Supplement
1.
Studies
assessing
exposure
neurodevelopmental/cognitive or behavioral outcomes.
to
cadmium
and
1
Authors &
Study design Location
Year
Neurodevelopment / Cognition
Jeong et al.
Prospective
South
2015 [45]
cohort
Korea
Sample
size
Exposure Measure
[Reported level]
Outcome
Measure
Confounders
Major Finding
119
Prospective
cohort
Spain
385
FSIQ,
VIQ, PIQ
(WPPSI)
at 5 yrs
MSCA at
4 yrs
Kim Y. et
al. 2013 [46]
Prospective
cohort
South
Korea
884
BSID-II at
6 mo
Kippler et
al. 2012 [47]
Prospective
cohort
Banglade
sh
1,305
Prenatal blood Cd
(“early” <20th week
and “late” near
deliverya)
[GMearly: 1.42 μg/L,
Range 0.03-9.87
μg/L]
Urine Cd (1st
trimester and child
at 5 yr)
[Mean: 0.63 μg/L at
1st trimester, 0.22
μg/L at 5 yrs]
Child’s gender,
parents’ education,
family income, and
maternal BMI.
Child’s age, quality of
test, gender, maternal
PIQ and VIQ, SES,
country of birth,
maternal mental
health, maternal age,
child’s mood changes,
and child’s diagnosis
of neuropsychological
disorder.
Child’s gender, birth
weight, maternal age,
maternal education
level, family income,
breastfeeding status
and residential area.
Significant inverse
association with PIQ.
Forns et al.
2014 [43]
Maternal blood Cd
in “early pregnancy”
(~20th week)
[Mean: 1.15 μg/L]
Maternal urine Cd
[Median: 9.08 and
11.52 μg/L at
1st and 3rd trimester]
Child’s age, gender,
tester (model 1) as
well as birth weight,
birth order, height-forage, HOME, maternal
BMI, maternal IQ,
SES (model 2) and
joint maternal and
Significant inverse
association between maternal
and concurrent urines with
VIQ, PIQ, and FSIQ.
FSIQ,
VIQ, PIQ
(WPPSI)
at 5 yrs
Inverse but not significant
association with 1st and 3rd
trimester exposure and
cognitive score of MSCA.
No significant association.
2
Tian et al.
2009 [49]
Prospective
cohort
China
106
Cord blood Cd
[Median: 0.06 μg/L,
Range 0.02-1.78
μg/L]
FSIQ,
VIQ, PIQ
(WPPSIR) at 4.5
yrs
Cao et al.
2009 [41]
Nested
cohort within
RCTa
USA
441
Blood Cd at 2 yrs,
[GM (95%CI): 0.21
(0.20–0.22) μg/La]
BSID-II at
2 yrs, IQ
(WPPSIR) at 5 yrs
and IQ
(WISCIII) at 7
yrs
Al-Saleh et
al. 2014 [40]
Crosssectional
Saudi
Arabia
1,578
Cord blood Cd,
maternal blood (at
delivery), and
placenta Cd
[Mediancord: 0.70
μg/L]
1- and 5minute
Apgar
score
RodriguezBarranco et
al. 2014 [48]
Crosssectional
Spain
261
Urine and hair Cd
[GMurine: 0.75 μg/g
creatinine, GMhair:
0.01 μg/g]
IQ
(WISCIV) at 6-9
yrs
concurrent urine Cd
(model 3)
Cord blood lead,
maternal age, height,
and weight, gravidity,
gestational age,
method of delivery,
breastfeeding, SES,
environmental
tobacco, annual
income, and nursery
school age.
Treatment group, age,
caregiver’s IQ, center
location, single parent,
language, race, gender,
parent’s employment
status, parents’
education, and
concurrent blood lead
level.
Maternal age, parity
(model 1) as well as
gestational age (model
2), and preterm births
excluded (model 3)
Child’s gender, age,
BMI, mother’s age,
IQ, and education,
monthly family
income, family status,
Significant inverse
association with PIQ and
FSIQ.
No significant associations.
Suggestive trends of an
inverse relationship with IQ
at ages 5 and 7.
Significant inverse
association between cord
blood Cd and 5-min Apgar
score. No association with 1min Apgar score.
Significant inverse
association between urine Cd
and verbal comprehension
(boys and girls) and FSIQ in
boys only.
3
Ciesielski et
al. 2013 [42]
Crosssectional
USA
(NHANE
S)
2,1892,196
Urine Cd
[Median: 0.11 μg/L,
Range: 0-14.94
μg/L]
LD and
special
education
assessed
by
parental
report at
6-15 yrs
GarciaEsquinas et
al. 2013 [44]
Crosssectional
Spain
112
Cord blood Cd
[Median: 0.29 μg/L,
GM: 0.27 μg/L]
1- and 5minute
Apgar
score
Behavior
Forns et al.
2014 [43]
Prospective
cohort
Spain
385
ADHDDSM-IV
at 4 yrs
Sieon et al.
2013 [52]
Prospective
cohort
Belgium
257
Urine Cd
[Median: 9.08 and
11.52 μg/L at
1st and 3rd trimester]
Cord blood Cd
[Mean: 0.22 μg/L]
SDQ
(emotion,
conduct,
hyperactiv
ity, peer,
and social
problem
domains)
gestational age,
vegetables and cereal
intake, and levels of
Mn, As, Pb, Hg in
urine.
Urinary creatinine
(model 1) as well as
child’s age, gender,
blood lead, smoker in
the home, serum
cotinine, prenatal
smoke exposure, and
poverty income ratio
(model 2).
Child’s gender,
gestational age,
maternal age, cigarette
smoking.
Child’s age, maternal
social class, and
maternal mental
health.
Child’s gender,
maternal BMI, age,
pregnancy weight
gain, smoking during
pregnancy, paternal
BMI, current smoking
by either parent,
grandmother smoking
Increasing Cd was
significantly associated with
increased LD and special
education.
Significant inverse
association with high
(>median) cord blood Cd and
lower 1- and 5-min Apgar
scores.
No significant association.
Increasing Cd was
significantly associated with
an increased risk of emotional
problems (boys only).
4
at 7-8 yrs
Cao et al.
2009 [41]
Nested
cohort within
RCTa
USA
441
Blood Cd at 2 yrs,
[GM (95%CI): 0.21
(0.20–0.22) μg/La]
RodriguezBarranco et
al. 2014 [48]
Crosssectional
Spain
261
Urine and hair Cd
[GMurine: 0.75 μg/g
creatinine, GMhair:
0.01 μg/g]
NEPSY
and
CPRS-R
at 5 yrs,
NEPSY,
CPT,
CVLTC,
WLPB-R,
NEES,
BASCTRS, and
BASCPRS at 7
yrs
Three
computeri
zed BARS
behavioral
tests
(RTT,
CPT, and
SAT) at 69 yrs
before mother’s birth,
parents’ education
level, and serious
infections since birth.
Treatment group, age,
caregiver’s IQ, center
location, single parent,
language, race, child’s
gender, parent’s
employment status,
parents’ education,
and concurrent blood
lead level.
Child’s gender, age,
BMI, mother’s age
and education,
monthly family
income, family status,
gestational age,
vegetables and cereal
intake, and levels of
Mn, As, Pb, Hg in
urine (SAT model) as
well as maternal IQ
(RTT model),
maternal occupation,
residence area, and
child’s weight and
No significant associations.
Suggestive trends of an
association between
increasing Cd and behavioral
problems.
No significant association.
5
Ciesielski et
al. 2013 [42]
Crosssectional
USA
(NHANE
S)
2,1892,196
Urine Cd
[Median: 0.11 μg/L,
Range: 0-14.94
μg/L]
ADHD
assessed
by
parental
report at
6-15 yrs
SzkupJablonska et
al. 2012 [53]
Crosssectional
Poland
78
Blood Cd
[Mean: 0.22 μg/L,
Range: 0.05-2.91
μg/L]
Bao et al.
2009 [50]
Crosssectional
China
549
Hair Cd
[Median: 7.33 μg/g]
ParentADHDrating
scale-IV
at yrs 2-18
CBCL at
7-16 yrs
Kim S. et al.
2013 [51]
Case-control
USA
129
(71/58)
Blood Cd
[GM: 0.02, Range:
0.0007-8.69 μg/L a]
ADHDDSM-IV
at 5-12 yrs
Yousef et al.
2011 [54]
Matched
case-control
UAE
92
Blood Cd
[Not reported;
Range: ~0 – 0.03
μg/L]
ADHD
(STICRS) and
at 5-15 yrs
a
height at birth (CPT
model)
Urinary creatinine
(model 1) as well as
child’s age, gender,
blood lead, smoker in
the home, serum
cotinine, prenatal
smoke exposure, and
poverty income ratio
(model 2).
None reported.
Child’s gender, age,
income, and parents’
education.
Age group, child’s
gender, race, location,
maternal smoking and
alcohol use, SES, and
environmental tobacco
smoke.
None reported.
No significant association.
No significant association.
Increasing Cd was
significantly associated with
increased withdrawn, social
& attention problems
No significant association.
No significant association.
See manuscript for detailed information. GM Geometric mean, CI confidence interval.
6
ADHD attention deficit hyperactivity disorder, ADHD-DSM ADHD Diagnostic and Statistical Manual of Mental Disorders,
BARS Behavioral Assessment Research System, BASC-PRS parent rating scale, BASC-TRS Behavioral Assessment System for
Children – Teacher rating scale, BSID Bayley Scales of Infant Development, CBCL Child behavior check-list, CPRS-R Conners’
Parent Rating Scale-Revised, CPT Continuous Performance Test, CVLT California Verbal Learning Test, CVLTC California Verbal
Learning Test for Children, FSIQ Full scale IQ, HOME Home Observation for Measurement of the Environment, IQ intelligence
quotient, LD Learning disability, MSCA McCarthy Scales of Children’s Abilities, NEES Neurologic Examination for Subtle Signs,
NEPSY Developmental Neuropsychological Assessment, NHANES National Health and Nutrition Examination Survey, PIQ
Performance IQ, RCT Randomized Clinical Trial, RTT Reaction Time Test, SAT Selective Attention Test, SDQ Strengths and
Difficulties Questionnaire, SES socioeconomic status, STI-CRS Short Ten-Item Conners’ Rating Scale, VIQ Verbal IQ, WISC
Wechsler Intelligence Scale for Children, WLPB-R Woodcock Language Proficiency Battery-Revised, WPPSI-R Wechsler Preschool
and Primary Scale of Intelligence Revised Edition.
7