DB 6 Environmental and Biological Effects on Intelligence and Achievement
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ImpactofLowBloodLeadsConcentrationsonIQSchoolPerformanceinChineseChildren.pdf
Impact of Low Blood Lead Concentrations on IQ and School Performance in Chinese Children Jianghong Liu1*, Linda Li1, Yingjie Wang1, Chonghuai Yan2, Xianchen Liu3,4
1 University of Pennsylvania, School of Nursing and School of Medicine, Philadelphia, Pennsylvania, United States of America, 2 Xinhua Hospital, MOE-Shanghai Key
Laboratory of Children’s Environmental Health, Shanghai Jiaotong University School of Medicine, Shanghai, China, 3 Indiana University, School of Medicine, Indianapolis,
Indiana, United States of America, 4 Shandong University, School of Public Health, Jinan, China
Abstract
Objectives: Examine the relationships between blood lead concentrations and children’s intelligence quotient (IQ) and school performance.
Participants and Methods: Participants were 1341 children (738 boys and 603 girls) from Jintan, China. Blood lead concentrations were measured when children were 3–5 years old. IQ was assessed using the Chinese version and norms of the Wechsler Preschool and Primary Scale of Intelligence – Revised when children were 6 years old. School performance was assessed by standardized city tests on 3 major subjects (Chinese, Math, and English [as a foreign language]) when children were age 8–10 years.
Results: Mean blood lead concentration was 6.43 mg/dL (SD = 2.64). For blood lead concentrations, 7.8% of children (n = 105) had $10.0 mg/dL, 13.8% (n = 185) had 8.0 to ,10.0 mg/dL, and 78.4% (n = 1051) had ,8.0 mg/dL. Compared to children with blood lead concentrations ,8 mg/dL, those with blood lead concentrations $8 mg/dL scored 2–3 points lower in IQ and 5–6 points lower in school tests. There were no significant differences in IQ or school tests between children with blood lead concentrations groups 8–10 and $10 mg/dL. After adjustment for child and family characteristics and IQ, blood lead concentrations $10 mg/dL vs ,8 mg/dL at ages 3–5 years was associated with reduced scores on school tests at age 8– 10 years (Chinese, b = 23.54, 95%CI = 26.46, 20.63; Math, b = 24.63, 95%CI = 27.86, 21.40; English, b = 24.66, 95%CI = 28.09, 21.23). IQ partially mediated the relationship between elevated blood lead concentrations and later school performance.
Conclusions: Findings support that blood lead concentrations in early childhood, even ,10 mg/dL, have a long-term negative impact on cognitive development. The association between blood lead concentrations 8–10 mg/dL and cognitive development needs further study in Chinese children and children from other developing countries.
Citation: Liu J, Li L, Wang Y, Yan C, Liu X (2013) Impact of Low Blood Lead Concentrations on IQ and School Performance in Chinese Children. PLoS ONE 8(5): e65230. doi:10.1371/journal.pone.0065230
Editor: Qinghua Sun, The Ohio State University, United States of America
Received September 24, 2012; Accepted April 23, 2013; Published May 29, 2013
Copyright: � 2013 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Funding was provided by the National Institute of Environment Health Sciences (NIEHS, R01-ES018858; K01-ES015 877; K02-ES019878-01); UPenn CEET P30 ES013508; The Wacker Foundation US; Jintan City Government; Jintan Hospital, China. The funders had no role in study design, data collection and analysis,decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: [email protected]
Introduction
Childhood lead exposure is still an important public health
problem in the world, predisposing children at risk of cognitive
deficits and behavioral problems [1–3]. Emerging evidence has
also suggested that even children with blood lead concentra-
tions,10 mg/dL are at significant risk for reduced cognitive development and functioning, including intelligence quotient (IQ)
deficits [4–10] and poor academic performance [11,12]. Alarm-
ingly, deficits in intellectual abilities and elevated risks for
behavioral problems may persist into adolescence and even
adulthood [13–17]. Despite increasing attention given to the
importance of both elevated ($10 mg/dL) and lower (,10 mg/dL) blood lead concentrations on children’s cognitive development,
however, several questions remain. Although previous studies have
revealed that blood lead concentrations ,10 mg/dL were related
to poorer neurocognitive outcomes in children (e.g. [3,5,18]),
studies in this area are still limited. Even more recently, the US
Centers for Disease Control (CDC) eliminated the terminology
‘‘level of concern’’. Children with elevated blood lead concentra-
tions will instead be identified using a reference value based on the
97.5th percentile of the National Health and Nutrition Examina-
tion Survey (NHANES)-generated blood lead concentration
distribution in children aged 1–5 years old; currently, this value
is 5 mg/dl [19]. Since most studies have used cohorts from Western countries, it is unclear whether their findings are
replicable in other developing countries, such as China, where
lead concentrations and prevalence of lead exposure are much
higher [3,20]. In areas of high lead exposure, effects of lower
concentrations of lead on children’s developmental function may
differ. In addition, the effects of lead on both IQ and school
performance have rarely been examined together. Although
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Surkan et al. [10] demonstrated significantly reduced IQ and
academic performance in 6–10 year old children, it is still unclear
whether IQ deficits due to lead exposure subsequently results in
poor academic achievement. Finally, regarding the effects of low
lead exposure on the specific type of IQ (e.g., Performance IQ
[PIQ]), some have argued that Verbal IQ (VIQ) (verbal skills) is
more negatively affected [10,21] while others have found only
significantly lowered PIQ (visual-spatial skills) [5]. More data
would be beneficial for understanding the impact of early lead
exposure on specific types of cognitive deficits to further investigate
the neurotoxicity of low blood lead on brain function as reflected
by cognitive outcomes.
Using a large, community-based, longitudinal cohort sample of
Chinese children for whom blood lead concentrations were
measured at 3, 4, or 5 years of age, IQ was assessed at 6 years
of age, and academic achievement in 3 major subjects (Chinese,
Math, and English) was assessed at 8–10 years of age, the present
study aims to: 1) assess whether elevated blood lead concentrations
are related to preschool children’s IQ and later academic
achievement in Chinese children; 2) examine whether and the
extent to which the relationship between blood lead concentra-
tions and school performance is mediated by IQ; 3) determine
which specific components of these aforementioned outcomes are
affected to delineate specificity of lead’s effect on verbal and
performance skills; and 4) identify at what blood lead concentra-
tions ,10 mg/dL are reduced cognitive outcomes observed for potential public health implications.
Participants and Methods
Subjects The current study is part of an ongoing longitudinal project, the
China Jintan Child Cohort Study, which consists of 1,656
preschool children accounting for 24.3% of all children aged 3–
5 years in Jintan city, Jiangsu province, China. Participants were
drawn from four preschools chosen to represent the entire city’s
geographical, social, and economic profiles. Between Fall 2004
and Spring 2005, children aged 3–5 years attending the preschools
were invited to participate in this study; signed consent forms were
obtained from the parents. Detailed information on this cohort,
including subjects, recruitment, and procedures, is reported
elsewhere [22–25]. Institutional Review Board approval was
obtained from the University of Pennsylvania and the ethical
committee for research at Jintan Hospital in China.
Measures Blood lead concentrations in preschool (3–5 years). Blood
specimens were collected only once for each child, when they
were 3, 4, or 5 years old, during November 2004 and March
2005 by trained pediatric nurses using a strict research protocol
to avoid lead contamination. Samples were frozen and shipped
to the Research Center for Environmental Medicine of Children
at Shanghai Jiaotong University for the analysis of lead using
graphite furnace atomic absorption spectrophotometer [25–27].
This laboratory has participated successfully in a CDC-
administered quality-control program (Blood Lead Proficiency
Testing Program) for the measurement of lead in whole blood.
Analysis of each specimen was conducted using a replication
procedure, and the mean of the repeated measurements was
taken as the final measure. Blood lead reference materials for
quality control (QC) were provided by Kaulson Laboratories,
New Jersey. QC samples were inserted blindly among the study
samples (one QC sample in every 10 study samples. Limit of
detection (LOD) of blood lead concentration was 1.8 mg/dL and
half of LOD was imputed for 3 (0.2%) samples under LOD,
which was among multiple runs (mean LOD).
IQ at age 6 years. IQ was assessed by the Chinese version
and norms of the Wechsler Preschool and Primary Scale of
Intelligence – Revised (WPPSI–R) during children’s last year of
preschool. The test was constructed by Wechsler [28] to assess the
intelligence of children aged 3–7 years and consists of 5 verbal and
5 performance subtests [28]. Verbal subtests are combined to
produce a VIQ reflecting verbal skills and crystallized intelligence.
Performance subtests combine to produce a PIQ indicative of
visual-spatial skills and fluid intelligence. All 10 subtests are
combined to produce a Full Scale IQ (FIQ), which is widely
recognized as a good measure of general intelligence defined as an
average of all cognitive abilities. The Chinese WPPSI was
standardized in 1984 and has shown good reliability in Chinese
children [29–32]. The test was administered by two research
assistants trained by a cognitive psychologist. Research assistants
who administered the WPPSI were blind to the blood lead
concentrations. Children were assessed in a quiet room at their
preschool. Detailed procedures and reliability are given in Liu &
Lynn [33] and Liu et al. [34].
School performance at age 8–10 years. School perfor-
mance was assessed by standardized city tests on 3 major subjects
in Chinese elementary schools: Chinese, Math, and English (as a
foreign language). The tests were administered to all children on
the same day during the final month of the Fall 2009 semester,
when children were in grades 3–5 (aged 8–10 years old). Each test
consists mainly of multiple-choice questions and is scored ranging
from 0–100. A higher score indicates better performance on the
test.
Sociodemographic and other Confounding variables. Parents
completed a socio-demographic questionnaire to assess family
environment at the time of children’s IQ testing. Potential
confounding variables considered include parent educational
and occupational status, father’s smoking history and frequency,
and mother’s smoking during pregnancy. Blood iron was also
analyzed at Nanjing Medical University using the same protocol
and at the same time as blood lead collection. Whole blood
concentrations of iron were determined by atomic absorption
spectrophotometry (BH model 5.100 manufactured by Beijing
Bohu Innovative Electronic Technology Corporation), with
duplicate readings taken with an integration time of two
seconds. Further details are provided elsewhere [35].
Representativeness of Groups The current study used a sample of 1,341 children (603 girls,
738 boys) for whom blood lead was measured at age 3 years, 4
years, or 5 years, which accounts for 81% of our original cohort.
The remaining 19% of the data was either not collected (e.g.:
children either moved to other schools or did not respond or
refused to participate in follow up) or was unavailable (e.g.: blood
samples were not available) for this statistical analysis. Character-
istics of the children and their families are summarized in Table 1.
There were no significant differences in demographics between
children with and without blood lead data [25]. For those children
who participated in follow-up for IQ and school performance
compared to those who did not participate in follow-up, blood lead
concentrations did not differ (t = 1.56; P = 0.120). Meanwhile,
complete data on both the IQ and school performance variables
were available on 561 subjects. Those with and without complete
data were compared on gender, age and grow-place, variables that
were available on all subjects at age 6. There was no significant
difference between those with complete data and those without
complete data on gender, age and grow-place. Therefore, the
Low Lead Levels and IQ and School Performance
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subjects with complete data are able to represent those without
complete data.
Statistical Analysis Sample characteristics were summarized by descriptive statistics
such as mean, standard deviation (SD), and percentage. To
examine the association between blood lead concentration and
cognitive function and school performance, we computed bivariate
correlations between blood lead concentration and IQ (VIQ, PIQ,
and FIQ) and scores on Chinese, Math, and English. We used a
nonlinear approach to model the relationship between blood lead
concentration and IQ by a locally weighted polynomial regression
LOESS model, with estimated 95% confidence band. We
identified 8.0 mg/dl, equal to the 80th percentile, as the blood lead concentration at which IQ started to decline. We then divided
children into 4 groups according to their blood lead concentration:
,6.0 (median), 6.0–8.0 (median to 80 th
percentile), 8.0–10.0, and
$10.0 mg/dl. Because the first 2 groups had no significant differences in both IQ and school performance (data available
upon request), we merged them and included 3 categories for this
report: blood lead concentration ,8.0, 8.0 to ,10 (8–10), and
$10 mg/dl. A series of analysis of variance (ANOVA) were performed to
examine the association between different concentrations of blood
lead and mean scores of IQ and school performance. General
linear models (GLM) were performed to examine the adjusted
associations between blood lead concentration and IQ and school
performance while controlling for child age at blood lead test,
child gender, residence as defined as school location, blood iron
level, parent education, parent occupation, and father’s smoking.
Maternal smoking was not included for analysis as only 3 mothers
reported smoking. These demographic variables were selected on
the basis of our previous study [25] and/or our preliminary
analyses indicating these variables were associated with either or
both blood lead concentration and IQ or school performance.
Finally, we examined if PIQ mediated the association between
blood lead concentration and school performance. We chose PIQ
as the potential mediating variable because PIQ is significantly
correlated with both the predictor (blood lead concentration) and
outcome measure (school performance), and PIQ was measured
before school performance data was collected. These two criteria
meet the conditions established by Baron and Kenny for potential
mediator variable [36]. A p-value,.05 was considered significant.
A nonlinear relationship between blood lead concentration and IQ
was done using R(2.14.0) loess model. All other analyses were
performed using SPSS, Version 17 (Chicago, IL).
Results
Sample characteristics The sample consisted of 603 girls (45.0%) and 738 boys (55.0%),
with a mean age of 4.84 years (SD = 0.86) at blood lead testing.
Child and family characteristics of the sample are summarized in
Table 1. Mean blood lead concentration was 6.43 mg/dL (SD = 2.64). Blood lead concentration was distributed as follows:
7.8% of children were $10.0 (N = 105), 13.8% were 8.0–10.0
(N = 185), 32.8% were 6.0–8.0 (N = 440), and 45.6% were ,6 mg/ dL (N = 611).
Bivariate correlations between blood lead concentration, IQ, and school performance
Mean IQ and standardized test scores and their bivariate
correlations are shown in Table 2. Blood lead concentration was
significantly and negatively related to PIQ and scores of Chinese,
Math, and English. FIQ was highly correlated with VIQ and PIQ;
the correlation between VIQ and PIQ was moderate. Chinese,
Math and English were moderately correlated. The correlations
between FIQ, VIQ, and PIQ and Chinese, Math, or English were
low to moderate.
The nonlinear relationship between blood lead concentration
and FIQ, PIQ, and VIQ, with estimated 95% confidence bands is
shown in Figure 1. FIQ started to decline at blood lead
concentration 8 mg/dl. Although both PIQ and VIQ declined at blood lead concentration 8 mg/dl, PIQ and VIQ at blood lead concentration ,8 mg/dL showed different patterns.
Table 1. Sample characteristics.
N` %
Sex 1341
Male 738 55.0
Female 603 45.0
Age at blood lead test, Mean (SD)
1341 4.84(0.86)
3 years 316 23.6
4 years 415 30.9
5 years 610 45.5
Residence/schools 1341
City (Jianshe) 538 40.1
Suburban (Huacheng)
521 38.9
Rural (Xuebu) 282 21.0
Father’s education 1304
#Middle school 503 38.6
High school 420 32.2
College or higher 381 29.2
Father’s occupation 1262
Unemployed 52 4.1
Physical worker 718 56.9
Professional worker 492 39.0
Mother’s education 1305
#Middle school 657 50.3
High school 384 29.4
College or higher 264 20.2
Father smoking 1273
No 563 44.2
Occasionally 454 35.7
Several times/wk 41 3.2
,10 cigarettes/wk 127 10.0
10–20 cigarettes/wk 71 5.6
.20 cigarettes/wk 17 1.3
Iron Status Mean (SD) 1341 8.13 (0.83)
Blood lead (mg/dL) Mean (SD) 1341 6.43(2.64)
,6.0 611 45.6
6.0 to ,8.0 440 32.8
8.0 to ,10.0 185 13.8
$10.0 105 7.8
` Number of children differs across sample characteristics due to missing values.
doi:10.1371/journal.pone.0065230.t001
Low Lead Levels and IQ and School Performance
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Differences in IQ and school performance across blood lead concentrations
IQ and school performance means (SD) by 3 categories of blood
lead concentration ($10.0, 8.0–10.0, and ,8 mg/dl) is presented in Table 3. All scores declined with increased blood lead
concentration. Compared to the blood lead concentration
,8 mg/dL group, the blood lead concentration 8.0–10.0 mg/dL group showed a significant 3.71 point PIQ decline and a 2.69
point FIQ decline. The change of VIQ was minor, about 1 point
decline.
Compared to the blood lead concentration ,8 mg/dL group, the blood lead concentration 8.0–10.0 mg/dL group also had significantly lower scores in Chinese, Math, and English. The
mean scores significantly declined by 5–6 points in the blood lead
concentration 8.0–10.0 mg/dL group compared to blood lead concentration ,8 mg/dl. Mean scores did not significantly differ between blood lead concentration 8.0–10.0 and $10.0 mg/dL groups.
Multivariate analysis of blood lead concentration on IQ and school performance
The independent effects of blood lead concentration on IQ and
school performance were examined using GLM analyses to adjust
for child and family factors. Children with blood lead concentra-
tion $10.0 mg/dL scored approximately 2 points lower on PIQ and VIQ than those children with blood lead concentration
,8 mg/dl (Table 4). However, associations were not significant after adjusting for potential confounders. All Chinese, Math, and
English scores significantly declined with elevated blood lead
concentration. Math scores declined the most, followed by English
and Chinese. Illustratively, compared to children with blood lead
concentration ,8 mg/dl, those with blood lead concentration 8.0– 10.0 mg/dL scored 3–5 points lower on Chinese (b = 23.20, 95%CI = 25.78, 20.63), Math (b = 25.25, 95%CI = 28.14, 22.36), or English (b = 24.33, 95%CI = 27.32, 21.34). Mean- while those with blood lead concentration $10.0 mg/dL scored much lower (Chinese, b = 24.02, 95%CI = 27.11, 20.93; Math, b = 25.27, 95%CI = 28.73, 21,81; English, b = 25.18, 95%CI = 28.76, 21.59) compared to children with blood lead
concentration ,8 mg/dl.
Mediating effect of PIQ on blood lead concentration and school performance
Blood lead concentration and IQ were both significantly
correlated with the three school tests, and blood lead concentra-
tion was significantly correlated with only PIQ (Table 2).
Consequently, it is possible that reduced PIQ could mediate the
main effect of blood lead concentration on school performance.
This possibility was tested by adding PIQ to Model 1 while
adjusting for child, school, and family factors (Table 4). As shown
in Model 2, blood lead concentration 8.0–10.0 mg/dL and $10.0 mg/dL were still significantly associated with reduced
Table 2. Pearson correlations between blood lead concentrations and IQ and school performance.
Mean (SD) N` Blood lead concentration VIQ PIQ FIQ Chinese Math
Blood lead concentrations (mg/dL) 6.43(2.64) 1341 1.00
IQ VIQ 103.95(14.84) 1331 .011 1.00
PIQ 104.06(15.07) 1331 2.056* .498*** 1.00
FIQ 104.19(14.38) 1331 2.026 .869*** .857*** 1.00
School Performance Chinese 87.87(11.11) 561 2.234*** .241*** .344*** .305*** 1.00
Math 88.80(11.67) 561 2.200*** .242*** .391*** .375*** .511*** 1.00
English 89.58(13.22) 562 2.207*** .153*** .334*** .294*** .666*** .696***
*p,.05; **p,.01, ***p,.001. ` Number of children differs across sample characteristics due to missing values.
doi:10.1371/journal.pone.0065230.t002
Figure 1. FIQ, VIQ, and PIQ test scores by blood lead concentration (mg/dl) with estimated 95% confidence bands. Note: The dotted line’s y-intercept is at the mean IQ test score. doi:10.1371/journal.pone.0065230.g001
Low Lead Levels and IQ and School Performance
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scores on Chinese, Math, and English except for Chinese in
children with blood lead concentration 8.0–10.0 mg/dl. Compared with blood lead concentration ,8 mg/dL at ages 3–5 years, blood lead concentration $10 mg/dL was associated with 3–5 points reduction on school tests at age 8–10 years (Chinese, b = 23.60, 95%CI = 26.58, 20.62; Math, b = 24.64, 95%CI = 27.91, 21.34; English, b = 24.62, 95%CI = 28.05, 21.18). However, the effect as measured by regression coefficient was reduced,
indicating that the associations between blood lead concentration
and school tests were partially mediated by PIQ.
Discussion
Lead exposure is an important public health concern, especially
in countries that are developing or undergoing rapid economic
growth with limited environmental regulations [37–39]. However,
little is known about the negative impact of low blood lead
concentration on later cognitive function in these developing
countries, where lead levels may be six-fold higher than in the US
[38–40]. This study examined the association between blood lead
concentration in children at 3–5 years, their IQ at 6 years, and
school performance at age 8–10 years. We report several key
findings. First, elevated blood lead concentration in early
childhood was associated with reduced IQ at age 6 years,
particularly for PIQ (visual-spatial skills). Second, even after
adjusting for potential confounding variables, including prenatal
smoke exposure (exposed to father’s smoking) and iron deficiency
in childhood, elevated blood lead concentrations were also
significantly associated with reduced scores on standardized school
tests at age 10 years. Third, IQ partially mediated the blood lead
concentration and school performance relationship. Finally and
importantly, significant impairments were identified at even 8–
10 mg/dL, supporting the view that lead exposure, even ,10 mg/ dL, is a risk factor for long-term cognitive impairment in children
and from a preventative perspective suggests that reduced early
childhood lead exposure could promote children’s long-term
cognitive development and school performance.
Our findings extend previous evidence for an inverse relation-
ship between blood lead concentration and IQ (e.g.: [3,5]). Our
results confirm previous findings by Chandramouli et al. [11] that
blood lead concentration ,10 mg/dL in early childhood my affect later academic achievement. The present study importantly
reports on both children’s early IQ and later academic achieve-
ment, two different indicators of children’s cognitive performance
which both have important late-life health and quality-of-life
outcomes [41–43].
Because of the time gap between IQ and academic achievement
assessment and because PIQ was significantly correlated with both
blood lead concentration and school performance, we were able to
observe a partial mediating effect of PIQ for the blood lead
concentration -academic achievement relationship. We hypothe-
size that lead exposure negatively effects brain growth and
development, and that brain alterations are linked to school
performance. The exact mechanism between lead exposure and
school performance is unclear. Lead is a neurotoxicant, and
animal studies suggest that lead exposure may lead to altered brain
biochemistry [44], which in turn may result in a disorder of
Table 3. Mean IQ and 2009 school performance by blood concentrations of lead in preschool children.
Blood concentrations of lead (mg/dL) ANOVA Post-hoc analysis, LSD (p)
,8 (A) 8- ,10(B) $10 (C) F p A vs. B A vs. C B vs. C
IQ N = 1016 N = 182 N = 103
PIQ 104.46(14.93) 103.32(15.58) 100.75(16.03) 3.04 .048 .349 .018 .168
VIQ 104.23(14.80) 103.65(15.03) 103.08(14.65) 0.36 .696 .627 .453 .755
FIQ 104.55(14.36) 103.66(14.22) 101.86(15.25) 1.78 .169 .442 .072 .313
School performance N = 421 N = 79 N = 49
Chinese 89.33(9.20) 83.44(13.97) 82.12(16.67) 17.30 .000 .000 ,.001 .503
Math 90.32(9.20) 84.29(14.66) 83.04(19.42) 16.32 .000 .000 ,.001 .545
English 91.29(10.41) 84.16(18.10) 83.37(19.71) 16.59 .000 .000 ,.001 .732
doi:10.1371/journal.pone.0065230.t003
Table 4. Impact of blood concentrations of lead on IQ and school performance in Chinese preschool children (n = 1341).
Blood concentrations of lead (mg/dL)
,8.0 8.0 – ,10.0 $10.0
IQ (Model 1)
PIQ Ref 20.96 (23.28, 1.36) 21.90 (24.89, 1.09)
VIQ Ref 20.48 (23.36, 2.40) 21.77 (24.01, 0.46)
FIQ Ref 21.28 (24.01, 1.46) 21.45 (23.50, 0.67)
School performance
Chinese: Model 1 Ref 23.20 (25.78, 20.63)* 24.02 (27.11, 20.93)*
Model 2 Ref 22.67 (25.16, 0.18)* 23.60 (26.58, 20.62)*
Math: Model 1 Ref 25.25 (28.14, 22.36)** 25.27(28.73, 21,81)**
Model 2 Ref 24.46(27.20, 21.72)** 24.64(27.91, 21.36)**
English: Model 1 Ref 24.33 (27.32, 21.34)* 25.18 (28.76, 21.59)**
Model 2 Ref 23.62 (26., 20.75)* 24.62 (28.05, 21.18)*
*p,.05, **p,.01. Model 1: Adjusting for age at blood lead test, sex, blood iron, school, father’s education, mother’s education, father’s occupation and smoking. Model 2: Adjusting covariates in model 1 plus PIQ. doi:10.1371/journal.pone.0065230.t004
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plasticity [45] and learning impairments. Our findings suggest that
lead may first alter brain development in children [46–49] that
subsequently impede further school achievement. This hypothesis
is further supported by a functional neuroimaging study demon-
strating an inverse correlation between childhood blood lead
concentration and activation of the left frontal cortex and middle
temporal gyrus, brain regions undergoing rapid development to
support language capabilities, during young adulthood [49]. While
Yuan et al. also found that dormant circuits in the right
hemisphere appeared to be recruited to compensate for these
brain deficits circuitry, such a compensatory pathway may not
necessarily produce equivalent performance to that achieved by
the normative cortical circuitry, and may thus still lead to poorer
long-term academic achievement [49].The impairing effects of
lead exposure on the brain also extends to adults: structural
imaging shows that accumulated occupational lead exposure in
adults is associated with changes in cerebral white matter which
further affects motor performance [50]. Since PIQ was observed
to have a partial mediating effect, our findings also suggest that
blood lead concentration may negatively impact other facets of
development, such as behavior, that also contribute to reduced
school performance. Furthermore, cognitive deficits which were
not directly measured, such as poor motivation and self-discipline,
may also lead to poor academic achievement [51].
In our sample, blood lead concentration was more strongly
associated with PIQ than VIQ. Poorer performance on visual-
spatial and visual-motor functioning tests are reported in previous
studies of lead exposure [52–56]. Notably, by using a large sample
size and testing the potential mediating effects of IQ on the blood
lead concentration-school performance association, our results
extends findings by Jusko et al. [5] that both lifetime average and
concurrent blood lead concentration in 6 year old children were
significantly associated with lower FIQ and PIQ (p,0.05), but not
VIQ (p.0.1). Jusko et al. also suggested that verbal abilities may
be more sensitive indicators to cognitive effects of lead exposure
during middle-late childhood [5]. In our current study, for the IQ
tests, our results showed a significant association between blood
lead concentration and only PIQ at age 6 years old, which is
almost congruent to children’s age at blood lead test, but not VIQ
or FIQ. However, for school performance, which was assessed 2–4
years after blood lead, we found significant associations between
blood lead concentration and all three tests. These findings suggest
that the effect of lead on cognitive deficits appear to be reflected in
later childhood (age 8–10 years) through measures of scholastic
achievement, which are indicative of verbal working memory and
crystallized intelligence [57]. The lack of a significant association
between blood lead concentration and VIQ or FIQ at age 6 years
could be due to the possibility that IQ is insensitive to brain injury,
which in turn is affected by lead exposure [58].
If low concentrations of lead exposure have long-lasting,
detrimental cognitive outcomes, a key concern is identifying at
what blood lead concentrations ,10 mg/dL these outcomes occur. Our results indicate that ,8 mg/dL, blood lead concentration was not uniformly associated with decreased outcomes, even after non-
linear analysis (Figure 1). IQ, particularly PIQ, noticeably started
to decline at $8 mg/dL. We also identified significant and pronounced differences between these two groups in later school
performance. However, previous studies have reported significant
cognitive deficits at blood lead concentration ,8 mg/dL in Western children [3]. It could be warranted to examine the
cultural and environmental factors associated with the effect of
lead on child cognitive development, especially since our study
examined Chinese children.
Several limitations in this study should be noted. First, blood
lead concentration was measured once for each child from 3–5
years of age. Thus, deficits seen in later childhood may reflect lead
exposure at measurement, during the first 2 years of life, or even
during the prenatal period. However, while lead susceptibility has
been assumed to be greatest during early childhood (e.g., ,2
years), several recent studies have shown that blood lead
concentrations beyond the age of 2 years are actually more
strongly associated with adverse cognitive outcomes, including IQ
[3,7,59]. Second, blood lead concentrations were measured at
different ages within the sample (range of 3–5 years). Nonetheless,
even with increasing age, lead concentrations remain fairly
constant in early childhood [52]. Third, the effects of low lead
exposure on IQ at 10 years were not assessed. However, strong
correlations exist in IQ deficits associated with blood lead
concentration across childhood and even into adulthood [15,60].
Still, we are currently collecting a second round of IQ data from
this cohort for further analysis. Because children’s IQ may not be
sensitive enough to detect certain neurocognitive deficits, we are
also currently collecting data using more extensive and sensitive
neurocognitive tests. Fourth, the present study did not examine
other potential confounders, such as the home environment using
HOME inventory [5,61], or additional predictors of neurodevel-
opmental outcomes, such as parental IQ. While we used parental
educational level as a proxy for parental IQ, our findings should
nonetheless be replicated in future prospective studies accounting
for greater potential confounding factors. Fifth, our findings may
also be limited by our high LOD, although only 3 samples (0.2%)
were under this LOD. Finally, this study sample was drawn from a
region (Jiangsu Province) in China. It is unknown if the findings
could be generalized to Chinese children in other regions and
children in other countries.
Conclusion
This study uses a large, Chinese cohort sample to examine the
effect of low blood levels in early childhood on specific
components of both IQ and school performance. Our findings
contribute to the existing evidence regarding low environmental
lead exposure and lasting, poor cognitive outcomes. This study
also identifies a partial mediating effect of blood lead concentra-
tion-IQ-school performance even for lead levels ,10 ug/dL. We
also examined blood lead concentrations ,10 ug/dL using
distinct cut-offs and were able to demonstrate that even at blood
lead concentration 8–10 ug/dL, children showed significant and
persistent poor neurocognitive outcomes. The impact of low-level
environmental lead exposure has important implications. Al-
though we focused on school performance as our long-term effect,
lead exposure has also been found to affect behavior in children
[62], delinquency in adolescence [2,63], and criminal behavior in
adults [17], and has also been shown to effect mental health such
as pessimism [64]. It is possible that the negative social and
psychological consequences of school failure may drive individuals
to negative behavior [65]. Continued follow-up and analysis of
multiple measures is necessary to help elucidate both long-term
effects and mechanisms through which low lead exposure,
particularly lead concentrations below 5 mg/dl (in accordance with the new CDC reference level), in early childhood can lead to
adverse neurobehavioral outcomes, which may ultimately result in
poor physical and mental well-being. These findings may have
important public health implications for early detection and
intervention of early childhood lead exposure, especially in
Chinese children.
Low Lead Levels and IQ and School Performance
PLOS ONE | www.plosone.org 6 May 2013 | Volume 8 | Issue 5 | e65230
Acknowledgments
Thanks are extended to participants from Jintan City and the Jintan
Cohort Study Group. We also thank research assistants Sophie Zhao,
Rebecca Loh, and Amy Yang for their help in this study. We are also very
grateful for Dr. Xiaoming Shen for his early contribution during blood lead
analysis, and Dr. Bruce Lanphear for his critical comments for the
manuscript development.
Author Contributions
Conceived and designed the experiments: JHL. Performed the experi-
ments: JHL CHY . Analyzed the data: YJW XCL JHL. Wrote the paper:
JHL LL YJW XCL.
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