UNIVERSITY OF CINCINNATI

June 23, 2008

Date:___________________

Marie McCabe
I, _________________________________________________________,
hereby submit this work as part of the requirements for the degree of:
Doctorate

in:
Philosophy

It is entitled:
Lead Exposure, Attentional Outcomes, and Socioenvironmental Influences

This work and its defense approved by:

Chair: Peter Chiu, Ph.D.

_______________________________
Paula Shear, Ph.D.
_______________________________
Steven Howe, Ph.D.
_______________________________
Kimberly Yolton, Ph.D.
_______________________________
Bruce Lanphear, M.D., M.P.H.
_______________________________
Lead Exposure, Attentional Outcomes, and Socioenvironmental Influences

A dissertation submitted to the

Division of Research and Advanced Studies

of the University of Cincinnati

in partial fulfillment of the

requirements for the degree of

Doctorate of Philosophy

in the Department of Psychology

of the McMicken College of Arts and Sciences

2008

by

Marie E. McCabe

M.A., University of Cincinnati, 2005

B.A., University of Dayton, 2002

Committee Chair: C.-Y. Peter Chiu, Ph.D.

Committee: Steven Howe, Ph.D.
Bruce Lanphear, M.D., M.P.H.
Paula Shear, Ph.D.
Kimberly Yolton, Ph.D.
 Abstract

Low-level lead exposure remains a public health concern in the United States, especially

among children living in older, impoverished, urban neighborhoods. Associated neurocognitive

effects have been reported in global cognitive functioning (Canfield et al., 2003) and in specific

neuropsychological domains (e.g., Surkan et al., 2007). This project aimed to explore the relation

between concurrent blood lead level (M = 5.41 μg/dL) and attention in a sample of 176 children.

The impact of specific socioenvironmental risk and resiliency variables as well as early (24-

month) blood lead concentration on the concurrent lead-attention relationship at 60-66-months

was explored. Attention outcomes were nine subscales from the Conners’ Parent Rating Scale –

Revised Long Form (CPRS-R:L; Conners, 1997) and three scores from subtests of the Test of

Everyday Attention for Children (TEA-Ch; Manly, Robertson, Anderson, & Nimmo-Smith,

1999). Principal components analysis (PCA) of the outcome variables revealed three

components, externalizing symptoms, selective attention/shifting, and internalizing symptoms.

These three components were the dependent variables in regression models with blood lead and

risk and resiliency variables as predictors. Although each of the three overall models was

significant, concurrent blood lead only emerged as a significant predictor of selective

attention/shifting, and then only when a lead x sex interaction term was included. Consistent with

recent reports (e.g., Ris et al., 2004; Froehlich et al., 2007), the results suggest that with respect

to attention outcomes, boys may be more vulnerable to the effects of lead. That blood lead

concentration was not a significant predictor of externalizing symptoms is somewhat surprising

given existing literature (e.g., Braun et al., 2006; Nigg et al., 2008), though differences in

outcomes, ages, and sample characteristics may explain this discrepancy. Blood lead was not

found to be a significant predictor of internalizing symptoms.

ii
iii
 Acknowledgements

There are several individuals I would like to thank for their support and mentorship with

this project and throughout my graduate school career. First, my advisor, Peter Chiu, for his

mentoring and, in particular, for his support of my interest in environmental toxins and pursuit of

this project, both of which fall well outside of my original interests and areas of research. Also to

Bruce Lanphear, Kim Yolton, and Yingying Xu, and all of the members of the HOME Study for

welcoming me on the study team, demonstrating a highly collaborative, team-based approach to

longitudinal research with young children and families, and providing an invaluable training

experience in countless ways. I am particularly grateful to Dr. Lanphear, the principal

investigator of the study from which the current project was drawn, for his generosity with the

data from that investigation and willingness to support my research and training interests. I am

additionally grateful for the strong support, mentorship, and training I have received from Steve

Howe and Paula Shear over the past several years. Finally, I would like to thank my parents,

sisters, and friends for their unwavering support of and enthusiasm for my education.

iv
 Table of Contents

Abstract ........................................................................................................................................... ii
Acknowledgements ........................................................................................................................ iv
List of Tables ................................................................................................................................. vi
List of Figures ............................................................................................................................... vii
Chapter 1: Introduction ................................................................................................................... 1
Lead Exposure in the United States ............................................................................................ 1
Intelligence as the Outcome Measure of Choice in Lead Research ........................................... 4
A Neuropsychological Profile of Lead Exposure ....................................................................... 8
Mechanisms of Lead Neurotoxicity .......................................................................................... 13
Attention and Lead Exposure ................................................................................................... 14
Risk and Resiliency in Children with Lead Exposure .............................................................. 21
Study Aims and Hypotheses ..................................................................................................... 27
Chapter 2: Method ........................................................................................................................ 29
Experimental Design and Participants ...................................................................................... 29
Measures ................................................................................................................................... 34
Dependent Variables: Attention ............................................................................................ 34
Independent Variables: Blood Lead...................................................................................... 36
Independent Variables: Risk and Resiliency ........................................................................ 37
Chapter 3: Results ......................................................................................................................... 43
Outlier Analysis and Sample Characterization ......................................................................... 43
Data Reduction ......................................................................................................................... 46
Aim 1: Multivariate Multiple Regression ................................................................................. 49
Aim 2: Hierarchical Multiple Regression with 24-month Blood Lead Level .......................... 66
Chapter 4: Discussion ................................................................................................................... 69
Aim 1: Lead and Attention ....................................................................................................... 69
Component 1: Externalizing Symptoms ............................................................................... 70
Component 2: Selective Attention/Shifting .......................................................................... 72
Component 3: Internalizing Symptoms ................................................................................ 75
Aim 2: Early Blood Lead Concentration .................................................................................. 76
Limitations ................................................................................................................................ 76
Conclusions and Implications ................................................................................................... 78
References ..................................................................................................................................... 80

v
 List of Tables

Table Page

1 Characterization of Samples with Complete vs. Incomplete Dependent 31

Variable Data

2 Characterization of Samples with Complete vs. Incomplete Independent 33

Variable Data

3 Sample Descriptive Statistics 44

4 Principal Components Analysis with OBLIMIN Rotation 48

5 Bivariate Correlations Between Independent and Dependent Variables 50

6 Initial Multiple Regression Models 51

7 Independent Variable Correlations 53

8 Stepwise Multiple Regression Models 56

9 Hierarchical Regression Analyses 58

10 Hierarchical Regression Analyses with Interaction Terms 64

11 Sample Descriptive Statistics by Sex 65

12 Standard Hierarchical Regression versus Robust Regression Analyses 62

13 Hierarchical Regression Analyses with 24-month Blood Lead Concentration 67

14 Standard Hierarchical Regression versus Robust Regression Analyses with 68

24-month Blood Lead Concentration

vi
 List of Figures

Figure Page

1 CPRS-R:L Subscale Means and Standard Deviations 45

2 Blood Lead Concentration and Attention by Child’s Sex 62

vii
 Chapter 1: Introduction

Lead Exposure in the United States

Lead exposure in early childhood has consistently been associated with reduced cognitive

performance, behavioral problems, and even delinquency (Needleman, 1979; Nigg, Knottnerus,

Martel, Nikolas, Cavanagh, Karmaus et al., 2008; Dietrich, Ris, Succop, Berger, & Bornschein,

2001; Ris, Dietrich, Succop, Berger, & Bornschein, 2004). Today, because of the federal

regulations banning the use of lead in common materials, levels of lead exposure are much lower

than in the past (Rogan & Ware, 2003). However, even at lower levels, deleterious and

persistent effects of lead exposure have been documented (Canfield, Henderson, Cory-Slechta,

Cox, Jusko, & Lanphear, 2003; Nigg et al., 2008).

The toxicity of lead was initially recognized by the ancient Romans, who observed

symptoms of acute toxicity in miners and more subtle symptoms among members of the upper

class who used lead-based cosmetics, dishes, and seasoning (Lewis, 1985). In the modern era,

lead toxicity was first described in Brisbane, Australia in the late 1800s, and flaking lead based

paint was identified as the source of the toxicity in 1904 (Gibson, 1904 as cited in Markowitz &

Rosner, 2000). For several decades, the detrimental effects of lead were thought to be only acute

in nature. However, in 1943, Randolph Byers, a neurologist, and Catherine Lord, a psychologist,

at Children’s Hospital Boston found that 19 of 20 children who had recovered from lead

encephalopathy had learning or behavioral disorders (Byers & Lord, 1943, as cited in Warren,

2000).

As a result of mounting evidence about the detrimental and persistent effects of lead, the

use of lead as a paint additive was banned in many European nations between 1909 and the late

1920s, and in Cuba in 1934 (Markowitz & Rosner, 2000). In contrast, in the United States, the

1
Consumer Products Safety Commission did not officially ban the use of lead in paint until 1978.

Additionally, although legislation passed in 1973 began phasing lead out of gasoline, the additive

was not officially outlawed until 1996 with the passage of the Clean Air Act. The lead and paint

industries in the United States have been implicated as contributing to the temporal discrepancy

between legislation in Europe and the United States regulating the use of lead as an additive

(e.g., Markowitz & Rosner, 2000; Warren, 2000).

As research has documented the lasting impact of lead at lower and lower blood levels,

the threshold of blood lead concentrations considered concerning by the Centers for Disease

Control and Prevention (CDC) has declined over the years; in the 1960s, levels above 60 μg/dL

were considered unsafe, while in the 1970s, levels in the 30-40 μg/dL range were thought to be

elevated. In the 1990’s, prompted by numerous studies documenting the detrimental effects of

low level lead exposure, both the CDC and the World Health Organization (WHO) issued

statements acknowledging negative effects of blood lead concentrations at or above 10 μg/dL in

children (CDC, 1991; WHO, 1995). The effects of blood lead concentrations above this marker

are widely accepted, while the effects of concentrations below 10 μg/dL are more controversial

and not as universally accepted.

Both in the Untied States and internationally, as legislation restricting the use of lead has

been passed, mean levels of blood lead in the general population have steadily declined (Annest

et al., 1983). While the mean blood lead level in children living in the United States in 1978 was

15 μg/dL, it fell to approximately 2 μg/dL by 1999-2000, and to 1.6 μg/dL by 2003-2004

(Centers for Disease Control, n.d.; Environmental Protection Agency, 2003; Rogan & Ware,

2003). In 2004, approximately 12% of children in North America had blood lead levels between

2
5 and 10 μg/dL, while about 7% of children had blood lead levels greater than 10 μg/dL

(Fewtrell, Pruss-Üstün, Landrigan, & Ayuso-Mateos, 2004).

Currently in the United States, exposure to lead in young children most commonly occurs

through ingestion of dust and soil containing lead. Lead is introduced into these dust and soil

particles from sources such as paint, automobile emissions, and industry. Infants and toddlers are

at particularly high risk for lead exposure because of their frequent hand to mouth behaviors,

which increase their likelihood of ingesting particles of potentially contaminated soil or dust.

Also, children are physiologically more susceptible to the neurotoxic effects of lead; compared to

adults, children absorb more lead, retain more lead in their bodies, and deposit proportionately

more lead in the brain (Agency for Toxic Substances and Disease Registry, 2007; Lidsky &

Schneider, 2003). Neurologically, the developing brain is also more vulnerable than the mature

brain to the effects of lead (Lidsky & Schneider, 2003). Although legislation has significantly

reduced the risk for lead exposure in the United States, inorganic lead remains in today’s

environment as a result of enduring past contamination, the longevity of the compound, and

older homes painted with lead-based paint. Thus, childhood lead exposure continues to be a

major public health concern in the United States.

Internationally, particularly in developing nations with fewer restrictions on the use of

lead, levels of exposure remain alarmingly high. For instance, in many Central and South

American countries, over 50% of children have blood levels greater than 5 μg/dL, with an

estimated 15% with levels greater than 20 μg/dL (Fewtrell et al., 2004). Additionally, in less

developed Asian and East Asian nations, over 2,600,000 disability-adjusted life years, including

both morbidity and mortality, are lost each year due to disability and death related to lead

exposure and toxicity (Fewtrell, Kaufman, & Pruss-Üstün, 2003). In addition to exposure

3
through lead in paint and gasoline, children (and adults) in less developed regions are exposed to

lead through drinking water carried via lead piping, food served in ceramics glazed with a lead-

containing substance, and industrial activity (Fewtrell et al., 2004).

Within the United States, children living in older, impoverished, urban neighborhoods are

at greatest risk for lead exposure (Hubbs-Tait, Nation, Krebs, & Bellinger, 2005). This is due to

at least two factors: (a) dwellings in such areas were likely built prior to 1978 and therefore

contain lead-based paint, and (b) such living spaces are often inadequately cared for and thus

permit exposure (Bellinger, Leviton, Waternaux, Needleman, & Rabinowitz, 1987; Hubbs-Tait

et al., 2005). According to data from 2001-2004, children living below the federal poverty line

have an average blood lead level of 2.3 μg/dL, while the average blood lead level among

children living above this guideline is 1.4 μg/dL (Environmental Protection Agency, 2003).

Racial and ethnic disparities, beyond what can be accounted for by level of income, also exist in

exposure to lead. African-American children, regardless of whether their families’ income is low

or high income, tend to have higher concentrations of lead in blood than their white counterparts

(Environmental Protection Agency, 2003). In summary, despite the dramatic reduction in the

average US childhood blood lead level, low-level lead exposure continues to represent a

substantial public health concern, particularly among low-income, urban, and African-American

children who are most at risk for heightened levels of lead in blood.

Intelligence as the Outcome Measure of Choice in Lead Research

Perhaps the most universal finding across recent studies of lead exposure is an associated

decrement in measured intelligence (IQ). In part, the salience of this finding is due to reliance,

until relatively recently, on measures of global cognitive functioning (i.e., IQ) to assess the

effects of lead (Dietrich, 2000; Lidsky & Schneider, 2006). The use of IQ as an outcome

4
measure across investigations has facilitated the comparison and replication of the effects of lead

exposure across sites and studies, thereby establishing the claim that lead deleteriously affects

cognitive functioning, particularly in the developing child (Cory-Slechta, 2003).

Two meta-analyses of the several major investigations of lead exposure nicely summarize

and confirm the robust effect of lead on IQ (Needleman & Gatsonis, 1990; Schwartz, 1994).

These analyses compile published data from several major international research teams studying

the developmental effects of lead exposure. The conclusion that lead exposure is negatively

associated with global cognitive performance in school-age children, although not statistically

supported by each individual investigation, remains the robust result of these meta-analyses. The

earlier meta-analysis (Needleman & Gatsonis, 1990) reported z-transformed effect sizes ranging

from -0.27 to 0.05 and clearly showed an association between lead exposure and intelligence.

Although estimates vary depending on the study population, Schwartz’s meta-analysis (1994)

concluded that as blood lead level increases from 10 to 20 μg/dL, an average of 2.57 IQ points

are lost.

Although individually or clinically, 2-3 point differences in IQ are not generally

meaningful, at the population level, such decrements are consequential. This is particularly true

given that lead exposure tends to be distributed unequally, with economically and socially

disadvantaged persons disproportionately exposed. Nation and Gleaves (2001) illustrate the

public health implications with an analogy, the effect of a half pound weight loss on morbidity

associated with obesity. At the individual level, half of a pound is unlikely to be significant, but a

half pound loss across a population is likely to result in a reduction of disease processes

associated with obesity.

5
 It is important to note that these meta-analyses utilized investigations in which the mean

lead level was relatively high compared to the average levels in today’s US population. For

instance, in Schwartz’s (1994) analysis, the average blood lead level was 15.19 μg/dL and the

mean levels reported for each individual study ranged from 6.5 to 23 μg/dL. Although these

investigations clearly illustrate the negative association between lead and intelligence, the

relevance to today’s US population may be limited given the reduction in blood lead

concentration.

As the population of children with blood lead indices greater than 10 μg/dL has dwindled

and the effects of such levels of exposure are established, research attention has shifted toward

investigation of children with lower levels of lead exposure (i.e., ≤ 10 μg/dL). There is

increasing evidence to suggest that deleterious effects of lead exposure persist below the 10

μg/dL cutoff indicated by the CDC as the level of concern (e.g., Canfield et al., 2003; Lanphear

et al., 2005). In fact, there is some evidence to suggest that decrements in IQ are more severe at

lower levels of lead exposure (Canfield et al., 2003; Schwartz, 1994).

Schwartz (1994) described an average loss of 2.57 IQ points as blood lead level increases

from 10 to 20 μg/dL. However, when studies were analyzed separately according to blood lead

level, an effect size of 3.23 IQ points was found for studies with average blood lead levels ≤ 15

μg/dL, while the effect size was smaller, 2.32 IQ points, when studies with mean blood lead

levels greater than 15 μg/dL were examined. Canfield et al. (2003) documented an IQ decrement

of 1.37 points per 1 μg/dL in children with lifetime average (through age 5) blood lead

concentrations below 10 μg/dL and a 0.46 IQ point decrement per 1 μg/dL in all sample

children, including those with lifetime averages greater than 10 μg/dL. Further, evidence for a

nonlinear relationship between blood lead level and IQ was supported; data showed a decline of

6
7.4 IQ points for lifetime blood lead concentration up to 10 μg/dL compared to an estimated

decline of 2.5 IQ points among children with lifetime average blood concentrations ranging from

10-30 μg/dL.

A pooled analysis of seven prospective studies of lead exposure initiated prior to 1995

estimated an IQ decrement of 3.9 points associated with an increase in blood lead concentration

from 2.4 to 10 μg/dL and a decrement of 1.9 IQ points associated with blood lead level

increasing from 10 to 20 μg/dL (Lanphear, Hornung, Khoury, Yolton, Baghurst, Bellinger et al.,

2005). Thus, consistent with previous findings, these data suggest both deleterious effects at

levels of lead exposure below 10 μg/dL and a non-linear exposure-outcome relationship such

that the detrimental effects of lead exposure are greater at lower levels.

Schwartz (1994) and others (e.g., Bae, Gennings, Carter, Yang, & Campain, 2001) have

offered a possible explanation for these findings by suggesting a “saturation phenomena” (p 53)

whereby at higher blood lead levels, feedback mechanisms responsible for maintaining

homeostasis intervene. Conversely, such mechanisms may not activate at lower blood lead

levels, presumably because homeostasis is less disrupted. The severity of cognitive effects found

among children with low-level lead exposure has led to the suggestion that there is not a safe

threshold for “the adverse consequences of lead exposure” (Canfield et al., 2003, p 1525),

meaning that the neurocognitive effects of low levels of lead exposure are detectable and

potentially irreversible. These findings have important public policy implications, particularly

given the 2004 estimate that 12% of North American children have blood lead levels between 5

and 10 μg/dL (Fewtrell et al., 2004).

7
 A Neuropsychological Profile of Lead Exposure

The excellent psychometric properties and standardized nature of intelligence tests have

made IQ a simple and clear outcome measure of the consequences of pediatric lead exposure; IQ

has been instrumental in identifying lead as a public health problem (Cory-Slechta, 2003; Lidsky

& Schneider, 2006). Despite the historical utility of intelligence as an outcome measure of lead

exposure, because it is by definition a global measure of cognitive functioning (Sattler, 2001),

comprising various skills, it is less useful in discerning specific abilities and brain regions

susceptible to the neurotoxic effects of lead. Additionally, intelligence testing is often less

sensitive to the effects of brain damage (e.g., Dlugos, Moss, Duhaime, & Brooks-Kayal, 1999;

Lezak, 1995), which, since lead has been associated with brain insult, may render it somewhat

less useful. In contrast, neuropsychological tests targeting specific cognitive abilities are

generally more sensitive to brain injury and are therefore likely to be useful in demonstrating the

specific neurocognitive domains, and potentially brain regions, impacted by exposure to lead.

While investigations of lead-exposed children have begun to explore specific

neuropsychological outcomes associated with exposure, to date “a distinct neurobehavioral

phenotype for early low lead exposure has not emerged” (Ris et al., 2004, p 264). Lidsky and

Schneider (2006) concur, noting that the neurocognitive impact of lead exposure appears to vary

by individual. Although there is likely individual variability, variability in neuropsychological

outcomes can also be accounted for by characteristic differences between samples of children

studied, variety in the measurement of blood lead, and neuropsychological assessment measures

utilized (Lidsky & Schneider, 2003).

Across investigations, differences among samples include, but are not limited to: the age

at which blood lead was measured, the age at which participants are assessed, the intervening

8
span of time between these two points, the average blood lead level, the range of blood lead

levels in a sample, exposure route (e.g., paint, smelter), exposure to other toxins (e.g., mercury,

environmental tobacco smoke, alcohol), and social and economic demographic markers (e.g.,

income, education). Additionally, although increasingly blood lead is the most universal

biomarker in studies of lead exposure, some past investigations utilized dentin lead levels (e.g.,

Needleman, Schell, Bellinger, Leviton, & Allred, 1990), and since the quantitative relationship

between blood and dentin lead levels is not well established (Lidsky & Schneider, 2003), it is

difficult to compare outcomes across samples. Finally, a wide variety of neuropsychological

assessment instruments have been employed, which additionally contributes to difficulties with

cross-sample comparisons. This significant variety across samples makes it difficult to concisely

summarize the neurogcognitive effects of lead exposure to delineate a characteristic cognitive

profile.

Investigations of neurocognitive outcomes have found deficits across a range of

neuropsychological domains, including attention (Bellinger, Hu, Titlebaum, & Needleman, 1994;

Chiodo, Jacobson, & Jacobson, 2004; Ris et al., 2004; Walkowiak, Altmann, Kramer, Sveinsoon,

Turfeld, Weishoff-Houben, et al., 1998; Winneke, Brockhaus, Ewers, Kramer, & Neuf, 1990),

executive function (Bellinger, Hu, Titlebaum, & Needleman, 1994; Canfield, Gendle, & Cory-

Slechta, 2004; Stiles & Bellinger, 1993), fine motor skills (Chiodo, Jacobson, & Jacobson, 2004;

Lidsky & Schneider, 2006; Needleman, Schell, Bellinger, Leviton, & Allred, 1990; Ris, Dietrich,

Succop, Berger, & Bornschein, 2004), visuomotor integration (Chiodo, Jacobson, & Jacobson,

2004; Dietrich, Berger, & Succop, 1993), visuoconstruction (Lanphear, Dietrich, Auinger, &

Cox, 2000; Ris, Dietrich, Succop, Berger, & Bornschein, 2004), processing speed (Chiodo,

Jacobson, & Jacobson, 2004; Needleman, Schell, Bellinger, Leviton, & Allred, 1990;

9
Walkowiak, Altmann, Kramer, Sveinsoon, Turfeld, Weishoff-Houben, et al., 1998; Winneke,

Brockhaus, Ewers, Kramer, & Neuf, 1990), language (Needleman, Schell, Bellinger, Leviton, &

Allred, 1990), balance/proprioception (Bhattacharya, Shukla, Dietrich, & Bornschein, 2006), and

memory (Canfield, Gendle, & Cory-Slechta, 2004; Chiodo, Jacobson, & Jacobson, 2004; Lidsky

& Schneider, 2006). However, due in part to both individual variability and sample

characteristics, a well-defined cognitive profile associated with lead exposure does not exist.

Lidsky and Schneider (2006) suggest that heterogeneity in affected cognitive abilities may be

related to the child’s age at exposure, particularly given that lead targets developing cells and

neuronal systems develop at various times during childhood, as well as genetic factors, which

may predispose or protect children from the neurotoxic effects of lead.

Recently, neuropsychological functioning in children with blood lead levels below 10

μg/dL has been investigated. In 2000, Lanphear, Dietrich, Auinger, and Cox (2000), using data

from the Third National Health and Nutrition Examination Survey (NHANES III), reported

inverse relationships between blood lead concentration and reading ability (Wide Range

Achievement Test), arithmetic skills (Wide Range Achievement Test), visuoconstructional

ability (Wechsler Intelligence Scale for Children-Revised Block Design), and attention/working

memory (Wechsler Intelligence Scale for Children-Revised Digit Span). When only children

with blood lead levels < 5 μg/dL were considered, deficits in reading and arithmetic skills

remained evident, supporting the supposition that a safe threshold for lead exposure does not

exist. Children in this sample fell between the ages of 6 and 16 and had an average concurrent

blood lead level of 1.9 μg/dL (2.1% of sampled children with blood lead concentrations ≥ 10

μg/dL).

10
 Using the same sample as that analyzed in the present study (Rochester sample),

Canfield, Kreher, Cornwell, and Henderson (2003) described executive deficits (Shape School

Task) in 48-54-month-old children with low-level lead exposure (M 48-month blood lead

concentration = 6.49 μg/dL). Deficits were such that children with higher levels of lead exposure

were slower to respond and had more difficulty inhibiting a pre-potent response. Additionally,

blood lead concentration was directly associated with increased difficulty completing tasks,

presumably due to difficulties with comprehension of the instructions, inhibition, and/or set-

shifting. Although children’s IQ was predictive of nearly all dependent variables considered,

only in one case did it significantly reduce the effect of lead, suggesting an association between

lead and executive deficits beyond IQ. In the same sample (Canfield, Gendle, & Cory-Slechta,

2004), lifetime average blood lead concentration (M through age 5-years = 7.2 μg/dL) was

inversely associated with inhibition, spatial memory, selective attention, set-shifting, and

planning in 66-month old children.

Chiodo, Jacobson, and Jacobson (2004) reported neuropsychological deficits in Full

Scale IQ (Wechsler Intelligence Scale for Children-III), reaction time (Magnitude Estimation

Task: Numbers and Color Naming, Mental Rotation Task), visuomotor integration (Beery Test

of Visual-Motor Integration), fine motor skills (pegs dropped on Grooved Pegboard task),

attention (number correct on Continuous Performance Task, Wechsler Intelligence Scale for

Children-III Digit Span and Arithmetic subtests), and executive functioning (number of errors

and conceptual level responses on the Wisconsin Card Sorting Task) associated with lead

exposure in a sample of 237 7.5-year-old children with a mean concurrent blood lead level of 5.4

μg/dL. All children in this sample were African-American and residing in inner-city

neighborhoods; additionally, children were predominantly from lower income homes (69%

11
receiving some form of public assistance). Mothers of children in this sample were originally

recruited as part of a study of the effects of prenatal alcohol use on child development. Although

this study assessed a wide range of neuropsychological abilities to determine their association

with low-level lead exposure, high rates of alcohol use among mothers of children in this sample,

means the relationship between lead exposure and neuropsychological outcomes is confounded

with alcohol exposure.

A recent investigation attempted to discern neuropsychological outcomes of low-level

lead exposure in a sample of 6-10-year-old children, all with concurrent blood lead levels < 10

μg/dL, by comparing children with average blood lead levels of 1-2 μg/dL (reference group) to

those with blood lead concentrations of 3-4 and 5-10 μg/dL (Surkan, Zhang, Trachtenberg,

Daniel, McKinlay, & Bellinger, 2007). In the 5-10 μg/dL group, deficits in academic skills

(Wechsler Individual Achievement Test reading, mathematics, reading and listening

comprehension), visual matching, some aspects of memory (Wide Range Assessment of

Memory and Learning Finger Windows and Memory for Sentences), and executive functioning

(Wisconsin Card Sorting Test perseveration errors and categories achieved) were found relative

to the 1-2 μg/dL group, while differences in working memory/attention (Wechsler Intelligence

Scale for Children-III Digit Span), visual memory (Wide Range Assessment of Memory and

Learning Finger Windows), and fine motor speed (bilateral finger tapping) were found, in the

expected direction, between the 3-4 and 1-2 μg/dL groups. When child’s Full Scale IQ

(Wechsler Intelligence Scale for Children-III) was controlled, associations between blood lead

level and academic skills outcomes remained significant in the 5-10 μg/dL, but not 3-4 μg/dL

group. There was evidence for a negative linear relationship between blood lead and

neurocognitive outcome in this sample.

12
 Although there is disagreement about specific cognitive domains affected by low-level

lead exposure, research clearly suggests that neuropsychological deficits, above and beyond what

can be accounted for by IQ, are associated with lead exposure at levels previously considered

safe. In children with average blood lead levels below 10 μg/dL, inverse associations between

blood lead concentration and academic skills, visuoconstruction, attention, executive

functioning, memory, psychomotor speed, and fine motor skills have been documented. In

addition to the above-noted neuropsychological decrements associated with low-level lead

exposure, these children are also at increased risk for behavioral difficulties (Chen, Cai, Dietrich,

Radcliffe, & Rogan, 2007), juvenile delinquency (Dietrich, Ris, Succop, Berger, & Bornschein,

2001), and Attention-Deficit/Hyperactivity Disorder (ADHD; Nigg et al., 2008).

Mechanisms of Lead Neurotoxicity

Despite well documented deleterious cognitive effects of lead exposure, the specific

mechanisms by which lead exerts its impact are less well defined. In blood, which circulates lead

throughout the body, the half-life of lead is approximately 35 days. From blood, lead is absorbed

by organs and bones, and its half-life in bones is in the range of decades. Lead taken into the

body when a child is young accumulates in bones (and teeth), and is thought to be released over

the course of its half-life, thereby extending the period of exposure beyond the toddler years

when hand-to-mouth behavior, and consequently, lead consumption, tends to peak. Lead is

believed to enter the brain by substituting for calcium ions, which allows it to cross the blood

brain barrier (Lidsky & Schneider, 2003); the half-life of lead in the brain is estimated to be

about two years. Once in the brain, lead has both direct effects on the developing and

differentiating central nervous system (e.g., apoptosis, excitotoxicity, hypo- and de-myelination)

as well as effects on neurochemical systems (e.g., suppressing neurotransmitter activity,

13
impairing neurotransmitter storage and receptors). In particular, lead is believed to affect

glutaminertic transmission, which is critical to neuronal development and plasticity, and the

dopaminergic system, which is involved in motor control, attention, memory, and executive

functioning (Lidsky & Schneider, 2003).

Lead’s impact on the dopaminergic system is of particular interest given that dopamine is

implicated in attention. Dopamine production primarily takes place in the substantia nigra pars

compacta and is distributed from there via three main pathways: the mesostriatal (sometimes

known as the nigrostriatal pathway), the mesolimbic, and the mesocortical. The mesostriatal

pathway projects predominantly to the putamen and caudate, both basal ganglionic structures. As

might be anticipated, mesolimbic pathways project to limbic structures, including the nucleus

accumbens, amygdala, cingulate gyrus, and medial orbital frontal cortex. Finally, mesocortical

projections are widely distributed in the prefrontal cortex.

Attention and Lead Exposure

Generally, attention has figured more prominently than other neuropsychological

domains as an outcome measure of interest in investigations of lead exposure, and it will be the

focus of the present study. There are several lines of evidence to support the importance of

attentional ability in the study of lead exposure. There is evidence that lead impacts

dopaminergic pathways, particularly in the frontal and subcortical brain areas, which are

implicated in attention functions. Attention tends to be a system sensitive to neuronal injuries or

insult (e.g., prematurity, traumatic brain injury). Attention skills are rapidly developing during

infancy and toddlerhood when children are at greatest risk for lead exposure and blood lead

concentrations tend to reach their peak. Attention is a critical skill known to impact other

14
cognitive areas as well as learning potential. Finally, there are many techniques for assessing

attention skills, even in preschool and early school age children.

There are two predominant theories detailing attentional development and delineating

specific components of attention, Posner’s cognitive neuroscience model of attention (e.g.,

Posner & Rothbart, 2007) and Mirsky’s neuropsychological theory of attention (e.g., Mirsky,

1996). Most theories and supporting data posit that the development of attention is highly related

to sensory development and begins very early in life, thereby allowing for the acquisition of

information (Posner & Rothbart, 2007; Luria, 1973). Luria (1973) postulated hierarchical

attentional systems that work collaboratively to monitor the environment for stimuli, select

important stimuli, inhibit the representation of non-target stimuli, and respond appropriately to

target stimuli.

Posner’s attentional theory, which can be viewed as an extension of Luria’s framework,

consists of three specific attentional systems. The first, an alerting system is, evolutionarily

speaking, the rather basic ability to regulate arousal (Posner & Rothbart, 2007). It is purported to

arise in the midbrain regions, namely the locus ceruleus, and to activate frontal and parietal

areas, with the right cerebrum tending to be more involved than the left. The second, an orienting

system, serves to monitor the environment and attend selectively to novel stimuli. Posner has

demonstrated that infants between 2 and 4 months of age show rapid development in their ability

to orient gaze and eye movements as well as attend selectively to novel objects (Posner &

Rothbart, 2007). These skills are believed to be the basis of selective attention, or the ability to

attend selectively to specific stimuli. Somewhat later in life begins the development of what

Posner has termed “executive attention,” which involves the ability to control attentional

resources, resolve conflict (e.g., between competing responses), and, to an extent, self-regulate

15
(Posner & Rothbart, 2007). Between 9 and 18 months, attention is gradually controlled by both

the orienting and executive systems (Ruff & Rothbart, 1996). Executive attention develops most

rapidly between the ages of 2 and 7 and continues to increase in efficiency and independence

(i.e., from external demands) throughout childhood and adolescence (Posner & Rothbart, 2007;

Ruff & Rothbart, 1996). The anterior cingulate, medial frontal cortex, fusiform gyri, and

cerebellar vermis have been shown to activate during tasks of executive attention (Fan,

McCandliss, Fossella, Flombaum, & Posner, 2005).

Mirsky further sub-divides attention into five components or processes, each associated

with functionally distinct brain regions (Mirsky, Anthony, Duncan, Ahearn, & Kellam, 1991;

Mirsky, 1996). The first component is focus/execute, which entails the ability to allocate

attentional resources to a specific task while disregarding distracting stimuli and to make a

response quickly. Lateral regions of the inferior parietal cortices (area of sensory convergence),

the superior temporal cortex, and striatal regions are purported to be central to this component.

The second identified skill is sustain, or vigilance to a task over time, and brainstem areas such

as the reticular activating system as well as the thalamus are primarily involved. Shift, or the

ability to flexibly switch attention, is the third component. Brain regions involved in shifting

include the anterior cingulate and the prefrontal cortex, specifically the dorsolateral prefrontal

region. The capacity to hold and manipulate information over a brief period of time is the fourth

identified component, labeled encode. This skill is thought to be dependent upon the

hippocampus and amygdala. Finally, the fifth component, added more recently to Mirsky’s

model, is stability, the regularity of response patterns over time. Like sustained attention,

stability is suspected to implicate brainstem and thalamic regions.

16
 Although there are differences between Posner and Mirsky’s theories of attention, there is

quite a bit of overlap in terms of the abilities and involved brain regions described. Both clearly

posit that attention is not a singular ability, but rather comprises multiple sub-components, each

of which relies on a network of brain regions. Regarding the development of attention, these

theories suggest that certain components of attention develop earlier than others. More

specifically, Posner’s alerting and orienting systems are believed to be fairly well developed

within the first year of life. Although there are less data to illustrate developmental timeframes

for Mirsky’s framework, given the overlapping abilities (with Posner’s model), one might

speculate that the sustain and focus/execute factors are among the first to develop.

With respect to lead exposed populations, although attention appears to be a

neuropsychological outcome of interest, the findings across investigations are somewhat

inconsistent. Similar to inconsistencies across studies of neuropsychological outcomes associated

with lead exposure, varied findings with respect to attention are the result of several factors,

including sample characteristics, the variety of theoretical frameworks from which investigators

have approached the construct of attention and resulting use of diverse measurement instruments,

and variation in the measurement of blood lead. What follows is a brief review of the recent

literature on the relationship between lead and attention, with a focus on samples with relatively

low blood lead levels.

Bellinger, Hu, Titlebaum, and Needleman (1994) adopted Mirsky’s theoretical

framework (Mirsky 1991), which, at that time, divided attention into four factors: Focus-execute,

sustain, encode, and shift. They found that the lead level in teeth shed during childhood (M =

13.7 mg/g) was related to the focus-execute and shift factors in early adulthood, but not to

sustained attention or encoding. The concurrent blood lead levels in this sample were described

17
as low, with most ≤ 5 μg/dL and only those of 2 participants > 10 μg/dL. In contrast, a second

investigation of attention outcomes in lead-exposed children utilizing Mirsky’s framework did

find a significant relationship between both the sustained attention and encoding factors and lead

exposure, but failed to find a relationship between the focus-execute factor and attention

(Chiodo, Jacobson, & Jacobson, 2004). The consistent finding between these studies is a

negative relationship between shift ability and lead exposure.

Animal models of attention in lead-exposed rats further complicate the picture with

inconsistent findings. For instance, Brockel and Cory-Slechta (1998), like Bellinger, Hu,

Titlebaum, and Needleman (1994), did not find sustained attention deficits in rats exposed to

lead. However, Morgan, Garavan, Smith, Driscoll, Levitsky, and Strupp (2001), similar to

Chiodo et al. (2004), present evidence of poorer sustained attention among lead-exposed, relative

to non-exposed, rats. Further, these two studies also present conflicting evidence with respect to

impulsivity: Brockel and Cory-Slechta (1998) provide evidence to support increased premature

lever-tapping among lead-exposed rats, while Morgan et al. (2001) found no evidence of

increased impulsivity. Given speculation that low-level lead exposure may be an etiology of

ADHD, impulsivity, a primary symptom, is certainly a domain worthy of further exploration.

Some studies examining a range of neuropsychological domains in lead-exposed children

provide evidence for impairments in attention. For instance, neuropsychological assessment of

15-17-year old lead-exposed children from the Cincinnati Lead Study (CLS) suggests a negative

relationship between sustained attention and blood lead level (Ris et al., 2004). Further, this

study found a significant interaction between lead-exposure and sex for attentional outcomes,

such that following inclusion of this interaction term in the model, associations between lead-

exposure and attention were only significant in males. The authors noted the increased incidence

18
of attention-related developmental disorders such as ADHD among males and speculated that

early lead exposure may exacerbate male susceptibility to attention problems. Additionally, both

auditory and visual attention/working memory (i.e., Mirsky’s encode factor) were found to be

reduced in children with 3-4 μg/dL blood lead concentrations (Surkan, et al., 2007).

An early investigation on attention and lead-exposure examined a group of middle

school-age boys with known attentional problems and hypothesized that these children would

have higher than expected levels of lead exposure (Minder, Das-Smaal, Brand, & Orlebeke,

1994). Results showed that level of lead exposure, measured using current hair samples,

predicted both simple reaction time and performance on Trails B, suggesting that lead interferes

with speeded processing as well as attentional flexibility (i.e., shifting). Because of the all male

sample, exploration of sex differences was precluded. Additionally, the use of current hair

samples as the index of lead exposure limits comparisons to other samples as well as the general

population because lead exposure is more frequently assessed by blood lead level.

A few recent investigations have explored the relationship between lead and attention by

directly examining ADHD in populations with lead exposure. Using 1999-2002 NHANES data,

Braun, Kahn, Froehlich, Auinger, and Lanphear (2006) found that both concurrent blood lead

and prenatal tobacco smoke exposure, but not postnatal exposure, were significant predictors of

ADHD, defined as both parent report of diagnosis and stimulant medication use. This group

estimated that children exposed prenatally to tobacco smoke, relative to those who were not,

were 2.5 times more likely to have ADHD. Further, in this sample with quite low blood lead

levels (approximate M = 1.2 μg/dL), increased blood lead concentration was still associated with

increased risk for ADHD. Interestingly, there was no interaction between blood lead

concentration and prenatal tobacco smoke exposure and the risk for ADHD among girls with

19
prenatal tobacco smoke exposure was found to be greater than that for boys, 4.6 versus 2.1 times,

respectively.

Similarly, Nigg et al. (2008), also in a group with low-level exposure (M = 1.03 μg/dL),

found higher blood lead concentrations in a group of children with clinically diagnosed

combined type ADHD versus control and ADHD-inattentive type peers; this effect persisted

after controlling for both IQ and externalizing disorders. However, symptoms of

hyperactivity/impulsivity were found to mediate the relationship between lead and IQ,

reinforcing the importance of exploring neuropsychological outcomes of lead exposure (as

opposed to solely IQ). Further, the relationship between lead exposure and ADHD (combined

type) was fully mediated by indicators of cognitive control, such as inhibition and reaction time

variability. Thus, this group speculated that low-level lead exposure may contribute to ADHD

via disruption of cognitive control processes supported by regions of the striatum and frontal

cortex, which are areas thought to be inervated by mesostriatial and mesocortical dopaminergic

projections.

Findings that a D4 dopamine receptor polymorphism is associated with impaired

executive functioning further support dopaminergic involvement in the relationship between lead

and cognitive outcomes (Froehlich et al., 2007). In the same sample as that used in the current

study, an interaction between lead exposure and DRD4 was reported, such that children lacking

DRD4-7 were more impaired by increasing lead levels on measures of rule-learning and reversal

and spatial working memory span. However, when models were stratified by sex, the lead x

DRD4 interaction for rule learning and reversal was significant for boys, but not for girls. Also

boys, but not girls, showed increasingly impaired planning with increasing blood lead

concentration. This study provides support for suggestions that boys may be more susceptible to

20
the cognitive and behavioral effects of increasing blood lead levels, even when the lead levels are

relatively low (M = 6.1 μg/dL).

There are many reasons to suspect that attention is affected by lead exposure. The

available research suggests that attentional deficits are present among children exposed to lead,

even at low levels. In particular, deficits in executive attention seem to be associated with lead

exposure, and impairments in shifting attention seem to be relatively consistent across

investigations. Increasing understanding of attention deficits related to lead exposure is

particularly important because the rate of attention deficits in the general pediatric population is

quite high and because attention is critical to learning as well as academic and adaptive success.

The present study focused on selective attention and attentional control or shifting, two

components of attention. The investigation examined not only behavioral measures of attention,

but also parent ratings of attention and other ADHD symptoms. These outcomes were explored

in children younger than many of those in previous studies; at the time of behavioral testing, the

children in this study were five-years old. The study examined the potentially moderating

influence of sex on the lead-attention relationship. The predictive utility of blood lead levels

gathered throughout participants’ infancy and childhood for attention outcomes was determined.

Finally, the study examined risk and resiliency factors that may moderate the lead-attention

relationship in an effort to improve understanding of the lead-attention relationship, which is

likely to vary at different levels of several socioenvironmental factors.

Risk and Resiliency in Children with Lead Exposure

The effects of lead exposure have been shown to vary by socioeconomic status (e.g.,

Bellinger, Leviton, Waternaux, Needleman, & Rabinowitz, 1988), maternal education (Stiles &

Bellinger, 1993), child’s sex (Froehlich et al., 2007; Ris et al., 2004), and environmental

21
stimulation (Guilarte, Toscano, McGlothan, & Weaver, 2003; Schneider, Lee, Anderson, Zuck,

& Lidsky, 2001). However, the effects of risk factors, those that endanger outcomes, and

protective factors, those that improve outcomes, have generally not been well explored in the

lead literature. Although there may be several reasons for this, an important one appears to be

core differences in the disciplines from which research on risk and resiliency versus lead

exposure originate.

The risk and resiliency literature is rooted in the fields of psychiatry and psychology,

disciplines that explore differences between groups and individuals. In contrast, research

exploring the neurobehavioral effects of lead exposure is deeply rooted in the fields of public

health and epidemiology, disciplines that describe phenomena at the population-level, often with

the intent to inform public policy. Given this cleavage in theoretical orientations, historically,

there has not been substantial overlap between the fields. That is, lead research has

predominantly focused on describing group and population based effects and has not,

traditionally, explored possible risk and resiliency variables, which may modify the effects of

exposure.

Viewed through a historical lens, the focus on the effects of lead at the population level

has been a phenomenal public health success: over the past several decades, the blood lead

concentration considered safe has declined precipitously, and the use of lead in gasoline and

paint has been eliminated in the United States. Risk and resiliency research also has a rich

history, with exploration of the dynamic processes of resilience in children of schizophrenic and

alcoholic parents being some of the original, and perhaps most significant and stimulating,

contributions from the field (Masten, Best, & Garmezy, 1990; Werner, 1996). Despite the

important contributions to the literature that have been made by each discipline, there has

22
historically been little overlap or collaboration. However, since there is now strong consensus

that lead exposure in childhood represents a real public health concern, and regulations have

been implemented to limit the severity and breadth of the problem, lead researchers have

substantially more freedom to explore variables that may alter the effects of exposure (i.e., risk

and resiliency variables). In many ways, this shift parallels the historical shift from dependence

on IQ as outcome of lead exposure to exploration of specific affected neuropsychological

domains.

Traditionally, research exploring the effects of lead exposure has dealt with potential risk

and resiliency variables by treating them as confounding variables. That is, by including

variables such as socioeconomic status, maternal intelligence, and quality of the home

environment as predictor variables in the modeling of neurobehavioral outcomes. However, as

Bellinger (2000, 2004) has pointed out, modeling a variable’s main effect does not allow for an

understanding of the potentially moderating effect of such a variable. Since identifying risk and

resiliency variables has not historically been the goal of research on the effects of lead exposure,

potential modifiers have generally been treated as covariates.

Despite the tendency not to explore potential risk and resiliency variables, lead

researchers have long recognized that neither exposure nor its deleterious effects are evenly

distributed within the population. As such, an impressive number of variables have been

included in models predicting the neurobehavioral effects of lead exposure. Generally, these

variables can be classified as related to either the child or mother/family. The specific variables

included as covariates vary across study samples and publications. However, child variables

often include, but certainly are not limited to, sex, age, race, perinatal complications, birth

weight, NICU admission, nutritional information (e.g., serum iron level), and exposure to other

23
toxins (e.g., tobacco smoke, alcohol, drugs). Maternal and family-related variables may include

parental intelligence, maternal depression, household income, receipt of public assistance, parent

education and occupation, caregiver marital status, and quality of the home environment. In

modeling the effects of lead on neurobehavioral outcomes, investigations tend to include

somewhere between two and nine covariates and often use the strength of the bivariate covariate-

outcome correlation to determine which variables to include as covariates in a model. Thus,

many more covariates are typically considered than are included in the final models, and the

choice of covariates tends to be empirically, rather than theoretically, driven.

Discerning the relative importance of specific covariates or risk and resiliency variables

is difficult because it varies substantially across samples. That is, whether a variable is included

in a model most often depends on the strength of its association with the outcome measures, and

this, in many cases, depends on characteristics of the sample. It also depends upon the variability

in the sample on the covariate of interest (e.g., Bellinger, 2000). For instance, using

socioeconomic status (SES) as an example, if a sample is relatively homogeneous for household

income or parent education level, these variables may not enter a regression model simply

because their correlation with the outcome of interest is low due to restricted range in the

covariate. Many samples are, intentionally or not, recruited from populations relatively

homogenous for certain characteristics. Thus, covariate variability is limited and potential risk

and resiliency variables may not enter a model. However, in a more representative sample,

variability in SES may be increased and the association between SES and the neurobehavioral

outcome may then be significant. The result is that covariates can vary dramatically across

studies due to sample differences, making it difficult to discern which variables are generally

important to the exposure-outcome relationship.

24
 Bellinger has highlighted the importance of effect modification, and its distinction from

confounding variables, in the relationship between lead and neurocognitive outcome. He notes

that failure to explore potential moderator variables can result in an error of inference, which

biases results either toward or away from the null hypothesis that lead exposure is unrelated to

outcome (Bellinger, 2000). For instance, if SES is related to both outcome and exposure, and

because of the strength of its association with the outcome is modeled as a covariate, the

variance accounted for by lead exposure may be reduced because the covariate (i.e., SES) is on

the causal pathway from lead exposure to cognitive outcome, but is being held constant.

Although only a few studies have explored covariates from the moderation or risk and

resiliency framework, SES and child’s sex are two variables that have been examined. Findings

suggest that relative to children from low-SES backgrounds, more advantaged children suffer

fewer deleterious neurocognitive effects at lower (e.g., 0-7 μg/dL) levels of exposure, although

the groups endure similar harmful effects at higher levels (e.g., ≥ 10 μg/dL) of lead exposure

(Bellinger, Leviton, Waternaux, Needleman, & Rabinowitz, 1988; Bellinger, 2000). Further

evidence for the import of socioeconomic factors comes from a study of lead-exposed children

from relatively financially advantaged and developmentally stimulating families (Stiles &

Bellinger, 1993). At age 10, these children displayed markedly fewer cognitive deficits than

many of their lead-exposed counterparts from comparatively disadvantaged backgrounds.

Some early work suggested that maternal education may moderate the lead exposure-IQ

relationship (Dudek & Merecz, 1997). Findings showed that across levels of lead exposure

ranging from 5-20 μg/dL, children of less educated mothers (i.e., no university level education)

had lower measured WISC-R Full Scale IQs, on the order of approximately 10 IQ points across

blood lead concentrations in this range. Sex has been purported to be a potential effect modifier

25
and, as discussed above, two recent studies have provided support for this supposition (Froehlich

et al., 2007; Ris et al., 2004). In addition to the role of sex as a two-way moderator, Bellinger

(2000) suggests the possibility that it may be involved in a three-way interaction, such that

exposure outcomes are modified by sex, but only within a group containing a certain genetic

polymorphism, for example, or with a certain socioeconomic level. Froehlich and colleagues’

(2007) recent work provides support for this notion.

Animal models, since they allow for random assignment, have allowed for exploration of

moderator effects and increased understanding of the potential effects of risk and resiliency

variables. Perhaps one of the most notable findings to emerge from the animal literature on lead

exposure is that rearing in an enriched environment has a buffering effect on the exposure-

outcome relationship. That is, rat pups who spend their youth in a stimulating environment (i.e.,

with toys and litter mates) sustain fewer deleterious effects of lead than their isolated and

unstimulated peers exposed to the same level of lead (Guilarte, Toscano, McGlothan, & Weaver,

2003; Schneider, Lee, Anderson, Zuck, & Lidsky, 2001). Animal models allow for strict

experimental control of additional factors that in humans may vary with modifiers of interest

(e.g., maternal warmth, genetic variety) and therefore provide a unique opportunity to truly

examine the effects of certain risk and resiliency variables.

Exploring the potentially modifying effects of variables historically considered covariates

and therefore partialed out of the exposure-outcome model is important for several reasons. First,

as discussed, failure to consider moderating effects can result in bias, in either direction, in the

estimated relationship between exposure and outcome. For instance, previously non-significant

exposure-outcome relationships may become significant when the effects of a moderator variable

are considered, as was the case when SES was considered in the exposure-IQ relationship

26
(Bellinger, 2000). Second, since it is now relatively well accepted that lead is a public health

concern, delineating differences in vulnerability to its effects has important implications for

prevention and remediation. For instance, since the effects of lead are not equally distributed

across SES classes, prevention and screening efforts might target high risk groups. Finally,

exploring the modifying effects of risk and resiliency variables is likely to explain

inconsistencies in reported effects of childhood lead exposure.

Study Aims and Hypotheses

The present study will examine the relationship between lead and attention outcomes,

including both parent-report and behavioral test data, as well as the potentially moderating

impact of specific risk and resiliency variables. The data utilized in this investigation are part of

a larger longitudinal study of the neurobehavioral effects of low-level lead exposure. The first

aim of this investigation is to explore the relationship between lead and attention outcomes at 60

to 66 months of age, as well as the contributions of specific risk and resiliency variables to this

relationship. Attention outcomes consist of subscales from the Conners’ Parent Rating Scale –

Revised Long Form (CPRS-R:L; Conners, 1997) and subtests from the Test of Everyday

Attention for Children (TEA-Ch; Manly, Robertson, Anderson, & Nimmo-Smith, 1999).

Covariates of interest include characteristics related to the child (sex, prenatal exposure to

tobacco smoke, postnatal environmental tobacco smoke exposure), mother (caregiver education,

maternal race, maternal IQ), and the family (household income, quality of the home

environment, average number of moves, and family routine). It is hypothesized that greater

caregiver education, maternal IQ, household income, environmental enrichment, and family

routine/structure will protect children from the effects of lead, whereas male sex, increased

27
prenatal tobacco smoke exposure, increased postnatal environmental tobacco smoke (ETS)

exposure, and greater number of moves will increase risk.

The second aim is to examine the contribution of blood lead concentration in early

childhood to the later relationship between lead and attention at 60-66 months of age. Blood lead

concentration measured at 24 months will be added to the final model resulting from Aim 1.

There are public health implications (i.e., treatment, prevention) if early blood lead concentration

has an effect on later outcome above and beyond the concurrent blood lead concentration. It is

hypothesized that early lead exposure may account for variance in attention at 60-months beyond

that accounted for by concurrent blood lead concentration.

28
 Chapter 2: Method

Experimental Design and Participants

The study sample originally consisted of 279 children enrolled at 6 months of age in an

investigation of the efficacy of dust control in reducing lead exposure among infants and

toddlers. Participants were recruited between 1994 and 1995 using sequential live birth lists from

five urban hospitals in Rochester, New York. Study staff contacted potential participants via

telephone until the family was reached or at least six phone calls had been attempted. Once a

family was determined to be eligible and indicated interest in participating, a study team visited

their home, obtained informed consent, conducted an initial interview, and collected biological

and environmental samples. Inclusion criteria were: residence in the city of Rochester, NY; no

family plans to move in the upcoming 3 months; and having a target child between five and

seven months of age at the baseline visit.

Study staff visited family homes when participants were 6, 12, 18, 24, and 72 months of

age. At these visits, an interview with the target child’s primary caregiver was conducted and

blood samples were collected from the child for blood lead analyses. Beginning at 30 months,

families had clinic visits every six months until children reached 72 months of age; a final clinic

visit took place at 84 months of age. Interviews and/or cognitive assessments were conducted at

each of these clinic visits. Additionally, blood lead was collected annually at the 36, 48, 60, and

84-months clinic visits. This investigation was initially approved by the University of Rochester

School of Medicine Institutional Review Board (IRB); informed consent was obtained from the

legal guardians of all participants. Upon submission to the University of Cincinnati IRB, the

present project was determined not to meet the regulatory criteria for human subject research

29
because the original study is now closed and all available information is completely deidentified;

therefore, the present project is not subject to IRB review.

The original study was designed to measure the effectiveness of preventing childhood

lead exposure through a home dust control program. Families in the intervention group had

regular home visits by study dust control advisors, provision of cleaning equipment and supplies,

and education about dust control. Families in the control group received no lead exposure

education or intervention. Results of that study indicated that the dust control program did not

significantly reduce blood lead levels and, thus, that the intervention was not effective (Lanphear

et al., 1999). Therefore, in later investigations utilizing this sample, including the present

investigation, participants from both the intervention and control groups are combined.

The original sample of children included 279 total participants. For the purposes of the

present investigation, three (1%) participants were excluded due to diagnoses of Down syndrome

(N = 2) and significant speech/hearing impairment (N = 1). Because the present study focuses on

attentional data collected at the 60-month visit, 100 (36%) participants who were missing

attentional data at this time point were also excluded from further analyses. Potential differences

between participants with and without attention dependent variables of interest at 60-66 months

were examined (Table 1). For the most part, effect sizes across variables were small, suggesting

that differences between the groups are small and unlikely to impact later results. However,

effect sizes were moderate for three variables, indicating that a greater proportion of children

with missing dependent variable data had exposure to tobacco smoke, both prenatally and

postnatally, were male, and identified as non-Black. Given these differences, which were

moderate, but not statistically significant, results of later analyses may not be as generalizable to

individuals with these characteristics.

30
Table 1
Characterization of Samples with Complete vs. Incomplete Dependent Variable Data
Complete data Incomplete data Group Comparisons
Variables N M or % SD N M or % SD t or χ2 p d or OR f
Continuous
Birthweight (g) 176 3233.93 471.80 96 3169.76 616.54 0.89 0.38 0.12
12 month blood lead (μg/dL) 166 6.93 4.78 85 7.08 4.64 -0.24 0.81 0.03
12 month serrum ferritin (ng/dL) 154 30.22 22.11 76 28.61 19.56 0.54 0.59 0.08
HOME inventory (total) 169 27.52 7.19 69 27.22 5.72 0.34 0.73 0.04
Maternal IQa 166 82.01 13.20 51 79.96 10.61 1.01 0.31 0.16
Number of moves (in the past 6 mos)b 151 0.43 0.84 42 0.45 0.83 -0.15 0.88 0.02
Family routinec 152 0.62 0.12 43 0.61 0.13 0.38 0.70 0.08
Discrete

31
Male (%) 176 46.59 52.08 96 0.75 0.39 0.80
Exposed to prenatal tobacco smoke (%) 175 24.57 27.84 97 0.35 0.56 1.18
Exposed to postnatal ETS (%)d 176 71.02 76.29 97 0.88 0.35 1.31
Maternal race (% Black) 176 57.39 52.08 96 0.71 0.40 0.81
Household income (%)e 175 94 3.20 0.20 0.11g
< $15,500/year 68.57 75.53
$15,500-$20,500/year 17.71 9.57
> $20,500/year 13.71 14.89
Caregiver education (%)e 176 96 0.03 0.85 1.06
0-12 years 80.11 79.17
> 12 years 19.89 20.83
a
As measured by the the Stanford-Binet IV quick screen battery. bAt 30 months of age. cExtent of family routine (e.g., bedtime, dinnertime) and structure at 30
months of age. dHousehold exposure between 6 and 24-months of age. eAt 24-months of age. fEffect size: Cohen's d or odds ratio. gCramer's V.
 Of the 176 participants with complete dependent variable data, an additional 25 (14%)

were missing independent variable values, including blood lead (N = 3), prenatal tobacco smoke

exposure (N = 1), caregiver education (N = 2), HOME Total score (N = 7), family moves (N =

11), family routine (N = 2), and maternal IQ (N = 10). No participants were missing data for the

following variables: sex, postnatal ETS exposure, income, and maternal race. Thus, 151

participants had complete data for the purposes of this investigation. However, the total number

of participants varied between models since the inclusion of predictor variables was dependent

upon the correlation between predictor and independent variables. Hence, if a correlation was too

low to warrant inclusion of the independent variable in a model, those participants missing data

on that independent variable were not excluded. The total number of participants included will

be reported for each analysis. Of those participants with complete dependent variable data (N =

176), differences between those with (N = 151) and without (N = 25) complete predictor variable

data were examined. Potential differences between these groups were explored using the same

variables as those utilized in assessing for differences between participants with and without

complete dependent variable data (Table 2). Small to moderate effect sizes suggest that

participants with incomplete independent variable data had higher 12-month blood lead

concentrations, lower scores on the HOME Inventory, more moves, were more likely to be

female, more likely to be exposed to prenatal tobacco smoke exposure, and more likely to

identify as Black. A fairly large effect size for postnatal ETS exposure suggested that

participants with incomplete data were more likely to be exposed to postnatal ETS. Given these

differences, results of later analyses may not generalize as well to individuals with these

characteristics.

32
Table 2
Characterization of Samples with Complete vs. Incomplete Independent Variable Data
Complete data Incomplete data Group Comparisons
Variables N M or % SD N M or % SD t or χ2 p d or OR f
Continuous
Birthweight (g) 151 3239.39 478.92 25 3200.92 433.85 0.38 0.71 0.08
12 month blood lead (μg/dL) 142 6.73 4.72 24 8.08 5.07 -1.28 0.20 0.28
12 month serrum ferritin (ng/dL) 131 30.38 21.36 23 29.30 26.53 0.21 0.83 0.05
HOME inventory (total) 151 27.82 7.21 18 25.00 6.71 1.58 0.12 0.39
Maternal IQa 151 82.03 13.11 15 81.73 14.61 0.08 0.93 0.02
Number of moves (in the past 6 mos)b 133 0.39 0.81 18 0.72 1.07 -1.57 0.12 0.39
Family routinec 137 0.62 0.12 15 0.60 0.12 0.61 0.54 0.17
Discrete

33
Male (%) 151 48.34 36.00 25 1.31 0.25 1.66
Exposed to prenatal tobacco smoke (%) 151 23.18 33.33 24 1.15 0.28 1.66
Exposed to postnatal ETS (%)d 151 68.87 84.00 25 2.38 0.12 2.37
Maternal race (% Black) 151 56.29 64.00 25 0.52 0.47 1.38
Household income (%)e 150 25 0.70 0.71 0.06g
< $15,500/year 68.00 72.00
$15,500-$20,500/year 18.67 12.00
> $20,500/year 13.33 16.00
Caregiver education (%)e 151 25 0.28 0.60 0.73
0-12 years 79.47 84.00
> 12 years 20.53 16.00
a
As measured by the the Stanford-Binet IV quick screen battery. bAt 30 months of age. cExtent of family routine (e.g., bedtime, dinnertime) and structure at 30 months of
age. dHousehold exposure between 6 and 24-months of age. eAt 24-months of age. fEffect size: Cohen's d or odds ratio. gCramer's V.
 Measures

Dependent Variables: Attention

Attention was the outcome of interest in the present study. Two instruments, each

containing several subscales, were used to assess attention in this sample: the Conners’ Parent

Rating Scale – Revised Long Form (CPRS-R:L; Conners, 1997), administered at 60-months of

age, and the Test of Everyday Attention for Children (TEA-Ch; Manly, Robertson, Anderson, &

Nimmo-Smith, 1999), administered at 66-months.

The CPRS-R:L is a standardized parent rating scale designed to assess attention and

symptoms of AD/HD as well as more general behavioral and emotional functioning. It is an 80-

item questionnaire on which parents are asked to rate a number of common problems that

children have using a four-point likert scale, with (0) not true at all/never/seldom, (1) just a little

true/occasionally, (2) pretty much true/often/quite a bit, and (3) very much true/very often/very

frequent. Parents are instructed to ask themselves, “How much of a problem has this been in the

last month?” and answer accordingly.

Advantages of the CPRS-R:L include the large and geographically diverse normative

sample (N = 2,482), its use of diagnostically relevant subscales, and its assessment of a broad

range of behavioral and emotional functioning. The CPRS-R:L contains scales designed to assess

whether or not a child meets DSM-IV criteria for any of the three AD/HD subtypes (DSM-IV:

Inattentive, DSM-IV: Hyperactive/Impulsive, DSM-IV: Total). However, in addition to

assessing externalizing behaviors, such as oppositionality, inattention, hyperactivity, and

impulsivity, the CPRS-R:L assesses internalizing problems such as anxiety, perfectionism,

psychosomatic symptoms, and social problems. The T scores from nine scales (Oppositional,

Cognitive Problems/Inattention, Hyperactivity, ADHD Index, Anxious-Shy, Perfectionism,

34
Social Problems, and Conners’ Global Index) from the CPRS-R:L were used for the purposes of

this analysis.

The TEA-Ch is a behavioral test of attention that is administered directly to the child.

Two subtests from the TEA-Ch were administered by trained examiners and used for the

purposes of this investigation: Opposite World and Map Mission. The Opposite World subtest

consists of a Same World task, which requires the child to follow a path containing the numbers

one and two and vocalize the numbers in order, and an Opposite World task that requires the

child to again follow a path containing the numbers one and two with their eyes, but to vocalize

the opposite number (e.g., if a one is viewed, vocalize “two”). The resulting score for the Same

World task is the total time required for the child to make his or her way through two separate

Same World paths. Similarly, the resulting score for the Opposite World task is the total time

required for the child to make his or her way through two separate Opposite World paths. Raw

scores were used for the purposes of the present analyses. This subtest is one of two that

comprise the TEA-Ch’s attentional control/switching factor and the skills needed to complete

this subtest are executive in nature, namely response regulation or inhibition (of the prepotent

response).

The Map Mission subtest provides the child with 60 seconds to view a 12 in (30.48 cm) x

16 in (40.64 cm) road map and circle as many of a specified target symbol (e.g., gas pump

symbol used to represent gas station locations) as possible. The resulting score for this task is the

total number of targets correctly identified within the time limit. Raw scores were used for the

purposes of the present analyses. This subtest is one of two that comprise the TEA-Ch’s selective

attention factor. This test assesses the child’s efficiency in filtering information to accommodate

the detection of relevant and rejection of distracting information. In the present study, these two

35
subtests, Opposite World and Map Mission, were utilized to assess attentional control/shifting

and selective attention, respectively.

The TEA-Ch was standardized using a group of 293 Australian school children ranging

from 6-15 years of age. Test-retest reliabilities across 6-15 days for Opposite World and Map

Mission are 0.85 and 0.65, respectively. Evidence for validity comes from subtests’ associations

with other measures of attention and dissociations with conceptually disparate domains of

cognitive functioning, such as intelligence. Correlations between the Opposite World subtest and

the Stoop task, Trails A, and number of errors on the Matching Familiar Figures Test are 0.24,

0.26, and 0.25, respectively, all significant when p is at least < 0.05. In contrast, Opposite World

is not significantly correlated with Full Scale IQ (FSIQ), Vocabulary, Similarities, Block Design,

or Object Assembly from the Wechsler Intelligence Scale for Children-III (WISC-III; Manly,

Robertson, Anderson, & Nimmo-Smith, 1999). Correlations between the Map Mission subtest

and the Stoop task, Trails A, and Trails B are 0.31, 0.37, and 0.31, respectively, all significant

when p is at least < 0.01. Map Mission is correlated with FSIQ as well as specific WISC-III

subtests, including Block Design and Object Assembly, that tax skills such as motor speed and

visuo-spatial ability that are also invoked by Map Mission (Manly, Robertson, Anderson, &

Nimmo-Smith, 1999).

Independent Variables: Blood Lead

Blood lead concentration at 60-months of age was the primary independent variable.

Venous blood samples were analyzed for lead by electrothermal atomization atomic absorption

spectrometry (New York State Department of Health, Wadsworth Laboratories, Albany, NY).

All lead values are the mean of six analyses of each blood sample (3 aliquots/day analyzed on

two consecutive days). The lower limit for detection was 1 μg/dL.

36
 Ten participants were missing 60-month blood lead data. Seven of these ten were missing

no more than two of the seven total blood lead data points (i.e., 6, 12, 18, 24, 36, 48, and 60-

months). Of these seven participants, four were missing only 60-month blood lead data (14.29%

missing data) and three were missing two total blood lead data points (i.e., 60 month plus one

other time point; 28.57% missing data). Of the three participants missing two blood lead data

points, one was missing data from 36 and 60 months and two were missing data from 48 and 60

months. In order to retain these seven participants in subsequent analyses, 60-month blood lead

concentration was predicted from all available blood lead data for each participant. Predicted 60-

month blood lead concentration was utilized in all analyses for these seven participants missing

actual 60-month blood lead data. The remaining three participants missing 60 month blood lead

data were also missing blood lead data from three of the seven total time points (two participants

missing 36, 48, and 60 month data and one participant missing 18, 48, and 60 month data).

Because this rendered approximately 43% of their blood lead data missing, they were excluded

from further analyses.

Independent Variables: Risk and Resiliency

Over the course of this study, extensive information about each child’s health, parent and

family characteristics, and quality of the home environment was gathered. For the purposes of

this investigation, eleven covariates were initially examined, including sex, prenatal tobacco

smoke exposure, postnatal ETS exposure, caregiver education, maternal race, maternal IQ,

household income, HOME total score, average number of moves, and family routine. These

covariates were chosen based on both theoretical interest and support from previous research.

Details about these variables are provided below.

37
 Prenatal tobacco smoke. Prenatal exposure to tobacco smoke was assessed

retrospectively when the child was 6-months of age. The head of household (most often the

biological mother) was asked whether or not the target child’s mother smoked while she was

pregnant. No information about quantity or type of smoking was collected until participants were

24-months of age, at which point the head of household was asked how many cigarettes per day

the child’s mother smoked while pregnant. These data were not used in the present analyses due

to concern about accurate recall as well as limited variability. The final unit of analysis was

dichotomous, representing exposure or non-exposure to tobacco smoke prenatally.

Postnatal environmental tobacco smoke. Postnatal ETS exposure was calculated using

data from across the lifespan. At 6, 12, 18, and 24 months of age, respondents were asked

whether or not anyone in the household smoked cigarettes; answers were binary. In contrast, at

30, 36, 42, 48, and 60 months of age, respondents were asked to identify the number of smokers

in the home over the past six months and to provide information about the amount and type of

smoke that the target child was exposed to each week. Due to limited variability, smoking

behavior at each time point between 30 and 60 months was dichotomized into ETS-exposed and

non-ETS-exposed groups. Examination of the table of bivariate correlations between

dichotomized postnatal ETS exposure at each 6-month interval between 6 and 60 months

revealed strong consistently associations; correlations ranged from 0.36 to 0.78 and all were

significant at p < 0.0001, suggesting that it would be appropriate to combine dichotomized

postnatal ETS exposure over time. A proportion representing ETS exposure was created for each

participant by summing the binary data points across time and dividing by the total number of

non-missing data points. This proportion of exposure to ETS was used in all subsequent

analyses.

38
 Household income. Monthly household income at 54- and 60-months was averaged to

yield a measure of household income. In addition to earned income, the following additional

sources of income were included in total monthly household income: Women, Infants, and

Children (WIC) assistance, unemployment, disability, Aid to Families with Dependent Children

(AFDC)/Temporary Assistance for Needy Families (TANF), food stamps, public housing

subsidies, child support, and other government assistance. This figure represented the final unit

of analysis for household income. Entwisle and Astone (1994) suggested that adjusting

household income to include sources of income such as these may more accurately reflect the

financial capital of a family. Seventy-two percent of participants reported having received

income from at least one of these additional sources at either 54 or 60 months. The Pearson

correlation between reported income at 54 and 60 months was strong (r = 0.73), suggesting that

averaging income over time was appropriate.

Parent education. The level of parent education was measured by averaging the

questionnaire respondent’s highest grade level completed across 54- and 60-months of age; this

figure was utilized as the final unit of analysis. In 87% of the cases, the respondent was the

biological mother of the child, while in approximately 5% of the cases the respondent was the

child’s biological father, and in the remaining cases, the respondent was a grandparent or other

guardian. Again, the Pearson correlation between reported education at 54 and 60 months was

high (r = 0.86), suggesting that averaging these values was appropriate.

Quality of the home environment. The HOME Inventory (Caldwell & Bradley, 1984)

was used to assess the quality of the home environment. In this investigation, the Infant/Toddler

version of the HOME Inventory was administered by trained staff when children were 24-

months-old. The measure consists of 45 items clustered into six subscales: (a) Parental

39
Responsivity, (b) Acceptance of Child, (c) Organization of the Environment, (d) Learning

Materials, (e) Parental Involvement, and (f) Variety in Experience. This measure is administered

in the home while the target child is awake and caregiver-child interactions can be observed.

Approximately 2/3 of the items are typically observational in nature, such that the administrator

is able to complete these items by observing the child, the environment, and the patterns of

interaction between the child and his/her primary caregiver. The remaining 1/3 of items are

assessed in an open-ended interview format. Individual items are scored in a binary fashion

according to whether or not the item is observed or endorsed. For the purposes of the present

investigation, appropriately trained study staff administered the HOME Inventory according to

these standard procedures. The HOME total score, which is the sum of the six subscales, was

used in the present analyses.

The HOME Inventory is intended to assess quality of the home environment in a more

detailed and holistic manner than economically based indicators, such as parental income or

occupation (Caldwell & Bradley, 1984, p 27). The inventory was originally developed in the

1960s when research was beginning to show that although children’s measured intelligence was

associated with family SES, factors such as income, education, and occupation alone left a

significant percentage of between-group variance unaccounted for (Caldwell & Bradley, 1984).

Additionally, substantial within SES-stratified group differences in cognitive outcome were

beginning to be observed, leading researchers to further question factors associated with such

outcomes. The reliability and validity of the Inventory have been established by examining the

relationship of the Total and subscale scores with family income as well as child cognitive

outcome measures. HOME Inventory Total Scores have been shown to be significantly

associated with all of the following factors: caregiver education, maternal occupation, paternal

40
presence, paternal education, paternal occupation, and crowing ratio (Caldwell & Bradley, 1984,

p 29). Additionally, the HOME Inventory total and subscale scores have been shown to be

significantly associated with and predictive of measured intelligence and language functioning at

a variety of ages (Caldwell & Bradley, 1984, p 32-34). Several analyses suggest that the HOME

Inventory is a better predictor of IQ than traditional measures of SES such as income and

occupation (Caldwell & Bradley, 1984, p 50-51). Finally, the HOME Inventory has been used

frequently in environmental toxin research and shown to be a significant covariate in the

relationship between toxin exposure and neurocognitive outcomes (e.g., Canfield et al., 2003).

Seven participants were missing the total score from the HOME Inventory and were excluded

from later analyses.

Family moves. The number of times a family moved was assessed by questionnaire at

30, 36, 42, 48, 54, 60 and 66 months of age. Respondents were asked to indicate the total number

of moves the family had made in the past six months. For each participant, the total number of

moves occurring between 30 and 66 months of age was summed; this variable was used in all

analyses. A total of 49 participants were missing at least one of the seven move data points.

Participants missing more than two of the seven data points (i.e., greater than 30% of the data)

were excluded from further analyses. Using this criterion, a total of eleven participants were

excluded. Of these, one participant was missing six data points, one was missing five data points,

two were missing four data points, and seven were missing three data points. There were four

participants that were missing two data points and 34 participants missing one data point; these

participants were included in further analyses.

Family routine. Family Routine was assessed by questionnaire at 30, 42, 48, and 54

months of age. At each time point, respondents were asked questions related to bed and mealtime

41
routines to assess structure and consistency in the household environment. Bedtime routine

questions included: (a) Did [CHILD] go to bed about the same time every night? (yes/no), and

(b) Description of [CHILD’S] bedtime routine (falls asleep in a place besides bed/gets himself

into bed/an adult goes through a routine to get child ready/settled for bed). Mealtime routine

questions (and responses) included: (a) Did [CHILD] eat breakfast at the same time every day?

(yes/no), (b) Did [CHILD] eat dinner at the same time every day? (yes/no), (c) Number of days

child eats with an adult (range), (d) Number of days family eats together (range). All responses

were coded such that higher values indicate greater routine. A single variable was created that

averaged information across both time and routine type. This variable was used in all subsequent

analyses. Two participants were missing data for this variable and were therefore excluded from

further analyses.

Maternal race. Maternal race was determined by self-report when the child was 6-

months-old. Fifty-seven percent of mothers in this sample identified themselves as Black (N =

101), 28% identified as White (N = 49), 12% identified as Hispanic (N = 21), 1% identified as

Asian (N = 2), 0.5% identified as Native American (N = 1), and 1% (N = 2) identified themselves

as other, or belonging to a group that was not specified by these choices. For the purposes of

these analyses, maternal race was dichotomized into a group that self-identified as Black (N =

49, 28%) and second group composed of all others (N = 127, 72%), including those who self-

identified as White, Asian, Hispanic, Native American, and other.

Maternal intelligence. Maternal IQ was assessed using the four-test, quick screening

battery from the Stanford Binet Intelligence Scale-IV, which was administered to mothers when

children were 36-months-old. This short form consists of the Vocabulary, Bead Memory,

42
Quantitative, and Pattern Analysis subtests and provides an estimate of global cognitive level

(Thorndike, Hagen, & Sattler, 1986), which was used in all analyses.

Chapter 3: Results

Outlier Analysis and Sample Characterization

All variable distributions were examined for the presence of outliers and for normality.

Variables were examined both graphically and by inspection of descriptive statistics (see Table

3). Of the independent variables, all were judged to be normally distributed except 60-month

blood lead and monthly household income. A log transformation was applied to 60-month blood,

which produced a normally distributed variable, and a square root transformation was applied to

monthly household income, which produced a distribution much closer to normal distribution. Of

the dependent variables, all were judged approximately normal except for the Social Problems

scale from the CPRS-R:L and the Same and Opposite World Subtest Scores from the TEA-Ch.

Log transformations were applied to each of these three variables.

Few outliers were observed. Since there was no reason to suspect incorrect data entry or

management, extreme data points were thought to reflect real observations from this sample. To

explore any potential effects of influential data points, final models were evaluated using the

SAS robust regression (ROBUSTREG) procedure (Chen, n.d.), which is designed to detect

outliers and improve the stability of results by reducing the influence of extreme data points.

Descriptive statistics for independent and dependent variables, including pre- and post-

transformed descriptive statistics for transformed variables, are shown in Table 3. Blood lead

concentration at 60 months ranged from 0.5 – 20.9 μg/dL. Participants in this sample tended to

have higher than average T scores (standardization sample M = 50, SD = 5) on subscales from

the CPRS-R:L. The means and standard deviations on each subscale are shown in Figure 1.

43
Table 3
Sample Descriptive Statistics
Variable N M or % SD skewness kurtosis
Independent Variables
60-month blood lead (μg/dL) 173 5.43 3.87 1.51 2.54
60-month blood lead (log transformed) 173 1.45 0.72 -0.32 0.25
Prenatal tobacco smoke (% exposed) 43/175 24.57%
Postnatal ETS (exposure proportion) 176 0.48 0.39 0.13 -1.61
Sex (% male) 82/176 46.59%
Monthly household income (US $) 176 1713.21 2007.30 3.34 13.58
Monthly household income (square root transformed) 176 36.19 20.15 0.96 2.89
Caregiver education (total years) 174 12.11 2.07 0.38 1.05
Maternal race (% white) 101/176 57.39%
Maternal IQ (m = 100) 166 82.00 13.20 0.42 0.05
HOME inventory (total; max = 45) 169 27.52 7.19 -0.50 -0.11
Number of moves 176 2.21 1.98 1.30 2.25
Family routine/structure 174 0.65 0.12 -0.45 -0.57
Dependent Variables
Conners Parent Rating Scale
Oppositional 176 57.36 11.68 0.72 -0.05
Cognitive Problems/Inattention 176 57.12 10.96 0.93 0.44
Hyperactivity 176 59.33 10.71 0.75 0.43
ADHD Index 176 55.21 11.30 0.85 0.20
Conners' Global Index (CGI): Total 176 57.66 11.59 0.75 0.01
Anxious-Shy 176 53.41 9.50 0.90 1.35
Perfectionism 176 57.36 11.00 0.63 -0.25
Social Problems 176 50.94 7.76 2.07 5.11
Social Problems (log transformed) 176 3.92 0.14 1.62 2.52
Psychosomatic 176 53.61 10.70 1.24 1.20
Test of Everyday Attention in Children
Map Mission 176 12.11 5.56 -0.08 -0.11
Same World 176 60.57 20.19 1.75 5.07
Same World (log transformed) 176 4.06 0.30 0.48 0.67
Opposite World 176 81.53 33.79 1.92 5.10
Opposite World (log transformed) 176 4.33 0.36 0.64 0.53

44
 75

70

65

60
T-score

55

50

45

40

35
y

l
p

p
I
HD

tic
ect
t

c ia
nat
CG

Sh
Hy

Op

ma
f

So
AD

x/

Per
g/I

So
An
Co

Figure Caption

Figure 1. CPRS-R:L subscale means and standard deviations. Scale abbreviations: Hyp –
Hyperactivity, ADHD – ADHD Index, CGI – Conners’ Global Index: Total, Opp – Oppositional,
Cog/Inatt – Cognitive Problems/Inattention, Anx/Shy – Anxious/Shy, Perfect – Perfectionism,
Somatic – Psychosomatic, Social – Social Problems.

45
 Data Reduction

A principal components analysis (PCA) was conducted on the outcome variables to

reduce the number of variables to be explored in later regression analyses. Given an interest in

encompassing all variability among the outcome measures toward a broad definition of attention,

as opposed to a goal of developing a reflective measurement model, a PCA was conducted

(Fabrigar, Wegener, MacCallum, & Stranhan, 1999; Bollen & Lennox, 1991). Twelve variables

were included in the PCA, including nine scales from the CPRS-R:L (Oppositional, Cognitive

Problems/Inattention, Hyperactivity, ADHD Index, Anxious-Shy, Perfectionism, Social

Problems, and Conners’ Global Index) and three scores from two subtests of the TEA-Ch (Map

Mission total correct, Same World total time, and Opposite World total time).

In the initial PCA, three components with eigenvalues greater than one were extracted,

which accounted for 66% of the total variance. Examination of the scree plot suggested a four

component solution might be appropriate; these accounted for 73% of the total variance and the

eigenvalue associated with the fourth component was 0.82. Therefore, two solutions were

examined, one with three components and one with four. Each of these solutions was rotated

using an oblique OBLIMIN rotation. The three-component solution was thought to be the better

of the two solutions since only one variable (Social Problems) loaded highly on the fourth

component in the four-component solution. In contrast, the three-component solution had five

variables loading highly on the first component, three variables loading highly on the second

component, and four variables loading highly on the third component (Table 4). Inter-component

correlations were as high as 0.46, justifying the use of an oblique rotation.

Relatively low communalities were observed in the psychosomatic and social problems

scales from the CPRS-R:L, suggesting that the three components account for less variance in

46
these variables than in the other variables. Therefore, analyses were run first excluding the Social

Problems scale and then excluding both the Social Problems and Psychosomatic scales excluded

to determine whether the exclusion of these subscales would substantially change or improve the

model. In both analyses, three components were retained (based on eigenvalue and scree plot

criteria), variables loaded on the same components, and component loadings were similar in

magnitude to the initial PCA. Given these similarities, these two scales were retained for the

final PCA model shown in Table 4. Component 1 appears to represent primarily externalizing

symptoms such as hyperactivity and oppositional behavior as well as inattention and learning

difficulties. Component 2 represents set-shifting and selective attention, more executive aspects

of attention. And, component 3 appears to represent internalizing symptoms including symptoms

of anxiety and depression.

47
Table 4
Principal Components Analysis with OBLIMIN Rotation
Factor Pattern Matrix
Components
Variable 1 2 3 h2
Conners Parent Rating Scale - Revised (CPRS-R)
Hyperactivity 0.93 -0.03 -0.07 0.80
ADHD Index 0.91 0.03 0.04 0.87
Conners' Global Index (CGI): Total 0.87 0.00 0.13 0.89
Oppositional 0.85 0.09 0.07 0.78
Cognitive Problems/Inattention 0.66 0.20 0.16 0.65
Anxious-Shy 0.00 0.03 0.79 0.62
Perfectionism 0.01 0.00 0.71 0.50
Psychosomatic 0.07 -0.06 0.62 0.42
Social Problems 0.06 0.02 0.53 0.32
Test of Everyday Attention in Children (TEA-Ch)
Same World 0.07 0.88 -0.02 0.79
Opposite World 0.21 0.83 -0.20 0.74
Map Mission 0.21 -0.70 -0.17 0.51

Eigenvalue 4.79 1.94 1.17

Variance Accounted (%) 39.91 16.16 9.76
h2 communality estimate

48
 Aim 1: Multivariate Multiple Regression

Three regression analyses were conducted, each with one of the components described

above as an outcome variable. Determination of predictor variables to include in each of the

three models began with examination of the bivariate correlations between each of the three

outcome variables (i.e., components 1-3) and the following predictors: blood lead, prenatal

tobacco smoke exposure, postnatal ETS, child’s sex, household income, caregiver education ,

total number of moves made by the family, family routine/structure, HOME Inventory total

score, maternal race, and maternal IQ.

Predictor variables were included in a model if the p value associated with the correlation

between it and the dependent variable was < 0.20 (see Table 5). The independent variable of

greatest interest was 60-month blood lead concentration, and so this variable was included in all

analyses, regardless of its correlation with each outcome component. Each of these initial models

was built using standard multiple regression; all independent variables were entered into the

regression equation simultaneously (Table 6). Given these criteria, 60-month blood lead, prenatal

tobacco smoke exposure, postnatal ETS, sex, caregiver education, HOME total score, and

maternal IQ were entered into a model to predict component 1. Sixty-month blood lead, sex,

caregiver education, HOME total score, maternal race, and maternal IQ were entered into a

model to predict component 2. And, 60-month blood lead, prenatal tobacco smoke exposure, sex,

household income, caregiver education, family routine/structure, HOME total score, and

maternal IQ were entered into a model to predict component 3.

49
Table 5
Bivariate Correlations Between Independent and Dependent Variables
Component 1 Component 2 Component 3
Variable r p r p r p
Component 1 1
Component 2 0.11 0.14 1
Component 3 0.46 <.01 0.09 0.24 1
a
60m Blood Lead 0.12 0.11 0.23 <0.01 0.18 0.02
24m Blood Leada 0.04 0.60 0.20 0.01 0.16 0.05
Prenatal tobacco smoke exposure 0.20 0.01 0.06 0.46 0.13 0.10
Postnatal ETS 0.22 <0.01 0.08 0.28 0.03 0.69
Sex 0.12 0.12 -0.23 <0.01 -0.10 0.19
Household incomeb 0.07 0.37 0.09 0.25 0.15 0.05
Caregiver education -0.18 0.02 -0.23 <0.01 -0.17 0.03
Number of moves 0.01 0.92 -0.04 0.59 0.08 0.29
Family routine 0.06 0.47 -0.06 0.47 -0.14 0.06
HOME inventory (total) -0.14 0.08 -0.24 <0.01 -0.24 <0.01
Maternal race (black/non-black) -0.04 0.63 0.24 <0.01 0.08 0.30
Maternal IQ -0.13 0.09 -0.33 <0.01 -0.26 <0.01
Note: Bolded correlations are those with p < 0.20.
a
Log transformed. bSquare root transformed

50
Table 6
Initial Multiple Regression Models
Component 1a Component 2b Component 3c
Independent Variables B t p B t p B t p
Blood lead (60m)d -0.07 -0.56 0.58 0.02 0.13 0.90 -0.01 -0.12 0.91
Prenatal tobacco smoke exposure 0.39 1.75 0.08 - - - 0.26 1.40 0.16
Postnatal ETS 0.20 0.81 0.42 - - - - - -
Sex 0.27 1.71 0.09 -0.39 -2.61 0.01 -0.15 -0.95 0.34
Household income - - - - - - 0.00 1.13 0.26
Caregiver education -0.06 -1.22 0.22 -0.07 -1.46 0.15 -0.05 -0.90 0.37

51
Family routine/structure - - - - - - 0.46 0.62 0.54
HOME inventory (total) -0.02 -1.29 0.20 0.00 -0.39 0.70 -0.03 -2.07 0.04
Maternal race - - - 0.16 0.89 0.37 - - -
Maternal IQ 0.00 -0.22 0.82 -0.02 -2.25 0.03 -0.01 -1.15 0.25
Overall F 2.60 0.01 5.57 <0.01 2.76 0.01
R-square 0.11 0.18 0.13
Adjusted R-square 0.07 0.15 0.08
Note: Independent variables were included in these models if the p-value associated with the bivariate independent-
a
N = 157. bN = 158. cN = 156. dLog transformed.
 All three overall models were significant, demonstrating that the selected independent

variables accounted for a significant amount of the variance in component 1, component 2, and

component 3. Although statistically significant, the percent of variance accounted for by the

independent variables in each model was relatively small, particularly for components 1 and 3. In

predicting component 1, none of the independent variable were significant predictors at the p <

0.05 level, although prenatal exposure to tobacco smoke and sex appear to be relatively more

important predictors. Prenatal exposure to tobacco smoke and female sex were associated with

increased externalizing symptoms at 60-months of age. Both sex and maternal IQ were

significant predictors of component 2; male sex and lower maternal IQ were associated with

poorer selective attention and set-shifting ability. HOME total score was a significant predictor

of component 3. Poorer quality of the home environment was associated with increased

internalizing symptoms. Of note, sixty-month blood lead was not a significant independent

predictor of attention in any of the three models.

Given that few of the individual predictor variables reached significance in the regression

models despite relatively strong bivariate correlations with the outcome variables, the predictor

variables in each of the three models were assessed for multicollinearity (i.e., predictor variables

that are highly correlated with one another) by examining both bivariate correlations between

independent variables and variance inflation factors (VIFs). Across models and independent

variables, the VIFs did not suggest substantial multicollinearity. However, some bivariate

correlations between independent variables (Table 7) were significant, suggesting overlap

between independent variables, as might be expected given the nature of these variables.

52
Table 7
Independent Variable Correlations
Prenatal Maternal
tobacco HOME race
smoke Postnatal Household Caregiver Number of Family inventory (black/non-
exposure ETS Sex incomeb education moves routine (total) black)
Prenatal tobacco smoke exposure 1

53
Postnatal ETS 0.52*** 1
Sex 0.02 0.06 1
Household incomea 0.10 0.07 -0.09 1
Caregiver education -0.19* -0.22* -0.03 -0.13 1
Number of moves 0.01 0.17* 0.04 -0.06 -0.19* 1
Family routine -0.01 -0.01 0.06 0.01 0.26** -0.09 1
HOME inventory (total) -0.01 -0.11 0.14 -0.08 0.30*** -0.16* 0.42*** 1
Maternal race (black/non-black) -0.10 -0.04 -0.07 0.10 -0.07 0.06 -0.22* -0.38*** 1
Maternal IQ -0.16* -0.08 0.07 -0.19* 0.51*** -0.11 0.32*** 0.37*** -035***
*p ² 0.05, **p < 0.001, ***p < 0.0001
a
Square root transformed
 Because relatively few of the independent variables emerged as significant predictors of

the three outcome variables and diagnostics did not suggest multicollinearity, exploratory

analyses using stepwise regression were conducted. These analyses were carried out with the

intention of determining the empirical importance of individual predictor variables to each of the

three outcomes. The results of these analyses were then used to inform subsequent sequential

(hierarchical) regression analyses, as this method allows for greater researcher control, relative to

stepwise methods, in determining the relative importance of predictor variables and model fitting

in general. For each of the three independent variables, two sets of stepwise analyses were

conducted, one including only predictor variables meeting the p < 0.20 bivariate correlation

(with the dependent variable) criterion and one including all eleven possible independent

variables. For all models, the criteria for entry and retention was p = 0.15.

For components 2 and 3, the pattern of results between each of the stepwise models was

very similar. For each component, both stepwise models contained the same three predictor

variables (component 2: maternal IQ, child’s sex, caregiver education; component 3: HOME

Total, maternal IQ, prenatal tobacco smoke exposure). In the model predicting component 1, two

additional predictor variables remained in the model when all possible predictors (not just those

meeting the p < 0.20 criterion) were considered. When all possible predictors were considered,

prenatal tobacco smoke exposure, caregiver education, family routine, HOME Total, and child’s

sex entered the model, while only prenatal tobacco smoke exposure, caregiver education, and

child’s sex entered the model when only those predictors with bivariate correlations meeting the

p < 0.20 criteria were considered. Given the similarities between each of the two sets of stepwise

models, the stepwise models that allowed all possible independent variables to enter, regardless

of the bivariate correlation with the dependent variable, were retained (Table 8).

54
 In the stepwise model predicting component 1, five variables were included in the final

model. The first predictor variable to enter the model was prenatal tobacco smoke exposure,

followed by caregiver education, family structure/routine, HOME total score, and finally sex. In

the stepwise model predicting component 2, three variables were included in the final model.

Maternal IQ was the first to enter the model, followed by sex, and then caregiver education. And,

in the stepwise regression model predicting component 3, there were also three variables were

included in the final model; HOME total was the first variable to enter the model, maternal IQ

followed, and prenatal tobacco smoke exposure was the final variable included.

55
Table 8
Stepwise Multiple Regression Models
Component 1 Component 2 Component 3
entry partial model entry partial model entry partial model
Independent Variables B t p B t p B t p
order R2 R2 order R2 R2 order R2 R2
Prenatal tobacco smoke exposure 1 0.52 2.87 <0.01 0.06 0.06 - - - - - - 3 0.28 1.57 0.12 0.01 0.11
Caregiver education 2 -0.06 -1.59 0.11 0.02 0.08 3 -0.06 -1.51 0.13 0.01 0.17 - - - - - -
Family routine 3 1.44 2.04 0.04 0.01 0.09 - - - - - - - - - - - -

56
HOME (total) 4 -0.02 -1.97 0.05 0.02 0.11 - - - - - - 1 -0.03 -2.44 0.02 0.07 0.07
Sex 5 0.24 1.61 0.11 0.02 0.13 2 -0.41 -2.80 0.01 0.04 0.16 - - - - - -
Maternal IQ - - - - - - 1 -0.02 -3.02 <0.01 0.12 0.12 2 -0.01 -1.81 0.07 0.02 0.10
Overall F-value 4.39 <0.01 10.59 <0.01 6.26 <0.01
R-square 0.13 0.17 0.11
Adjusted R-square 0.10 0.16 0.09
Note: N = 156. Independent Variables were included in these models based on stepwise regression analysis in which the criteria for entry and exit were p < 0.15.
A "-" indicates that the associated independent variable was not included in the model. Values in bold are significant at p < 0.05.
 The findings from stepwise regression analyses clarify which independent variables are

predictive of each dependent variable. This information was utilized to inform subsequent

models built using hierarchical regression (Table 9). As the first step, the independent variables

identified by the stepwise analyses were entered into each model. Second, the contribution of 60-

month blood lead level to each of the dependent variables, beyond the other predictor variables,

was examined. Results show that blood lead did not contribute significantly to the models

predicting component 1, component 2, or component 3 after accounting for the other predictor

variables. However, each of the groups of non-lead predictor variables did account for significant

variance in attention outcomes (Table 9).

57
Table 9
Hierarchical Regression Analyses
Component 1a Component 2b Component 3c
Variables B F /t p Variables B F /t p Variables B F /t p
Step 1 4.10 <0.01 8.61 <0.01 4.75 <0.01
Prenatal tobacco smoke exposure 0.53 3.05 <0.01 Maternal IQ -0.02 -2.71 0.01 HOME (total) -0.03 -2.29 0.02
Caregiver education -0 -1.09 0.28 Sex -0.46 -3.17 <0.01 Maternal IQ -0.01 -1.77 0.08
Family routine 1.37 1.94 0.05 Caregiver education -0.06 -1.32 0.19 Prenatal tobacco smoke exposure 0.28 1.53 0.13
HOME (total) -0 -2.06 0.04

58
Sex 0.22 1.52 0.13
Step 2 0.04 0.85 0.46 0.50 0.00 0.99
Blood lead (60m)d 0.02 0.19 0.85 Blood lead (60m)d 0.08 0.68 0.50 Blood lead (60m)d 0.00 -0.01 0.99
Overall F-value 3.67 <0.01 8.68 <0.01 4.73 <0.01
R-square 0.12 0.18 0.11
Adjusted R-square 0.09 0.16 0.09
a
N = 163. bN = 164. cN = 157. dLog transformed.
 Interactions between lead and other selected independent variables were examined next

for each of the three components (Table 10). Centered interaction terms were added to the

hierarchical models presented in Table 9 as a third step. To the model predicting component 1,

interactions between lead and each of the five independent variables in step 1, including prenatal

tobacco smoke exposure, caregiver education, family routine, HOME total score, and sex were

added to the model. Although the overall model and step 1 remained significant, neither any of

the individual interaction terms nor the group of interaction terms comprising step 3 emerged as

significant predictors of component 1. Also, including interaction terms did not improve the

overall model or the strength of lead as a predictor (Table 9, Table 10).

To the model predicting component 2, interactions between lead and sex, lead and

maternal IQ, and lead and education were added. The lead by sex interaction accounted for

significant variance in component 2 (b = -0.40, t = -2.04, p = 0.04). The interaction was such that

at higher levels of lead exposure, boys’ set-shifting and selective attention skills are more

significantly impacted by lead exposure than girls’ abilities. For boys, an increase in blood lead

from 0 to 15 μg/dL resulted in an approximately 1 SD decline in performance. Figure 2 shows

the real and predicted values on component 2 by sex; the interaction is apparent and the included

variables account for substantially more variance in boys’ attention than girls’.

Finally, to the model predicting component 3, interactions between lead and HOME Total

score, lead and maternal IQ, and lead and prenatal tobacco smoke exposure were added. Like

component 1, none of these interaction terms emerged as significant predictors of component 3,

nor did they improve the overall model or the strength of lead as a predictor. As a final check,

each of these three hierarchical interaction models (Table 10) were examined using a selected

individual subscale/subtest as the dependent variables, in place of the components derived from

59
the PCA. The ADHD Index subscale from the CPRS-R:L was used in place of component 1, the

Opposite World Subtest from the TEA-Ch was used in place of component 2, and the Anxious-

Shy subscale from the CPRS-R:L was used in place of component 3. Models utilizing

components vs. subscales as dependent variables were compared for each of the three outcomes.

For each of the three sets of two models, the pattern of results obtained, whether the component

or subscale was used as the dependent variable, were similar. However, in general, less variance

was accounted for when individual subscales/subtests were utilized as outcome variables versus

components. The components will be used as the primary dependent variables in all subsequent

analyses.

60
Table 10
Hierarchical Regression Analyses with Interaction Terms
Component 1a Component 2b Component 3c
Variables B F /t p Variables B F /t p Variables B F /t p
Step 1 4.29 <0.01 9.80 <0.01 5.35 <0.01
Prenatal ETS 0.55 3.06 <0.01 Maternal IQ -0.02 -3.07 0.01 HOME (total) -0.03 -2.66 0.01
Caregiver education -0 -1.07 0.28 Sex -0.46 -3.20 <0.01 Maternal IQ -0.01 -1.61 0.11
Family routine 1.43 1.99 0.05 Caregiver Education -0.06 -1.50 0.13 Prenatal ETS 0.28 1.53 0.13
HOME (total) -0 -2.30 0.02
Sex 0.21 1.41 0.16
Step 2 0.10 0.75 0.84 0.36 0.10 0.75

61
Blood lead (60m)d -0 -0.32 0.75 Blood lead (60m)d 0.11 0.92 0.36 Blood lead (60m)d -0.04 -0.32 0.75
Step 3 0.73 0.60 2.47 0.06 1.10 0.35
Lead x Prentl ETS -0.19 -0.73 0.46 Lead x Maternal IQ 0.00 -0.46 0.65 Lead x HOME 0.02 1.56 0.12
Lead x Education 0.01 0.20 0.84 Lead x Sex -0.40 -2.04 0.04 Lead x Maternal IQ-0.01 -0.77 0.45
Lead x Routine -0.11 -0.09 0.93 Lead x Education -0.07 -1.29 0.20 Lead x Prentl ETS -0.22 -0.85 0.40
Lead x HOME 0.02 1.21 0.23
Lead x Sex -0.15 -0.70 0.48
Overall F-value 2.32 0.01 6.15 <0.01 3.18 <0.01
R-square 0.14 0.22 0.13
Adjusted R-square 0.08 0.18 0.09
a
N = 163. bN = 164. cN = 157. dLog transformed.
2.4

R2 =
1.4

0.4

R2 = 0.11

-0.6

Male

-1.6
Female
Male
Female
-2.6
-1.2 -0.7 -0.2 0.3 0.8 1.3
Predicted Values

Figure Caption

Figure 2. Actual and predicted scores on Component 2 by sex. Predicted scores based on
variables identified in Table 10 through hierarchical multiple regression including interaction
terms; predictor variables include: 60-month log blood lead concentration, maternal IQ, maternal
education, child’s sex, lead x maternal IQ interaction, lead x child’s sex interaction, and lead x
maternal education interaction. Higher scores on component 2 represent poorer performance on
attention measures. Greater variance in boys’ attention is accounted for by the combination of
these variables.

62
 Given the sex by lead exposure interaction on component 2, potential differences

between boys and girls on independent and dependent variables were explored further (Table

11). Generally, effect sizes were small, suggesting few differences between boys and girls on the

measured independent and dependent variables. However, on component 2, the magnitude of the

difference was moderate and was such that girls’ performance was improved relative to boys’ on

tasks loading on component 2. Additionally, a small to moderate sex difference on 24-month log

blood lead concentration was observed, suggesting that boys’ average blood lead concentration

was higher than girls at 24 months of age.

To assess for outliers, the final model (Table 10) was run through the SAS robust

regression procedure (Chen, n.d.). Robust regression limits the influence of outlying data points

by scaling back influential points and making each observation equally important. It was used

presently as a check to ensure that the models presented are robust and not unduly influenced by

outlying data points. The pattern of results from the robust regression procedures was similar to

that observed in the regression analyses, suggesting that the models are robust and results may be

interpreted based on the results of the standard regression models (Table 10). Table 12

summarizes the results of the regression and robust regression models for the hierarchical

analysis including interaction terms.

63
Table 11
Sample Descriptive Statistics by Sex
Boys Girls Group Comparisons
Variable N M or % SD N M or % SD t or χ2 p d or OR c
Component 1 82 -0.12 0.90 94 0.11 1.07 -1.55 0.12 0.23
Component 2 82 0.25 1.03 94 -0.21 0.93 3.11 < 0.01 0.47
Component 3 82 0.11 1.10 94 -0.09 0.89 1.31 0.19 0.20
60m Blood Leada 81 1.47 0.73 92 1.44 0.72 0.27 0.79 0.04
24m Blood Leada 80 2.13 0.64 80 1.92 0.64 2.11 0.04 0.33

64
Household incomeb 82 38.07 19.50 94 34.55 20.67 1.16 0.25 0.17
Caregiver education 82 12.17 2.02 92 12.05 2.13 0.37 0.71 0.06
Number of moves 82 2.12 2.10 94 2.29 1.87 -0.55 0.58 0.09
Family routine 82 0.64 0.12 92 0.66 0.12 -0.77 0.44 0.17
HOME inventory (total) 80 26.45 7.63 89 28.48 6.67 -1.85 0.07 0.28
Maternal IQ 78 81.00 12.86 88 82.91 13.51 -0.94 0.35 0.14
Exposed to prenatal tobacco smoke (%) 81 23% 94 26% 0.10 0.75 1.12
Exposed to postnatal ETS (%) 82 45% 94 50% 20.87 0.53 0.34d
Maternal race (% Black) 82 61% 94 54% 0.81 0.37 0.76
a
Log transformed. bSquare root transformed. cEffect size: Cohen's d or odds ratio. dCramer's V.
Table 12
Standard Hierarchical Regression versus Robust Regression Analyses
Component 1a (N = 163) Component 2b (N =164) Component 3c (N = 157)
F p Variables F /t p Variables F /t p
Standard Hierarchical Regression
Step 1a 4.29 <0.01 Step 1d 9.80 <0.01 Step 1f 5.35 <0.01
Step 2b 0.10 0.75 Step 2b 0.84 0.36 Step 2b 0.10 0.75
Step 3c 0.73 0.60 Step 3e 2.47 0.06 Step 3g 1.10 0.35
Overall F-value 2.32 0.01 Overall F-value 6.15 <0.01 Overall F-value 3.18 <0.01
R-square 0.14 R-square 0.22 R-square 0.13
Adjusted R-square 0.08 Adjusted R-square 0.18 Adjusted R-square 0.09

65
χ2 p χ2 p χ2 p
Robust Regression
Step 1a 17.34 <0.01 Step 1d 22.65 <0.01 Step 1f 11.82 0.01
Step 2b 0.04 0.85 Step 2b 1.95 0.16 Step 2b 0.27 0.60
Step 3c 4.03 0.55 Step 3e 7.62 0.06 Step 3g 5.61 0.13
R-square 0.11 R-square 0.18 R-square 0.10
Note: Independent Variables Entered: aPrenatal ETS, Caregiver Education, Family Routine, HOME (total), Sex. b60-
month Blood Lead (log transformed). cLead x Prenatal ETS, Lead x Education, Lead x Family Routine, Lead x HOME,
Lead x Sex. dMaternal IQ, Sex, Caregiver Education. eLead x IQ, Lead x Sex, Lead x Education. fHOME (total),
 Aim 2: Hierarchical Multiple Regression with 24-month Blood Lead Level

A log transformation was applied to 24-month blood lead concentration to improve the

distribution’s approximation of normality. The bivariate correlations between log-tranformed 24-

month blood lead concentration and components 2 and 3 were significant, while the correlation

with component 1 was not (see Table 5). To address the second aim, 24-month blood lead level

was added as the fourth step in each of the three hierarchical models (Table 10). Results suggest

that 24-month blood lead did not contribute significantly to any of the three models (Table 13).

Given the high correlation between the log transformed 24- and 60-month blood lead levels (r =

0.75), the influence of 24-month blood lead level on attention outcomes was also explored

without 60-month blood lead in the models. Again, these results did not support the hypothesis

that 24-month blood lead contributes significantly to the overall model.

As with the previous model (Table 10), the model including 24-month blood lead

concentration as the fourth step in each of the three hierarchical models (Table 13) was run

through the SAS robust regression procedure (Chen, n.d.). Again, the pattern of results from the

robust regression procedures was similar to that observed in the regression analyses, suggesting

that the models are robust and results may be interpreted based on the results of the standard

regression models (Table 13). Table 14 summarizes the results of the regression and robust

regression models for the hierarchical analysis including interaction terms and 24-month blood

lead concentration.

66
Table 13
Hierarchical Regression Analyses with 24-month Blood Lead
Componenta 1 Componentb 2 Componentc 3
Variables B F/t p Variables B F/t p Variables B F/t p
Step 1 3.97 <0.01 9.17 <0.01 4.81 <0.01
Prenatal ETS 0.54 2.98 <0.01 Maternal IQ -0.02 -3.22 <0.01 HOME (Total) -0.04 -2.64 0.01
Caregiver Educa -0.04-1.01 0.32 Sex -0.44 -2.83 0.01 Maternal IQ -0.01 -1.45 0.15
Family Routine 1.48 2.01 0.05 Caregiver Educa -0.06 -1.31 0.19 Prenatal ETS 0.28 1.47 0.14
HOME (Total) -0.03-2.12 0.04
Sex 0.18 -0.71 0.48
Step 2 0.17 0.68 0.53 0.47 0.57 0.45
d d d
Blood lead (60m)
-0.08-0.41 0.68 Blood lead (60m)0.13 0.73 0.47 Blood lead (60m)
-0.14 -0.76 0.45

67
Step 3 0.78 0.57 2.45 0.06 1.07 0.36
Lead x Prentl ETS
-0.19-0.71 0.48 Lead x Maternal -0.01
IQ -0.69 0.49 Lead x HOME 0.03 1.60 0.11
Lead x Education0.00 0.04 0.97 Lead x Sex -0.42 -2.02 0.05 Lead x Maternal 0.00
IQ -0.54 0.59
Lead x Routine 0.04 0.03 0.98 Lead x Education-0.06 -1.07 0.29 Lead x Prentl ETS
-0.18 -0.67 0.50
Lead x HOME 0.02 1.19 0.24
Lead x Sex -0.22-1.02 0.31
Step 4 0.03 0.86 0.22 0.64 0.39 0.53
d d d
Blood Lead (24m)
0.03 0.17 0.86 Blood Lead (24m)
-0.09 -0.47 0.64 Blood Lead (24m)
0.13 0.63 0.53
Overall F-value 1.99 0.03 4.94 <0.01 2.71 0.01
R-square 0.15 0.22 0.13
Adjusted R-square 0.07 0.17 0.09
a
N = 152.bN = 151.cN = 148.dLog transformed.
Table 14
Standard Hierarchical Regression versus Robust Regression Analyses with 24-month Blood Lead Concentration
Component 1a (N = 152) Component 2b (N =151) Component 3c (N = 148)
F p Variables F /t p Variables F /t p
Standard Hierarchical Regression
Step 1a 3.97 <0.01 Step 1d 9.17 <0.01 Step 1f 4.81 <0.01
Step 2b 0.17 0.68 Step 2b 0.53 0.47 Step 2b 0.57 0.45
Step 3c 0.78 0.57 Step 3e 2.45 0.06 Step 3g 1.07 0.36
Step 4h 0.03 0.86 Step 4h 0.22 0.64 Step 4h 0.39 0.53
Overall F-value 1.99 0.03 Overall F-value 4.94 <0.01 Overall F-value 2.71 0.01
R-square 0.15 R-square 0.22 R-square 0.13
Adjusted R-square 0.07 Adjusted R-square 0.17 Adjusted R-square 0.09

68
χ2 p χ2 p χ2 p
Robust Regression
Step 1a 14.79 0.01 Step 1d 21.58 <0.01 Step 1f 10.63 0.01
Step 2b 0.00 0.98 Step 2b 1.03 0.31 Step 2b 1.13 0.29
Step 3c 4.03 0.55 Step 3e 6.84 0.07 Step 3g 5.39 0.15
Step 4h 0.01 0.92 Step 4h 0.19 0.67 Step 4h 0.71 0.40
R-square 0.11 R-square 0.18 R-square 0.11
Note: Independent Variables Entered: aPrenatal ETS, Caregiver Education, Family Routine, HOME (total), Sex. b60-
month Blood Lead (log transformed). cLead x Prenatal ETS, Lead x Education, Lead x Family Routine, Lead x
HOME, Lead x Sex. dMaternal IQ, Sex, Caregiver Education. eLead x IQ, Lead x Sex, Lead x Education. fHOME
 Chapter 4: Discussion

Results show that boys’ set-shifting and selective attention skills (component 2) are

deleteriously affected by lead exposure at relatively low levels. As blood lead concentration

increased from 0 to 15 μg/dL, boys’ performance declined by approximately one standard

deviation. In contrast, girls with increasing blood lead concentrations in the same range showed a

much smaller decrement in attentional skills. This finding provides support for the hypothesized

relationship between lead exposure and attention as well as for the hypothesis that male sex is

associated with increased risk for deleterious effects of lead exposure.

However, results from the other two components, components 1 and 3, did not support

the hypothesized independent relationship between lead exposure and attention outcomes.

Although other independent variables (e.g., maternal IQ, child’s sex, HOME total score) were

associated with internalizing and externalizing symptoms, in the expected directions, in this

sample, blood lead concentration was not associated with these outcomes independent of these

risk and resiliency variables. Additionally, results did not support the hypothesis that

socioenvironmental risk and resiliency variables would moderate the exposure-outcome

relationship. Finally, across each of the three components, there was not support for the

hypothesis that earlier blood lead concentration (i.e., 24-months) would account for additional

variance in outcomes.

Aim 1: Lead and Attention

As noted, in none of the three final hierarchical models examining the relationship

between lead exposure and attention (Table 10) was blood lead concentration a significant

independent predictor of attention. After other independent variables were accounted for, blood

69
lead concentration did not predict unique variance in the attention outcomes, though the

combined risk and resiliency variables did.

Component 1: Externalizing Symptoms

In the final hierarchical regression model predicting externalizing symptoms (Table 10),

the combined risk and resiliency variables (i.e., prenatal tobacco smoke exposure, caregiver

education, family routine, HOME, and sex) accounted for significant independent variability in

externalizing symptoms, although neither blood lead concentration nor the interaction terms did.

The overall model accounted for about 14% of the variance in externalizing symptoms (Table

10), leaving much remaining variance to be explained. This is fairly consistent with the literature

(e.g., Nigg et al., 2008), although many reports on the predictive relationship between blood lead

concentration and attention/cognitive outcomes do not state an R2 value.

The individual predictor variables that accounted for most of the variance in externalizing

symptoms were prenatal tobacco smoke exposure, sex, and family routine. As well as sex,

prenatal tobacco smoke exposure has been associated with ADHD (e.g., Braun et al., 2006; Nigg

& Breslau, 2007). Component 1 represents externalizing symptoms broadly, including both

symptoms characteristic of ADHD (i.e., inattention, hyperactivity, and impulsivity) and,

although to a lesser extent, oppositional symptoms more characteristic of ODD. The combined

nature of this outcome limits comparability across investigations, since many utilize diagnosis of

ADHD as the outcome of interest.

However, externalizing symptoms are often comorbid with ADHD and the small overall

effect sizes observed presently are consistent with the multiplicity of factors thought to

contribute to ADHD (cf. Swanson, Kinsbourne, Nigg, Lanphear, Stefanatos, Volkow et al.,

2007). Many of these factors were not considered in the present investigation, namely genetic

70
predisposition for the disorder and gene-environment interactions. Although these small effect

sizes may signify limited clinical or individual significance, at the public health level, small

effects can be of great significance. Braun and colleagues (2006) estimated that in children

between the ages of 4 and 15 years, prenatal tobacco smoke exposure accounts for 18.4%

(270,000 individuals) of ADHD cases, while blood lead concentrations > 2.0 μg/dL account for

21.1% (290,000 individuals) of annual ADHD cases.

The association between exposure to prenatal tobacco smoke and externalizing symptoms

is consistent with Nigg and Breslau’s (2007) findings. However, this group also found that when

history of maternal substance use disorders and caregiver education were added to the model,

prenatal exposure to tobacco smoke was no longer a significant predictor of ADHD, though it

was of later Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD). A relation

between caregiver education and externalizing symptoms was not supported presently and

history of maternal substance use was not explored, thus it is not possible to examine whether

this might account for significant variance.

That blood lead concentration did not account for significant variance in externalizing

symptoms is inconsistent with the literature (e.g., Braun et al., 2006; Minder, Das-Smaal, Brand,

& Orlebeke, 1994; Nigg et al., 2008). Variation in outcomes, ADHD diagnosis in previous

studies and ADHD-related symptoms in the present investigation, may explain, at least in part,

differences in findings. Children in the current sample may not have had symptoms as severe or

functionally impairing as those in other samples and therefore, if it had been assessed, may not

have met diagnostic criteria for ADHD. If this were true and symptoms in the current sample

were milder, the importance of blood lead concentration as a predictor of attention outcome may

be reduced. However, rates of externalizing symptoms in the present sample were generally

71
increased relative to population averages (see Figure 1), suggesting that these symptoms are

manifest functionally, at least per parent report, though how they would compare to children with

diagnosed ADHD is not known.

Component 2: Selective Attention/Shifting

Unlike the other two components, 60-month blood lead concentration was associated

with component 2, which represents set-shifting and selective attention, but only through the lead

x sex interaction term. These results suggest that in boys, as lead exposure increases from 0 to 15

μg/dL, performance on these measures of attention declines by approximately one standard

deviation. These results provide preliminary support for lead-related deficits, in boys, in the

focus/execute and shift components of Mirsky’s attentional framework, consistent with Bellinger

et al., (1994) who showed deficits in these domains, but did not explore potential moderators,

such as sex.

These results are consistent both with the higher rates of attention deficits (i.e., ADHD)

observed in boys (American Psychiatric Association, 1994) as well as with recent research

suggesting that boys may be more vulnerable than girls to the effects of lead (Ris et al., 2004;

Froehlich et al., 2007). Ris and colleagues’ (Ris et al., 2004) reported a statistically significant

relationship between blood lead, whether measured prenatally, across childhood (averaged from

over the first five years of life), or at 78-months, and sustained attention on a continuous

performance task in adolescent boys, but not girls. These findings are based on the Cincinnati

Lead Study (CLS) sample, which was initially recruited at the time of birth between 1979 and

1985, and, in general, had higher average blood lead concentrations than children in the present

study. During the first five years of life, 79% of the CLS sample had at least one blood lead

concentration ≥ 15 μg/dL and 99% of the sample had at least one reading ≥ 10 μg/dL.

72
 However, another recent investigation, also utilizing the Rochester sample, on which the

present study is based, has also suggested that boys, relative to girls, may be more vulnerable to

the effects of lead, even at low levels of exposure (Froehlich et al., 2007). With increasing blood

lead levels, 66-month-old boys, but not girls, were found to have poorer planning as well as rule

learning/reversal on the Stockings of Cambridge and Intra-Extra Dimensional Set Shift subtests,

respectively, from the Cambridge Neuropsychological Testing Automoated Battery (CANTAB).

This study also explored a genetic polymorphism (DRD4-7) and found, in boys only, evidence

for a genetic vulnerability to the effects of environmental lead exposure on rule learning/reversal,

which requires shifting of one’s strategy or response style. There was no evidence for DRD4-7

genetic susceptibility, either in boys or girls, for planning deficits, though boys with increased

lead exposure showed poorer planning than girls with similar levels of exposure.

Thus, accumulating evidence, from these two reports as well as the current investigation,

suggests that boys may be particularly susceptible to the neurocognitive effects of lead. The

current findings support this sex discrepancy on attention outcomes including shifting and

selective attention. Froehlich and colleagues (Froehlich et al., 2007) suggest sex discrepancies on

planning and shifting ability, while Ris and colleagues (Ris et al., 2004) data supports differences

on a test of sustained attention. Given these findings, it can be cautiously said that sex moderates

the relationship between lead exposure and attention, at least when measured via behavioral

tests. This finding appears to be robust across components of attention and possibly across level

of lead exposure. Further investigation of sex differences in vulnerability to lead is certainly

warranted. This is particularly important given that data from the present investigation and

Froehlich et al. (2007) are from the same sample; additional documentation of this effect in other

samples is therefore critical.

73
 However, some recent investigations have examined the potentially moderating effects of

sex on the exposure-outcome relationship and found that results did not vary by sex. For

instance, Braun and colleagues (Braun et al., 2006) reported an insignificant lead x sex

interaction in a large study using NHANES III data to explore ADHD diagnosis and

environmental toxin exposure. Of note, the outcome in this study, ADHD diagnosis, is different

from the cognitive outcomes for which a lead x sex interaction has been reported. It is possible

that this difference in outcomes may explain, at least in part, the discrepancy in the effect of sex

as a modifier.

Genetic status likely offers an additional explanation for differences in findings across

studies. Genetic polymorphisms were not investigated in the current study, but, Froehlich and

colleagues’ (Froehlich et al., 2007), using the Rochester sample, found a three-way interaction

between sex, genetic status, and lead exposure, such that in non-DRD4-7 boys, as blood lead

concentration increased, shifting outcomes worsened significantly. Given this finding,

exploration of genetic markers as variables impacting risk and resilience to lead exposure will be

important in future studies. Eventually, this may improve knowledge of mechanisms by which

lead exposure impacts the brain and brain development as well as more generally augment

understanding of developmental psychopathology and cognitive dysfunction.

Results also show that the predictor variables (i.e., 60 month blood lead, maternal IQ,

maternal education, and the interactions of these variables with blood lead) account for

substantially more variance in component 2 scores in boys than in girls (Figure 2). This finding

has not been investigated elsewhere, but in combination with the assertion that boys may be

more vulnerable to the effects of lead, suggests that they may also be more vulnerable to the

effects of maternal characteristics, such as measured IQ and education, than girls.

74
Component 3: Internalizing Symptoms

Blood lead concentration was not a significant independent predictor of internalizing

symptoms (component 3). However, the significant bivariate correlation between 60-month

blood lead concentration and component 3 (Table 5) suggests an association between blood lead

and attention, though not independent of the other predictor variables included in the model

(Table 10). However, the overall model (Table 10) was significant and quality of the home

environment (HOME Total score) accounted for significant variance in internalizing symptoms.

Research exploring the effects of toxin exposure, either lead or ETS, on internalizing

symptomotology is quite limited. However, Wasserman, Liu, Pine, & Graziano (2001) did report

an association between prenatal tobacco smoke exposure and internalizing symptoms on the

Child Behavior Checklist. Taken together, the extant literature provides greater support for an

association between externalizing symptoms/disorders and toxin exposure, rather than

internalizing symptoms (Hermann, King, & Weitzman, 2008).

The association between quality of the home environment and internalizing symptoms

was in the expected inverse direction, such that higher quality home environments were

associated with fewer internalizing symptoms. In this sample of children from largely resource-

limited backgrounds, this finding suggests that quality of the home environment may protect

against the development of internalizing symptoms in early childhood. Support for this

possibility comes from a recent study exploring the effects of parenting practice, family routines,

maternal depression, and family conflict on internalizing and other problems in a sample of low-

income, urban, African-American preschoolers (Koblinsky, Kuvalanka, & Randolph, 2006). In

line with the present findings, this study found that increased positive parenting (e.g., nurturance,

responsiveness, consistency, control) and reduced maternal depression were protective against

75
the development of internalizing symptoms. However, there is very little research on the

association between the home environment and internalizing symptoms, so no conclusions can

be drawn presently, though certainly further investigation is warranted.

Aim 2: Early Blood Lead Concentration

Across each of the three outcomes, 24-month blood lead concentration did not account

for significant additional variance in any of the three models. This is consistent with the recent

literature, which suggests that concurrent blood lead concentration, as opposed to levels

measured earlier in life, was most predictive of cognitive outcome, namely intelligence, in 5-7-

year-old children (Chen, Dietrich, Ware, Radcliffe, & Rogan, 2005; Lanphear, Hornung,

Khoury, Yolton, Baghurst, Bellnger, et al., 2005). Associations between concurrent blood lead

concentration and attention and executive deficits as well as externalizing symptoms have also

been reported (e.g., Braun et al., 2006; Froehlich et al., 2007; Nigg et al., 2008), though none of

these studies were longitudinal in nature and therefore could not explore the effects, if any, of

adding early blood lead concentration to the predictive models. Also, since in the present study

concurrent blood lead concentration was not predictive of outcomes, it is not surprising that

earlier blood lead concentration also did not account for significant variance.

Limitations

Although this investigation certainly contributes to knowledge about low-level lead

exposure, particularly as it relates to attention and behavior problems in children, several

limitations bear mention, many of which have already been touched upon. First, in terms of

outcome variables, this study would have benefited from having a wider array of attention

measures to explore, including clinical diagnosis of ADHD. As it was, the outcomes included

tests of selective attention and set-shifting ability as well as parent-report measures of child

76
behavior problems. However, had there been additional measures to include as outcomes, a

broader understanding of the impact of low-level lead exposure on developing attention (cf

Mirsky’s neuropsychological theory of attention), and potentially corresponding brain regions,

may have been gleaned. Additionally, inclusion of ADHD diagnosis as an outcome may have

improved the comparability and generalizability of results.

Second, since an aim of this project was to explore the potentially moderating effects of

risk and resiliency variables, the restricted variability in many of the sample attributes considered

as potential risk and resiliency variables (e.g., household income, caregiver education) represents

a significant limitation. In fact, Bellinger (2000, p 137) noted that “tests of EM [effect

modification] are usually biased towards a Type II error of inference (i.e., the conclusion that

EM is absent when it is a true characteristic of the association).” Reduced variability in potential

moderator variables prohibits, or at least limits, moderation in the exposure-outcome

relationship.

An additional limitation is that certain variables that have been found to be related to the

lead exposure-cognitive outcome relationship in past research were not included in this analysis.

Maternal depression, child IQ, perinatal complications, and maternal substance use are examples

of such variables. In addition to being unable to control for the impact of these variables on

outcomes of interest in the present investigation, it was also not possible to explore whether such

variables may moderate the lead exposure-outcome relationship. Although exclusion of these

variables certainly represents a limitation, as Bellinger has noted, there is no “logical end point”

to the number of factors one might include, “one could propose an endless succession of

unmeasured…factors that might result in residual confounding…” (Bellinger, 2004, p 384).

77
 Conclusions and Implications

Despite limitations, this investigation contributes to the existing childhood lead exposure

literature, particularly by providing additional evidence to support recent findings that boys,

relative to girls, may be at increased risk for suffering deleterious attention outcomes associated

with lead exposure. Although average blood lead concentrations have dropped precipitously over

the years, research has documented deleterious effects of lead exposure even at the low levels

found in children today (e.g., Canfield et al., 2003; Lanphear et al., 2005). Although it is

accepted that not all children are at equal risk for exposure to lead, the factors that place children

at risk, and, alternatively, protect them from harm are not well elucidated. Bellinger has asserted

that the exploration of effect modification in the relationship between lead exposure and

cognitive/behavioral outcomes is critical and encouraged the design of investigations to explore

such effects (Bellinger, 2000).

These results, which demonstrate the moderating effect of sex, provide support for

Bellinger’s (2000) assertion that failure to explore potential moderators may result in biased

results. Because many investigations have not explored sex as an effect modifying variable (e.g.,

Chiodo, Jacobson, & Jacobson, 2004; Surkan et al., 2007), it is possible that sex plays a greater

role than is known currently in the lead exposure-cognitive outcome relationship. Socioeconomic

status (Bellinger, Leviton, Waternaux, Needleman, & Rabinowitz, 1988) and maternal education

(Dudek & Merecz, 1997) have been shown to moderate the cognitive effects of lead exposure in

children. And in animals, enriched environment has been shown to be protective against lead

exposure (Guilarte, Toscano, McGlothan, & Weaver, 2003; Schneider, Lee, Anderson, Zuck, &

Lidsky, 2001). However, relatively few investigations are designed to examine the effects of

potential moderators. Additional research to this end may help to identify populations at greatest

78
risk for the negative outcomes associated with lead exposure as well as variables that protect

against the negative effects of lead exposure and promote resiliency. The accumulation of such

knowledge may serve to focus efforts aimed at treatment and prevention.

79
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