Jacqueline Glorieux

Intellectual development at age 12 years of children with congenital hypothyroidism diagnosed by neonatal screening

Twenty-seven patients with congenital hypothyroidism diagnosed by neonatal screening were examined at the age of 12 years. The 12 patients with severe hypothyroidism at diagnosis (thyroxine < 2 micrograms/dl (< 26 nmol/L), and area-of-the-knee epiphyses < 0.05 cm2 had a lower IQ than the 15 patients with less severe hypothyroidism (mean +/- SD, 89 +/- 17 vs 104 +/- 10; p < 0.007). Comparisons of patients and siblings confirm that this difference was due to the severity of hypothyroidism.

Useful parameters to predict the eventual mental outcome of hypothyroid children

ABSTRACT: The Quebec Network for Genetic Medicine has followed the development of some 100 hypothyroid children treated by 1 month of age and evaluated at 18 months, 3 and 5 yr and the Griffiths Mental Development Scales, then at 7 and 9 yr with the Wechsler Intelligence Scale for Children Revised. Results show that the children as a group reach scores within the normal range of the tests. However, a few patients have low scores at each evaluation. Previously, we showed a correlation between a low serum thyroxine concentration, or a relatively retarded bone maturation before treatment, and low mental scores. To better characterize the significance of this relationship we correlated these pretreatment factors and the Wechsler Intelligence Scale for Children Revised results of 43 subjects reaching the age of 7 yr. Again, the same correlation was observed. Calculating a predictive factor (low thyroxine, <2 μg/dl and retarded bone surface, <0.05 cm2) from data recorded before therapy initiation, 10 of 13 children were correctly predicted to have I.Q. values <90. The use of these parameters might permit early intervention, and allow specific guidance of the more affected subjects.

Auditory brainstem response audiometry in congenitally hypothyroid children under early replacement therapy.

ABSTRACT. Using auditory brainstem response audiometry, we evaluated 34 congenital hypothyroidism children under thyroid hormone therapy and 24 age- and sex-matched controls between 5 and 12 yr of age. Two main auditory brainstem response abnormalities were encountered: first, prolonged wave I latencies, secondary to a peripheral impairment, were found in seven congenital hypothyroidism children (20%): three of these showed signs of serious otitis media, unilaterally in two and bilaterally in the other, at the time of the evaluation. Second, shortened I-V interpeak latencies were observed in 10 children (29%). No correlation was found between the interpeak latencies and the L-thyroxine serum values at the time of the test or just prior to treatment initiation. Also, there was no correlation with estimated bone age at treatment initiation or with the Griffiths global mental development quotients assessed at 5 yr of age. These preliminary results suggest a significant incidence of auditory brainstem response abnormalities in treated hypothyroid children.

Nursery Neurobiologic Risk Score and outcome at 18 months

The aim of this study was to confirm the predictive value of the nursery Neurobiologic Risk Score. Prospectively, 121 infants (mean birthweight 961 ± 179 g, gestation 27.0 ± 1.2 weeks) were followed at 18 months. The nursery Neurobiologic Risk Score was correlated to the developmental quotient (r=– 0.54). From low (scores 0‐4), to moderate (scores 5–7) to high (scores ≥8) risk groups, respectively, significant differences were found in mean developmental quotient (101 ± 9 vs 92 ± 19 vs 76 ± 24) and in prevalence of developmental quotients < 90 (12 vs 24 vs 71%), of cerebral palsy (4 vs 19 vs 41%), of severe disabilities (0 vs 24 vs 50%) and of any disability (16 vs 30 vs 71%). Sensitivity, specificity, positive and negative predictive values for any disability were 81, 54,49 and 84% for a score ≥ 5 and 56, 87, 71 and 78% for a score ≥ 8. The nursery Neurobiologic Risk Score was useful in predicting 18 months outcome of very premature infants.

Outcome in three siblings with antibody-mediated transient congenital hypothyroidism

A woman receiving thyroxine substitution therapy for acquired hypothyroidism caused by autoimmune thyroiditis gave birth to three babies who had transient primary hypothyroidism. All three babies had elevated thyrotropin levels on neonatal screening, but one had normal thyroxine values. Thyrotropin receptor-blocking antibodies were present in maternal serum and in the three neonates. Each baby also had a different congenital malformation. The neurodevelopmental outcome of the children appeared related in part to maternal thyroxine levels, which suggests that transplacental transfer of thyroxine may protect the fetal brain.

Developmental pathways leading to externalizing behaviors in 5 year olds born before 29 weeks of gestation

&NA; Longitudinal data for 62 infants born before 29 weeks of gestation were used to assess the influence of four factors (i.e., neonatal health, family environment, language skill, and nonverbal ability) on the parental report of hyperactive and oppositional behaviors of children at 5 years 9 months. The proposed path analysis model tested the following: (1) whether neonatal health and family environment have a direct influence on language skill and nonverbal ability both measured at 18 months corrected age, (2) the predictive value of language skill and nonverbal ability on oppositional and hyperactive behaviors, and (3) whether the effects of neonatal health and/or family environment on oppositional and hyperactive behaviors can be conceived as mediated by language skill and/or nonverbal ability. The results revealed three main pathways. First, family environment predicted language skill, which, in turn, was negatively associated with childrens hyperactivity. Second, neonatal health predicted nonverbal ability, which was positively linked to oppositional behaviors. Third, a direct negative relation between neonatal health and hyperactive outcome was observed. The implications of these substantially different pathways for hyperactive and oppositional behaviors are discussed.

Somatosensory evoked potentials and auditory brain-stem responses in congenital hypothyroidism. II: A cross-sectional study in childhood. Correlations with hormonal levels and developmental quotients

We report the results of somatosensory evoked potentials (SEPs) and auditory brain-stem responses (ABRs) done in 48 congenital hypothyroid (CH) treated children, early detected and aged 18 months, 3 and 5-9 years of age. We report also the results of SEP and ABR done in 9 3-year-old CH children, before and after a 1 month therapy interruption to reassess the thyroid status. The more frequent abnormalities were increased wave I latencies for 18 month and 3-year-old CH children. In some children, these increases were not associated with signs of otitis media. No significant difference was seen between CH children and controls for SEP latencies and ABR and SEP interpeak latencies (IPLs). Similarly, no significant difference was seen between the two recording sessions in the 9 3-year-old CH children for ABR and SEP. On an individual basis, we observed abnormalities of central conduction time for ABR and SEP in several CH children. Moreover, significant partial correlations were found between ABR and SEP IPLs and thyroxine (T4) serum levels at diagnosis and thyrotropin (TSH) serum levels at the time of recording. There was also a significant partial correlation between N19-P22 IPLs and the practical reasoning scale of the Griffiths test considering the whole group of CH children. These results indicate that SEP might eventually be used to detect CH children at risk of presenting developmental abnormalities.

Somatosensory evoked potentials and auditory brain-stem responses in congenital hypothyroidism. I. A longitudinal study before and after treatment in six infants detected in the neonatal period

We report the results of a longitudinal study of auditory brain-stem responses (ABRs) and somatosensory evoked potentials (SEPs) performed in 6 children with congenital hypothyroidism. These infants were detected by the Quebec Network for Genetic Medicine and treated early. ABRs and SEPs were recorded both before and 2 weeks after the initiation of therapy and at 6 months of age. Before treatment, for SEP, we found increased wave N19, P22 latencies and N13-N19, N19-P22 interpeak latencies (IPLs) in congenital hypothyroid (CH) children. For ABR, there were increased wave I latencies with normal I-V IPLs. Substitutive therapy improved these abnormalities although this improvement was more evident after a shorter period of time for ABRs than for SEPs. Even at 6 months, 2 CH children still showed increased N13-N19 IPLs. Both had very low serum T4 levels at the time of diagnosis and one had also a very small knee surface area, both criteria indicating a severe hypothyroidism. It will be interesting to verify if initial and persisting increase of N13-N19 IPL is associated with later neuropsychological problems.

Extreme prematurity in healthy 5-year-old children: A re-analysis of sex effects on event-related brain activity

A male disadvantage has been reported in several outcome studies of children born preterm. Twenty-two healthy premature children (10 girls, 12 boys) born between 25 and 28 weeks of gestation and 20 controls born full-term (10 boys, 10 girls) were matched on socioeconomical status and age. Event-related potentials (ERPs) were recorded by using 14 electrodes in a visual oddball task, with 75% frequent and 25% rare stimuli. This task elicited a larger P3 to the rare than to the frequent stimuli, with a prominent parietocentral localization. However, the amplitude was larger in full-term boys than in full-term girls, a difference that was not observed between preterm boys and preterm girls, especially to targets and on the central electrodes. In addition, the preterm group was characterized by a frontal slow wave larger in boys than in girls. In these prematures, the lack of the sex-related difference may be accounted by differences in the strength of the neuronal generators in males, as they might have been affected by the high level of androgens by the fetal testis under the control of placental gonadotropes during the first two thirds of gestation.

293 PRELIMINARY REPORT ON PSYCHOLOGICAL DEVELOPMENT AT AGE ONE OF TREATED HYPOTHYROID INFANTS DETECTED BY THE QUEBEC SCREENING NETWORK FOR METABOLIC DISEASES

Since April 1974, the Quebec Screening Network for Metabolic Diseases has been screening every infant born in the P.Q. for neonatal hypothyroidism. Since January 1977 every infant detected and treated is tested for its psychological and neuromuscular development at age 12, 18 and 36 months by the Griffith test. Over that period 20 infants age 12 months have been assessed. This assessment comprises 5 different test for locomotor development, social behavior, verbal, fine coordination and performance.Nine of these infants have been retested at 18 months of age, with similar scores. These results appears to indicate that early treatment of congenital hypothyroidism if effective in preventing neuromuscular and mental retardation in 12 and 18 months infants as assessed by the Griffith test.