Crecimiento y maduración de los pacientes con hipotiroidismo congénito detectados por el programa de cribado neonatal en Cataluña (1986–1997) / Growth and maturation in the patients with congenital hypothyroidism detected by the neonatal screening program in Catalonia, Spain (1986–1997)

Fundamento y objetivo: En muchos países se han establecido programas de detección precoz del hipotiroidismo congénito (HC) que consiguen un crecimiento y un cociente intelectual normales. El objetivo de este estudio es realizar el seguimiento de los casos de HC detectados mediante el programa de detección precoz del HC en Cataluña. Pacientes y método: El estudio es descriptivo, longitudinal, de una serie de 136 casos de HC detectados mediante el programa de detección precoz en Cataluña del año 1986 al año 1997 y controlados en el Hospital Materno-infantil Vall d´Hebron de Barcelona. Se han valorado los parámetros que indican la intensidad y duración del hipotiroidismo neonatal. Se ha hecho el seguimiento del crecimiento y una exploración psicológica (test de McCarthy y la escala de inteligencia de Wechsler para niños). Resultados: Los niños (30 casos, el 22,1%) y las niñas (106 casos, el 77,9%) con HC de este estudio han tenido un crecimiento, peso e índice de masa corporal que no son distintos de los de la población actual de Barcelona. La talla se ha situado 0,5 DE por encima de los valores de Tanner de 1966 y el índice de masa corporal se ha situado una DE por encima de los valores de Roland-Cachera de 1982. Esta aceleración secular del crecimiento se ha observado en todos los países desarrollados. En una muestra del 37,5% de los casos, el desarrollo psicológico no ha diferido del de la población de referencia. Sin embargo, una mayor intensidad del hipotiroidismo neonatal y la normalización más tardía de éste ha correlacionado negativamente con la puntuación en los test psicológicos. Conclusiones: Una vez conseguida la normalización del crecimiento y del desarrollo psicológico, se debería optimizar el programa de detección precoz para el HC en Cataluña e iniciar el tratamiento lo más precozmente posible para evitar que algunos niños no alcancen su potencial intelectual completo (AU)

Background and objective: Many countries have developed screening programs for CH that bring about a normal somatic and psychological development. The aim of this study is to evaluate the evolution of cases detected by the screening program of congenital hypothyroidism in Catalonia. Patients and methods: The was a descriptive, longitudinal study of a series of 136 cases of congenital hypothyroidism detected by the screening program in Catalonia from 1986 to 1997 and who had been checked in the Maternal-infantile Vall d´Hebron Hospital in Barcelona. Follow-up was carried out for growth and a psychological exploration was performed (McCarthy test and WISC-R).Results Males (30 cases, 22.1%) and females (106 cases, 77.9%) with congenital hypothyroidism of this study had a height, weight and BMI that were not different from those of the current population of Barcelona. Height was 0.5 SD above the Tanner reference values of 1966 and BMI was one SD above the Roland-Cachera reference values of 1982. This secular acceleration of growth has been observed in all developed countries. Results: In a sample of 37.5% of the cases, psychological development did not differ from that of the reference population. However, a greater intensity of neonatal hypothyroidism and its most delayed normalization correlated negatively with the score in the psychological tests. Conclusions: Once normalization of growth and psychological development are achieved, the screening program of congenital hypothyroidism in Catalonia should be optimized by initiating treatment as soon as possible to avoid the possibility that some children do not reach their complete intellectual potential (AU)

[Growth and maturation in the patients with congenital hypothyroidism detected by the neonatal screening program in Catalonia, Spain (1986-1997)]. / Crecimiento y maduración de los pacientes con hipotiroidismo congénito detectados por el programa de cribado neonatal en Cataluña (1986-1997).

BACKGROUND AND OBJECTIVE: Many countries have developed screening programs for CH that bring about a normal somatic and psychological development. The aim of this study is to evaluate the evolution of cases detected by the screening program of congenital hypothyroidism in Catalonia. PATIENTS AND METHODS: The was a descriptive, longitudinal study of a series of 136 cases of congenital hypothyroidism detected by the screening program in Catalonia from 1986 to 1997 and who had been checked in the Maternal-infantile Vall d'Hebron Hospital in Barcelona. Follow-up was carried out for growth and a psychological exploration was performed (McCarthy test and WISC-R). RESULTS: Males (30 cases, 22.1%) and females (106 cases, 77.9%) with congenital hypothyroidism of this study had a height, weight and BMI that were not different from those of the current population of Barcelona. Height was 0.5 SD above the Tanner reference values of 1966 and BMI was one SD above the Roland-Cachera reference values of 1982. This secular acceleration of growth has been observed in all developed countries. In a sample of 37.5% of the cases, psychological development did not differ from that of the reference population. However, a greater intensity of neonatal hypothyroidism and its most delayed normalization correlated negatively with the score in the psychological tests. CONCLUSIONS: Once normalization of growth and psychological development are achieved, the screening program of congenital hypothyroidism in Catalonia should be optimized by initiating treatment as soon as possible to avoid the possibility that some children do not reach their complete intellectual potential.

Children born small for gestational age (SGA) who fail to achieve catch up growth by 2-8 years of age are short from infancy to adulthood. Data from a cross-sectional study of 486 Spanish children.

AIMS AND METHODS: Postnatal growth was evaluated in a cross-sectional study of 486 Spanish children, 241 girls and 245 boys, born small for gestational age (SGA), without height catch-up growth between the ages of 2 and 8 years [height <-2SD of age- and sex-matched controls born appropriate for gestational age (AGA)]. SGA was defined as birth weight and/or length values <-2SD of those of the born AGA control population. Weight and height values were grouped in 0.5+/-0.15-year intervals from birth to adult height and compared with those of age- and sex-matched controls born AGA. A total of 1,985 height measurements were recorded in girls and 2,113 in boys. Adult or near-adult height was reached in 50 girls and 42 boys. Mean, SD and mean Z-score values at each age interval were calculated. Dysmorphic syndromes and chronic illnesses were excluded. RESULTS: Mean height Z-score values ranged from -5.56 to -3.12 during the first two years of life and remained between -5.25 and -2.42 thereafter until adult height, and mean weight Z-score values ranged from -3.66 to -2.26 from birth to two years of age and remained between -3.05 and -0.94 thereafter until adult height. Mean Z-score values of near-adult or adult height were -2.83 in girls (n=50) and -2.74 in boys (n=42). Midparental adult height corrected for sex was -1.45 +/- 0.5 in girls (n=150) and -1.60 +/-0.6 in boys (n=185). Height +2SD values of SGA children were similar to -2SD values of age- and sex-matched AGA controls (non statistically significant). CONCLUSIONS: Our data show that short children born SGA are shorter than children born AGA from the age of two years onwards and that their adult height is below that of their corresponding midparental height by more than 1 SD.

Functional study of a novel single deletion in the TITF1/NKX2.1 homeobox gene that produces congenital hypothyroidism and benign chorea but not pulmonary distress.

CONTEXT: We studied two sisters with congenital hypothyroidism and choreoathetosis but not respiratory distress. OBJECTIVE: The aim of this study was to establish the genetic defect that causes this phenotype and study the molecular mechanisms of the pathology by means of functional analysis. DESIGN: Sequencing of DNA, expression vectors generation, EMSAs, transfections experiments as well as bioinformatics analysis were performed. RESULTS: We found a new single deletion (825delC) in one allele of the TITF1/NKX2.1 gene. The mutation located in the C-terminal domain generates a nonsense thyroid transcription factor 1 (TTF1) protein, with 22 amino less and rich in positive charges. This protein shows diminished binding to DNA, does not interfere with wild-type (wt) TTF1 binding, and fails to activate reporter genes harboring the thyroglobulin (Tg), thyroperoxidase (TPO), or surfactant protein B (SP-B) promoters. In addition, the mutant (mut) protein has a dominant-negative effect on the transcriptional activity of wt TTF1 in a promoter-specific manner, inhibiting the transcription of Tg and TPO but not of SP-B. Using a Gal4 reporter system, we demonstrate that the mut protein is not transcriptionally active and does not likely compete with the wild type for coactivators. Interestingly, the mut protein impairs the wt capacity to synergize with paired box 8 (PAX8). This cooperation is necessary for Tg and TPO transcription but dispensable for SP-B expression. CONCLUSION: These results are concordant with the phenotype of the two sisters studied and demonstrate a differential role for TTF1 in the different tissues in which it is expressed.

Fetal growth regulation and intrauterine growth retardation.

Gestational age and neonatal anthropometric parameters are currently used to evaluate fetal growth and are predictive factors of perinatal and postnatal morbidity and mortality. We performed a retrospective analysis of neonatal anthropometric parameters (weight, vertex-heel length and head circumference) in 1,470 live preterm neonates born between 1997 and 2002 and a prospective analysis of the same parameters in 1,786 live newborns of both sexes born in 2001 and 2002, products of single 37-42 week uncomplicated pregnancies in healthy Spanish Caucasian mothers. A progressive increase in these parameters with gestational age and sexual dimorphism were observed from the 30th week of gestational age onwards, with statistically-significant differences (p<0.05) at 38-42 weeks of gestational age. An increase in weight and length values in relation to previous Spanish studies was also documented in preterm newborns. It is estimated that 10-15% of children born small for gestational age (SGA) do not experience catch-up growth by the age of 3 years and may have short stature in adulthood. Preliminary data of a cross-sectional study on spontaneous growth in boys and girls born SGA without postnatal catch-up growth show that their +2 SD values of height are similar to -2 SD values of our normal control population of children born with adequate weight and length for gestational age (AGE). However, weight +2 SD values are similar to mean values of control children born AGE. In summary, our data show sexual dimorphism in neonatal anthropometric growth parameters and that these parameters change with time and may be updated. In addition children born SGA without postnatal catch-up are shorter and have higher weight than age-, height- and sex-matched controls born AGE.