Effect of temperament on metabolic control in children with diabetes mellitus.

Fifty-one children with insulin-dependent diabetes mellitus (IDDM) and 24 healthy sibling controls were compared on one of two temperament questionnaires completed by parents. Children with IDDM did not provide a characteristic temperament profile or show any problem areas. A regression analysis to predict diabetic control as measured by most recent glycosylated hemoglobin (HbA1c) values revealed that five of the nine temperament scales accounted for a significant 42% of the variance in HbA1c (P less than .001). Children with higher activity levels, greater regularity in routines, milder reactions to external stimuli, distractibility, and negative moods were achieving better glycemic control. The results are discussed in terms of how individual differences in behavioral organization, energy consumption, and stress modulation may affect blood glucose levels.

Intellectual deficits associated with early onset of insulin-dependent diabetes mellitus in children.

Twenty-seven children with early-onset (less than 4 yr) diabetes (EOD), 24 children with late-onset (greater than 4 yr) diabetes (LOD), and 30 sibling controls were compared in their performance on tests of intellectual functioning and school achievement. The results indicated that children with EOD, particularly girls, scored lower than the other groups of diabetic children and siblings on tests of visuospatial (P less than .05) but not verbal ability. Many of the girls with EOD were also having difficulty at school, and several were receiving special education. Children with EOD had more hypoglycemic convulsions than those with LOD. Both convulsions and age of onset were associated with poorer performance on spatial tasks. Girls with EOD had lower spatial test scores regardless of convulsion history, whereas boys with EOD scored lower only if they had had a convulsion.

Psychoeducational outcome in children with early-treated congenital hypothyroidism.

OBJECTIVES: To describe the psychoeducational characteristics of children with congenital hypothyroidism (CH) identified through newborn screening and to study changes over time. METHOD: Examined were 83 children with early-treated CH, who were long-time participants in a prospective study of outcome after newborn screening, and 120 control children who were classmates (n = 80) or siblings (n = 42). Children were tested during the third (53 children with CH and 46 control children) or the sixth (51 children with CH and 76 control children) grades at school with 21 children with CH being seen in both grades. Test instruments included multiple measures of achievement and cognitive abilities as well as behavior rating scales completed by parents and teachers. RESULTS: CH was associated with a slightly increased risk of learning disabilities in grade 3 but not grade 6. Third grade CH children scored lower than control children on tests of reading comprehension and arithmetic but did not differ on word recognition, writing, or spelling. Sixth grade CH children performed similar to controls on basic achievement tests but were reported to be doing poorer in several subject areas. For children with CH in grade 3, delayed skeletal maturity at diagnosis was associated with poorer word recognition ability and a longer period for normalizing thyroid hormone in infancy was correlated with weaker skill in learning sound-symbol correspondences. CONCLUSION: Early-treated CH is associated with mild delays in several basic achievement areas (reading comprehension and arithmetic) at the third grade level, with catch up by the sixth grade. However, as other findings indicate cognitive problems do persist into adolescence in memory, attention, and visuospatial processing areas, the implications of these deficits for other educational accomplishments needs additional follow-up.congenital hypothyroidism, thyroid hormone, newborn screening, achievement, behavior, attention.

Congenital hypothyroidism: long-term outcome.

Although mental retardation associated with congenital hypothyroidism (CH) is prevented by newborn screening and early treatment, affected children still undergo a brief period of thyroid hormone deficiency reflecting etiology of thyroid disease, illness severity, and treatment factors. Because thyroid hormone is essential for normal brain development and because some processes require thyroid hormone in the period when thyroid hormone was lacking, children with CH treated early may still have subtle neurocognitive deficits. As the period when thyroid hormone is needed differs for different brain regions, there may be different types of deficits depending on when thyroid hormone levels were insufficient. Since 1980, we have been following a large cohort of Toronto-based children with congenital hypothyroidism identified by newborn screening from infancy to adolescence. Early findings revealed a 5-10-point decline in IQ, poorer visuomotor and visuospatial abilities, delayed speech and language development, selective neuromotor deficiencies, and poorer attention and memory skills, which were correlated with different disease and treatment factors. Now a comparison between 48 subjects at adolescence and matched controls indicates that deficits persist in visuospatial, memory, and attention domains and these are correlated with severity of early hypothyroidism. Negative relationships between attention indices and thyroxine (T4) elevations at time of testing also suggest a role for thyroid hormone in the regulation of attention.

Prenatal exposure to organic solvents and child neurobehavioral performance.

The present study compared the cognitive and behavioral functioning of 3- to 7-year-old children (n=33) whose mothers worked with organic solvents during pregnancy with a group of unexposed children (n=28) matched on age, gender, parental socioeconomic status (SES), and ethnicity. Participants were recruited prospectively by the Motherisk Program, an antenatal counseling service in Canada. An exposure index was estimated using questionnaire data obtained at the time of initial contact. Groups were compared on a variety of tasks, including subtests from the NEPSY, a visual CPT, as well as on parent-rated measures of children's behavior. Regression analyses indicated lower composite scores in children with increased exposure on Receptive language (P<.01), Expressive language (P<.01), and Graphomotor ability (P=.001), adjusted for demographics. No group differences were observed on measures of Attention (P=.97), Visuo-spatial ability (P=.33), and Fine-motor ability (P=.33). On the Child Behavior Checklist (CBCL), overall mean differences on broad- and narrow-band scales were not significant, but significantly more exposed children were rated as having mild or severe problem behaviors. The findings suggest that maternal occupational exposure to organic solvents during pregnancy is associated with poorer outcome in selective aspects of cognitive and neuromotor functioning in offspring.

Neurodevelopment after in utero amiodarone exposure.

It is not known whether amiodarone is neurotoxic to the fetus, as it is to adults. We evaluated neurodevelopment of a historical cohort (N = 10) of children exposed transplacentally to amiodarone. Scores on standardized tests of cognitive and language skills were compared (by Wilcoxon signed rank test) between eight toddlers and matched controls. It was not possible to obtain controls for older amiodarone-exposed children (aged 9.7 and 12.0 years), whose test results were compared descriptively with normative data. There was no difference in IQ scores between amiodarone-exposed toddlers and controls. All had favorable temperaments. However, amiodarone-exposed toddlers showed expressive language skills that were relatively poorer than verbal skills, when compared with controls (p = 0.046). One amiodarone-exposed toddler exhibited global developmental delay. The older amiodarone-exposed children had well-developed social competence, favorable global IQ scores, but problems with reading comprehension, written language, and arithmetic. This picture is reminiscent of the Nonverbal Learning Disability Syndrome. There may be neurotoxicity associated with transplacental exposure to amiodarone. Follow-up is warranted, although most mothers were happy with the development of their children.

Visual integration difficulties in a 9-year-old girl with Turner syndrome: parallel verbal disabilities?

Turner syndrome (TS) is a genetic disorder in females that arises from the loss of X chromosome material. Affected individuals demonstrate a characteristic neuropsychological profile of strengths in verbal processing and weaknesses in visuospatial processing, consistent with the Nonverbal Learning Disabilities syndrome. Previous research has described a wide range of visuospatial deficits in TS; however, their verbal abilities are less extensively studied. The present paper describes the processing difficulties of a 9-year-old girl with TS who demonstrated problems in integrating details of a complex visual display and using organizational terms to describe visual scenes or events. Her specific cognitive disabilities were thought to underlie some of the social and behavioral problems she was currently experiencing. Her pattern of results is consonant with the neuropsychological pattern that others have attributed to right hemisphere dysfunction and/or white matter abnormality.

The effect of abnormal intrauterine thyroid hormone economies on infant cognitive abilities.

OBJECTIVE: To evaluate how intrauterine and neonatal thyroid hormone deficiencies affect infant cognitive abilities. METHOD: 26 infants with intrauterine or neonatal thyroid hormone deficiency and 20 full-term infants with normal thyroid economies were studied at 6 months of age or corrected age. Reasons for thyroid hormone deficiency were maternal hypothyroidism, maternal hyperthyroidism treated with antithyroid medication, congenital hypothyroidism, and low-risk prematurity. A computer-generated task during which infants' eye-movements were videotaped was used to assess attention, memory, and learning abilities RESULTS: Data from transcribed videotapes showed the study group was significantly less attentive and had longer reaction times than controls but did not differ on indices of sustaining attention or learning. Within thyroid-deficient groups, offspring of treated hyperthyroid mothers showed an atypical profile suggestive of hypervigilance. CONCLUSION: A decreased fetal or maternal thyroid hormone supply in pregnancy is associated with infants' poorer attention and altered rates of information processing.

Visual search for features and conjunctions in development.

Visual search performance was examined in three groups of children 7 to 12 years of age and in young adults. Colour and orientation feature searches and a conjunction search were conducted. Reaction time (RT) showed expected improvements in processing speed with age. Comparisons of RT's on target-present and target-absent trials were consistent with parallel search on the two feature conditions and with serial search in the conjunction condition. The RT results indicated searches for feature and conjunctions were treated similarly for children and adults. However, the youngest children missed more targets at the largest array sizes, most strikingly in conjunction search. Based on an analysis of speed/accuracy trade-offs, we suggest that low target-distractor discriminability leads to an undersampling of array elements, and is responsible for the high number of misses in the youngest children.

The psychoeducational characteristics of children with Turner syndrome.

Turner syndrome (TS) is a condition that affects 1 in 2,500 females due to a loss of some X chromosome material. It is characterized by a number of common physical features, including short stature, sexual infantilism, and infertility, as well as by specific learning and behavior problems. This article compares abilities, achievement, behavior, and self-esteem in 67 children with TS and 27 nonaffected controls. Results indicate selective impairments in visuospatial and memory areas and significant underachievement in arithmetic, particularly numerical ability, mental calculation, geometry, and reasoning. Learning problems, a major concern for parents, were not being satisfactorily addressed at school. Poor social competence and increased behavior problems, particularly in the area of hyperactivity, were also noted. Although self-esteem was only marginally lower, issues related to poor peer relations were most problematic.

Psychoeducational characteristics of children and adolescents with insulin-dependent diabetes mellitus.

In recent years, researchers have observed selective neuropsychological impairment associated with insulin-dependent diabetes mellitus in childhood. At increased risk are children who develop diabetes before the age of 5, who experience severe hypo- and hyperglycemia, or who have frequent episodes of mild to moderate hypoglycemia. This article explores the existing literature to establish frequency and consistency of general and specific neurocognitive deficits in this pediatric patient population, as well as the impact of these deficits on school achievement and learning disabilities. Studies are integrated to identify contributing diabetes and nondiabetes factors. This is followed by a reanalysis of the data from two studies of diabetic children to determine the learning disability characteristics of this population and the factors contributing to dysfunctional school performance. Findings are discussed in terms of the impact of different factors reflecting adequacy of diabetes control on specific psychoeducational abilities.

Long-term neuropsychological sequelae of early-treated congenital hypothyroidism: effects in adolescence.

A cohort of over 100 children with congenital hypothyroidism (CH) detected via newborn screening was followed regularly throughout childhood and into adolescence. They were studied using a variety of different tests as part of three consecutive research components: semiannual/annual psychological assessments using age-appropriate intelligence tests (phase I), detailed psychoeducational evaluations in grades 3 and 6 (phase II) and a thorough neuropsychological evaluation during adolescence (phase III). Controls for phase I were siblings and for phase II, classmates and siblings. Phase III controls were drawn from a larger control pool and were individually matched with each CH case for age and gender. The results showed that although the CH group was intellectually functioning well within the normal range by adolescence, the children were performing significantly below expectation. Longitudinal analyses showed significant declines in IQ with age, signifying that the CH group was failing to make the same age-related gains as controls. Children with CH showed significantly poorer performance in visuospatial, language and fine motor areas as well as selective attention and memory deficits. At school, they were initially below par in arithmetic but were able to catch up by grade 6; however, their teachers reported that they were not performing as well as controls in the classroom and they demonstrated more difficulty with more complex school subjects such as science and social studies. Correlational analyses indicated different manifestations of early hypothyroidism versus later treatment factors, suggesting that while some effects can be improved by better treatment and management approaches, others caused by prenatal and perinatal thyroid hormone insufficiency may persist.

Does breast-feeding protect the hypothyroid infant whose condition is diagnosed by newborn screening?

Neuropsychological abilities at 1, 3, 5, and 6 years of age were compared in 107 children with congenital hypothyroidism identified by newborn screening who had been either breast-fed or formula fed during infancy. The thyroxine level was significantly higher in breast-fed children than formula-fed children at 1 and 2 months of age, but the level was not higher later during the first year of life. Controlling for parent IQ, socioeconomic status, and dose level, no differences in overall neuropsychological functioning were observed. Children with ectopic glands showed a significant advantage with breast-feeding on several tasks at 3 years of age. These results signify that thyroxine levels in infancy from breast-feeding are not necessarily reflected in improved intellectual functioning later in childhood.

Attention problems in adolescents with congenital hypothyroidism: a multicomponential analysis.

Even though early treatment of congenital hypothyroidism (CH) with newborn screening prevents the mental retardation previously seen in cretinism, affected children still exhibit subtle persisting neurocognitive deficits. One of their commonest problems is poor attention, which reflects both early disease severity and later (high) circulating thyroid hormone levels. While attention is currently regarded as multicomponential in nature, with different processing components supported by different brain regions, the specific components of attention affected by CH have not been identified. In light of animal evidence showing that neonatal thyroid hormone deficiencies impede the neurodevelopment of structures important for selective aspects of attention, we proposed a multicomponential approach to study attention in children with CH. This was accomplished via retrospective analysis of existing data on adolescents with CH whose attention was previously evaluated using multiple tests. Results showed significantly poorer overall attention in CH than controls with differences occurring mainly on focus and inhibit indices. However, performance on various indices was associated with different disease parameters. Poor encode and focus were correlated with more severe hypothyroidism and a longer period of thyroid hormone insufficiency and poor select and shift with higher thyroid hormone levels at testing. These results signify that thyroid hormone is important for the development and later regulation of brain structures supporting distinct aspects of attention.

Dissociating attention deficits in children with ADHD and congenital hypothyroidism using multiple CPTs.

Recent studies suggest that children with different etiologies of attention disorder also differ as to the types of errors they make on attention tasks. Because these errors are reflective of the core deficits underlying their attention problems, we sought to compare error patterns in children with different attention disorders. Studied were 144 children aged 7-12 years, 43 with attention deficit hyperactivity disorder (ADHD), 35 with congenital hypothyroidism (CH), and 68 controls. Two variations of the continuous performance task (CPT) that differed in demands on inhibitory control and memory were used. One variation, the CPT:A-not-X task, required subjects to observe a continuous stream of letters shown at different rates on the computer screen and respond to all stimuli except "X". The other variation, the CPT:AX task, required them to respond whenever a specified combination of letter such as "A" followed by "X" appeared on the screen. On the CPT:A-not-X task, children with ADHD differed from controls in commission errors, signifying difficulty with inhibitory control, whereas children with CH differed in perceptual sensitivity or signal detection. Although the CH and ADHD groups both performed more poorly than controls on the CPT:AX task, children with CH made more errors to the first stimulus item, suggesting a problem holding information in memory, whereas children with ADHD made more errors to the second item, suggesting impulsivity. These results therefore signify the utility of these tasks in identifying the different mechanisms underlying the specific attention deficits of different groups of children.

Long-term effects of L-thyroxine therapy for congenital hypothyroidism.

OBJECTIVE: To study the effects of initial and concurrent dose levels of L-thyroxine on ability and behavior in children with congenital hypothyroidism. METHODS: An existing database, involving a large cohort of children with congenital hypothyroidism detected by neonatal screening, was analyzed retrospectively. There were 94 children: 89 were assessed at age 7 years for intelligence and selective cognitive abilities, and 87 at age 8 years for behavior, achievement, and selective abilities. RESULTS: Subjects were stratified by median split into low and high starting dose groups. The high-dose group performed better on indexes of intelligence, verbal ability, and memory but had more behavior problems reflecting increased anxiety, social withdrawal, and poorer concentration. The dose of L-thyroxine at age 8 years was negatively correlated with memory task performance. CONCLUSION: A higher starting dose of L-thyroxine is beneficial for subsequent intellectual outcome in children with congenital hypothyroidism but may be associated with internalizing behavior problems.

The effect of hypoglycemic seizures on cognitive function in children with diabetes: a 7-year prospective study.

Sixteen children with insulin-dependent diabetes mellitus were evaluated at diagnosis and after 1, 3, and 7 years. They showed significant declines in verbal but not visuospatial abilities, particularly if they had any seizures from hypoglycemia. At the 7-year assessment those with hypoglycemic seizures showed deficits on perceptual, motor, memory, and attention tasks.

Specific intellectual deficits in children with early onset diabetes mellitus.

27 children with early onset (less than 4 years) diabetes (EOD), 24 with late onset (greater than 4.0 years) diabetes (LOD), and 30 sibling controls were compared in their performance on tests of intellectual functioning and school achievement. The results indicated that children with EOD, particularly girls, scored lower than the other groups of diabetic children and siblings on tests of visuospatial but not verbal ability. Many of the children with EOD were also having difficulty at school, and a number were currently receiving special education. Diabetic children with earlier onset had more hypoglycemic convulsions than those with later onset. Regression analyses revealed that duration of illness, age of onset, and hypoglycemic convulsions significantly predicted spatial ability.

Effect of thyroid hormone level on temperament in infants with congenital hypothyroidism detected by screening of neonates.

To determine the effect of congenital hypothyroidism and its treatment on infant behavior, we assessed temperament in 50 six-month-old infants with congenital hypothyroidism detected by means of screening of neonates. Intelligence and temperament were also evaluated at 12, 18, 24, and 36 months. More of these children were classified as "difficult" than children in the nonhypothyroid standardization sample. Temperamental difficulty was associated with increased nervous system sensitivity, reflecting more intense responses and a lower threshold of response to external stimulation. Greater temperamental difficulty was found to persist until at least age 2 years of age and to be associated with higher circulating triiodothyronine and thyroxine levels between 1 and 3 months of age. Our results suggest that behavioral features should be considered, as well as circulating hormone levels, in determining the proper dose of thyroid hormone replacement in infants with congenital hypothyroidism.