TABLE 3. Summary of Studies.
|
Study |
Age diagnosed |
Iron therapy |
Follow-up |
Outcome |
Measurement |
Test subject |
Result |
|
Algarín et al.,32 2003 (cohort, Chile) |
6, 12, and 18 months |
Age 6 months: 15 mg/day ferrous sulfate for 1 year Age 12 and 18 months: 30 mg/day for at least 6 months |
Age 4 years |
Auditory brainstem responses |
Nicolet compact four machine |
29 early childhood IDA vs. 35 control |
The early childhood IDA group had longer absolute latencies (ms) in wave I (1.64 ± 0.02 vs. 1.51 ± 0.02, p < 0.001), wave III (3.78 ± 0.03 vs. 3.63 ± 0.02, <em>p</em> < 0.001), and wave IV (5.7 ± 0.03 vs. 5.4 ± 0.03, <em>p</em> 0.001) |
|
Visually evoked potentials |
Nicolet compact four machine |
40 early childhood IDA vs. 40 control |
The early childhood IDA group had a longer P100 latency (ms) (104.7 ± 0.7 vs. 97.3 ± 0.7, p 0.001) |
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|
Angulo-Barroso et al.,33 2013 (cohort, Chile) |
6, 12, and 18 months |
Age 6 months: 15 mg/day ferrous sulfate for 1 year Age 12 and 18 months: 30 mg/day for at least 6 months |
Age 4 years |
Motor activity during daytime sleep |
Actigraph |
23 early childhood IDA vs. 24 control |
The early childhood IDA group had more leg movements in active sleep (3.5 movement units/15 min ± 3.9 vs. 2.0 movement units/15 min ± 1.6, p = 0.04) |
|
Intra-individual variability in motor activity during daytime |
Actigraph |
23 early childhood IDA vs. 24 control |
The early childhood IDA group had a larger IIV in active sleep compared to the controls (114.3 ± 69.3 vs. 83.4 ± 46.2, p = 0.04) |
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|
Chang et al.,25 2011 (cohort, China) |
< 24 months |
Food supplement (6 mg iron, 4.1 mg zinc, 385 calcium, 0.2 mg vitamin B12, 7 ug vitamin D, 3.8 g protein), vitamin A every 6 months |
Age 4 years |
Positive effect during delay of gratification |
Designed the laboratory assessment |
27 early childhood IDA vs. 64 control |
Lower in the early childhood IDA group (4.7 ± 5.2 vs.11 ± 3.4, p 0.05) |
|
70 corrected IDA vs. 64 control |
Not significantly different (p > 0.05) between corrected IDA vs. control (9.7 ± 3.2 vs. 11 ± 3.4) |
||||||
|
Frustration tolerance |
Designed the laboratory assessment |
27 early childhood IDA vs. 64 control |
Lower in the early childhood IDA group (7.8 ± 11.4 vs. 24.8 ± 7.9, p 0.05) |
||||
|
70 corrected IDA vs. 64 control |
Not significantly different (p > 0.05) between corrected IDA vs. control (21.1 ± 3.5 vs. 24.8 ± 7.9) |
||||||
|
Passive behavior |
Designed the laboratory assessment |
27 early childhood IDA vs. 64 control |
Higher in the early childhood IDA group (23 ± 6.6 vs. 14.8 ± 4.3, p 0.05) |
||||
|
70 corrected IDA vs. 64 control |
Not significantly different (p > 0.05) between corrected IDA vs. control (18.1 ± 4.2 vs. 14.8 ± 4.3) |
||||||
|
Congdon et al.,26 2012 (cohort, Chile) |
6, 12, and 18 months |
Age 6 months: 15 mg/day ferrous sulfate for 1 year Age 12 and 18 months: 30 mg/day for at least 6 months |
Age 10 years |
Behavior |
Reaction time first phase (ms) |
50 early childhood IDA vs. 41 control |
Early childhood IDA group was slower than the control (1,085 ms ± 176 vs. 1,003 ms ± 205, p = 0.044) |
|
Reaction time second phase (ms) |
49 early childhood IDA vs. 42 control |
The article only stated that there is no significant difference and did not present exact numbers |
|||||
|
Memory searching process |
FN400 latency (ms) |
49 early childhood IDA vs. 40 control |
Early childhood IDA group was slower than the control (1,085 ms ± 176 vs. 1,003 ms ± 205, p = 0.044) |
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|
Neuronal process of wording |
P300 amplitude |
50 early childhood IDA vs. 42 control |
Early childhood IDA is lower than control (presented by a figure in the article); there was a main effect of childhood IDA with electrode interaction, F(2.87) = 4,878, p = 0.030 |
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|
Corapci et al.,27 2006 (cohort, Costa Rica) |
12-23 months |
IM iron or 3 mg/kg/day ferrous sulfate orally divided into two doses for 3 months |
5 years |
Positive effect |
PARCHISY and EC-HOME |
40 early childhood ID vs. 102 control |
Control group is higher (OR: 0.43, 95% CI: 0.22-0.86, p = 0.02) |
|
Physical activity |
PARCHISY and EC-HOME |
40 early childhood ID vs. 102 control |
Control group is higher (OR: 0.31, 95% CI: 0.15-0.66, p = 0.01) |
||||
|
Verbalization |
PARCHISY and EC-HOME |
40 early childhood ID vs. 102 control |
Control group is higher (OR: 0.39, 95% CI: 0.18-0.81, p = 0.01) |
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|
Doom et al.,28 2018 (cohort, Chile) |
12 and 18 months |
No iron formula, high iron formula (12 mg/l), low iron formula (2.3 mg/l) |
Age 11-17 years |
Social problems |
Youth self-report and child behavior checklist |
Early childhood ID (310) and IDA (135) vs. control (545) |
The early childhood ID group had greater social problems in adolescents (T-score contrast estimate = 2.71, 95% CI: 0.58-4.85, p = 0.01) |
|
ADHD problems |
Youth self-report and child behavior checklist |
Early childhood ID (310) and IDA (135) vs. control (545) |
The early childhood ID group had greater ADHD problems in adolescents (T-score contrast estimate = 2.63, 95% CI: 0.6-4.67, p = 0.01) |
||||
|
Oppositional defiant problems |
Youth self-report and child behavior checklist |
Early childhood ID (310) and IDA (135) vs. control (545) |
The early childhood ID group had greater oppositional defiant problems in adolescents (T-score contrast estimate = 3.33, 95% CI: 1.35-5.31, p = 0.01) |
||||
|
Conduct problems |
Youth self-report and child behavior checklist |
Early childhood ID (310) and IDA (135) vs. control (545) |
Early childhood ID has greater conduct problems in adolescents (T-score contrast estimate = 0.05, 95% CI: 0.02-0.08, p = 0.004) |
||||
|
Aggressive problems |
Youth self-report and child behavior checklist |
Early childhood ID (310) and IDA (135) vs. control (545) |
The early childhood ID group had greater aggressive problems in adolescents (T-score contrast estimate = 3.86, 95% CI: 1.56-6.16, p = 0.001) |
||||
|
Rule-breaking problems |
Youth self-report and child behavior checklist |
Early childhood ID (310) and IDA (135) vs. control (545) |
The early childhood ID group had greater rule-breaking problems in adolescents (T-score contrast estimate = 0.04, 95% CI: 0.01-0.07, p = 0.02) |
||||
|
PTSD problems |
Youth self-report and child behavior checklist |
Early childhood ID (310) and IDA (135) vs. control (545) |
The early childhood ID group had greater PTSD problems in adolescents (T-score contrast estimate = 2.52, 95% CI: 0.22-4.83, p = 0.03) |
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|
East et al.,17 2017 (cohort, Chile) |
6, 12, and 18 months |
Iron supplementation is considered as a covariate |
Age 5 years |
Dull effect |
CABI |
Early childhood ID (248) vs. control (483) |
Early childhood ID was not significantly related to dull effect at 5 years (beta = 0.06, B = 0.21, SE = 0.23) |
|
Early childhood IDA (142) vs. control (483) |
Early childhood IDA was significantly related to dull effect at 5 years (beta = 0.09, B = 0.5, SE = 0.26, p 0.05) |
||||||
|
East et al.,18 2019 (cohort, Chile) |
6, 12, and 18 months |
Iron supplementation is considered as a covariate |
Age 5 years |
Dull effect at 5 years |
CABI |
Early childhood ID (254) and IDA (140) vs. control (481) |
Early childhood ID was significantly related to dull effect at 5 years (beta = 0.1, B = 0.26, SE = 0.12, p 0.05) |
|
Felt et al.,19 2012 (cohort, Chile) |
6, 12, and 18 months |
Oral iron 15 mg/day for 1 year for infants identified at 6 months; oral iron 30 mg/day for at least 6 months for children identified at 12 and 18 months |
Age 10 years |
Cortisol 30 min and 45 min after venipuncture |
Electrochemiluminescence assays |
Early childhood IDA at age 6 (13) vs. control (23) |
The article only stated that there is no significant difference and did not present exact numbers |
|
Early childhood IDA at age 12 (24) vs. control (23) |
The early childhood IDA group at age 12 months had lower cortisol level significantly (30 min, 43.4 ± 13.5 mcg/dl vs. 97.8 ± 13.3 mcg/dl; 45 min, 36.4 ± 12.7 mcg/dl vs. 90.1 ± 12.5 mcg/dl) The curvature of the response pattern was significantly blunted for IDA-12 compared with the control (41.1 vs. -88.3, p 0.001) |
||||||
|
Gunnarsson et al.,31 2007 (cohort, Iceland) |
1 year |
Not stated |
Age 6 years |
Fine motor score |
Icelandic developmental inventory |
Early childhood ID (10) vs. control (56) |
Lower score in the early childhood ID group (46.7 ± 4.1 vs. 49.3 ± 2, p = 0.011) |
|
Early childhood iron depletion (26) vs. control (40) |
Lower score in the iron-depleted group (48 ± 3.3 vs. 49.5 ± 1.8, p = 0.045) |
||||||
|
Hossain et al.,20 2023 (cohort, Bangladesh) |
6-24 months |
IDA, 30 mg iron syrup daily for 6 months; stimulation, weekly play sessions at home for 9 months using a curriculum designed in Jamaica |
After 6 years (age 8-9 years) |
FSIQ, combined from the PRI and the VCI |
WASI-II |
Early childhood IDA with stimulation (102) vs. non-anemic with stimulation (92) |
Lower FSIQ in the early childhood IDA group (63.1 ± 7.2 vs. 65.7 ± 7), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
|
Early childhood IDA no stimulation (94) vs. non-anemic with no stimulation (84) |
Lower FSIQ int he early childhood IDA group (62.2 ± 6.1 vs. 62.8 ± 6.5), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||||
|
PRI |
WASI-II |
Early childhood IDA with stimulation (102) vs. non-anemic with stimulation (92) |
Lower PRI int he early childhood IDA group (71.8 ± 7.6 vs. 74.4 ± 8.2), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||
|
Early childhood IDA no stimulation (94) vs. non-anemic with no stimulation (84) |
Lower PRI in the early childhood IDA group (70.2 ± 7.4 vs. 71 ± 7.6), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||||
|
VCI |
WASI-II |
Early childhood IDA with stimulation (102) vs. non-anemic with stimulation (92) |
Lower VCI in the early childhood IDA group (57.4 ± 10.3 vs. 61.3 ± 10.5), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||
|
Early childhood IDA no stimulation (94) vs. non-anemic with no stimulation (84) |
Lower VCI in the early childhood IDA group (58.2 ± 8.3 vs. 58.5 ± 8.2), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||||
|
Word reading |
Wide Range Achievement test |
Early childhood IDA with stimulation (102) vs. non-anemic with stimulation (92) |
Lower word reading in the early childhood IDA group (88.1 ± 24.5 vs. 96.5 ± 22.6), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||
|
Early childhood IDA no stimulation (94) vs. non-anemic with no stimulation (84) |
Lower word reading in the early childhood IDA group (91.5 ± 23 vs. 92.5 ± 21.9), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||||
|
Word spelling |
Wide Range Achievement test |
Early childhood IDA with stimulation (102) vs. non-anemic with stimulation (92) |
Lower word spelling in the early childhood IDA group (80.8 ± 22.9 vs. 89.8 ± 21.4), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||
|
Early childhood IDA no stimulation (94) vs. non-anemic with no stimulation (84) |
Lower word spelling in the early childhood IDA group (83 ± 21.3 vs. 88.2 ± 20.8), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||||
|
Math computation |
Wide Range Achievement test |
Early childhood IDA with stimulation (102) vs. non-anemic with stimulation (92) |
Lower math computation in the early childhood IDA group (74 ± 14.8 vs. 80.6 ± 14.6), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||
|
Early childhood IDA no stimulation (94) vs. non-anemic with no stimulation (84) |
Lower math computation in the early childhood IDA group (77 ± 17.2 vs. 78 ± 16.5), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
||||||
|
- |
- |
- |
- |
Motor development |
MABC-2 |
Early childhood IDA with stimulation (102) vs. non-anemic with stimulation (92) |
Lower motor development in the early childhood IDA group (24 ± 6.8 vs. 25.2 ± 6.9), analysis of variance not performed between the IDA and non-anemic groups (significancy not reported) |
|
- |
- |
MABC-2 |
Early childhood IDA no stimulation (94) vs. non-anemic with no stimulation (84) |
Higher motor development in the early childhood IDA group (22.6 ± 7.6 vs. 22 ± 7.1), analysis of variance not performed between the IDA and non-anemic groups (significances not reported) |
|||
|
Hua et al.,21 2023 (cohort, China) |
9 months |
Iron therapy was given but not clearly described |
Age 8-9 years |
Behavioral performance (overall accuracy) |
Computer-based behavioral task |
Early childhood ID at 9 months (24) vs. control (27) |
Lower in the early childhood ID group (beta-coefficient = -0.08; 95% CI: -0.12–-0.04) |
|
Lozoff et al.,15 1991 (cohort, Costa Rica) |
12-23 months |
Iron therapy was given but not clearly described |
Age 5 years |
Gross motor |
Bruininks-Oseretsky test of motor proficiency |
Early childhood IDA (30) vs. control (64) |
Lower in the early childhood IDA group (52.1 ± 14.3 vs. 57.7 ± 13.3, p 0.05) |
|
ID corrected (50) vs. control (64) |
Higher in the early childhood ID-corrected group (62.1 ± 12.7 vs. 57.7 ± 13.3, not significant p > 0.05) |
||||||
|
Fine motor |
Bruininks-Oseretsky test of motor proficiency |
Early childhood IDA (30) vs. control (64) |
Lower in the early childhood IDA group (37 ± 11.6 vs. 41.9 ± 11, p 0.05) |
||||
|
ID corrected (50) vs. control (64) |
Higher in the early childhood ID-corrected group (43.9 ± 10.3 vs. 41.9 ± 11, not significant p > 0.05) |
||||||
|
Verbal IQ |
WPPSI |
Early childhood IDA (30) vs. control (64) |
Lower in the early childhood IDA group (101.1 ± 13.3 vs. 101.8 ± 12.3, not significant p > 0.05) |
||||
|
ID corrected (50) vs. control (64) |
Higher in the early childhood ID-corrected group (105.6 ± 11.9 vs. 101.8 ± 12.3, not significant p > 0.05) |
||||||
|
Performance IQ |
WPPSI |
Early childhood IDA (30) vs. control (64) |
Lower in the early childhood IDA group (98.9 ± 12.1 vs. 105.2 ± 11.2, p 0.05) |
||||
|
ID corrected (50) vs. control (64) |
Lower in the early childhood ID corrected group (105.1 ± 10.7 vs. 105.2 ± 11.2, not significant) |
||||||
|
FSIQ |
WPPSI |
Early childhood IDA (30) vs. control (64) |
Lower in the early childhood IDA group (100 ± 12.1 vs. 103.8 ± 11.3, p > 0.05) |
||||
|
ID corrected (50) vs. control (64) |
Lower in the early childhood ID-corrected group (105.9 ± 10.9 vs. 103.8 ± 11.3, not significant p > 0.05) |
||||||
|
McCarthy et al.,22 2021 (cohort, Ireland) |
At birth |
Not stated |
Age 5 years |
Internal problems |
CBCL |
Early childhood ID at birth (45) vs. control (534) |
Higher in the early childhood ID group [7 (2.5-12) vs. 5 (3-9.3), not significant p = 0.089] |
|
External problems |
CBCL |
Early childhood ID at birth (45) vs. control (534) |
Higher in the early childhood ID group [7 (4-12.5) vs. 5 (2-10), p = 0.018] |
||||
|
Total problems |
CBCL |
Early childhood ID at birth (45) vs. control (534) |
Higher in the early childhood ID group [21 (14-35) vs. 17 (9-29), not significant p = 0.054] |
||||
|
TABLE 3. Continued | |||||||
|
Study |
Age diagnosed |
Iron therapy |
Follow-up |
Outcome |
Measurement |
Test subject |
Result |
|
- |
- |
- |
- |
Verbal knowledge |
KBIT-2 |
Early childhood ID at birth (37) vs. control (499) |
Lower in the early childhood ID group [101 (99-105) vs. 109 (101-114), not significant p = 0.254] |
|
Non-verbal knowledge |
KBIT-2 |
Early childhood ID at birth (37) vs. control (500) |
Lower in the early childhood ID group [97 (94-100) vs. 100 (94-104), not significant p = 0.320] |
||||
|
IQ composite |
KBIT-2 |
Early childhood ID at birth (37) vs. control (497) |
Lower in the early childhood ID group [101 (99-105) vs. 104 (99-110), not significant p = 0.070] |
||||
|
Shafir et al.,34 2006 (cohort, Costa Rica) |
12-23 months |
Iron therapy was given but not clearly described |
Age 5-12 years |
Motor scores |
Bruininks-Oseretsky |
Early childhood ID (53) vs. control (132) |
Early childhood ID group has lower motor score across all age (5-12 years), p 0.001 |
|
Thorisdottir et al.23 2013 (cohort, Iceland) |
12 months |
Not stated |
Age 6 years |
Gross motor |
Icelandic-Developmental Inventory |
Early childhood iron depletion (6) vs. control (102) |
Lower in the early childhood iron-depleted group (adjusted mean diff -2.9, 95% CI: -6.9, 1.1), not significant p = 0.152 |
|
Fine motor |
Icelandic-Developmental Inventory |
Early childhood iron depletion (6) vs. control (102) |
Lower in the early childhood iron-depleted group (adjusted mean diff -0.2, 95% CI: -2.6, 2.3), not significant p = 0.896 |
||||
|
Self-help |
Icelandic-Developmental Inventory |
Early childhood iron depletion (6) vs. control (102) |
Lower in the early childhood iron-depleted group (adjusted mean diff -4, 95% CI: -7.4, -0.7, p = 0.019) |
||||
|
Comprehension |
Icelandic-Developmental Inventory |
Early childhood iron depletion (6) vs. control (102) |
Lower in the early childhood iron-depleted group (adjusted mean diff -0.7, 95% CI: -3.6, 2.1), not significant p = 0.612 |
||||
|
Expression |
Icelandic-Developmental Inventory |
Early childhood iron depletion (6) vs. control (102) |
Higher in the early childhood iron-depleted group (adjusted mean diff 1.1, 95% CI: -2, 4.1), not significant p = 0.493 |
||||
|
Learning |
Icelandic-Developmental Inventory |
Early childhood iron depletion (6) vs. control (102) |
Higher in the early childhood iron-depleted group (adjusted mean diff 0.7, 95% CI: -5.4, 6.7), not significant p = 0.831 |
||||
|
Motor, combined |
Icelandic-Developmental Inventory |
Early childhood iron depletion (6) vs. control (102) |
Lower in the early childhood iron-depleted group (adjusted mean diff -5.5, 95% CI: -11.1, 0.03), not significant p = 0.051 |
||||
|
Verbal, combined |
Icelandic-Developmental Inventory |
Early childhood iron depletion (6) vs. control (102) |
Lower in the early childhood iron-depleted group (adjusted mean diff -0.3, 95% CI: -8.3, 7.7), not significant p = 0.939 |
||||
|
Total developmental index |
Icelandic-Developmental Inventory |
Early childhood iron depletion (6) vs. control (102) |
Lower in the early childhood iron-depleted group (adjusted mean diff -2.6, 95% CI: -8.1, 2.8), not significant p = 0.336 |
||||
|
Yehuda and Yehuda,24 2006 (cohort, Israel) |
12 months |
Not stated |
Age 10 years |
Auditory function |
Auditory test |
Early childhood ID (17) vs. control (17) |
Both groups showed normal function (hearing threshold < 20 dB) |
|
FSIQ |
WISC revised |
Early childhood ID (17) vs. control (17) |
Lower in the early childhood ID group (96.7 ± 2.1 vs. 105.1 ± 1.3, significant p = 0.001) |
||||
|
Verbal IQ |
WISC |
Early childhood ID (17) vs. control (17) |
Lower in the early childhood ID group (99.1 ± 2.4 vs. 104.5 ± 1.8, significant p = 0.05) |
||||
|
Performance IQ |
WISC |
Early childhood ID (17) vs. control (17) |
Lower in the early childhood ID group (95.9 ± 2.2 vs. 104.9 ± 2.4, significant p = 0.001) |
||||
|
Behavioral: appetite |
5-point rating scale |
Early childhood ID (17) vs. control (17) |
Lower in the early childhood ID group (3.5 ± 0.6 vs. 4.9 ± 0.7, not significant p > 0.05) |
||||
|
Behavioral: good mood |
5-point rating scale |
Early childhood ID (17) vs. control (17) |
Lower in the early childhood ID group (3.8 ± 0.8 vs. 4.8 ± 0.8, not significant p > 0.05) |
||||
|
Behavioral: ability to concentrate |
5-point rating scale |
Early childhood ID (17) vs. control (17) |
Lower in the early childhood ID group (3.5 ± 0.6 vs. 4.7 ± 0.5, not significant p > 0.05) |
||||
|
Behavioral: fatigue during the day |
5-point rating scale |
Early childhood ID (17) vs. control (17) |
Lower in the early childhood ID group (3 ± 0.5 vs. 4.5 ± 0.8, significant p = 0.05) |
||||
|
Behavioral: organizing academic materials |
5-point rating scale |
Early childhood ID (17) vs. control (17) |
Lower in the early childhood ID group (4 ± 0.6 vs. 4.8 ± 0.6, not significant p > 0.05) |
||||
|
Behavioral: quality of sleep |
Early childhood ID (17) vs. control (17) |
Lower in the early childhood ID group (3.1 ± 1.3 vs. 4.8 ± 1, significant p = 0.05), |
|||||
|
Morning saliva cortisol levels |
Radioimmunoassay |
Early childhood ID (17) vs. control (17) |
Higher in the early childhood ID group (2.8 ± 0.4 nmol/l vs. 2.5 ± 0.7 nmol/l, significant p = 0.001) |
||||
ID, iron deficiency; IDA, iron deficiency anemia; PARCHISY, Parent-Child Interaction System; EC-HOME, Early Childhood version of the Home Observation for Measurement of the Environment; OR, odds ratio; CI, confidence interval; ADHD, attention deficit hyperactivity disorder; PTSD, posttraumatic stress disorder; CABI, Children Adaptive Behavior Inventory; FSIQ, Full-Scale Intelligence Quotient, PRI, Performance Reasoning Index; VCI, Verbal Comprehension Index; WASI, Wechsler Abbreviated Scale of Intelligence; MABC, Movement Assessment Battery for Children; WPPSI, Wechsler Preschool and Primary Scale of Intelligence; CBCL, Child Behavior Checklist; KBIT, Kaufman Brief Intelligence Test; WISC, Wechsler Intelligence Scale for Children.