Association between congenital hypothyroidism and in-hospital adverse outcomes in very low birth weight infants / 中华儿科杂志

Objective: To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1st, 2019 to December 31st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results: A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) (OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above (OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above (OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion: There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Progress of newborn screening in China / 浙江大学学报·医学版

Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and regulations and the leadership of the national health administration, approved screening centers in public hospitals took the responsibility for publicity, screening, diagnosis, treatment, follow-up and management of birth defects. As of 2022, 31 provinces (autonomous regions and municipalities directly under the central government) have carried out NBS for phenylketonuria, congenital hypothyroidism, and hearing loss, 23 provinces have carried out screening for glucose-6-phosphate dehydrogenase (with a screening rate of 89.24%), and 24 provinces have carried out screening for congenital adrenal cortical hyperplasia (91.45% screening rate). Over the past four decades, screening techniques have evolved from bacterial inhibition, fluorescence analysis, and tandem mass spectrometry for the detection of biochemical markers to genetic testing, which has greatly contributed to the expansion of the types of diseases screened for. The combined use of metabolomics and genomics is currently being explored. Effective management and rigorous quality control of NBS are prerequisites for improving the quality and ensuring the accuracy of screening. The Quality Management System for Newborn Screening System Network (QMS-NBS), established by the National Center for Clinical Laboratories, covers all screening centers and related blood collection agencies. The operation of the QMS-NBS allows the quality and performance of screening to be transparent and measurable, ensuring the quality and efficiency of screening. This article provides an overview of the history of NBS, especially the evolution of policies for the NBS in China, the construction of screening institutions, the number of newborns screened, the incidence rates of screened diseases, the changes in screening technology, the expansion of new diseases screened for, and the quality control of NBS. Overall, the progress in NBS in China has not only benefited from the development and standardization at the technological level, but also benefited from the construction of policies, regulations and ethics.

Results of neonatal screening for congenital hypothyroidism and hyperphenylalaninemia in Zhejiang province from 1999 to 2022 / 浙江大学学报·医学版

OBJECTIVES@#To analyze the results of neonatal screening for congenital hypothyroidism (CH) and hyperphenylalaninemia (HPA) in Zhejiang province from 1999 to 2022.@*METHODS@#A total of 11 922 318 newborns were screened from September 1999 and December 2022 in Zhejiang province. The blood thyroid stimulating hormone (TSH) levels were measured by a fluorescence method and blood phenylalanine (Phe) levels were measured by fluorescence method or tandem mass spectrometry. TSH≥9 μIU/mL was considered positive for CH, while Phe>120 μmol/L and/or Phe/Tyr ratio>2.0 were considered positive for HPA. The positive newborns in screening were recalled, and the gene variations were detected by high-throughput sequencing and MassARRAY tests.@*RESULTS@#The overall neonatal screening rate during 1999-2022 was 89.41% (11 922 318/13 333 929) and the screening rate was increased from 6.46% in 1999 to 100.0% in 2022. A total of 8924 cases of CH were diagnosed among screened newborns with an incidence rate of 1/1336. A total of 563 cases of HPA were diagnosed, including 508 cases of classic phenylketonuria (cPKU) and 55 cases of tetrahydrobiopterin deficiency (BH4D), with an incidence rate of 1/21 176. Ninety-seven out of 8924 cases of CH underwent genetic analysis. Gene mutations were detected in 9 CH related genes, the highest frequency mutations were found in DUOX2 gene (69.0%) with c.3329G>A (p.R1110Q) (18.2%) and c.1588A>T (p.K530X) (17.3%) as the hotspot mutations. There were 81 PAH gene variants detected in a total of 250 cases of cPKU, and c728G>A (p.R243Q) (24.4%), c.721C>T (p.R241C) (15.0%) were the hotspot mutations. Meanwhile 7 novel variants in PAH gene were detected: c.107C>A (p.S36*), c.137G>T (p.G46V), c.148A>G(p.K50E), c.285C>T (p.I95I), c.843-10delTTCC, exon4-7del and c.1066-2A>G. There were 12 PTS gene variants detected in 36 cases of BH4D, and c.259C>T (p.P87S) (31.9%) was the hotspot mutation.@*CONCLUSIONS@#The incident of CH has increased from 1999 to 2022 in Zhejiang province, and it is higher than that of national and global levels; while the incidence of HPA is similar to the national average. DUOX2 gene variation is the most common in CH patients; c.728G>A (p.R243Q) is the hotspot mutation in cPKU patients, while c.259C>T (p.P87S) is the hotspot mutation in BH4D patients.

Newborn Screening Center Mindanao census from 2019 to 2022

@#Congenital disorders cause a global estimate of 240,000 deaths in newborns and 170,000 deaths in children ages 1 month up to 5 years every year. 1 In order to detect metabolic, hematologic, or endocrine disorders in newborns, newborn screening (NBS) is conducted in many countries around the world. In the Philippines, NBS was introduced by the Newborn Screening Study Group in 1996, with the aim of establishing the incidence of six metabolic conditions, namely, congenital hypothyroidism, congenital adrenal hyperplasia, galactosemia, phenylketonuria, homocystinuria, and glucose-6-phosphate dehydrogenase deficiency, and creating recommendations for the adoption of NBS nationwide.2 The Republic Act No. 9288, otherwise known as the Newborn Screening Act of 2004, requires that the Department of Health shall ensure the establishment and accreditation of newborn screening centers (NSCs) in strategically located areas across the Philippines.3 At present, there are seven operational NSCs in the country,4 with the Newborn Screening Center-Mindanao (NSC-Mindanao) in Southern Philippines Medical Center (SPMC) as the only center catering to all NBS facilities all over Mindanao.5 NSC-Mindanao initially performed screening tests for five disorders, but now tests for a panel of 29 metabolic and other congenital disorders.

Clinical phenotype and genetic analysis of a child with 14q12q13 microdeletion syndrome manifesting as congenital hypothyroidism / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic etiology for a child featuring congenital hypothyroidism (CH).@*METHODS@#Whole exome sequencing (WES), copy number variation (CNV) sequencing and chromosomal microarray analysis (CMA) were carried out for a newborn infant who had presented at Linyi People's Hospital for CH. Clinical data of the child was analyzed, in addition with a literature review.@*RESULTS@#The main characteristics of the newborn infant had included peculiar face, vulvar edema, hypotonia, psychomotor retardation, recurrent respiratory tract infection with laryngeal wheezing and feeding difficulties. Laboratory test indicated hypothyroidism. WES suggested a CNV deletion on chromosome 14q12q13. CMA further confirmed a 4.12 Mb deletion at chromosome 14q12q13.3 (32649595_36769800), which has encompassed 22 genes including NKX2-1, the pathogenic gene for CH. The same deletion was found in neither of her parents.@*CONCLUSION@#Through the analysis of clinical phenotype and genetic variant, the child was diagnosed with 14q12q13.3 microdeletion syndrome.

Atipicidad en el hipotiroidismo congénito: síndrome de Kocher-Debré-Semelaigne. Reporte de caso / Atypicality in congenital hypothyroidism: Kocher-Debré-Semelaigne. Case report

El síndrome de Kocher Debré Semelaigne (SKDS) se describe dentro de las formas clínicas atípicas asociadas al hipotiroidismo congénito (HC) severo, no tratado y de larga evolución, con manifestaciones de pseudohipertrofia muscular difusa y debilidad muscular predominantemente proximal, reversible al reemplazo con tiroxina. Es raro en países con programas de pesquisa neonatal. Objetivo: reportar el caso de un niño con diagnóstico de HC por disembriogenesis (atireosis), que se mantuvo con mal control de la enfermedad durante el primer año de vida y manifestaciones miopáticas desde la etapa neonatal. Resultados: se confirma el diagnóstico a través de estudios específicos, con evidencias de patrones miopáticos característicos. Se logra regresión clínica parcial a los nueve meses de mantener estabilidad de la TSH y las hormonas tiroideas (HT), coincidiendo con la normalización de la enzima de músculo creatinfosfoquinasa (CPK). A los 12 años de seguimiento, mantenía ligera hipertrofia de la musculatura de las extremidades superiores, dorsales y glúteos, a pesar de mantenerse eutiroideo. Conclusiones: la presencia de hipertrofia muscular debe considerarse un dato clínico de sospecha de hipotiroidismo, aun con la implementación de los programas de pesquisa neonatal. Es posible la regresión parcial de la pseudohipertrofia muscular con el restablecimiento de la función tiroidea. Se debe tomar en cuenta en el diagnóstico diferencial de otras miopatías primarias

Kocher-Debré-Semelaigne Syndrome (SKDS) is described within the atypical clinical forms associated with severe, untreated and long-standing congenital hypothyroidism with manifestations of diffuse muscle pseudohypertrophy and predominantly proximal muscle weakness, reversible to replacement with levothyroxine. objective: To report the case of a child with congenital hypothyroidism due to disembriogenesis (atyreosis), who remained with poor control of the disease during the 1st year of life and myopathic manifestations from de neonatal stage. Results: The diagnosis is confirmed through specific studies, with evidence of characteristic myopathic patterns. Partial clinical regression is achieved 9 months after maintaining stability of TSH and thyroid hormones, coinciding with the normalization of the muscle enzyme creatine phosphokinase (CPK). At 12 years of follow-up, he maintained slight hypertrophy of the muscle of the upper extremities, dorsal and buttocks, despite remaining euthyroid. Conclusions: The presence of muscular hypertrophy should be considered a clinical finding of suspected hypothyroidism, even with the implementation of neonatal screening programs. Partial regression of muscle pseudohypertrophy is possible with restoration of thyroid function, and should be taken into account in the differential diagnosis of other primary myopathies

Desarrollo físico y neuropsicológico de pacientes diagnosticados con hipotiroidismo congénito en el Hospital Universitario San Ignacio entre los años 2001 y 2017 / Neuropsychological and physical development of patients diagnosed with congenital hypothyroidism at the San Ignacio University Hospital between 2001 and 2017

Introducción. El hipotiroidismo congénito es la principal causa de discapacidad cognitiva prevenible en el mundo. Para detectarlo se han desarrollado programas de tamización, con el fin de disminuir las secuelas neurológicas asociadas. El seguimiento y las evaluaciones a mediano y largo plazo de estos pacientes son fundamentales. Objetivo. Describir las características demográficas, el tratamiento y el seguimiento de los pacientes con diagnóstico de hipotiroidismo congénito en el marco del programa de tamización del Hospital Universitario de San Ignacio en Bogotá, Colombia. Materiales y métodos. Se hizo un estudio observacional de corte transversal. La población de estudio fueron los pacientes con diagnóstico de hipotiroidismo congénito en el Hospital Universitario San Ignacio entre el 2001 y el 2017. Resultados. Se contactó a 14 de los 19 pacientes con diagnóstico de hipotiroidismo congénito en el programa de tamizaje del Hospital. Los 14 niños estaban escolarizados, y la mayoría tenía el peso y la talla adecuados, aunque hubo talla baja en dos de ellos. El diagnóstico etiológico más frecuente fue hipoplasia tiroidea. Todos empezaron su tratamiento y el seguimiento oportunamente. La alteración más frecuente en las pruebas neuropsicológicas se registró en la memoria. El nivel de educación materno podría estar relacionado con el resultado anormal en el dominio del lenguaje. Conclusión. En el presente estudio, las alteraciones en las pruebas de memoria fueron las más prevalentes; sin embargo, dado el diseño y el tipo de estudio, se requieren más investigaciones que permitan establecer asociaciones. El crecimiento y el desarrollo puberal presentaron una frecuencia baja de alteraciones.

Introduction: Congenital hypothyroidism is the leading cause of preventable cognitive disability in the world. Therefore, screening programs have been developed in order to reduce the neurological sequelae associated with this pathology. Objective: To describe the demographic characteristics, the treatment, and the follow-up of patients diagnosed with congenital hypothyroidism in the screening program at the San Ignacio University Hospital in Bogotá, Colombia. Materials and methods: We conducted an observational cross-sectional study. The study population was patients diagnosed with congenital hypothyroidism at the Hospital between 2001 and 2017. Results: Fourteen of the 19 patients diagnosed with congenital hypothyroidism in the hospital screening program were contacted. All of the patients had schooling, most of them had adequate weight and height, and two had short stature. In most of them, the etiological diagnosis was thyroid hypoplasia, and all began the treatment and follow-up in an adequate way. The most frequent alteration in the neuropsychological tests was in the memory domain and the level of maternal education could be related to an abnormal result in the domain of language. Conclusion: In our study, alterations in the memory tests were the most prevalent; however, due to the design and type of study, more research is required to establish associations. A low frequency of abnormal growth and puberty was found.

Calidad de vida relacionada con la salud en adolescentes con hipotiroidismo congénito permanente / Health-related quality of life of adolescents with congenital hypothyroidism

Introducción: El hipotiroidismo congénito puede afectar el estado emocional, las relaciones sociales y el nivel de independencia del adolescente. Estos aspectos pueden influir en la percepción de su calidad de vida relacionada con la salud. Objetivo: Evaluar la calidad de vida relacionada con la salud en adolescentes con hipotiroidismo congénito permanente e identificar su posible relación con algunas características sociodemográficas y clínicas. Método: Se realizó un estudio observacional descriptivo de corte transversal en 40 adolescentes, varones y mujeres entre 10 y 19 años, registrados por el Programa Cubano de Diagnóstico Precoz de Hipotiroidismo Congénito, con el cuestionario genérico PedsQL TM ®, versión 4.0 para uso pediátrico. Resultados: Los mayores puntajes correspondieron a los adolescentes entre 10-14 años, del sexo masculino, nivel educacional primario, sin consumo de sustancias nocivas y que mostraron satisfacción con la vida familiar y un buen control de la enfermedad. Conclusiones: La mayoría de los adolescentes tienen una buena percepción de su calidad de vida relacionada con la salud. La dimensión y la función que más aportaron fueron la física y la social, respectivamente(AU)

Introduction: Congenital hypothyroidism can affect the emotional state, social relationships and the level of independence of adolescents. These aspects can influence the perception of their health-related quality of life. Objective: To evaluate the health-related quality of life of adolescents with permanent congenital hypothyroidism and to identify possible relationship with some sociodemographic and clinical characteristics. Methods: A cross-sectional descriptive observational study was carried out in 40 adolescents, male and female, between 10 and 19 years old, who were registered by the Cuban Program for Early Diagnosis, using the generic PedsQL TM ® questionnaire, version 4.0 for pediatric use, as an instrument. Results: The highest scores corresponded to adolescents between 10-14 years old, male, primary educational level, without harmful substance use and who showed satisfaction with family life and good control of the disease. Conclusions: Most adolescents have good perception of their health-related quality of life. The dimension and function that contributed the most were physical and social, respectively(AU)

A case of brain-lung-thyroid syndrome / 中南大学学报(医学版)

Brain-lung-thyroid syndrome is a rare autosomal dominant disorder. More than 100 cases have been reported worldwide, but few cases have been reported in China. In December 2018, a boy with brain-lung-thyroid syndrome, aged 3 years and 10 months, was admitted to Xiangya Hospital of Central South University due to repeated cough for more than 3 years. In infancy of the boy, psychomotor retardation, repeated cough, and hypothyroidism were found. Gene detection showed that there was c.927delc heterozygous variation in NKX2-1 gene (NM-001079668: exon3: c.927delC). The variation of this gene locus has not been reported in relevant literature so far, which indicates a new mutation. According to the above clinical manifestations and examination results, the boy was diagnosed as brain-lung-thyroid syndrome, which mainly characterized by nervous system disorders, accompanied by respiratory manifestations and hypothyroidism. The boy was treated with oral dopasehydrazine to relieve tremor and levothyroxine sodium tablets to relieve hypothyroidism. Anti-infection, atomization, rehabilitation training and other symptomatic supporting treatment were also administered. The boy's language and movement have improved, the thyroid hormone level is normal, and there are still repeated respiratory tract infections.

Transient hypothyroxinemia of prematurity and its risk factors in an extramural neonatal intensive care unit

ABSTRACT Objective: Thyroid functions in preterm newborns may be altered in the first week of life. Hypothyroxinemia has been commonly reported in these babies, which could be due to the immaturity of the hypothalamic pituitary thyroid axis or acute illness. It could have a long-term impact on the developing brain of these babies. We conducted this study to estimate the incidence of transient hypothyroxinemia of prematurity (THOP) and to determine its risk factors. Materials and methods: We analyzed thyroid stimulating hormone (TSH) and free T4 levels of 64 preterm neonates admitted in the neonatal intensive care unit. TSH and free T4 levels were measured in the first week and then at 14-21 days of life to estimate the incidence of THOP and determine its risk factors. We also estimated the incidence of congenital hypothyroidism (CH) and delayed TSH elevation in CH. Risk analysis was conducted using simple and multiple logistic regression, and numerical data was compared using the Mann Whitney U test and t test. Results: THOP was seen in 25% of the preterm babies. Caesarean delivery, presence of one or more morbidities, mechanical ventilation, birth weight ≥ 1,500 g, and gestational age ≥ 32 weeks were identified as risk factors for THOP based on simple logistic regression. In multiple regression, mechanical ventilation and gestational age ≥ 32 weeks were significantly associated with THOP. CH was seen in 2 (3.1%) babies, and 1 of these cases had delayed TSH elevation. Conclusion: Thyroid abnormalities are common in preterm admitted neonates. Mechanical ventilation is an independent risk factor for development of THOP.

Genética del hipotiroidismo congénito / The genetics of congenital hypothyroidism

Se realizó una revisión narrativa sobre la genética del hipotiroidismo congénito (HC). Se utilizaron las bases de datos Medline/PubMed, LILACS-BIREME y SciELO. Se identificaron los estudios originales publicados entre 2000 y agosto de 2020. Las palabras clave utilizadas durante la búsqueda fueron las siguientes: "hipotiroidismo congénito (congenital hypothyroidism)", "genética (genetic)", "polimorfismos de nucleótido único (SNP) (single polymorphisms nucleotid)". Se revisaron 58 estudios originales que informan las bases moleculares del HC. Se ha definido el concepto básico del HC, así como las bases moleculares que están asociados con la aparición de dicho trastorno. La revisión de la literatura ha permitido identificar al menos 12 genes que codifican las proteínas, las cuales, al producirse mutaciones, están implicadas en el HC. De los 12 genes informados que desempeñan un papel importante en el HC, errores en 6 genes se han vinculado con el HC con disgenesia tiroidea, lo cual implica alteraciones en la morfogénesis de la glándula tiroides, mientras que mutaciones en otros 6 genes se han asociado con dishormonogénesis, que genera un bloqueo total o parcial de los procesos bioquímicos implicados en la síntesis y secreción de hormonas tiroideas. La prevalencia en Sudamérica varía aproximadamente desde 1 por cada 1170 hasta 1 por cada 8285 neonatos. El estudio de la genética molecular pone de manifiesto que, en el futuro, aportará datos importantes en cuanto a la identificación de nuevas mutaciones y asociaciones con fenotipos clínicos que podrían relacionarse con el HC, para, de esta manera, potenciar el diagnóstico y tratamiento

A narrative review was conducted on the genetics of congenital hypothyroidism. The Medline/PubMed, LILACS-BIREME, and SciELO databases were used. Original studies published between 2000 and August 2020 were identified. The keywords used during the search were as follows: "congenital hypothyroidism", "genetics", "polymorphisms SNPs". Fifty-eight original studies reviewing the molecular basis of congenital hypothyroidism were reviewed. The basic concept of congenital hypothyroidism has been defined as well as the molecular bases that are associated with the development of this disorder. The literature review has identified at least 12 genes encoding proteins that, when mutations occur, are involved in congenital hypothyroidism. Of the 12 genes reported to play an important role in congenital hypothyroidism, errors in 6 genes have been associated with congenital hypothyroidism with thyroid dysgenesis, which implies alterations in the morphogenesis of the thyroid gland. On the other hand, mutations in 6 other genes have been associated with dyshormonogenesis that generates a total or partial blockage of the biochemical processes involved in the synthesis and secretion of thyroid hormones. The prevalence in South America is reported to vary from approximately 1 per 1000 to 1 per 8000 newborns. The study of molecular genetics shows that in the future it will contribute to the identification of new mutations and associations with clinical phenotypes that could be related to congenital hypothyroidism, thus enhancing diagnosis and treatment

Historia familiar de enfermedad tiroidea y riesgo de hipotiroidismo congénito en neonatos con síndrome de Down / Family history of thyroid disease and risk of congenital hypothyroidism in neonates with Down syndrome

Resumen Introducción: La historia familiar de enfermedad tiroidea (HFET) como factor de riesgo para hipotiroidismo congénito (HC), en síndrome de Down (SD) aún no ha sido explorada. Objetivo: Determinar si la HFET está asociada a mayor riesgo de HC en neonatos con SD. Método: Estudio de casos y controles en 220 neonatos con SD. Se compararon las pruebas de función tiroidea (PFT) de 37 con SD e HFET (casos), frente a las PFT de 183 recién nacidos con SD sin HFET (grupo de referencia). Se realizó análisis de regresión logística multivariante y se calculó la razón de momios (RM) y sus respectivos intervalos de confianza del 95 % (IC 95 %). Resultados: Nueve casos HC (4.1 %). El HC mostró asociación con la HFET (RMa = 8.3, IC 95 %: 2.0-34.3), particularmente en los varones (RMa = 9.0, IC 95 %: 1.6-49.6). La ausencia de HFET tuvo una RM de protección para HC (RMa = 0.4, IC 95 %: 0.1-0.8). Conclusiones: La HFET puede es una estrategia fácil y accesible para identificar pacientes con SD con mayor riesgo de HC.

Abstract Introduction: Family history of thyroid disease (FHTD) as risk factor for congenital hypothyroidism (CH) in patients with Down syndrome (DS) has not yet been explored. Objective: To determine whether FHTD is associated with an increased risk for CH in DS. Method: Case-control study in 220 neonates with DS. Thyroid function tests of 37 infants with DS and FHTD (cases) were compared with those of 183 DS newborns without FHTD (reference group). Data were analyzed using multivariate logistic regression analysis and adjusted odds ratios (aORs) with their respective 95 % confidence intervals (CI) were calculated. Results: Nine newborns with DS in our sample had CH (4.1 %). FHTD showed an association with CH in neonates with DS (aOR = 8.3, 95 % CI: 2.0-34.3), particularly in males (aOR = 9.0, 95 % CI: 1.6-49.6). In contrast, newborns with DS without FHTD were less likely to suffer from CH (aOR = 0.4, 95 % CI: 0.1-0.8). Conclusions: FHTD detailed evaluation can be an easy and accessible strategy to identify those newborns with DS at higher risk for CH.

Risk factors for neonatal congenital hypothyroidism: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To investigate the risk factors for congenital hypothyroidism (CH) in neonates, and to provide a reference for the prevention of CH.@*METHODS@#The databases including China Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Data, and Weipu Periodical Database, PubMed, Web of Science, Embase, SpringerLink, and Elsevier/ScienceDirect were searched for studies on the risk factors for CH in neonates published up to August 1, 2020. R 3.6.2 and RevMan 5.3 software were used to perform a Meta analysis.@*RESULTS@#A total of 20 studies were included, with 13 case-control studies and 7 cross-sectional studies. There were 11 564 neonates in total, with 3 579 neonates in the case group and 7 985 neonates in the control group. The Meta analysis showed that advanced maternal age (@*CONCLUSIONS@#Advanced maternal age, gestational thyroid disease, gestational diabetes mellitus, anxiety, medication during pregnancy, radiation exposure during pregnancy, family history of thyroid disease, low birth weight, fetal macrosomia, preterm birth, post-term birth, twin pregnancy or multiple pregnancy, and birth defects may increase the risk of CH in neonates.

Identification of a novel missense variant of the KAT6B gene in a child with Say-Barber-Biesecker-Young-Simpson syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child suspected for Say-Barber-Biesecker-Young-Simpson syndrome.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing was carried out for the proband. Suspected variants were validated by Sanger sequencing. The impact of the variants was predicted by bioinformatic analysis.@*RESULTS@#The child was found to harbor a de novo missense variant c.2623C>T (p.Asp875Tyr) in exon 13 of the KAT6B gene. The variant was previously unreported, and was not recorded in the major allele frequency database and predicted to be pathogenic based on PolyPhen-2, MutationTaster and PROVEAN analysis. As predicted by UCSF chimera and CASTp software, the variant can severely impact the substrate-binding pocket of histone acetyltransferase, resulting in loss of its enzymatic activity. Based on standards and guidelines by the American College of Medical Genetics and Genomics, the variant was classified to be likely pathogenic (PS2+PM2+PP3).@*CONCLUSION@#The child's condition may be attributed to the de novo missense c.2623C>T (p.Asp875Tyr) variant of the KAT6B gene.

Geographic variations in the incidence of congenital hypothyroidism in China: a retrospective study based on 92 million newborns screened in 2013-2018 / 中华医学杂志(英文版)

BACKGROUND@#Although congenital hypothyroidism (CH) has been widely studied in Western countries, CH incidence at different administrative levels in China during the past decade remains unknown. This study aimed to update the incidence and revealed the spatial pattern of CH incidence in the mainland of China, which could be helpful in the planning and implementation of preventative measures.@*METHODS@#The data used in our study were derived from 245 newborns screening centers that cover 30 provinces of the Chinese Newborn Screening Information System. Spatial auto-correlation was analyzed by Global Moran I and Getis-Ord Gi statistics at the provincial level. Kriging interpolation methods were applied to estimate a further detailed spatial distribution of CH incidence at city level throughout the mainland of China, and Kulldorff space scanning statistical methods were used to identify the spatial clusters of CH cases at the city level.@*RESULTS@#A total of 91,921,334 neonates were screened from 2013 to 2018 and 42,861 cases of primary CH were identified, yielding an incidence of 4.66 per 10,000 newborns screened (95% confidence interval [CI]: 4.62-4.71). Neonates in central (risk ratio [RR] = 0.84, 95% CI: 0.82-0.85) and western districts (RR = 0.71, 95% CI: 0.69-0.73) had lower probability of CH cases compared with the eastern region. The CH incidence indicated a moderate positive global spatial autocorrelation (Global Moran I value = 0.394, P  < 0.05), and the CH cases were significantly clustered in spatial distribution. A most likely city-cluster (log-likelihood ratio [LLR] = 588.82, RR = 2.36, P  < 0.01) and 25 secondary city-clusters of high incidence were scanned. The incidence of each province and each city in the mainland of China was estimated by kriging interpolation, revealing the most affected province and city to be Zhejiang Province and Hangzhou city, respectively.@*CONCLUSION@#This study offers an insight into the space clustering of CH incidence at provincial and city scales. Future work on environmental factors need to focus on the effects of CH occurrence.

Adhesion to treatment by children with congenital hypothyroidism: knowledge of caregivers in bahia state, brazil / Adesão ao tratamento de crianças com hipotireoidismo congênito: o conhecimento dos cuidadores no estado da bahia, brasil

ABSTRACT Objective: To investigate knowledge of caregivers of children with congenital hypothyroidism (CH), followed in a public reference service, as well as their associations with treatment adherence. Methods: Exploratory, descriptive, cross-sectional study with convenience sample. Medical records of 158 patients diagnosed with congenital hypothyroidism were analyzed, and data were evaluated by applying a previously prepared questionnaire to caregivers from 2014 to 2016. Statistical analysis used the chi-square and the Spearman's correlation tests, being significant p-value ≤0.05. Results: Females were predominant among caregivers (94.3%), with a mean age of 31 years, from inland cities (77.8%). There was a predominance of socioeconomic class C (59.5%) and incomplete primary education (35.7%). More than half of patients (53.2%) with CH had an adequate hormonal control. Approximately one third of caregivers had poor knowledge (37.3%) or was unaware (24.1%) about the meaning of congenital hypothyroidism. The low knowledge level of the disease was observed to be related to caregivers' educational level (p=0.004). Conclusions: Lack of education of caregivers was a barrier to be faced when monitoring children with CH. This reality requires greater attention from health professionals to ensure that they use clear language when giving instructions to caregivers, and that caregivers have adequately understood the proposed recommendations.

RESUMO Objetivo: Investigar o conhecimento dos cuidadores das crianças com hipotireoidismo congênito (HC) acompanhadas em um serviço público de referência, bem como as suas associações com a adesão ao tratamento. Métodos: Trata-se de um estudo exploratório, descritivo, de corte transversal, com amostra de conveniência. Foram analisados os prontuários de 158 pacientes com diagnóstico de HC e avaliados os dados obtidos pela aplicação de um questionário previamente elaborado, destinado aos cuidadores, durante o período de 2014 a 2016. A análise estatística foi feita com o teste do qui-quadrado e a Correlação de Spearman, para correlacionar a pontuação do questionário, sendo significante o valor de p≤0,05. Resultados: Os cuidadores eram predominantemente do sexo feminino (94,3%), com média de idade de 31 anos, proveniente de cidades do interior (77,8%). Verificou-se predomínio da classe socioeconômica C (59,5%) e ensino fundamental incompleto (35,7%) na amostra dos cuidadores. Metade dos pacientes (53,2%) apresentava controle hormonal adequado. Aproximadamente 1/3 dos cuidadores demonstraram conhecimento ruim (37,3%) ou até mesmo desconheciam (24,1%) o HC. Observou-se que o baixo nível de conhecimento da doença estava diretamente relacionado com o nível educacional dos cuidadores (p=0,004). Conclusões: Os achados sugerem que a falta de instrução dos cuidadores é uma barreira a ser enfrentada durante o acompanhamento de crianças com HC, o que requer uma maior atenção do profissional de saúde, para garantir uma linguagem clara e um entendimento adequado das recomendações propostas.

Impact of the reduction in TSH cutoff level to 6 mIU/L in neonatal screening for congenital hypothyroidism in Santa Catarina: final results

ABSTRACT Oubjective: To assess the implications of changing the cutoff level of TSH from 10 to 6 mIU/L. Subjects and methods: The study population was constituted by 74.123 children screened for congenital hypothyroidism by the National Screening Program in Santa Catarina, from March 2011 to February 2012. The cutoff of TSH was 6 mIU/L. If TSH between 6-10 mIU/L, the newborn was recalled for a second TSH measurement on filter paper. If TSH > 6 mIU/L in the second sample, the child was sent for medical evaluation. In children with normal topic thyroid, levothyroxine was suspended for 1 month at the age of 3 years for identification of the etiology and evaluation of the need to continue treatment. Results: Among the children screened, 435 were recalled for presenting TSH between 6 and 10 mIU/L in the first sample, 28 remained TSH > 6 mIU/L in the second sample. Among these, 11 had a final diagnosis of dyshormonogenesis, two of ectopic thyroid, two of thyroid hypoplasia and one of transient hypothyroidism. Ten children presented normal TSH levels on the first medical evaluation and two lost follow-up. Conclusion: A decrease in the TSH cutoff level from 10 to 6 mIU/L in a neonatal screening program for congenital hypothyroidism reduced the number of false-negative results, increasing the sensitivity of the test, but increased the number of false-positive results and recalls. Since a TSH cutoff level of 6 mIU/L detects thyroid function abnormalities requiring treatment, the adoption of this cutoff level is justified.

Queixas de tontura em indivíduos com hipotireoidismo congênito em idade escolar e suas implicações nas habilidades acadêmicas e comunicativas / Dizziness complaints in school-aged individuals with congenital hypothyroidism and the implications for academic and communication skills

Introdução: o hipotireoidismo congênito (HC) pode causar danos nas estruturas do sistema vestibular ocasionando sintomas de tontura que pode acarretar em implicações nas habilidades linguísticas e acadêmicas dos indivíduos. Objetivo: verificar a ocorrência de queixas de tontura em crianças com HC e as suas implicações nos aspectos comunicativos e desempenho acadêmico por meio de uma entrevista estruturada com os cuidadores. Metodologia: estudo exploratório de caráter descritivo, seccional, realizado no município de Salvador, sendo incluídos crianças de ambos os sexos, com diagnóstico de hipotireoidismo congênito e idade entre 5 a 10 anos. Os dados foram coletados entre 2014 a 2018 em um Serviço de Referência em Triagem Neonatal no Estado da Bahia. Para avaliar as variáveis qualitativas foi utilizado o teste qui-quadrado e para as variáveis quantitativas foi utilizado o teste t-student, adotando nível de significância de 5%. Resultados: os indivíduos com disgenesia apresentaram uma frequência de 64% de queixas relacionadas a tontura. Verificou-se uma frequência considerável de dificuldade nas competências de escrita e com perfil comunicativo de maior relevância para a habilidade de conversação por meio de frases curtas. Conclusão: os achados sugerem que a presença de queixas de tontura nos os indivíduos com HC pode predispor a insucessos nos aspectos acadêmicos e comunicativos.

Introduction: congenital hypothyroidism (CH) can damage the structures of the vestibular system, causing dizziness symptoms that can have implications for the linguistic and academic skills of individuals. Objective: to verify the occurrence of dizziness complaints in children with CH and its implications for communicative aspects and academic performance through a structured interview with caregivers. Methodology: an exploratory, descriptive, sectional study carried out in the city of Salvador, including children of both sexes, diagnosed with congenital hypothyroidism and aged between 5 and 10 years. Data were collected between 2014 and 2018 at a Neonatal Screening Reference Service in the State of Bahia. To assess qualitative variables, the chi-square test was used and for quantitative variables, the t-student test was used, adopting a significance level of 5%. Results: individuals with dysgenesis had a frequency of 64% of complaints related to dizziness. There was a considerable frequency of difficulty in writing skills and with a communicative profile of greater relevance to the ability to converse through short sentences. Conclusion: the findings suggest that the presence of complaints of dizziness in individuals with CH may predispose to failures in academic and communicative aspects.