Soo-Young Bhang

Phthalates Exposure and Attention-Deficit/Hyperactivity Disorder in School-Age Children

BACKGROUNDnVery few studies have examined the association between attention-deficit/hyperactivity disorder (ADHD) and phthalate exposure in humans. The aim of this study was to investigate the impact of phthalates on symptoms of ADHD in school-age children.nnnMETHODSnA cross-sectional examination of urine phthalate concentrations was performed, and scores on measures of ADHD symptoms and neuropsychological dysfunction with regard to attention and impulsivity were obtained from 261 Korean children, age 8-11 years.nnnRESULTSnMono-2-ethylheyl phthalate (MEHP) and mono-2-ethyl-5-oxohexylphthalate (MEOP) for metabolites of Di-2-ethylhexylphthalate (DEHP) and mono-n-butyl phthalate (MNBP) for metabolites of dibutyl phthalate (DBP) were measured in urine samples. The mean concentrations of MEHP, MEOP, and MNBP were 34.0 microg/dL (SD = 36.3; range: 2.1-386.7), 23.4 microg/dL (SD = 23.0; range: .75-244.8), and 46.7 microg/L (SD = 21.4; range: 13.2-159.3), respectively. After adjustment for covariates, teacher-rated ADHD scores were significantly associated with DEHP metabolites but not with DBP metabolites. We also found significant relationships between the urine concentrations of metabolites for DBP and the number of omission and commission errors in continuous performance tests (CPT) after adjustment for covariates.nnnCONCLUSIONnThe present study showed a strong positive association between phthalate metabolites in urine and symptoms of ADHD among school-age children.

Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children

Background Concern over phthalates has emerged because of their potential toxicity to humans. Objective We investigated the relationship between the urinary concentrations of phthalate metabolites and children’s intellectual functioning. Methods This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuropsychological tests were obtained from both the children and their mothers. Results We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 μg/L [geometric SD (GSD) = 2.2 μg/L; range, 0.5–445.4], 18.0 μg/L (GSD = 2.4; range, 0.07–291.1), and 48.9 μg/L (GSD = 2.2; range, 2.1–1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children’s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables. Conclusion Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.

Co-exposure to environmental lead and manganese affects the intelligence of school-aged children

BACKGROUNDnExposure to environmental levels of lead (Pb) and manganese (Mn) has been associated with detrimental effects to neurodevelopment. However, little is known about the potential association between environmental levels of Pb and Mn on intelligence of children. The aims of the study were to investigate the association of community level of Pb and Mn with the intelligence of school-aged children, and to explore the implications of joint exposure to these two heavy metals.nnnMETHODSnA cross-sectional examination of blood Pb and Mn concentrations was performed, and the intelligence quotient (IQ) was determined for 261 Korean children aged 8-11 years.nnnRESULTSnThe mean blood concentrations of Pb and Mn were 1.73 microg/dL (SD=0.8; median=1.55; range=0.42-4.91) and 14.3 microg/L (SD=3.8; median=14.0; range=5.30-29.02), respectively. Both Pb and Mn showed significant linear relationship with full-scale IQ (Pb, beta=-0.174, p=0.005; Mn, beta=-0.123, p=0.042) and verbal IQ (Pb, beta=-0.187, p=0.003; Mn, beta=-0.127, p=0.036). Blood Pb (DeltaR(2)=0.03) and Mn (DeltaR(2)=0.01) explained 4% of the variances of the full-scale IQ and 5% of the variances of the verbal IQ. When Pb and Mn levels were entered as predictive variables, additive increase in the explained variances was observed. Finally, full-scale IQ and verbal IQ of the children with blood Mn>14 microg/L showed significant association with Pb, whereas group with Mn<14 microg/L did not, suggesting effect modification between Pb and Mn.nnnCONCLUSIONSnThe present study suggests the presence of additive interaction and effect modification between Pb and Mn on the intelligence of school-aged children, suggesting more attention should be paid to preventing the exposure of disadvantaged children to various combinations of toxic materials.

Effect of environmental exposure to lead and tobacco smoke on inattentive and hyperactive symptoms and neurocognitive performance in children.

BACKGROUNDnThe present study assessed the association between blood lead and urinary cotinine levels and inattentive and hyperactive symptoms and neurocognitive performance in children.nnnMETHODSnA total of 667 children (age range 8-11) were recruited from nine schools in five Korean cities. The teachers and parents completed the Korean version of the Attention-deficit/hyperactivity disorder Rating Scales (K-ARS), and the children performed neurocognitive tests. Blood lead and urinary cotinine levels were then measured.nnnRESULTSnThe inattentive, hyperactive, and total scores of the teacher-rated K-ARS were positively associated with blood lead level, and the results of the continuous performance test (CPT), Stroop Color-Word Test, and Childrens Color Trails Test were inversely associated with urinary cotinine level when controlled for age, gender, fathers educational level, maternal IQ, childs IQ, residential area, birth weight, and cotinine (for lead) or lead (for cotinine). The association between blood lead level and commission errors score on the CPT disappeared when the effect of urinary cotinine level was controlled.nnnCONCLUSIONSnThese findings indicate that environmental exposure to tobacco smoke in children is associated with poor neurocognitive performance, and low levels of lead are associated with inattention and hyperactivity symptoms.

Bisphenol A in relation to behavior and learning of school-age children

BACKGROUNDnBisphenol A (BPA) has been shown to affect brain and behavior in rodents and nonhuman primates, but there are few studies focusing on its relationship to human neurobehavior. We aimed to investigate the relationship between environmental exposure to BPA and childhood neurobehavior.nnnMETHODSnUrinary BPA concentrations and behavioral and learning characteristics were assessed in a general population of 1,089 children, aged 8-11 years. The main outcome measures were the Child Behavior Checklist (CBCL) and the Learning Disability Evaluation Scale (LDES).nnnRESULTSnUrinary levels of BPA were positively associated with the CBCL total problems score and negatively associated with the learning quotient from the LDES. The linear association with the CBCL anxiety/depression score and the quadratic association with the LDES listening score were significant after correction for multiple comparisons.nnnCONCLUSIONSnEnvironmental exposure to BPA might be associated with childhood behavioral and learning development. The results suggest possible nonmonotonic relationships.

Relationship between blood manganese levels and children's attention, cognition, behavior, and academic performance—A nationwide cross-sectional study

Manganese (Mn) is neurotoxic at high concentrations. However, Mn is an essential element that can protect against oxidative damage; thus, extremely low levels of Mn might be harmful. Our aim was to examine whether either high or low environmental Mn exposure is related to academic and attention function development among school-aged children. This cross-sectional study included 1089 children 8-11 years of age living in five representative areas in South Korea. Blood Mn, blood lead, and urine cotinine were measured. We assessed IQ with the Wechsler Abbreviated Scale of Intelligence; attention with a computerized continuous performance test called the Attention-deficit/hyperactivity disorder (ADHD) Diagnostic System (ADS), the Korean version of the Stroop Color-Word Test, the Childrens Color Trails Test (CCTT), and the ADHD Rating Scale; academic functions with the Learning Disability Evaluation Scale (LDES); and emotional and behavioral problems with the Korean version of the Child Behavior Checklist (CBCL). We further assessed the presence of ADHD using a highly structured diagnostic interview, the Diagnostic Interview Schedule for Children Version IV (DISC-IV). The median blood concentration of Mn was 14.14 µg/L. We observed a nonlinear association between the CCTT2 completion time and the CPT commission error (F=3.14, p=0.03 and F=4.05, p=0.01, respectively). We divided the data into three groups: lower (<8.154 µg/L), and upper 5th percentile (>21.453 µg/L) and middle 90th percentile to determine whether a lack or overload of Mn could cause adverse effects. After adjusting for urine cotinine, blood lead, childrens IQ, and other potential confounders, the high Mn group showed lower scores in thinking (B=-0.83, p=0.006), reading (B=-0.93, p=0.004), calculations (B=-0.72, p=0.005), and LQ (B=-4.06, p=0.006) in the LDES and a higher commission error in the CPT (B=8.02, p=0.048). The low Mn group showed lower color scores in the Stroop test (B=-3.24, p=0.040). We found that excess Mn in children is associated with lower scores of thinking, reading, calculation, and LQ in the LDES and higher scores of commission error in the ADS test. In contrast, lower Mn in children is associated with lower color scores in the Stroop test. The findings of this cross-sectional study suggest that excess exposure or deficiency of Mn can cause harmful effects in children.

Association between blood lead levels (< 5 μg/dL) and inattention-hyperactivity and neurocognitive profiles in school-aged Korean children

OBJECTIVESnThe association between low blood lead levels (<5 μg/dL) and the inattention-hyperactivity symptoms and neurocognitive profiles of school-aged Korean children was investigated.nnnMETHODSnWe measured blood lead levels in 256 Korean children aged 8-10 years. Teachers completed the Attention-Deficit Hyperactivity Disorder Rating Scale (T-ARS)-IV to assess inattentive and hyperactive symptoms. Parents completed the Korean version of the Learning Disability Evaluation Scale (K-LDES). Children performed neurocognitive tests [The Continuous Performance Test (CPT), the Childrens Color Trails Test, and the Stroop Color and Word Test (SCWT)].nnnRESULTSnA linear regression analysis indicated that the blood lead concentrations were associated with the inattention scores [B=4.8, S.E.=1.6, 95% confidence interval (CI): 1.5-8.0], the hyperactivity subscores (3.1, 1.4, 0.3-5.9), and the total score (7.9, 2.9, 2.1-13.6) on the T-ARS; the number of omission errors on the CPT (20.6, 7.1, 6.5-34.6); the listening (-1.4, 0.7, -2.8 to -0.1), reading (-2.1, 0.7, -3.4 to -0.7), writing (-2.0, 0.7, -3.4 to -0.6), spelling (-2.2, 0.7, -3.7 to -0.7), and calculating (-1.8, 0.7, -3.1 to -0.4) scores on the K-LDES; and the color-word score on the SCWT (-6.7, 3.4, -13.3 to -0.1). A logistic regression analysis indicated that the probability of inattentive and hyperactive symptoms was increased with higher blood lead levels in boys with an odds ratio of 2.768 [B=1.018, S.E.=0.487, p=0.036, 95% CI: 1.066-7.187].nnnCONCLUSIONnThis study suggests that even low blood lead levels (<5 μg/dL) are associated with inattentive and hyperactivity symptoms and learning difficulties in school-aged children.

Environmental lead exposure and attention deficit/hyperactivity disorder symptom domains in a community sample of South Korean school-age children.

Background Low-level environmental exposure to lead has been associated with both reduced intelligence and symptoms of attention deficit/hyperactivity disorder (ADHD). However, few studies have estimated the association of lead and intelligence independent of ADHD, and it is not clear from previous studies whether lead is associated with both inattention and impulsivity ADHD symptoms. Objectives We estimated mutually adjusted associations of environmental lead exposure with both intelligence and ADHD symptoms, and associations between lead and specific ADHD-related domains. Methods Blood lead concentrations were measured in a general population of 1,001 children 8–11 years of age. We used multivariable linear regression models to estimate associations of blood lead concentrations with IQ scores, teacher and parent ratings of ADHD symptoms, and measures of inattention and impulsivity. Models were adjusted for demographic variables and other environmental exposures (blood levels of mercury and manganese, urinary concentrations of cotinine, phthalate metabolites, and bisphenol A). Results Associations of blood lead with lower IQ and higher impulsivity were robust to adjustment for a variety of covariates. When adjusted for demographic characteristics, other environmental exposures, and ADHD symptoms or IQ, a 10-fold increase in blood lead concentration was associated with lower Full-Scale IQ (–7.23; 95% CI: –13.39, –1.07) and higher parent- and teacher-rated hyperactivity/impulsivity scores (ADHD Rating Scale, 1.99; 95% CI: 0.17, 3.81 and 3.66; 95% CI: 1.18, 6.13, respectively) and commission errors (Continuous Performance Test, 12.27; 95% CI: –0.08, 24.62). Blood lead was not significantly associated with inattention in adjusted models. Conclusions Low-level lead exposure was adversely associated with intelligence in school-age children independent of ADHD, and environmental lead exposure was selectively associated with impulsivity among the clinical features of ADHD. Citation Hong SB, Im MH, Kim JW, Park EJ, Shin MS, Kim BN, Yoo HJ, Cho IH, Bhang SY, Hong YC, Cho SC. 2015. Environmental lead exposure and attention deficit/hyperactivity disorder symptom domains in a community sample of South Korean school-age children. Environ Health Perspect 123:271–276;u2002http://dx.doi.org/10.1289/ehp.1307420

Subthreshold attention-deficit/hyperactivity disorder is associated with functional impairments across domains: a comprehensive analysis in a large-scale community study

This study compared children who experience attention-deficit/hyperactivity disorder (ADHD) symptoms but do not meet criteria (i.e., subthreshold ADHD) with those with the full syndrome and healthy controls. Presence of ADHD symptoms was determined in a nationwide community sample of 921 children, aged 8–11xa0years. The main outcome measures comprised attentional symptoms, comorbidity profiles, academic performance, and neurocognitive ability (i.e., ADHD Rating Scale, Child Behavior Checklist, Learning Disability Evaluation Scale, and Stroop Color-Word Test, respectively). Subthreshold ADHD was equally prevalent in boys and girls, and more prevalent in low-income families. Throughout all the outcome measurements, subthreshold ADHD was both a significantly milder condition than full syndrome ADHD and a significantly more severe condition than non-ADHD status. The findings were consistent across the total as well as the subtest scores, and after correction for multiple comparisons (pxa0<xa00.0017). Children with subthreshold ADHD were found to experience significant symptoms and functional impairments. The results of this study support the clinical relevance of subthreshold ADHD in a childhood population. Subthreshold diagnostic criteria for ADHD may be more sensitive in detecting ADHD symptoms in girls than the full syndrome criteria, and subthreshold clinical, cognitive, and behavioral symptoms of ADHD may occur in a subset of children who are possibly more sensitive to their environment. Further consideration about the diagnostic threshold for ADHD may particularly benefit girls and children in low-income families.

Are Teacher Ratings and Parent Ratings Differently Associated with Children's Intelligence and Cognitive Performance?

Objective The present study investigated whether teacher ratings and parent ratings of inattentive or hyperactive/impulsive symptoms were differently associated with intelligence or cognitive performance in Korean children. Methods Six hundred sixty-seven children were recruited from nine schools in five Korean cities. The teachers and parents of 580 of these children (9.0±0.7 years old, 333 boys and 306 girls) completed the Korean version of the Attention-Deficit/Hyperactivity Disorder Rating Scales (K-ARS), and the children performed the abbreviated form of the Korean Educational Development Institute-Wechsler Intelligence Scales (KEDI-WISC) and a neurocognitive battery consisting of the continuous performance test, the Childrens Color Trails Test, and the Stroop Color-Word Test. Diagnosis of full-syndrome and subthreshold attention-deficit/hyperactivity disorder (ADHD) were based on the Diagnostic Interview Schedule for Children Version-IV (DISC-IV). Results The level of agreement between teacher and parent ratings was low (r=0.21-0.26) in children with full-syndrome and subthreshold ADHD and low to moderate (r=0.31-0.41) in the normative sample. Teacher-rated ARS showed significant correlations with most sub-scores of KEDI-WISC and the neurocognitive battery both in the normative sample (r=-0.50-0.37) and in children with full-syndrome and subthreshold ADHD (r=-0.26-0.29). Correlations between parent-rated ARS and cognitive tests were lower and were found in fewer subscales of tests. Conclusion These results suggest the importance of considering the teachers report of a childs school functioning during the assessment of ADHD.