Effect of Iron Supplementation in Children with Attention-Deficit/Hyperactivity Disorder and Iron Deficiency: A Randomized Controlled Trial.

OBJECTIVES: To determine the effectiveness of combined iron supplementation and methylphenidate treatment on attention-deficit/hyperactivity disorder (ADHD) symptoms in children/adolescents with ADHD and iron deficiency compared with methylphenidate alone. METHODS: In total, 116 children/adolescents with ADHD were screened for iron deficiency. Participants who exhibited iron deficiency were randomized into 2 groups (ferrous supplementation vs placebo). Vanderbilt ADHD rating scales were completed by parents and teachers at prestudy and poststudy periods. Student's t tests were used to determine improvements of Vanderbilt scores between the groups. RESULTS: Among 116 children who participated in this study, 44.8% (52/116) met the criteria for iron deficiency. Of the total 52 participants with iron deficiency, 26 were randomized to the ferrous group and 26 to the placebo group. Most participants in each group had been prescribed short-acting methylphenidate twice daily in the morning and at noon. After a 12-week study period, total parents' Vanderbilt ADHD symptom scores showed a significant improvement between the groups (mean decrement = -3.96 ± 6.79 vs 0 ± 6.54, p = 0.037). However, teachers' Vanderbilt ADHD symptom scores showed no difference between the groups. CONCLUSION: Children with ADHD and iron deficiency being on methylphenidate and iron supplementation had shown improvement of ADHD symptoms that were reported by parents.

Effectiveness of neurofeedback versus medication for attention-deficit/hyperactivity disorder.

BACKGROUND: Neurofeedback (NF) is an operant conditioning procedure that trains participants to self-regulate brain activity. NF is a promising treatment for attention-deficit/hyperactivity disorder (ADHD), but there have been only a few randomized controlled trials comparing the effectiveness of NF with medication with various NF protocols. The aim of this study was therefore to evaluate the effectiveness of unipolar electrode NF using theta/beta protocol compared with methylphenidate (MPH) for ADHD. METHODS: Children with newly diagnosed ADHD were randomly organized into NF and MPH groups. The NF group received 30 sessions of NF. Children in the MPH group were prescribed MPH for 12 weeks. Vanderbilt ADHD rating scales were completed by parents and teachers to evaluate ADHD symptoms before and after treatment. Student's t-test and Cohen's d were used to compare symptoms between groups and evaluate the effect size (ES) of each treatment, respectively. RESULTS: Forty children participated in the study. No differences in ADHD baseline symptoms were found between groups. After treatment, teachers reported significantly lower ADHD symptoms in the MPH group (P = 0.01), but there were no differences between groups on parent report (P = 0.55). MPH had a large ES (Cohen's d, 1.30-1.69), while NF had a moderate ES (Cohen's d, 0.49-0.68) for treatment of ADHD symptoms. CONCLUSION: Neurofeedback is a promising alternative treatment for ADHD in children who do not respond to or experience significant adverse effects from ADHD medication.

Chromosomal microarray analysis in a cohort of underrepresented population identifies SERINC2 as a novel candidate gene for autism spectrum disorder.

Chromosomal microarray (CMA) is now recognized as the first-tier genetic test for detection of copy number variations (CNVs) in patients with autism spectrum disorder (ASD). The aims of this study were to identify known and novel ASD associated-CNVs and to evaluate the diagnostic yield of CMA in Thai patients with ASD. The Infinium CytoSNP-850K BeadChip was used to detect CNVs in 114 Thai patients comprised of 68 retrospective ASD patients (group 1) with the use of CMA as a second line test and 46 prospective ASD and developmental delay patients (group 2) with the use of CMA as the first-tier test. We identified 7 (6.1%) pathogenic CNVs and 22 (19.3%) variants of uncertain clinical significance (VOUS). A total of 29 patients with pathogenic CNVs and VOUS were found in 22% (15/68) and 30.4% (14/46) of the patients in groups 1 and 2, respectively. The difference in detected CNV frequencies between the 2 groups was not statistically significant (Chi square = 1.02, df = 1, P = 0.31). In addition, we propose one novel ASD candidate gene, SERINC2, which warrants further investigation. Our findings provide supportive evidence that CMA studies using population-specific reference databases in underrepresented populations are useful for identification of novel candidate genes.

Common Clinical Characteristics and Rare Medical Problems of Fragile X Syndrome in Thai Patients and Review of the Literature.

Background. Clinical characteristics of fragile X syndrome (FXS) have been well documented in Caucasians, whereas in Asians they have rarely been described. Those that have been conducted used small cohorts that utilized DNA for diagnosis and larger cohorts that utilized cytogenetics for diagnosis. This study is to describe clinical characteristics of FXS in a large cohort of Thai patients diagnosed by standard molecular methods. Methods. Seventy-seven index cases and 46 affected relatives diagnosed with FXS were recruited into the study. To determine frequencies of common characteristics of FXS in prepubertal boys, we reviewed 56 unrelated cases aged between 18 and 146 months. To list rare medical problems, we reviewed 75 cases aged between 8 months to 71 years old, including 53 index cases and 22 affected relatives. In addition, we selected 16 clinical studies from various ethnicities for comparison with our findings. Results. In prepubertal boys with FXS, attention deficit and/or hyperactivity, prominent ears, macroorchidism, and elongated face were observed in 96%, 80%, 53%, and 48% of patients, respectively, whereas recognizable X-linked inheritance presented in 11% of patients. IQ scores ranged between 30 and 64 (mean ± SD = 43 ± 9, n = 25). We observed clinical findings that rarely or have never been reported, for example, medulloblastoma and tetralogy of Fallot. Conclusion. Attention deficit and/or hyperactivity and prominent ear are the most common behavioral and physical features in prepubertal boys with FXS, respectively. There are differences in frequencies of clinical characteristics observed between ethnicities; however, it is difficult to draw a solid conclusion due to different recruitment criteria and sample sizes within each study.

Emergent Literacy in Thai Preschoolers: A Preliminary Study.

OBJECTIVE: To investigate emergent literacy skills, including phonological awareness when presented with an initial phoneme-matching task and letter knowledge when presented with a letter-naming task in Thai preschoolers, and to identify key factors associated with those skills. METHODS: Four hundred twelve typically developing children in their final kindergarten year were enrolled in this study. Their emergent reading skills were measured by initial phoneme-matching and letter-naming tasks. Determinant variables, such as parents' education and teachers' perception, were collected by self-report questionnaires. RESULTS: The mean score of the initial phoneme-matching task was 4.5 (45% of a total of 10 scores). The mean score of the letter-naming task without a picture representing the target letter name was 30.2 (68.6% of a total of 44 scores), which increased to 38.8 (88.2% of a total of 44 scores) in the letter-naming task when a picture representing the target letter name was provided. Both initial phoneme-matching and letter-naming abilities were associated with the mother's education and household income. Letter-naming ability was also influenced by home reading activities and gender. CONCLUSION: This was a preliminary study into emergent literacy skills of Thai preschoolers. The findings supported the importance of focusing on phonological awareness and phonics, especially in the socioeconomic disadvantaged group.

Longitudinal Case-Control Study of Imitation in Younger Siblings of Children with Autism Spectrum Disorder.

Background: Siblings of children with autism spectrum disorders (ASD) have higher prevalence of ASD with a recurrence of 19%. Children with ASD demonstrate significant impairment in all types of imitative skills. Imitation is markedly developed in the first few years of life; therefore, a study of imitation in younger siblings in this period may reveal early deviation. Objective: To study the development of imitation skills from 9- to 18-months, specifying types of imitation, in siblings of children with ASD compared with typically developing children. Method and Material: A longitudinal case-control study was conducted on eight siblings of children with ASDs and nineteen typically developing children who were age- and gender-matched. Data collection consisted of parental recording of emerging imitative abilities and structured direct observation of imitative skills at 9, 12 and 18 months. Three types of imitative skills were targeted including vocal, object and gesture imitation. Results: The development of vocal imitation in siblings of children with ASD between 12 to 18 months was delayed in comparison with typically developing children with significant statistical difference at 18 months. Object and gesture imitations were not significantly different between the two groups. Conclusion: Siblings of children with ASDs had some delays in vocal imitation skills at the age of 12 to 18 months, compared with typically developing children.

A new structured interview for children with autism spectrum disorder based on the DSM-IV.

BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder in children. The clinical spectrum of ASD includes autism, childhood disintegrative disorder Asperger syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS). Although the DSM-IVcriteria are well acceptedforASD diagnosis, there are some known limitations for clinicians. The most important issue is lack'ofspecific age-appropriate items in each domain. Thus, the DSM-IVneeds some modifications in order to be appropriate for clinical use. OBJECTIVE: To develop a structured interview for children based on the DSM-IVdiagnostic criteria ofautism and PDD-NOS. MATERIAL ANDMETHOD: From June 2006 to December 2008, 140 Thai children, 121 boys and 19 girls, already diagnosed with ASD, were recruited through the child development clinics of Ramathibodi and Thammasat University Hospitals in Thailand. A 26-item structured interview was developed with scoring according to the DSM-IVdiagnostic criteria for autism andPDD- NOS. To test the accuracy of the structured interview and its reliability, 32 children with ASD were selected and interviewed by four clinicians using the new instrument. One clinician interviewed the parents or caregivers, while three others independently took notes and observed the play behavior of the children. All items from the structured interview as scored by each clinician were compared using inter-rater agreement statistics (Kappa). All of the original 140 patients were then clinically diagnosed again using the structured interview and the results were compared with the initial diagnoses. RESULTS: Ofthe 140patients originally diagnosed with ASD, 110 and 30patients were finally diagnosed with the new interview as having autism and PDD-NOS, respectively. The initial diagnoses from 15 cases (10.7%) were changed according to the structured interview Inter-rater reliability among the four clinicians showed a good level ofagreement (Kappa = 0.897) with statistical significance (p<0.001). The authors only compared the items in the structured interview between the autism and PDD-NOSgroups from 105 cases aged 2-5 years (79 cases with autism and 26 cases with PDD-NOS) because there were only 4 cases with PDD-NOS in the other age groups. Highly significant differences (p<0.001) in clinical items between patients with autism and patients with PDD-NOS from the final diagnoses were noted in 6 of 8 items in the category of restricted, repetitive and stereotyped patterns ofbehavior, interests and activities, which were more common in the autism group than the PDD-NOS group. In addition, the autism group had higher frequencies of using finger-pointing to indicate interest rather than verbalization, and idiosyncratic language, than the PDD-NOS group. CONCLUSION: The newly developed structured interview for Thai children with ASD had a high level ofinterrater reliability between four clinicians. However, most children tested using this structured interview were 2-5years ofage, and the study did not include non-autistic groups. The application ofthis structured interview needs further study with a wider variety ofcases, such as ASD cases from different age groups, children with delayed development and normal children.

A case with a ring chromosome 13 in a cohort of 203 children with non-syndromic autism and review of the cytogenetic literature.

Autistic spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impairments of social interaction, communication and restricted, repetitive and stereotyped patterns of behavior, interests and activities. Frequencies of chromosomal abnormalities in cohorts of individuals with ASD varying between 1.2 and 28.6% have been reported. In this study, we evaluated 203 Thai children who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), for autistic disorder or pervasive developmental disorder not otherwise specified (PDD-NOS), and who had neither major dysmorphic features nor CGG repeat expansions of the FMR1 gene. A routine G-banding chromosome analysis was performed at a minimum of ISCN 400-550 bands. A chromosomal abnormality was observed in one child (0.5%), a 41-month-old boy with a ring chromosome 13 detected by G-banding analysis and subsequently confirmed by FISH. SNP microarray analysis detected a 2.11-Mb deletion of chromosome 13q34, encompassing 23 genes. The MCF2L and UPF3A genes are among those genes that may explain the autistic features in our case. To the best of our knowledge, only one autistic case with a ring chromosome 13 has been previously reported. In this article, we also systemically reviewed 21 studies that utilized a conventional cytogenetic method to detect chromosomal abnormalities in patients with ASD. When we summed all cases with chromosomal abnormalities, including the case from our study, the frequency of chromosomal abnormalities detected by conventional cytogenetics in patients with ASD was 3.2% (118/3,712).

Mutation screening of the neurexin 1 gene in thai patients with intellectual disability and autism spectrum disorder.

AIM: Neurexin 1 has two major protein isoforms using alternative promoters, coding for the alpha-neurexin 1 (α-NRXN1) and beta-neurexin 1 (ß-NRXN1) genes. This study is to explore the possibility that variants of the NRXN1 gene predispose to intellectual disability (ID) and autism spectrum disorder (ASD). METHODS: The coding regions in 24 exons and exon-intron boundaries of the NRXN1 gene were investigated in 115 Thai patients with ID and ASD by direct DNA sequencing. RESULTS: Nine novel variants of the NRXN1 gene were identified. Four novel variants were found in the ß-NRXN1 gene, one variant of six GGC repeats in exon 1, and three variants at the 5'UTR. Five novel variants were identified in the α-NRXN1 gene, four intronic variants and one missense variant in exon 14 (c.2713T>A or p.F905I). CONCLUSION: Mutation screening of the NRXN1gene in patients with ID and ASD may be useful to identify potential variants predisposing to ID and ASD. However, further studies utilizing protein functional analysis of the novel variants are required for a more definite conclusion.

Translation and validation of the Children's Communication Checklist to evaluate pragmatic language impairment in Thai children.

BACKGROUND: The Children's Communication Checklist (CCC) was developed to provide an assessment of domains of language impairment in children, particularly the pragmatic domain. This study examined the effectiveness of the CCC-Thai version in discriminating children with autism spectrum disorders (ASD) from typically developing children. METHODS: The parents of two groups of 50 children aged 4-6 years, one with clinically ascertained ASD, and one with typical development, completed the CCC-Thai version. RESULTS: The mean pragmatic composite score was significantly lower in the ASD group (124.6) than in the typical development group (142). The optimal receiver operating characteristic curve cut-off score was found to be identical to the original English version (132). Corresponding sensitivity and specificity were 94% and 86%, respectively. The positive predictive value and the negative predictive value were 87% and 93%, respectively. The corresponding area under the curve was 0.95 (95% confidence interval: 0.91-0.99). CONCLUSION: The CCC-Thai version is a promising instrument to assess pragmatic language impairment in Thai children.

Effect of television viewing on social-emotional competence of young Thai children.

Exposure time, program content and cultural context may affect the impact of television (TV) on the social-emotional competence (SEC) of children. This study examined the effects of TV viewing on the SEC of Thai infants. The study was based on a Thai birth cohort study from which duration and content of TV viewing and data from the Modified Infant-Toddler Social and Emotional Assessment instrument at 1 and 3 years of age were available. Generalized estimating equations were used to examine whether scores below the 10th national percentile were associated with TV viewing duration. The relationship between viewing duration and SEC risk was quadratic rather than linear. Viewing duration of 30-120 min/day was associated with a decreased risk of low overall SEC compared to non-viewers after adjustments for confounding factors. However, the beneficial effect diminished when the duration exceeded 120 min/day. Viewing educational programs was associated with a risk reduction of having low overall SEC compared to non-educational programs. These results suggest that a short period of TV viewing may be beneficial for the SEC of Thai infants, especially if the programs are educational.

Sleep education in pediatric residency programs: a cross-cultural look.

BACKGROUND: The objective of this study was to assess the prevalence of education about sleep and sleep disorders in pediatric residency programs and to identify barriers to providing such education. METHODS: Surveys were completed by directors of 152 pediatric residency programs across 10 countries (Hong Kong, India, Indonesia, Japan, Singapore, South Korea, Thailand, United States-Canada, and Vietnam). RESULTS: Overall, the average amount of time spent on sleep education is 4.4 hours (median = 2.0 hours), with 23% responding that their pediatric residency program provides no sleep education. Almost all programs (94.8%) offer less than 10 hours of instruction. The predominant topics covered include sleep-related development, as well as normal sleep, sleep-related breathing disorders, parasomnias, and behavioral insomnia of childhood. CONCLUSIONS: These results indicate that there is still a need for more efforts to include sleep-related education in all pediatric residency programs, as well as coverage of the breadth of sleep-related topics. Such education would be consistent with the increased recognition of the importance of sleep and under-diagnosis of sleep disorders in children and adolescents.

Effect of current breastfeeding on sleep patterns in infants from Asia-Pacific region.

AIM: The aim of this study was to assess the relationship between breastfeeding and sleep patterns in infants from Asia-Pacific region. METHODS: Parents of 10 321 infants (0-11 months) from Australia, China, Hong Kong, India, Indonesia, Korea, Japan, Malaysia, New Zealand, the Philippines, Singapore, Taiwan, Thailand and Vietnam completed an expanded version of the Brief Infant Sleep Questionnaire. RESULTS: Overall, 4714 (45.72%) were currently being breastfed; 61.3% of those between 0 and 5 months and 36.6% of those between 6 and 11 months. Currently breastfed infants, when compared with not currently breastfed infants, had a significant increase in the number and duration of night-time wakings and less consolidated sleep. Interestingly, currently breastfed infants less than 6 months also showed longer duration of daytime sleep and obtained more sleep overall. Of note, of those who were currently breastfed, those infants who were nursed back to sleep during night, woke up more often at night (2.41 vs. 1.67 times) and had shorter continuous night-time sleep period (5.58 vs. 6.88 h; P < 0.001). There was no significant difference between breastfeeding and non-breastfeeding infants in the number of night wakings, when the nursing to sleep variable was controlled for in the analysis of variance. CONCLUSION: Breastfeeding is associated with reduced sleep consolidation in infants. This relationship, however, may be moderated by parenting practices of nursing to sleep and back to sleep during the night. Thus, parents of infants with night waking problems should be encouraged to limit the association between nursing and falling to sleep, to improve sleep while maintaining breastfeeding.

Translation and validation of the developmental, dimensional and diagnostic interview (3Di) for diagnosis of autism spectrum disorder in Thai children.

This study aimed to examine the effectiveness of a translated version of the short version of the Developmental, Dimensional and Diagnostic Interview (3Di) in discriminating children with autism spectrum disorders (ASDs) from typically developing children. Two groups, comprising 63 children with clinically ascertained ASDs and 67 typically developing children, were interviewed with the short 3Di translated version. Mean 3Di scale scores in each domain of autistic symptoms (social reciprocity, communication, and repetitive/stereotyped behaviors) were significantly higher in the ASD group than in the typically developing group. The optimal receiver operating characteristics curve cut-off scores were found to be 10, 8, and 3 for social reciprocity domain, communication domain, and repetitive/stereotyped behaviors domain, respectively, which are identical to the original English standardization. Corresponding sensitivities and specificities were 76.2% and 80.9% for the social reciprocity domain; 85.7% and 73.5% for the communication domain; and 66.7% and 80.9% for the repetitive behaviors domain. The areas under the curve were 0.89 (95% CI = 0.84-0.94), 0.88 (95% CI = 0.82-0.94), and 0.79 (95% CI = 0.71-0.87), respectively. The short 3Di-Thai version is found to be a useful diagnostic instrument for differentiating between clinically diagnosed children with ASDs and typically developing children, although further replication is needed.

Sleep education in medical school curriculum: a glimpse across countries.

BACKGROUND: The objective of this study was to assess the prevalence of education about sleep and sleep disorders in medical school education and to identify barriers to providing such education. METHODS: Surveys were sent to 409 medical schools across 12 countries (Australia, India, Indonesia, Japan, Malaysia, New Zealand, Singapore, South Korea, Thailand, United States, Canada and Viet Nam). RESULTS: Overall, the response rate was 25.9%, ranging from 0% in some countries (India) to 100% in other countries (New Zealand and Singapore). Overall, the average amount of time spent on sleep education is just under 2.5h, with 27% responding that their medical school provides no sleep education. Three countries (Indonesia, Malaysia, and Viet Nam) provide no education, and only Australia and the United States/Canada provide more than 3h of education. Paediatric topics were covered for a mere 17 min compared to over 2h on adult-related topics. CONCLUSION: These results suggest that there continues to be very limited coverage of sleep in medical school education despite an incredible increase in acknowledgement of the importance of sleep and need for recognition of sleep disorders by physicians.

Infant toilet training in Thailand: starting and completion age and factors determining them.

OBJECTIVE: To study the age at which Thai infants start and achieve toilet training and its associated factors. MATERIAL AND METHOD: The parents of fifty infants in a research entitled "Bowel movements of normal Thai infants" were interviewed about age at which toilet training started, the process of toilet training and age at which infant successfully completed toilet training. RESULTS: Forty-seven infants from the 50 infants registered had data of the date of beginning toilet training. Five of them (10.6%) started toilet training at 4 months and 38 (80.9%) by 12 months. Most of the infants (73.7%) were initially trained when they showed urging signs. Only 45 infants had complete data of successful toilet training. Twenty-two cases (48.9%) were trained successfully by 12 months and most of them (16/22) succeeded within one month. The infants, who were not the first child and were taken care of by a well-educated mother, were found to start toilet training late. CONCLUSION: The youngest age at which normal Thai infants start to be toilet trained was 4 months. About 50% of the infants aged 12 months had successful toilet training. Being raised by a well-educated mother and a having a later birth order in a family were factors associated with late toilet training.

Bowel movements of normal Thai infants.

The aim of this study was to define the bowel movements of healthy Thai infants up to 12 months of age. Fifty infants were evaluated at 1, 2, 4, 6, 9 and 12 months of age. Data regarding bowel habits was recorded by parents daily for 2 days before coming to the hospital at each visit. The mean frequency of bowel movements per day was maximal (3.16 stools) during the newborn period and declined (1.59 stools) by the age of 12 months. At birth stool consistency was mostly runny, and became consistently more solid by 4 months of age. With increasing age, infants produced larger stools: mean volume of stool was 32.7 ml at 1 month of age and increased to 45.34 ml at 12 months. Infants started to have regular bowel movements at 4 months of age, most of them stopped having bowel movements at night by 3 months.

Television viewing in Thai infants and toddlers: impacts to language development and parental perceptions.

BACKGROUND: Effects of television to language development in infants and toddlers, especially in the Asian children, are inconclusive. This study aimed to (a) study time spent on television in Thai infants and toddlers (age < 2 years), (b) investigate the association between time spent on television (as recommended by the American Academy of Paediatrics (AAP), < 2 hours per day) and language development in Thai 2-year-old children, and (c) explore parental perceptions on television toward their child's development. METHODS: Two hundred and sixty children and their parents were recruited into the study. Time spent on television and parental perceptions on television viewing toward their child's development were recorded during face-to-face and telephone interviews. Language development was assessed at the age of 2 years using the Clinical Linguistic Auditory Milestone Scale (CLAMS), and parents' report. Association between delayed language development and time spent on television viewing, as well as other various parameters such as gender, maternal education and family income, were analysed using a multivariate logistic regression model. RESULTS: Most Thai infants and toddlers watched television at the age of 6 months, 1 year and 2 years old (98.0, 95.3 and 96.7%, respectively). On average, 1-year-old children watched television 1.23 +/- 1.42 hours per day. This increased to 1.69 +/- 1.56 hours per day when they were 2 years old. However, watching television longer than 2 hours per day did not associate with delayed language development. On multivariate logistic regression analysis, gender (male) was the only significant factor associated with delayed language development (OR = 6.9, 95% CI = 1.5-31.3). Moreover, 75%, 71%, and 66% of Thai parents believed that television viewing yielded benefits to children's developments. CONCLUSION: Thai children commenced watching television at an early age and the amount of television viewing time increased by age. Most parents had positive perceptions to television viewing. The study found no association between time spent on television viewing (>or= 2 hours per day) and delayed language development at the age of 2 years. Gender (male) was the only variable associated with delayed language development.