Intellectual outcome in children with fetal hypothyroidism

Eighty children with congenital hypothyroidism detected by newborn screening were grouped for presence of fetal hypothyroidism using skeletal maturity at the time of diagnosis as the index. Forty-five children with bone age less than 36 weeks were assigned to the delayed group; 35 with bone age 37 weeks to term were assigned to the nondelayed group. Although most children with athyrosis were found in the delayed group, the groups did not differ in birth weight, hormone levels, or family background. Assessments of intellectual and behavioral characteristics at 1, 2, 3, 4, and 5 years of age revealed that, although children in the delayed group performed within the normal range, their scores were significantly lower than those of the nondelayed group from age 2 years on. Perceptual-motor, visuospatial, and language areas were most affected. There were no differences in behavior or temperamental characteristics.     

Relationship of etiology to treatment in congenital hypothyroidism

We examined the patterns of TSH, T(4), and treatment schedules from diagnosis to 4 yr of age in 125 children (50 males anf 75 females) with congenital hypothyroidism (CH). Subjects were divided into 3 groups based on their thyroid scans: 1) athyreosis (n = 31), 2) dysgenesis (n = 54; 49 lingual and 5 hypoplastic), and 3) dyshormonogenesis (n = 40). Follow-up evaluation was carried out at 2-4 wk and 3, 6, 9, 12, 24, 36, and 48 months of age. Median gestational age, age at onset of therapy, and starting L-T(4) dose were similar in the three groups. In infants with athyreosis median screening TSH levels were higher (P < 0.02) and confirmatory T(4) levels were lower than in the other two groups (P < 0.01 vs. dysgenetic; P < 0.05 vs. dyshormonogenetic CH). During the first 6 months of therapy, mean TSH levels were highest in the athyrotic group, intermediate in the dysgenetic group, and lowest in the dyshormonogenetic group. In children with athyreosis, TSH levels normalized by 12 months of age. At 12 months dysgenetic patients had the highest TSH levels (P < 0.05). During the entire study period, TSH levels were lowest in patients with dyshormonogenesis (except at 48 months) and normalized earlier. Mean T(4) levels normalized by 2-4 weeks in all groups. At 3 and 6 months, the percentage of patients who required dose changes was highest in the athyrotic group, and at 12 months it was highest in the dysgenetic group. The athyrotic group received the highest dose of L-T(4), and dyshormonogenetic group received the lowest dose. We conclude that treatment and follow-up schedules for CH may differ in the three etiological categories based on the different hormonal patterns and responses to therapy. Children with athyreosis need close monitoring particularly early in life, whereas those with dysgenesis and dyshormonogenesis require more attention later in life.     

Hypothyroxinemia of prematurity and infant neurodevelopment: a pilot study

To assess whether hypothyroxinemia has specific effects on neurodevelopment in premature infants, thyroid hormone levels were determined at 2 weeks of life and 40 weeks postconceptional age (PCA), and infants were evaluated at 3 months corrected age using the Bayley Scales of Infant Development and Early Infancy Temperament Questionnaire. Additional attention scales were derived from the factor analysis of relevant Bayley items. Fifteen infants born between 30 and 35 weeks and 21 full-term infants were studied. Results indicated no group differences on the Bayley or derived attention scales, whereas the temperament questionnaire revealed lower sensory thresholds and greater reactivity in the preterm group. The preterm group had normal thyroxine (T4) levels at 2 weeks of age, which declined by 40 weeks PCA for both free T4 (p < .01 for reference value and p < .0001 for gestational age-adjusted value) and total T4 (p < .05 for age-adjusted value). Correlations revealed that higher 40-week PCA free T4 levels were associated with better attentiveness ratings (p < .01 for reference and p < .0001 for gestational-age values) and sustained attention (p < .05) and higher 40-week total T4 with better motor skills (p < .05 for gestational-age value). These findings signify that a mild degree of hypothyroxinemia is evident in preterm infants without neurological risk and predicts subsequently poorer cognitive and motor abilities.     

Atypical Hemispheric Lateralization in Turner Syndrome Subjects

This study compares the dichotic listening task performance of 35 Turners syndrome (TS) and 35 normal females matched for age and verbal intelligence. The task consisted of 24 pairs of digit triads presented simultaneously to both ears. The results indicated that the TS subjects were less likely than controls to show a right ear advantage and more likely than controls to show a left ear advantage. The absence of an ear advantage was also found to be associated with the greatest nonverbal deficits, but only among TS subjects. The findings are discussed in terms of diminished hemispheric specialization in TS females.     

Novel approaches to the diagnosis of fetal alcohol spectrum disorder

The diagnosis of fetal alcohol spectrum disorder is a difficult task, especially in cases where clear, physical markers of in utero alcohol exposure are not apparent. Reviewed in the following paper are some older tools for screening alcohol use in pregnancy and present novel approaches to the diagnosis of FASD, including ethanol biomarker development to behavioural phenotyping. Improving current FASD diagnostic methodology through more novel approaches may provide the possibility of earlier and wider diagnosis, allowing intervention and treatment at stages where the advanced effects of alcohol can still be mitigated.     

Turner syndrome in a pair of dizygotic twins: A single case study

A pair of female dizygotic twins, one of whom had Turner syndrome (TS), was given a battery of psychological tasks. Results revealed that the TS twin showed deficits on tasks requiring spatial analyses, visual form discrimination, and visual memory. Differences in the serial recall characteristics on visual memory tasks were also noted. Results are discussed in terms of the reliability of the TS spatial deficit and the relationship between memory and spatial functioning.This research was supported by the Ontario Mental Health Foundation and the Medical Research Council of Canada.     

Identifying the behavioural phenotype in fetal alcohol spectrum disorder: sensitivity, specificity and screening potential

Summary Background: In most cases of Fetal Alcohol Spectrum Disorder (FASD), the pathognomonic facial features are absent making diagnosis challenging, if not impossible, particularly when no history of maternal drinking is available. Also because FASD is often comorbid with Attention Deficit Hyperactivity Disorder (ADHD), children with FASD are frequently improperly diagnosed and receive the wrong treatment. Since access to psychological testing is typically limited or non-existent in remote areas, other diagnostic methods are needed to provide necessary interventions. Objectives: To determine if a characteristic behavioural phenotype distinguishes children with FASD from typically developing children and children with ADHD and use this information to create a screening tool for FASD diagnosis. Methods: Parents and caregivers completed the Child Behavior Checklist (CBCL), a well-established standardized tool for evaluating children’s behavioural problems. Results from 30 children with Fetal Alcohol Syndrome or Alcohol-Related Neurodevelopmental Disability, 30 children with ADHD, and 30 typically developing healthy children matched for age and socioeconomic status with FASD were analyzed. Based on our previous work, 12 CBCL items that significantly differentiated FASD and control groups were selected for further analyses. Stepwise discriminant function analysis identified behavioural characteristics most strongly differentiating groups and Receiver Operating Characteristics (ROC) curve analyses determined sensitivity and specificity of different item combinations. Results: Seven items reflecting hyperactivity, inattention, lying and cheating, lack of guilt, and disobedience significantly differentiated children with FASD from controls. ROC analyses showed scores of 6 or higher on these items differentiated groups with a sensitivity of 86%, specificity of 82%. For FASD and ADHD, two combinations of items significantly differentiated groups with high sensitivity and specificity (i) no guilt, cruelty, and acts young (sensitivity = 70%; specificity = 80% (ii) acts young, cruelty, no guilt, lying or cheating, steals from home, and steals outside (sensitivity = 81%; specificity = 72%). These items were used to construct a potential FASD screening tool. Conclusions: Our findings identifying the behavioural characteristics differentiating children with FASD from typically developing children or children with ADHD have the potential for development of an empirically derived tool for FASD tool to be used in remote areas where psychological services are not readily available. This technique may speed up diagnosis and intervention for children without ready access to formal assessments.     

Developmental thyroid hormone disruption: prevalence, environmental contaminants and neurodevelopmental consequences

Thyroid hormones (TH) are critical for growth and development and particularly brain development. There are numerous environmental agents that lead to marginal reductions of circulating TH. Although it is clear that severe developmental hypothyroidism is profoundly detrimental to neurodevelopment, there is less information regarding the consequences of modest degrees of thyroid. The impact of low level TH disruptions induced by environmental contaminants has not been defined. This paper is a synopsis from four invited speakers who presented at the 13th International Neurotoxicology Association meeting held in Xi'an, China during the summer of 2011. An overview of the role of TH in brain development and a review of human and animal data on the neurological sequelae of disruption of the thyroid axis in the pre- and early post-natal periods were presented by Mary Gilbert and Joanne Rovet. Iodine deficiency, a common cause of TH insufficiency and mental retardation in many countries, including China, was addressed by Zupei Chen. In this presentation the current incidence of iodine deficiency and neurological outcome in China and the efficacy of recently implemented iodinization programs to eliminate this cause of mental retardation were reviewed. Joanne Rovet described the impact of TH disruption during pregnancy and under conditions of congenital hypothyroidism. Children born with normal thyroid function, but who experienced TH insufficiency in the womb, display subtle cognitive impairments and abnormalities in brain imaging. Despite early detection and treatment, deficiencies also exist in children born with thyroid disorders. Different patterns of cognitive effects result from prenatal versus postnatal TH insufficiency. Mary Gilbert reported on the effects of environmental contaminants with thyroid disrupting action on brain development in animals. Results of neurophysiological, behavioral, structural and molecular alterations that accompany modest perturbations of the thyroid axis were reviewed. Noriyuki Koibuchi described molecular targets of TH-mediated signalling accompanying exposure to persistent organic pollutants. Both polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are prevalent environmental contaminants that disrupt TH signalling at the receptor level. This action by these chemical classes could contribute to the negative impact of these chemicals on brain function. In summary, epidemiological, preclinical and animal research has clearly identified the critical role of TH in brain development. Additional work is required to understand the impact of low level perturbations of the thyroid axis to evaluate the risk associated with environmental contaminants with thyroid action.     

Visuospatial associative memory and hippocampal functioning in congenital hypothyroidism

Congenital hypothyroidism is a pediatric endocrine disorder caused by insufficient endogenous thyroid hormone production. Children with congenital hypothyroidism have difficulties with episodic memory and abnormalities in hippocampal structure, suggesting deficient hippocampal functioning. To assess hippocampal activation in adolescents with congenital hypothyroidism (N = 14; age range, 11.5-14.7 years) compared with controls (N = 15; age range, 11.2-15.5 years), a functional magnetic resonance imaging visuospatial memory task was used. In this task, participants had to decide if object pairings were novel or were previously studied or if object pairs were in the same location as they were at study or had switched locations. Despite no group differences in task performance, adolescents with congenital hypothyroidism showed both increased magnitude of hippocampal activation relative to controls and bilateral hippocampal activation when only the left was observed in controls. Furthermore, the increased activation in the congenital hypothyroidism group was correlated with the severity of the hypothyroidism experienced early in life. These results suggest that perinatal deprivation of thyroid hormone has longstanding effects on hippocampal function and may account for memory problems experienced by adolescents with congenital hypothyroidism.