new exposure variable defined as the 

ratio of the BPb level at 6 years of age to the BPb

level at 2 years of age. Because a high BPb concentration at 6 years could simply reflect an even 

higher BPb level at 2 years, we added the log of 

the childhood average BPb (6 months to 6 years) 

to the model in order to compare the effects of a 

range of ratios of 6-year to 2-year BPb levels 

while holding the overall childhood lead exposure constant. Our objective was to determine 

whether early or late childhood lead exposure 

was more detrimental to cognitive development 

while avoiding the collinearity problem associated with previous analyses containing multiple 

BPb measures. We assessed the linearity of the 

relationship of IQ to the ratio by testing the 

statistical significance of quadratic and cubic 

terms in the ratio. We also tested whether the 

ratio effect could be considered constant across 

the full range of childhood average BPb levels 

by testing the interaction of the ratio with the 

childhood average BPb levels. After developing 

final multiple regression models, we examined 

regression diagnostics to determine whether collinearity or influential observations could have 

caused bias in our results (Belsley et al. 1980). 

We also tested the residuals of the final model to 

determine whether they followed a normal distribution and then plotted the residuals against 

the predicted values to determine whether 

they were homogeneous across the range of 

predicted values.

We also wanted to determine whether 

our ratio approach was valid when examining 

behavioral outcomes other than cognitive development. Accordingly, in addition to examining 

age effects on IQ scores, we also analyzed the 

temporal pattern in lead exposure related to 

adult criminal behavior. A recent analysis of the 

Cincinnati Lead Study cohort found a statistically significant positive relationship between 

adult criminal arrest rates and 6-year BPb levels 

(Wright et al. 2008). In a manner similar to 

that described for IQ scores, we used the same 

covariates identified in the model of adult criminal behavior, while adding the childhood average BPb and the 6-year:2-year BPb ratio to that 

model. Our objective was to examine the effect 

of variation in temporal patterns of BPb levels 

on a behavioral outcome other than IQ.

Results

Of the 462 children in the Cincinnati and 

Rochester cohorts, complete data on BPb levels 

and covariates were available for 397 (86%) 

children. We found no significant mean differences for IQ scores or covariates between the 

397 included children and the 65 children with 

one or more missing covariates. Characteristics 

of each cohort are similar, except for BPb levels and the proportion of nonwhite children 

(Table 1). The Cincinnati children had mean 

childhood average BPb concentrations that 

were approximately twice as high as those of 

the Rochester children (11.7 vs. 5.8 μg/dL) 

primarily because they enrolled 12–15 years 

Table 1. Characteristics of 397 children in Cincinnati and Rochester cohorts.

Cincinnati Rochester Combined

Characteristic (n = 221) (n = 176) (n = 397)

Birth weight (g) 3,144 ± 457 3225.7 ± 506 3,180 ± 480

Maternal IQ 75.2 ± 9.4 81.1 ± 12.6 77.8 ± 11.3

HOME score 32.4 ± 6.5 31.9 ± 6.3 32.3 ± 6.4

Maternal education (grade) 11.2 ± 1.4 12.2 ± 2.0 11.6 ± 1.8

Child IQ 87.0 ± 11.4 84.9 ± 14.4 86.1 ± 12.9

Child female sex 108 (48.9) 84 (47.7) 192 (48.4)

Child race (nonwhite) 197 (89.1) 125 (71.0) 322 (81.1)

BPb measures (μg/dL)

Peak 17.9 (9.0–38.0) 9.5 (4.0–23.3) 13.6 (4.6–34.4)

Early childhood 12.0 (6.6–26.6) 5.9 (2.5–13.7) 8.9 (3.0–23.8)

Lifetime mean 11.7 (5.8–24.9) 5.8 (2.4–12.7) 8.5 (3.0–22.1)

Concurrent 7.5 (3.5–20.0) 4.2 (1.5–12.0) 6.0 (1.9–17.9)

Values are arithmetic mean ± SD, no. (%), or geometric mean (5th–95th percentile).

Figure 1. Annual BPb levels and 95% confidence 

intervals for Cincinnati and Rochester cohorts,

individually and combined.

20

15

10

5

0

BPb (μg/dL)

0 1 2 3

Age (years)

4 5 6

Cincinnati

Combined

Rochester
Age of greatest susceptibility to lead exposure

Environmental Health Perspectives • volume 117 | number 8 | August 2009 1311

earlier when lead exposures were more prevalent. The Cincinnati cohort also had a somewhat higher proportion of nonwhite children 

(89.1 vs. 71.0%). In each of the cohorts, as 

well as the combined data, the mean BPb levels were highest at 2 years of age (14.1 μg/dL, 

combined data) and lowest at 6 years of age 

(7.3 μg/dL) (Figure 1). Childhood average 

BPb from 6 months to 6 years of age in the 

combined cohorts was 9.9 μg/dL, with 58% 

of the children having childhood average BPb

< 10 μg/dL. The mean of the ratio of 6-year 

to 2-year BPb concentrations was 0.58, with 

a range of 0.11–4.09. There were 25 children 

(6.3%) with a ratio > 1.0, meaning that the 

6-year BPb was greater than the 2-year BPb. 

The average IQ for children at 6 years of age 

was 85.9.

Our first step was to calculate the correlation 

matrix for the log of annual BPb measurements 

at 1–6 years of age. Table 2 clearly indicates the 

high degree of serial correlation among these 

measurements from the combined Cincinnati 

and Rochester cohorts. This high degree of 

collinearity precluded us from fitting a model 

with all six yearly BPb levels in the same model. 

Instead, we produced six separate models, one 

for each of the six annual BPb measurements. 

Table 3 shows the results of these six models. 

Similar to the results of Brubaker (2008), the 

estimated coefficients for a log-linear relationship clearly indicate that BPb concentrations at 

later ages are more strongly related to IQ on a 

cross-sectional basis. We then specified a model 

containing terms for the log of mean childhood 

BPb from 6 months to 6 years of age and the 

ratio of 6-year to 2-year BPb levels, as well as 

the five covariates identified above. Because the 

analysis of BPb at individual years indicated 

that 5-year BPb was also strongly related to IQ, 

we created an additional model to examine the 

5-year to 2-year ratio.

We examined the effect of variation in the 

usual pattern of BPb peaking at approximately 

2 years of age. The parameter estimates for 

the 6-year:2-year BPb ratio showed a statistically significant negative effect of the ratio 

(β = –7.00; 95% confidence interval, –10.00 

to –3.99; p < 0.001) on IQ after controlling 

for the average lead exposure during childhood as well as covariates (Table 4). We found 

no departure from linearity in the ratio effect 

and no significant interaction of the ratio with 

childhood average BPb (p = 0.28). In a secondary analysis, we also examined the ratio 

effect after controlling for 6-year BPb instead 

of average childhood exposure. Results were 

very similar (β = –6.3, p < 0.001), and all subsequent analyses were adjusted for childhood 

average exposure. Table 5 shows the final 

model, including all covariates. 

This result indicated that for two groups 

of children with the same average childhood 

lead exposure, those children who had relatively 

higher BPb concentrations at 6 years of age had 

greater decrements in IQ measured at age 6. 

Figure 2 illustrates this effect for three exposure 

scenarios: one characterizing the typical pattern 

with BPb twice as great at 2 years of age as at 

6 years of age, another with BPb levels 25% 

greater at age 6 than at age 2, and a third with 

BPb constant at the average childhood mean 

for the first two scenarios. Even though their 

average BPb from 1 to 6 years of age was identical, the child whose BPb was higher at age 6 

had an estimated 5.3 point greater loss in IQ 

compared with the child whose BPb peaked at 

age 2. Results were similar when we examined 

the ratio of BPb levels at age 5 to those at age 

2. However, analyses of ratios involving BPb

levels at 3 and 4 years of age showed no significant effects (data not shown). Regression diagnostics indicated no problems with collinearity 

or influential observations in these models. 

To address internal validity, we also repeated 

the analyses separately for the Cincinnati and 

Rochester cohorts. For each individual cohort, 

the 6-year:2-year ratio was significantly associated with IQ after controlling for average 

childhood BPb and covariates. In a secondary 

analysis following our approach in the international pooled analysis (Lanphear et al. 2005), 

we fit the same model to data from children in 

the Cincinnati and Rochester cohorts whose 

maximum BPb level never exceeded 10 μg/dL. 

Similar to our results in the pooled analysis, the 

effect of the ratio was even stronger in terms 

of a larger estimated decrement in IQ for this 

analysis restricted to less exposed children (β = 

–12.5, p = 0.002). Thus, this statistical approach 

is applicable to populations with BPb levels in 

the range above, as well as below, the current 

CDC “action level” (CDC 1991, 2002).

Adult criminal arrests. To extend this 

analysis beyond standardized measures of psychometric intelligence, we next examined the 

relationship of temporal patterns of lead exposure during childhood to adult criminal arrest 

rates. As previously described (Wright et al. 

2008), we used negative binomial regression to 

analyze arrest rates from 19 to 24 years of age 

among 250 members of the Cincinnati Lead 

Study. The results reported by Wright et al. 

indicated a statistically significant relationship 

between arrest rates and prenatal maternal BPb

and 6-year BPb concentrations. Following 

the same analytic strategy that we used in the 

combined Cincinnati and Rochester study of 

IQ, our model included mean childhood BPb

and the 6-year:2-year BPb ratio plus covariates used in the model developed by Wright 

et al. (2008): maternal IQ, sex, socioeconomic 

Table 2. Correlations of log of annual BPb levels (years of age).

1 2 3 4 5 6

1 1.00 0.75 0.76 0.64 0.72 0.72

2 1.00 0.89 0.80 0.83 0.81

3 1.00 0.91 0.89 0.87

4 1.00 0.96 0.91

5 1.00 0.93

6 1.00

Table 3. Log-linear relationship between IQ and 

BPb level at each of six ages.

a

Age (years) β SE p-Value

1 –0.08 1.02 0.934

2 –0.46 1.08 0.670

3 –2.61 1.05 0.013

4 –2.85 1.07 0.008

5 –4.39 0.95 < 0.001

6 –3.49 1.03 < 0.001

aAdjusted for study site, birth weight, HOME score, maternal education, and IQ.

Table 4. Relationship of IQ to ratio of 5- and 6-year 

BPb to 2-year BPb (n = 397).

Ratioa β SE p-Value

6 years:2 years –7.00 1.54 < 0.001

5 years:2 years –4.57 1.07 < 0.001

aAdjusted for log of average childhood BPb, site, HOME 

score, maternal IQ, maternal education level, and birth 

weight.

Table 5. Final model relating IQ to 6-year:2-year 

ratio, adjusted for site, average childhood BPb, 

HOME score, birth weight, maternal IQ, and maternal education level.

Variable β SE p-Value

Ratio –7.00 1.54 < 0.001

Ln(BPb) (childhood average) –3.19 1.23 0.010

Study site 6.50 1.45 < 0.001

HOME score 2.23 0.81 0.007

Birth weight (g) 0.82 0.60 0.170

Maternal IQ 7.29 1.07 < 0.001

Maternal education 0.07 1.02 0.948

(highest grade)

Figure 2. Estimated IQ in combined Cincinnati and 

Rochester cohorts for three patterns of BPb levels 

from 1 through 6 years of age: peak at 2 years (diamonds), peak at 5 years (triangles), and constant 

BPb level (squares). All three scenarios have identical mean BPb level of 10 μg/dL.

18

16

14

12

10

8

6

4

2

0

BPb (μg/dL)

1 2 3

Age (years)

4

6-year:2-year

ratio = 1.0

IQ = 85.5

6-year:2-year

ratio = 1.25

IQ = 83.7

6-year:2-year

ratio = 0.5

IQ = 89.0

5 6
Hornung et al.

1312 volume 117 | number 8 | August 2009 • Environmental Health Perspectives

status (Hollingshead score) (Cirino et al. 

2002), and maternal education. Results were 

similar to those that we found in the IQ analysis (Table 6). The ratios of 6-year and 5-year 

BPb level to the 2-year BPb level were both 

significantly and positively associated with the 

adult arrest rate after controlling for the mean 

childhood average BPb level. These results 

indicate that children with the same average 

lead levels but who had greater lead exposure 

later in childhood were at increased risk of 

adult criminal behavior. Specifically, a oneunit increase in the 6-year:2-year ratio (e.g.,

from 0.5 to 1.5) would be associated with an 

arrest rate 3.35 (e1.21) times greater than the 

arrest rate for subjects with the lower ratio, 

given an equal childhood average BPb. Thus, 

behavioral problems such as criminal activity 

were also more strongly associated with higher 

BPb concentrations at 6 years when examined 

using this new statistical approach.

Discussion

Although the weight of evidence from a 

number of studies conducted during the last 

15 years indicates that adverse effects on cognitive development occur at childhood BPb

levels < 10 μg/dL, the age of greatest susceptibility has not been well defined. Several recent 

analyses have suggested that lead exposures 

at school age may be more strongly related 

to decrements in IQ scores or neuroanatomical deficits (Chen et al. 2005; Lanphear 

et al. 2005; Wasserman et al. 2000). These 

studies encountered problems in separating 

the effects at various ages due to the close 

tracking of BPb concentrations during childhood. Current CDC guidelines for screening 

children focus on 1- and 2-year olds (CDC 

1991), making a better determination of the 

age of greatest susceptibility very important to 

clinical practice. The analyses presented here, 

for example, suggest that screening school-age 

children who are undergoing evaluation for 

cognitive deficits or behavioral problems may 

help to identify underlying reasons for their 

learning or behavioral problems.

We applied a new method that avoids the 

problem of serial correlation in BPb concentrations during childhood. Our method instead 

focused on the pattern of BPb concentrations 

over time by comparing the usual pattern of 

BPb peaking at around 2 years of age with that 

of children whose highest childhood exposure 

occurred at school age, while holding average 

childhood exposure constant. We found that 

the greatest susceptibility to both cognitive and 

behavioral development was at 5–6 years of 

age. These results suggest that several crosssectional analyses showing stronger associations 

between BPb in older children and reductions 

in IQ scores are not simply residual effects 

from higher exposures at 2 years of age.

Our results are also consistent with those of 

Chen et al. (2005), who reported that BPb concentrations at 7 years of age had a stronger association with IQ measured at 7 years compared 

with BPb measured at 2 years. Our approach, 

however, avoided the collinearity problems of 

including BPb measurements at both younger 

and older ages in the same model.

Although the relatively large size of the combined cohorts, availability of serial BPb measurements, and numerous covariates are strengths of 

these analyses, there are also a few limitations. 

Relatively few children in these analyses had 

higher BPb levels at 6 years than at 2 years of 

age (n = 25, 6.3%). The model estimates, therefore, depend somewhat on the upper end of the 

distribution of 6-year:2-year ratios. Although 

relatively few children were in this upper range 

of the ratio, regression diagnostics did not indicate that our results were disproportionately 

dependent on these data. We also compared 

child characteristics among the 25 children with 

ratios > 1 with the children with lower ratios 

and found no significant differences for any of 

the covariates listed in Table 1.

Another potential limitation is that our 

method focuses on temporal patterns in BPb

levels relative to the 2-year BPb concentration. 

We chose the 2-year measurement as our reference because it is typically the highest level 

during childhood and because it has been the 

focus of clinical screening efforts. Serial BPb

level patterns relative to BPb measurements at 

ages other than 2 years may produce different 

results. In support of our method, however, 

we investigated ratios relative to ages 1 and 

3 years and found similar results, although 

ratios using 2-year levels showed the strongest 

relationship to IQ and criminal arrest rates.

In conclusion, the results of this new 

statistical approach strengthen the emerging evidence that lead exposure in schoolage children may be more strongly related 

to cognitive and behavioral development 

than exposures during earlier childhood. This 

finding has important implications regarding 

testing of children for high lead exposure. 

Although it is still very important to reduce 

lead contamination in early childhood, these 

analyses indicate that efforts to reduce lead 

exposure should continue as children progress 

to school age. Perhaps more directly relevant, 

this analysis suggests that BPb testing might 

be an important part of a diagnostic workup 

for school-age children who have cognitive 

delay or behavioral problems, such as attention-deficit disorder and related behavioral 

and learning problems. Finally, we believe 

that this statistical approach may be useful 

for disentangling the age of greatest vulnerability to other serially measured environmental toxicants such as pre- and postnatal 

tobacco smoke.

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Table 6. Relationship of criminal arrest rate in 

young adults to ratio of 5- and 6-year BPb to 2-year 

BPb (n = 250).

Ratioa β SE p-Value

6 years:2 years 1.21 0.36 < 0.001

5 years:2 years 1.29 0.33 < 0.001

aAdjusted for average childhood BPb, maternal IQ, socioeconomic status (mean Hollingshead score), sex, and 

parental education level.