Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies.

Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance.

Neurocognitive abnormalities in offspring of mothers with systemic lupus erythematosus.

Offspring of systemic lupus erythematosus (SLE) patients delivered during follow-up in the lupus clinic from 1973 to 1998 were assessed for SLE and by age-appropriate neurocognitive tests. Nine domains were evaluated. Controls, matched for age, sex, race and socio-economic status, underwent the same neurodevelopmental/neuropsychological evaluation. A domain was considered 'abnormal' if at least one of the tests in the domain yielded abnormal results. The number of offspring with normal/abnormal results was compared in each of the nine domains using McNemar test for matched analysis. In addition, an unmatched analysis using chi-square tests was performed. Logistic regression was run on both the matched pairs and unmatched groups to adjust for possible gender differences. A total of 106 children, 49 pairs of SLE offspring and matched controls (20 male and 29 female) and an extra eight offspring (three male and five female) of SLE patients without a control match were included. Of the 57 SLE offspring, none were diagnosed with SLE. The matched analyses of the neuropsychological domains revealed impairment in SLE children compared with matched controls in two of the nine domains: learning and memory and behaviour.

Identifying the behavioural phenotype in Fetal Alcohol Spectrum Disorder: sensitivity, specificity and screening potential.

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.

Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings.

Abstract The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congenital hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions.

Binge alcohol consumption by non-alcohol-dependent women during pregnancy affects child behaviour, but not general intellectual functioning; a prospective controlled study.

Effects of binge ethanol consumption during early gestation on child neurodevelopment have not been elucidated. To study whether binge drinking affects cognitive abilities and behavior of exposed children, a prospective observational study comparing 51 children exposed to binge drinking during the first trimester of pregnancy to 51 children not exposed to any teratogens was conducted. The children's physical development, intelligence, language abilities and behavior were assessed. Temperament test results showed that children exposed in utero to maternal binge drinking displayed a greater degree of disinhibited behavior and that this behavior was associated with early drinking variables. Although binge alcohol drinking by non-alcohol-dependent women during the first trimester of pregnancy does not appear to affect intelligence or cognitive and language development of young children, binge drinking in pregnancy does increase the likelihood of certain behavioral characteristics that might predispose these children to later behavioral dysfunction.

The Toronto experience in diagnosing alcohol-related neurodevelopmental disorder: a unique profile of deficits and assets.

BACKGROUND: Fetal alcohol syndrome (FAS), which involves the triad of features reflecting facial dysmorphology, growth retardation and intellectual impairments, encompasses a relatively small proportion of the children affected prenatally by alcohol. Unfortunately, in the absence of facial dysmorphology, the diagnosis is difficult in the majority of children, who are considered to have alcohol-related neurodevelopmental disorder (ARND). Because accepted clinical methods are not pathognomonic, a novel profile approach was used to examine neuropsychological abilities and disabilities to identify children with ARND who do not meet the diagnostic criteria of FAS. OBJECTIVE: To establish a set of criteria, to be validated in future studies, for characterizing the neuropsychological profile of children with ARND. By describing the procedures at this preliminary stage of our work, the goal is to draw attention to this neglected topic and to suggest a model that can be replicated and validated by others, and to provide the first systematic clinical report on diagnosing ARND in Canada. PROCEDURES: On the basis of the literature, parents' descriptions and the authors' own experience with ARND, a profile of neuropsychological characteristics, including both deficits and assets, that are associated with prenatal alcohol exposure was hypothesized. A group of children was then evaluated, mostly adoptees or children in foster care, who were referred for learning and behavioural problems potentially associated with gestational exposure. Their results were submitted to a profile analysis by comparing their deficits and assets according to a list describing a hypothetical ARND profile to determine whether each child fit or did not fit the ARND profile. Groups were compared for background characteristics, FAS symptomatology, and results on specific neuropsychological and behavioural tests. Finally, the characteristics most strongly differentiating the two groups were identified. SETTING: Hospital-based outpatient program. PARTICIPANTS: Fifty-two children aged four to 18 years who were referred for a diagnostic assessment related to suspected or known prenatal alcohol exposure. OUTCOME MEASURES: Each child's assessment results were compared against a list of 21 deficits and six assets by two independent raters. Children with an average of more than 60% deficits and 50% assets were considered to have ARND, while the remainder were not. RESULTS: Twenty-eight children (54%) were assigned to the ARND group and 24 to the non-ARND group. The groups did not differ in physical features or home background characteristics, with the exception of higher parental intelligence quotient in the non-ARND group. The ARND group was more likely to have repeated a grade or received special education and scored lower on standardized measures of intelligence, language and memory abilities. Frequency of behaviour or social problems were equivalent in both groups. CONCLUSIONS: A profile approach used to identify children with ARND discriminates problems in neuropsychological but not behavioural domains. Because elevated scores on behavioural tasks in both ARND and non-ARND groups were clinically significant, more research is needed to identify what behavioural problems are unique to children with ARND compared with other clinic-referred children.

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.

Effects of maternal occupational exposure to organic solvents on offspring visual functioning: a prospective controlled study.

BACKGROUND: Previous studies in adults and animals with high level exposure to organic solvents suggested impairments in visual functioning. The objective of this pilot study was to examine the effects of maternal occupational exposure to organic solvents during pregnancy on offspring color vision and visual acuity, the development of which may be especially vulnerable to organic solvent exposure. METHODS: We conducted a prospective cohort study of 32 offspring of women who were exposed occupationally to organic solvents during pregnancy compared with 27 nonexposed children. Monocular and binocular color vision and visual acuity were assessed using the Minimalist Test and the Cardiff Cards, respectively. Children with known hereditary color vision loss were excluded. RESULTS: Solvent-exposed children had significantly higher error scores on red-green and blue-yellow color discrimination, as well as poorer visual acuity compared with the control group. Exposure index (an estimated measure of exposure intensity) was not significantly related to color discrimination or visual acuity score. Despite excluding all children with a known family history of color vision loss, clinical red-green color vision loss was found among 3 of the 32 exposed children compared with none of the matched controls. CONCLUSIONS: These preliminary findings suggest that occupational exposure to organic solvents during pregnancy is associated with an increased risk of color vision and visual acuity impairment in offspring. The importance of routine visual function screening in risk assessment after prenatal exposure to chemicals warrants further attention.

Neurodevelopment of adopted children exposed in utero to cocaine: the Toronto Adoption Study.

BACKGROUND: Published studies of children's neurodevelopment after in utero exposure to cocaine have not separated intrauterine from postnatal environmental effects as cocaine-using mothers cluster in low socioeconomic classes and have other risk factors. METHODS: To overcome this limitation, a study was done to assess physical and neurodevelopmental characteristics of 52 children: 26 were adopted by parents who sought counselling in the Motherisk Program at the University of Toronto for prenatal cocaine exposure, and 26 were controls matched for maternal intelligence quotient (IQ), socioeconomic status and gestational age. MAIN OUTCOME MEASURES: Head circumference, McCarthy General Cognitive Index (GCI) score, language performance and temperament tests. RESULTS: The children in the study group had smaller head circumferences (34th versus 54th percentiles p = 0.009), lower McCarthy GCI scores (102.8 versus 114.2, p = 0.02), poorer receptive and expressive language performance on the Reynell test, and higher activity levels, less persistence and increased distractibility on temperament tests. On multivariate analysis, cocaine exposure was significantly (p = 0.001) associated with lower IQ and poorer language development independent of intrauterine growth retardation and other potential confounders. INTERPRETATION: By controlling for postnatal environmental factors, this adoption study documents intrauterine developmental risks associated with cocaine exposure. Follow-up into school years is warranted to evaluate the extent of these effects.

Where and what visuospatial processing in adolescents with congenital hypothyroidism.

Visuospatial processing is accomplished in distinct neuroanatomic pathways. One such pathway, known as the where pathway, involves a dorsal route through magnocellular thalamic cells to occipital and parietal cortices and conveys location and motion information. A second pathway, known as the what pathway, involves a ventral route through parvocellular thalamic cells to occipital and temporal cortices and conveys color and form information. The where pathway is thought to be responsible for processing spatial relationships while the what pathway is responsible for object identification. Children with early-treated congenital hypothyroidism (CH) who exhibit selective visuospatial deficits may provide a good model to study the differential development of these pathways. Because children with CH lacked thyroid hormone at a time when needed by developing brain regions such as the parietal cortex, these children may be affected to a greater degree on tasks tapping where but not what pathway processing. We tested this hypothesis via retrospective analysis of their performance on 6 spatial tasks. Compared were 49 adolescents with CH and 49 matched control participants. On the basis of confirmatory factor analysis, tasks were assigned to either where or that pathway groupings. A repeated measures ANOVA showed the CH group was impaired relative to a normal comparison group only on where pathway tasks. Regression analyses indicated that severity of early hypothyroidism was the strongest predictor of where pathway processing but had no effect on what pathway tasks. It is concluded that thyroid hormone is required during late gestation and early life for the normal development of the where aspects of visuospatial processing.

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.

Piracetam therapy does not enhance cognitive functioning in children with down syndrome.

BACKGROUND: Piracetam is widely used as a purported means of improving cognitive function in children with Down syndrome. Its efficacy, however, has not been rigorously assessed. OBJECTIVE: To determine whether 4 months of piracetam therapy (80-100 mg/kg per day) enhances cognitive function in children with Down syndrome. DESIGN: A randomized, double-blind, placebo-controlled crossover study. PARTICIPANTS AND METHODS: Twenty-five children with Down syndrome (aged 6.5-13 years) and their caregivers participated. After undergoing a baseline cognitive assessment, children were randomly assigned to 1 of 2 treatment groups: piracetam-placebo or placebo-piracetam. MAIN OUTCOME MEASURE: The difference in performance while taking piracetam vs while taking placebo on tests assessing a wide range of cognitive functions, including attention, learning, and memory. RESULTS: Eighteen children completed the study, 4 withdrew, and 3 were excluded at baseline. Piracetam therapy did not significantly improve cognitive performance over placebo use but was associated with central nervous system stimulatory effects in 7 children: aggressiveness (n = 4), agitation or irritability (n = 2), sexual arousal (n = 2), poor sleep (n = 1), and decreased appetite (n = 1). CONCLUSION: Piracetam therapy did not enhance cognition or behavior but was associated with adverse effects.

Neurophysiological correlates of verbal and nonverbal short-term memory in children: repetition of words and faces.

The neurophysiological correlates of verbal and nonverbal memory have been extensively studied in adults, but comparable investigations of children are limited. A memory paradigm that is well established with adults is the repetition task, which finds a positive shift in the ERP waveform in response to repeated items, called the "repetition effect." This is thought to represent the brain's memory trace for previously seen information and is reported predominantly at midline frontal and parietal electrodes. We recorded ERPs in thirteen 11- to 14-year old children during repetition tasks of words and faces. Performance was better and ERP latencies shorter for the word than the face task. Although a repetition effect similar to adults was seen at parietal electrodes with increased positivity to repeated items, increased negativity was observed at frontal electrodes; this suggests that the neural substrates of recognition memory continue to develop beyond 11 to 14 years of age. The demonstration of a repetition effect in children provides a basis for studying the neural correlates of specific childhood memory deficits.

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.

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.

The influence of etiology and treatment factors on intellectual outcome in congenital hypothyroidism.

To determine the effects of hypothyroidism and hormonal patterns on outcome, we tested 65 7- to 12-year-old children with congenital hypothyroidism using standardized tests of intelligence, neuropsychological functioning, memory, and achievement. Results were analyzed by etiology, time to thyrotropin normalization, and hormone levels at testing. Children with athyreosis scored below other etiologies on visuospatial, attention, and arithmetic indices. Children whose thyroid-stimulating hormone levels normalized by 1 to 2 months of age scored higher than later normalizers on indices of visual memory, attention, and arithmetic. Normalization of thyroid-stimulating hormone by 3 months of age was associated with better memory and learning abilities than later normalization. Thyroid hormone levels at testing were correlated with indices of sensorimotor, spatial, and language abilities. Two children with persistently elevated thyrotropin levels were not adversely affected. Present findings signify the need to establish etiology, normalize thyrotropin early, and maintain hormone levels in the normal range throughout childhood in children with congenital hypothyroidism.

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.

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.

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.