Early-treated Congenital Hypothyroidism Research Articles

Intelligence quotient (IQ) outcome in children with early-treated congenital hypothyroidism: a systematic review and meta-analysis

Background Congenital hypothyroidism (CH) is the most common congenital endocrine disorder in childhood and is one of the most preventable causes of intellectual disability (ID). Late initiation of thyroid hormone substitution therapy has a negative impact on intellectual abilities in CH patients.
 Objective To compare Intelligence Quotient (IQ) between children with CH who underwent early treatment among the children without CH.
 Methods We performed online literature searches of ScienceDirect, Pubmed, Cochrane Library, and Google Scholar. We included clinical studies that examined IQ scores in patients with early-treated CH and without CH. Review Manager 5.4 was used to perform the meta-analysis.
 Results Twelve studies comparing pediatric patients with and without CH were included in this meta-analysis, for a total of 808 patients. Based on data analysis, IQ levels of verbal IQ [mean difference (MD) -9.05; (95%CI -14.51 to -3.59); (P<0.00001)], performance IQ [MD -11.70; (95%CI -17.41 to -5.99); (P<0.00001)], and total IQ [MD -10.78; (95%CI -14.03 to -7.54); (P<0.00001)]. While verbal, performance, total, of the early-treated CH group were within the normal range, they were each significantly lower than those in the non-CH group.
 Conclusion This meta-analysis reveals that IQ scores in early-treated CH subjects were within normal limits, but significantly lower than that of normal controls.

Comparison of Developmental Status between Early Treated Congenital Hypothyroid and Healthy Control Children

Background: Early diagnosis and treatment of congenital hypothyroidism is the primary goal of neonates and children screening programs. This study aimed to evaluate and compare developmental skills in children with early-treated congenital hypothyroidism with healthy children using the Ages and Stages Questionnaires test (ASQ).
 Methods: A total of 40 neonates with congenital hypothyroidism diagnosed during neonatal screening (thyroid stimulating hormone (TSH) > 10 mu/l) who were treated with Levothyroxine (10-15µ/kg) promptly within the first month of birth (after treatment, TSH < 4 mu/l) were evaluated for developmental skills using the ASQ test at 4, 8, and 12 months of age. The control group consisted of 40 healthy children matched with the case group in terms of age, sex, and socio-economic status. Chi-square and Fisher exact test were used with SPSS statistical software version 21 for analyzing the results.
 Results: The overall mean ASQ score in case group was 262.7 ± 9.07, and in control group was 261.2 ± 8.49, which indicates no significant difference (P > 0.05). The ASQ test score increased significantly by age (P < 0.05). The girls' mean score of the ASQ test was significantly higher than boys in the case group (P < 0.05). Moreover, no significant difference was observed between the mean ASQ test score and the delivery type (P < 0.05).
 Conclusion: This study showed that the developmental skills in children under-treatment of congenital hypothyroidism were at the standard level, indicating the effectiveness of early treatment to avoid developmental disorders.

Developmental Outcomes in Early-treated Congenital Hypothyroidism: Specific Concern in Tc99m Thyroid Scan Role

Background Congenital hypothyroidism (CH) may cause alterations in the child's global development. The current study aimed to screen the global development of children with and without congenital hypothyroidism, focusing on communication, and cognitive abilities and to investigate the influence of illness severity, clinical history, and treatment factors in the evaluated results. Materials and Methods A case control study was conducted on 20 children with early-treated congenital hypothyroidism (CH), and controls without CH (n=100), both groups were matched for age and sex. Patients were subjected to a protocol of assessment applied in Pediatric and Phoniatrics Unit Sohag, Egypt. Assessments included detailed history and medical data, language development testing, intelligence quotient (IQ). According to TSH and T4 levels, case group was divided into controlled group and uncontrolled group. 99m pertechnetate scintigraphy of thyroid (Tc-99m TS) was recommended for all CH children. Results Children’s ages ranged between 3-7 years with a mean age of (4.6 ±1.9year). There were statistically significant differences between study and control group in presence of middle ear effusion, delayed language development, IQ scores (p<0.001). Interestingly, there was a negative correlation between IQ test and total language age with TSH level (r = -0.06, p= 0.004; r =-0.4, p=0.06), respectively. Tc-99m pertechnetate scintigraphy of thyroid confirmed transient CH diagnosis in three cases. Conclusion Despite early treatment in the studied CH children, language and cognitive skills impairments were detected. The magnitude of these impairments significantly related to TSH values and regularity of hormone replacement therapy. TS confirmed transient CH diagnosis in three cases, replacement therapy stopped in those children.

Maternal Thyroid Function During Pregnancy or Neonatal Thyroid Function and Attention Deficit Hyperactivity Disorder: A Systematic Review.

Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in children, yet its etiology is poorly understood. Early thyroid hormone disruption may contribute to the development of ADHD. Disrupted maternal thyroid hormone function has been associated with adverse neurodevelopmental outcomes in children. Among newborns, early-treated congenital hypothyroidism has been consistently associated with later cognitive deficits. We systematically reviewed literature on the association between maternal or neonatal thyroid hormones and ADHD diagnosis or symptoms. We searched Embase, Pubmed, Cinahl, PsycInfo, ERIC, Medline, Scopus, and Web of Science for articles published or available ahead of print as of April 2018. We identified 28 eligible articles: 16 studies of maternal thyroid hormones, seven studies of early-treated congenital hypothyroidism, and five studies of neonatal thyroid hormones. The studies provide moderate evidence for an association between maternal thyroid hormone levels and offspring ADHD, some evidence for an association between early-treated congenital hypothyroidism and ADHD, and little evidence for an association between neonatal thyroid hormone levels and later ADHD. The reviewed articles suggest an association between maternal thyroid function and ADHD, and possibly between early-treated congenital hypothyroidism and ADHD. Study limitations, however, weaken the conclusions in our systematic review, underlining the need for more research. Importantly, there was much variation in the measurement of thyroid hormone function and of ADHD symptoms. Recommendations for future research include using population-based designs, attending to measurement issues for thyroid hormones and ADHD, considering biologically relevant covariates (e.g., iodine intake), and assessing nonlinear dose-responses.

Phonological acquisition in children with early-treated congenital hypothyroidism: association with clinical and laboratory parameters.

To evaluate the phonological characteristics of children with congenital hypothyroidism (CH). Observational, analytical, cross-sectional, ambispective study including prepubertal children with CH (n=100; study group, SG) and controls without CH ( n=100; control group, CG). Assessments included a speech language pathology interview, the phonological evaluation of the ABFW Child Language Test, medical data, and neuropsychological tests in the first three years of life. On treatment onset of the SG, the median chronological age of the participants was 18.0 days and 48.4% had total T4 <2.5 µg/dL (31.75 nmol/L). At the age of 7 years, children in the SG had higher rates of consonant cluster simplification and lower rates of complete phonological system compared to those in the CG. On analysis of combined age groups (4+5 and 6+7 years), the CG had a higher frequency of complete acquisition versus the SG. On multivariate analysis, thyroid agenesis, abnormal scores on the Clinical Linguistic and Auditory Milestone Scale and developmental quotient tests were associated with the occurrence of phonological disorders. Children with CH present delay in phonological acquisition, despite early diagnosis and adequate treatment, especially between the ages of 6-7 years. The etiology of CH and the results of neuropsychological tests in the first years of life seem to be related to this delay.

Effects of Early Thyroid Hormone Deficiency on Children's Autobiographical Memory Performance

Memory deficits and hippocampal abnormalities have been described in individuals with thyroid hormone (TH) insufficiencies; however, no study has yet examined their autobiographical memory (AM) abilities, which are known to be compromised by hippocampal damage. Investigations in adults have shown that AM consists of both episodic and semantic components and that the hippocampus is preferentially involved in episodic AM. The present study used the Children's Autobiographical Interview (CAI) to study episodic and semantic AM in 79 children aged 9 to 14 years, including 26 with early-treated congenital hypothyroidism (CH), 23 born to women with inadequately treated hypothyroidism during pregnancy (HYPO), and 30 typically developing controls. Results showed that relative to controls, CH and HYPO groups both exhibited weaknesses in episodic AM, but not semantic AM. In particular, CH and HYPO groups showed difficulty in recalling event details (i.e., the main happenings) and visual details from past experiences. Overall, this study highlights the importance of TH for early neurodevelopment and provides critical new insight into the effects of early treated TH deficiency on long-term memory performance. Furthermore, the present study indicates that the CAI is an effective tool for investigating episodic AM impairment in clinical pediatric populations.

An Investigation of Impulsivity in Children With Early-Treated Congenital Hypothyroidism

The main feature of congenital hypothyroidism (CH) is a total or partial absence of thyroid hormone, caused by a developmental disorder of the thyroid gland. Introduction of neonatal thyroid screening allows early treatment with replacement hormone. As a result the prognosis of CH has greatly improved but neuropsychological problems do still occur. Claims that early-treated CH is associated with impulsivity were tested with a memory search task comprising 2 response probability conditions: a baseline condition in which "yes" and "no" responses were equally probable and a response bias condition in which the probability of a "no" response was raised to 70%. Impulsivity was defined as the ability to stop and change a response set and was assessed from the amount of inaccurate "no" responses made. Comparisons were made between 47 children with early-treated CH and 35 controls at the age of 7.5 years. Children with early-treated CH were notably slow and variable in their overall task performance but, most important, did not show signs of poor impulse control. Suggested short-term memory problems in these children could not be confirmed. Performance could not be attributed to early disease-related factors or lowered intelligence.

Hypothyroidism, Motor Clumsiness, and ADHD

The behavioral characteristics of 63 children with early-treated congenital hypothyroidism (CH) were evaluated by parent and teacher ratings and compared to 34 healthy controls (ages 7.5-9.5 yrs) at the University of Jyvaskyla, Finland.

Behavioural correlates of early‐treated congenital hypothyroidism

Parents' and teachers' ratings were used to evaluate the behavioural characteristics of children with early‐treated congenital hypothyroidism (CH). Comparisons were made between 63 children with early‐treated CH and 34 healthy controls at the ages of 7.5 and 9.5 y. Additional comparisons were made between the two largest CH subgroups (thyroid agenesis, thyroid dysgenesis) and controls. The most marked differences were found on the introversion cluster and the motor clumsiness scale within it. Children with CH, particularly those with thyroid agenesis, showed introversion and motor clumsiness rather than social negativity and inattention. It is suggested that this behavioural profile may well have its origins in the often‐reported inefficient motor behaviour of these children. Results are discussed in the light of recent findings suggesting an association between thyroid hormone problems and attention deficit hyperactivity disorder. Conclusion: Early‐treated CH is associated with introversion rather than with social negativity.

Behavioural correlates of early-treated congenital hypothyroidism.

Parents' and teachers' ratings were used to evaluate the behavioural characteristics of children with early-treated congenital hypothyroidism (CH). Comparisons were made between 63 children with early-treated CH and 34 healthy controls at the ages of 7.5 and 9.5 y. Additional comparisons were made between the two largest CH subgroups (thyroid agenesis, thyroid dysgenesis) and controls. The most marked differences were found on the introversion cluster and the motor clumsiness scale within it. Children with CH, particularly those with thyroid agenesis, showed introversion and motor clumsiness rather than social negativity and inattention. It is suggested that this behavioural profile may well have its origins in the often-reported inefficient motor behaviour of these children. Results are discussed in the light of recent findings suggesting an association between thyroid hormone problems and attention deficit hyperactivity disorder. Early-treated CH is associated with introversion rather than with social negativity.

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.

Psychoeducational outcome in children with early-treated congenital hypothyroidism

Psychoeducational outcome in children with early-treated congenital hypothyroidism

Psychoeducational outcome in children with early-treated congenital hypothyroidism.

To describe the psychoeducational characteristics of children with congenital hypothyroidism (CH) identified through newborn screening and to study changes over time. 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. 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. 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.

Neuropsychological follow-up in early-treated congenital hypothyroidism: a problem-oriented approach.

Screening programs for congenital hypothyroidism (CH) dramatically improved the neuropsychological prognosis in affected children. However, mild impairments in cognitive performances, poorer motor skills, defective language abilities, and learning problems have been reported in some studies of early-treated CH children. The occurrence of these defects makes neuropsychological follow-up mandatory. The aim of the present study was to identify those neuropsychological functions that are more frequently affected in early-treated CH children and that might require prompt rehabilitation treatment to prevent permanent defects. The study group involved 24 CH children. Levothyroxine (LT4) treatment (initial dose 8-10 microg/kg per day) was started at mean age of 28 days (range 15-45) and was then adjusted with the goal to keep thyrotropin (TSH) and free thyroid hormone levels in the normal range. Cognitive evaluation was performed at 3, 5, and 7 years of age and did not significantly differ from that of controls. Mean neurological scores were lower in children 5 years of age than in controls. Children with severe neonatal hypothyroidism (serum thyroxine [T4] < 2 microg/dL) had significantly lower neurological scores compared to less affected CH children and normal controls. The most affected functions were balance, extremity coordination, fine motricity, quality of movements, associated movements, and head movements. Language disorders were observed in half of CH children at 3 and 5 years of age, but moderately severe defects were restricted to those with severe neonatal hypothyroidism. In conclusion, a problem-oriented, simplified neuropsychological follow-up of early-treated children with CH should not systematically include the frequent repetition of time-consuming and expensive psychometric tests because individual IQ scores are in the normal range of tests in almost all CH children and can be differentiated from those of normal controls only on a population-statistic basis. Selected tests of motor proficiency are indicated at 3 and 5 years of age to detect those defects in motor skills that appear to be more specifically affected in CH children. Language performances are at particular risk in CH children, and should be always checked at 3 and 5 years of age. Children with even mild language disorders or delayed language achievements should be regularly reevaluated at 6-month intervals and, if no spontaneous improvement is observed, they should receive specific rehabilitation treatment. No further motor and language evaluation is warranted in CH children with normal tests at age 5 years.

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

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

Motor problems in children with early-treated congenital hypothyroidism: A matter of failing cerebellar motor control?

This study addresses the question of whether “clumsiness” in children with early treated Congenital Hypothyroidism (CH) might be attributable to cerebellar dysfunction. CH is known to affect rapid perinatal growth of the cerebellum. If this would affect the supposed motor timing function of the cerebellum this should be especially reflected by difficulty in producing fast aiming movements. An experiment was devised in which children made sequences of fast, goal directed movements in order to examine two aspects of fast voluntary movements that are known to be affected by cerebellar injury: dysmetria and dysdiadochokinesis. Three groups of children between the ages of 9 and 11 participated: a group with severe CH (thyroid agenesis, n=18), a group with mild CH (thyroid dysgenesis, n=23) and a control group ( n=31). In comparison with controls, motor performance in children with severe CH was characterized by more overshoots, shorter movement times, higher velocity and a larger initial force impulse. In line with previous findings from the same population, it is concluded that motor problems in early treated CH are primarily related to peripheral processes associated with motor execution rather than to central cerebellar processes associated with motor timing. PsycINFO classification: 2330;2240

Timing variability in children with early-treated congenital hypothyroidism

This study reports on central and peripheral determinants of timing variability in self-paced tapping by children with early-treated congenital hypothyroidism (CH). A theoretical model of the timing of repetitive movements developed by Wing and Kristofferson was applied to estimate the central timekeeper (clock) and peripheral implementation (motor delay) variances from the variability in the response intervals. Before it is diagnosed and treated, CH is known to affect proper development of the cerebellum. If this would affect the time-keeper function of the cerebellum, it should be reflected by an increased central clock variability rather than by an increased peripheral motor-delay variability in terms of the Wing and Kristofferson model. Results of 46 children with early-treated CH, differing in severity (21 severe, 25 mild), and 34 normal controls are reported. A refinement of the Wing and Kristofferson model is applied to estimate central clock and peripheral motor delay timing variability more precisely than has been done before. Results show that for children with early-treated CH the estimate of the motor delay variance is four times higher than for the controls, while the estimate of the clock variance does not differ between the groups. It is concluded that motor problems in early-treated CH are associated with peripheral rather than with central timing deficiencies.

Neuropsychological development in a child with early-treated congenital hypothyroidism as compared with her unaffected identical twin.

Neonatal screening for congenital hypothyroidism (CH) prevents the serious neuropsychological features of CH, but the question remains whether intelligence and motor skills of CH children treated early are completely normal. In this report we describe the rare case of two genetically identical twins, only one of whom was affected by CH due to thyroid agenesis. L-Thyroxine (9 microg/kg body weight/day) therapy was initiated at 27 days of age and was adequate throughout the follow-up. Neuropsychological evaluation was performed on the twins in parallel from 3 months to 8 years of age. The CH twin (NB) did not show major neuromotor impairments but, compared with the unaffected twin (EB), she had a slight delay in postural/motor achievements and in language development that completely disappeared at 8 years of age. On standardised tests of intelligence, NB was indistinguishable from control children but, compared with her twin, she had lower IQ scores in most testing occasions up to 7 years of age (NB = 108 vs EB = 115). School achievements of NB did not significantly differ from those of her classmates but, compared with her twin, she scored worse in writing, mechanical reading, verbal memory, and possibly in arithmetic. Because the twins were genetically and phenotypically identical, were raised in the same environment, and received a similar education, it is concluded that hypothyroidism in utero and in the first neonatal month was responsible for the lower neuropsychological achievements of the CH twin. While foetal hypothyroidism is at present unavoidable, earlier diagnosis and initiation of treatment in neonates with CH are important and highly recommended.

Motor and cognitive development in children with congenital hypothyroidism: A long-term evaluation of the effects of neonatal treatment

Although neonatal thyroid screening programs have been of value in preventing cerebral damage, it is still controversial whether patients with congenital hypothyroidism achieve normal motor and cognitive skills. We studied the motor and cognitive skills of 72 children with early-treated congenital hypothyroidism and 35 control subjects at the ages of 7 1/2 and 9 1/2 years. The relative influence of cause, blood thyroxine concentration at the time of screening, and age at the start of thyroxine replacement therapy on motor and cognitive development was investigated. Despite having received treatment at a mean age of 23 days, children with low neonatal thyroxine concentrations (< 50 nmol/L) at screening, particularly children with thyroid agenesis, had significant motor problems and borderline intelligence scores as late as 9 1/2 years of age. Balance and gross motor functions seemed to decline between 7 1/2 and 9 1/2 years of age, whereas language and memory functions seemed to be maintained. Significant correlations between the start of therapy and both motor scores and performance IQ scores at the age of 7 1/2 years in children with severe hypothyroidism show the importance of early treatment for these patients.

Intelligence, motor skills and behaviour at 5 years in early-treated congenital hypothyroidism

The cognitive functioning, motor skills and behaviour of 5-year-old children with early-treated congenital hypothyroidism was assessed. The study group was 57 children with congenital hypothyroidism (CH) diagnosed by neonatal screening in N.E. and N.W. Thames regions between 1978 and 1981 along with 51 non-affected controls matched for age, sex, social class and language background. Small differences in I.Q. and behaviour between the patients and the controls were not statistically significant. However, children with CH showed significant deficits in motor skills (M 79.9 SE 3.7) compared to the controls (M 99.8 SE 4.0) (P = 0.0003). Deficits were particularly marked for balance. In addition, children with more severe hypothyroidism at diagnosis (Plasma thyroxine less than 20 nmol/l) did significantly less well in respect to I.Q. and motor skills than those with less severe hypothyroidism (plasma thyroxine greater than 60 nmol/l). These findings provide further evidence for the importance of the severity of hypothyroidism in determining the outcome for intelligence and motor skills in children with early-treated congenital hypothyroidism. Deficits in motor skills, particularly in relation to balance, suggest that early impairment of the vestibular system may occur despite early treatment.