RESUMO
BACKGROUND: Newborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies. METHODS: We designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS. With this panel, a large-scale, multicenter, prospective multidisease analysis was conducted on dried blood spot (DBS) profiles from 21,442 neonates nationwide. RESULTS: We presented the positive detection rate and carrier frequency of diseases and related variants in different regions; and 168 (0.78%) positive cases were detected. Glucose-6-Phosphate Dehydrogenase deficiency (G6PDD) and phenylketonuria (PKU) had higher prevalence rates, which were significantly different in different regions. The positive detection of G6PD variants was quite common in south China, whereas PAH variants were most commonly identified in north China. In addition, NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants, which were normal in conventional NBS, but were confirmed later as abnormal in repeated biochemical testing after recall. Eighty percent of high-frequency gene carriers and 60% of high-frequency variant carriers had obvious regional differences. On the premise that there was no significant difference in birth weight and gestational age, the biochemical indicators of SLC22A5 c.1400C > G and ACADSB c.1165A > G carriers were significantly different from those of non-carriers. CONCLUSIONS: We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods. Our data also showed that the prevalence of diseases has significant regional characteristics, which provides a theoretical basis for screening diseases in different regions.
Assuntos
Triagem Neonatal , Fenilcetonúrias , Humanos , Recém-Nascido , Triagem Neonatal/métodos , Estudos Prospectivos , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas de Transporte da Membrana Mitocondrial/genética , Membro 5 da Família 22 de Carreadores de Soluto/genéticaRESUMO
BACKGROUND: Fragile X syndrome (FXS), caused by CGG-repeat expansion in FMR1 promoter, is one of the most common causes of mental retardation. Individuals with full mutation and premutation alleles have a high risk of psychophysiological disorder and of having affected offspring. Frequencies of FMR1 alleles in general newborns have been reported in Caucasians but have not been investigated in the large-scale population in the mainland of China. METHODS: The sizes of FMR1 CGG-repeats were analyzed in 51,661 newborns (28,114 males and 23,547 females) and also in a cohort of 33 children diagnosed with developmental delay using GC-rich polymerase chain reaction (PCR) and triple repeat primed PCR. RESULTS: The frequency of CGG repeats > 100 was 1/9371 in males and 1/5887 in females, and the frequency of CGG repeats > 54 was 1/1561 in males and 1/1624 in females. FMR1 full mutation and premutation were identified in 27.27% of children who had Ages and Stages Questionnaire scores less than two standard deviations from the cutoff value. CONCLUSIONS: Our study revealed the prevalence of FXS in China and improved the sample databases of FXS, suggesting that the prevalence of FXS in Chinese is higher than estimated previously and that FXS screening can be advised to high-risk families.
Assuntos
Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil , Alelos , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/epidemiologia , Síndrome do Cromossomo X Frágil/genética , Frequência do Gene , Humanos , Recém-Nascido , Masculino , MutaçãoRESUMO
The pathogenesis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is highly heterogeneous and still unclear. Additional novel variants have been recently detected in the population. The molecular and cellular effects of these previously unreported variants are still poorly understood and require further characterization. To address this problem, we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD deficiency. Marked deficiencies in fatty acid oxidation (FAO) and other mitochondrial defects were observed in cells carrying one of these six variants (c.541C>T, c.863T>G, c.895A>G, c.1238T>C, c.1276G>A, and c.1505T>A), including reductions in mitochondrial respiratory-chain function and adenosine triphosphate (ATP) production, and increased levels of mitochondrial reactive oxygen species (ROS). Intriguingly, higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited stress. Moreover, the stability of the mutant homodimer was disturbed, and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics (MD) simulation. The data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.
Assuntos
Acil-CoA Desidrogenase de Cadeia Longa/deficiência , Erros Inatos do Metabolismo Lipídico/genética , Mitocôndrias/metabolismo , Mutação , Polimorfismo de Nucleotídeo Único , Acil-CoA Desidrogenase de Cadeia Longa/genética , Trifosfato de Adenosina/metabolismo , Apoptose , Ácidos Graxos/metabolismo , Genótipo , Glucose/metabolismo , Células HEK293 , Humanos , Recém-Nascido , Simulação de Dinâmica Molecular , Oxigênio/metabolismo , Consumo de Oxigênio , Espécies Reativas de Oxigênio , Superóxidos/metabolismoRESUMO
OBJECTIVE: To investigate the epidemiological characteristics, phenotype, genotype, and prognosis of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in the Chinese population. METHODS: A retrospective analysis was performed for the clinical data of the neonates who underwent screening with high-performance liquid chromatography-tandem mass spectrometry from January 2009 to June 2018 and were diagnosed with MCADD by gene detection. RESULTS: A total of 2 674 835 neonates underwent neonatal screening, among whom 12 were diagnosed with MCADD. Gene detection was performed for 10 neonates with MCADD and found 13 mutation types at 16 mutation sites of the ACADM gene, among which there were 7 reported mutations (p.T150Rfs*4, p.M1V, p.R206C, p.R294T, p.G310R, p.M328V, and p.G362E), 5 novel mutations (p.N194D, p.A324P, p.N366S, c.118+3A>G, and c.387+1del G), and 1 exon 11 deletion; p.T150Rfs*4 was the most common mutation (4/16). The detection rate of mutation sites in the ACADM gene was 80%. No phenotype-genotype correlation was observed. Dietary guidance and symptomatic treatment were given after confirmed diagnosis. No acute metabolic imbalance was observed within 4-82 months of follow-up. All neonates had good prognosis except one who had brain dysplasia. CONCLUSIONS: MCADD is relatively rare in southern China, and p.T150Rfs*4 is a common mutation in the Chinese population. Cases with positive screening results should be evaluated by octanoylcarnitine C8 value and gene detection.
Assuntos
Acil-CoA Desidrogenase/deficiência , Erros Inatos do Metabolismo Lipídico , Carnitina , China , Seguimentos , Humanos , Recém-Nascido , Mutação , Triagem Neonatal , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the levels of primary health care services for children and their changes in Zhejiang Province, China from 1998 to 2011. METHODS: The data were drawn from Zhejiang maternal and child health statistics collected under the supervision of the Health Bureau of Zhejiang Province. Primary health care coverage, hospital deliveries, low birth weight, postnatal visits, breastfeeding, underweight, early neonatal (<7 days) mortality, neonatal mortality, infant mortality and under-5 mortality were investigated. RESULTS: The coverage rates for children under 3 years old and children under 7 years old increased in the last 14 years. The hospital delivery rate was high during the study period, and the overall difference narrowed. There was a significant difference (P<0.001) between the prevalence of low birth weight in 1998 (2.03%) and the prevalence in 2011 (2.71%). The increase in low birth weight was more significant in urban areas than in rural areas. The postnatal visit rate increased from 95.00% to 98.45% with a significant difference (P<0.001). The breastfeeding rate was the highest in 2004 at 74.79% and lowest in 2008 at 53.86%. The prevalence of underweight in children under 5 years old decreased from 1.63% to 0.65%, and the prevalence was higher in rural areas. The early neonatal, neonatal, infant and under-5 mortality rates decreased from 6.66, 8.67, 11.99 and 15.28 to 1.69, 2.36, 3.89 and 5.42, respectively (P<0.001). The mortality rates in rural areas were slightly higher than those in urban areas each year, and the mortality rates were lower in Ningbo, Wenzhou, and Jiaxing regions and higher in Quzhou and Lishui regions. CONCLUSION: Primary health care services for children in Zhejiang Province improved from 1998 to 2011. Continued high rates of low birth weight in urban areas and mortality in rural areas may be addressed with improvements in health awareness and medical technology.
Assuntos
Serviços de Saúde da Criança/estatística & dados numéricos , Mortalidade , Aleitamento Materno/tendências , Criança , Serviços de Saúde da Criança/tendências , Pré-Escolar , China/epidemiologia , Humanos , Lactente , Recém-Nascido , Mortalidade/tendências , Atenção Primária à Saúde/estatística & dados numéricos , Atenção Primária à Saúde/tendências , Magreza/epidemiologiaAssuntos
Atresia Biliar/diagnóstico , Proteínas de Ligação ao Cálcio/deficiência , Colestase Intra-Hepática/diagnóstico , Citrulinemia/diagnóstico , Mutação , Transportadores de Ânions Orgânicos/deficiência , Atresia Biliar/etiologia , Atresia Biliar/terapia , Bilirrubina/sangue , Biomarcadores/sangue , Colangiopancreatografia por Ressonância Magnética , Colestase Intra-Hepática/etiologia , Colestase Intra-Hepática/terapia , Citrulinemia/etiologia , Citrulinemia/terapia , Análise Mutacional de DNA , Humanos , Lactente , Icterícia/diagnóstico , Icterícia/etiologia , Icterícia/terapia , Testes de Função Hepática , Masculino , Proteínas de Transporte da Membrana Mitocondrial/genéticaRESUMO
OBJECTIVE: By analyzing the under 5 mortality rate (U5MR) and its contributors in Zhejiang Province of China from 2000 to 2009, we tried to understand the trend of U5MR change in Zhejiang Province and thus propose strategies to reduce child mortality. METHODS: Thirty cities/counties/districts from Zhejiang Province were selected using stratified cluster sampling approach. Children under five years in these areas were enrolled as the subjects. The U5MR and its contributors were analyzed in terms of age, migration status of mothers, and other indicators using classic descriptive methods and Chi square test. RESULTS: The U5MR in Zhejiang Province showed a declining trend from 14.83 in 2000 to 9.49 in 2009. In 2009, the U5MR was significantly higher in the rural areas than in the urban areas (9.14 vs.6.50, P<0.01) and among floating populations than among local residents (12.12 vs. 6.42, P<0.01). Preterm birth/low birth weight was the leading cause of U5MR in 2009. More specifically, preterm birth/low birth weight, congenital heart disease, and birth asphyxia were the top three causes of deaths among infants (<1 year), while drowning, traffic accidents, and accidental falls were the leading causes of deaths among children (1-4 years). CONCLUSION: The U5MR in Zhejiang Province in 2009 differed between urban areas and rural areas and between floating populations and local residents. The main causes of death differ between infants and young children. Prevention of preterm birth/low birth weight and congenital anomalies will reduce infant death, while the main intervention for young children is to avoid accidental injuries.
RESUMO
BACKGROUND: It has been 11 years since newborn screening started in Zhejiang in 1999. The aim of this study was to analyze and summarize the status of newborn screening in Zhejiang from 1999 to 2009. METHODS: Blood samples were collected from the heels of newborns 72 hours after birth. We have conducted laboratory tests that the congenital hypothyroidism (CH) and circulating levels of thyroid-stimulating hormone (TSH) was detected. Blood phenylalanine (Phe) was detected for phenylketonuria (PKU). Dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) was used for detection. RESULTS: From 1999 to 2009, 3 875 228 newborns were screened and 2309 cases were confirmed as CH and 155 cases were confirmed as PKU. The incidence of CH and PKU were 1:1678 and 1:25 001 respectively. CONCLUSION: In 11 years, the Zhejiang newborn screening center screened more than 3.8 million newborns, and helped more than 2000 CH and PKU patients to obtain early treatment in order to prevent physical disability and mental retardation.
Assuntos
Triagem Neonatal/métodos , China , Hipotireoidismo Congênito/diagnóstico , Humanos , Recém-Nascido , Fenilcetonúrias/diagnósticoRESUMO
OBJECTIVE: To study the under-five mortality rate and the causes of death in Zhejiang Province between 2000 and 2009 in order to provide a basis for reducing the mortality rate in the region. METHODS: By stratified random cluster sampling, all the children under 5 years old from 30 sampling areas of Zhejiang Province between 2000 and 2009 were enrolled. The under-five mortality rate and the leading causes of death were investigated by descriptive analysis and Chi-square test. RESULTS: The under-five mortality rate demonstrated a decreased trend in Zhejiang Province between 2000 and 2009, with the under-five mortality rate of 14.83 in 2000 compared to 9.49 in 2009. In 2009, the under-five mortality rate in rural regions was significantly higher than that in urban regions (9.14 vs 6.50; P<0.01). Compared with the resident population, there were an increased under-five mortality rate in floating population (12.12 vs 6.42; P<0.01). Preterm delivery/low birth weight was the top death cause in children under 5 years old. The top three causes of death in infants less than 1 year old were preterm delivery/low birth weight, congenital heart disease and birth asphyxia compared to drowning, traffic accident and falling in children aged 1-4 years. CONCLUSIONS: There are differences in the under-five mortality rate between rural and urban children as well as between the floating and resident population in 2009. The leading causes of death in different age groups are different. It is essential to reduce the mortality rate by preventing preterm delivery, low birth weight and congenital malformations to infants and preventing accidental injuries to children aged 1-4 years.
Assuntos
Mortalidade da Criança , Mortalidade Infantil , Causas de Morte , Pré-Escolar , China/epidemiologia , Humanos , Lactente , Recém-Nascido , Fatores de TempoRESUMO
OBJECTIVES: The purposes of this study were to determine thyroid volumes in healthy Chinese infants aged 0 to 12 months and to provide reference data for normal thyroid growth. METHODS: A total of 408 healthy infants (229 male and 179 female) were enrolled in the study. The length, breadth, and depth of the thyroid gland were measured with sonography. The volume of each lobe was calculated by the correct ellipsoid formula (volume = length × breadth × depth × 0.479). RESULTS: All of the infants' thyroids showed a normal uniform echo texture on sonography. The thyroid volume increased with age (r = 0.519; P < .001). Moreover, positive associations were noted between thyroid volume and height and weight (r = 0.517; P < . 001; r = 0.499; P < .001, respectively). No significant differences based on sex were found (t = 1.784; P = .075). CONCLUSIONS: The thyroid volumes in these healthy Chinese infants varied from those reported in the published literature on healthy European infants. It is important to establish local reference ranges for thyroid volumes in healthy infants.
Assuntos
Glândula Tireoide/diagnóstico por imagem , Análise de Variância , China , Feminino , Humanos , Hipotireoidismo/diagnóstico por imagem , Lactente , Recém-Nascido , Masculino , Valores de Referência , Glândula Tireoide/crescimento & desenvolvimento , UltrassonografiaRESUMO
BACKGROUND: This study was undertaken to explore the clinical outcome and prognosis of subclinical hypothyroidism detected by newborn screening. METHODS: Newborn screening was conducted at 1156 health care institutions in Zhejiang Province from October 1999 to September 2006. Included were (1) infants who had thyroid-stimulating hormone (TSH) ≥ 20 mU/L, and normal or lower normal levels of triiodothyronine (T(3)) and thyroxine (T(4)) and (2) infants with TSH between 5.6 mU/L and 20 mU/L at a confirmatory examination and follow-up showing TSH levels ≥ 20 mU/L or delayed reduction in T(4) levels. These infants were considered as having subclinical hypothyroidism and levothyroxine (L-T(4)) at an initial dose of 3-5 µg/kg per day was administered. The levels of TSH and T(4), developmental quotient (DQ), and index of growth were evaluated. RESULTS: A total of 204 infants met our criteria for subclinical hypothyroidism, with an incidence of 1/8809. After 2-4 weeks of standard therapy, serum TSH level dropped to normal and T(4) reached a higher normal level in all the 204 infants. Evaluations of 60 patients after 2 years of therapy showed that their average DQ was 101 ± 14.61, and body weight and height were within the normal ranges. Bone age test for 54 patients revealed normal development in 44, slightly retarded development in 7, and advanced development in 3. CONCLUSIONS: Newborns with high TSH levels should be given particular attention to ensure early diagnosis. A L-T(4) dose of 3-5 µg/kg per day was effective in the initial treatment of subclinical hypothyroidism.
Assuntos
Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/terapia , Triagem Neonatal , Feminino , Humanos , Recém-Nascido , Masculino , Prognóstico , Tireotropina/sangue , Tiroxina/administração & dosagem , Tiroxina/sangueRESUMO
OBJECTIVE: To determine the impact of expanded newborn screening using tandem mass spectrometry (MS/MS) on the overall detection rate of inborn errors of metabolism in Zhejiang province and to assess the outcome of the patients who were diagnosed. METHOD: Blood spots were collected between days 3 and 6 of life from the newborns. All samples were subjected to MS/MS analysis using Waters Quattro API. Confirmation tests included amino acid analysis, urinary organic acids by GC-MS, routine blood analysis, biochemistry, blood gas analysis, blood glucose and ammonia tests, blood homocysteine, lactate and pyruvate tests, urine acetone tests, biotin and biotin enzyme profile and DNA analysis. Standard treatment protocol was given to the patients. Protein restricted diet, special powdered formula and medicines recommended for the patients with amino acidemias. Protein restricted diet and L-carnitine, folic acid and Vitamin B12 supplementation were given for the patients with organic acidemia. L-carnitine was given to the patients with primary carnitine deficiency. The overall epidemiology, prognosis, follow-up of the screening program were also investigated in the neonates. RESULT: A total of 129 415 neonates were investigated for 26 inborn errors of metabolism during the period. Twenty-three newborns were confirmed as having inborn errors of metabolism, including 13 with amino acidemias, 6 with organic acidemias and 4 with fatty acid oxidation disorders. The prevalence was 1:5626. Positive predictive value was 2.10%, specificity was 99.72% and sensitivity 100%. Seventeen children remain asymptomatic during the follow-up. Five patients had motor and mental developmental delay. One patient presented metabolic disorders during the follow-up. No death occurred in this series of patients. CONCLUSION: This strategy represents a valuable preventive medicine approach by enabling diagnosis and treatment before the onset of symptoms.
Assuntos
Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal/métodos , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/metabolismoRESUMO
OBJECTIVE: To study the best observation time for drug administration and withdrawal in the treatment of children with transient congenital hypothyroidism,seeking an objective basis for the safe drug withdrawal. METHODS: Levothyroxine was prescribed for 1 144 children diagnosed with congenital hypothyroidism (CH) and according to the results levothyroxine was adjusted to a maintenance dosage. Examinations were performed periodically including physical and mental development, thyroid ultrasonography,and blood levels of T3, T4, TSH. For the patients with a small maintenance dosage of levothyroxine (15.0 - 16.6 g/d) and all the examinations normal, levothyroxine was withdrawn at 2 - 3 years, and the children were followed up and reexamined after 1 month, 2 months, and 10 months, respectively. Permanent drug withdrawal was determined for children with all the examinations normal. Once abnormal TSH occurred, levothyroxine was prescribed again, and followed up continuously. RESULT: Levothyroxine was withdrawn from 157 children. During the follow up, for 15 children (9.55%) levothyroxine were prescribed continuously, and for 142 children permanent drug withdrawal (confirmed with transient CH) was determined. Abnormal TSH of various degrees was detected in 48 cases: 25.48 % (40/157),4.46 % (7/157), and 0.64 % (1/157) were detected at 1, 2 and 10 months after drug withdrawal, respectively. In 15 children levothyroxine was prescribed again for the remarkably high TSH, and the other 33 with mildly abnormal TSH finished the treatment since TSH normalized during follow-up. CONCLUSION: After 2 - 3 years of regular treatment, levothyroxine can be withdrawn from children with normal T3, T4, TSH, physical and mental development, and thyroid function. The best observation time for drug withdrawal should be 2 - 3 months. If T3, T4 and TSH levels are in the normal range, drug can be withdrawn safely. Once abnormal results were detected during follow-up, levothyroxine should be administrated continuously.
Assuntos
Hipotireoidismo Congênito/tratamento farmacológico , Tiroxina/uso terapêutico , Criança , Pré-Escolar , Hipotireoidismo Congênito/sangue , Esquema de Medicação , Feminino , Seguimentos , Humanos , Lactente , Masculino , Tireotropina/sangue , Tiroxina/administração & dosagem , Tiroxina/sangue , Fatores de Tempo , Tri-Iodotironina/sangue , Suspensão de TratamentoRESUMO
OBJECTIVE: To investigate the correlation of congenital hypothyroidism (CH) with birth weight and gestational age in newborn infants. METHODS: The screening of CH was conducted in all the live births in 2005 of Zhejiang Province, the blood samples were collected from heel stick. The thyroid stimulating hormone (TSH) was measured by time-resolved fluorescence immunoassay (TRFIA). If TSH was>9.0 mU/L, the infant was recalled for further examination. RESULTS: A total of 387,926 infants were screened in 2005, of whom 289 cases were identified with CH. The prevalence rate was 1/1,342. Among the 289 CH cases, the prevalence of premature infants, term infants and post term infants were 1/1,454, 1/1,469 and 1/246, respectively. The CH prevalence of post term infants was significantly higher than that in other two groups (P<0.01). The prevalence of low birth weight infants, normal weight infants and macrosomia was 1/575, 1/1,505 and 1/473, respectively. The prevalence of low birth weight infants and macrosomia was significantly higher than that of normal weight group (P<0.01). CONCLUSION: The prevalence of CH is associated with the birth weight and gestational age. To reduce the prevalence of CH in children, it is crucial to prevent post term, low birth weight, and macrosomia cases.
Assuntos
Peso ao Nascer , Hipotireoidismo Congênito/fisiopatologia , Idade Gestacional , China/epidemiologia , Hipotireoidismo Congênito/sangue , Hipotireoidismo Congênito/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Triagem Neonatal , Prevalência , Tireotropina/sangueRESUMO
OBJECTIVE: To know the blood lead levels (BLL) of preschool children in Zhejiang Province between 1997 to 2003. METHODS: The BLL of preschool children was investigated in this province with cluster sampling in 2003, and compared with the results with that of 1997. The BLL was determined with graphite oven atom absorption spectrography method. RESULT: The average BLL of 2013 preschool children in 2003 was (0.34 +/- 0.13) micromol/L, similar with that of 1997 [(0.35 +/- 0.26)micromol/L (P >0.05)]. There were 274 children with BLL >or= 0.483 micromol/L, and the rate of lead poisoning was 13.61 %, lower than that of 1997 (when there were 448 children with BLL >or= 0.483 micromol/L, and the rate of lead poisoning was 23.84%). In 2003, the rates of lead poisoning among preschool children of Hangzhou, Shangyu, Zhoushan and Changshan were 7.69%, 15.37%, 10.87% and 20.15 %, respectively. There were significant differences among the four areas (P < 0.01). In comparison with the results of 1997, the lead poisoning rates of Hangzhou and Shangyu children decreased significantly, while that of Changshan children increased significantly (P <0.01), and that of Zhoushan children didn't change significantly. The highest rate of lead poisoning was found in children of 4-6 years group as 6 years ago. CONCLUSION: The rate of lead poisoning among preschool children has decreased significantly now in Zhejiang Province. But the condition of BLL in preschool children is still far from optimistic. The environmental lead pollution in remote mountain areas and island areas should be highly concerned by the government.
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Exposição Ambiental/análise , Intoxicação por Chumbo/sangue , Chumbo/sangue , Criança , Pré-Escolar , China/epidemiologia , Exposição Ambiental/prevenção & controle , Feminino , Humanos , Incidência , Lactente , Intoxicação por Chumbo/epidemiologia , Masculino , Programas de RastreamentoRESUMO
OBJECTIVE: To study the clinical therapy and prognosis in children with transient congenital hypothyroidism (CH). METHODS: Fifty-seven children with CH diagnosed after neonatal screening were treated with low-dosage levothyroxine (L-T4). Follow-up evaluation included the determination of TT3, TT4 and TSH serum levels and the assessment of thyroid gland morphology, bone age, growth development and development quotients (DQ). A full check-up was performed at age 2, when the affected children first discontinued the L-T4 treatment for 1 month, and one year later. Development quotients were compared with a control group of 29 healthy peers. RESULTS: The initial L-T4 dosage administered was 3.21-5.81 microg/(kg.d) with an average of (16.25+/-3.87) microg/d. Mean duration of therapy was (28.09+/-9.56) months. No significant difference was found between study group and control group in the DQ test (average score (106.58+/-14.40) vs (102.4+/-8.6), P>0.05) and 96.49% of the CH children achieved a test score above 85. Bone age, 99mTc scans and ultrasonographic findings were all normal, and evaluation of physical development was normal too, as were the serum levels of TT3, TT4 and TSH after one year of follow-up. CONCLUSION: A L-T4 dosage of 3.21-5.81 microg/(kg.d) was found sufficient for the treatment of transient CH. The treated children showed satisfactory overall mental and physical development at age 2. So it is possible for CH children to stop taking medicine if their laboratory findings and physical development are all normal after regular treatment and 2-3 years of follow-up.
Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Hipertireoidismo/congênito , Hipertireoidismo/tratamento farmacológico , Glândula Tireoide/efeitos dos fármacos , Tiroxina/uso terapêutico , Feminino , Seguimentos , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/diagnóstico , Lactente , Recém-Nascido , Masculino , Prognóstico , Fatores de Tempo , Resultado do Tratamento , Tri-Iodotironina/sangueRESUMO
OBJECTIVE: To investigate the mechanism for the apoptosis of hippocampus neuron induced by hypothyroidism in perinatal rats. METHODS: Hypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at 1, 5, 10 and 15d, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free triiodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by chemoluminescence. Hippocampus specimens were collected from the control and hypothyroid pups.Mitochondia was examined under transmission electron microscopy. Translocation of apoptogenic molecules (Bax, cytochrome C and AIF) and activation of caspase-3 were analyzed by Western Blotting. RESULT: Significantly low circulating FT(3) and FT(4) levels confirmed the hypothyroid status of the experimental pups. Electron microscopy showed that altered morphology of mitochondria significantly increased under hypothyroid conditions. The expression of Bax in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.05),and significantly higher in mitochondria (P<0.001). The expression of cytochrome c in the cytosol of hypothyroid pups was significantly higher than that of control pups at all stages of development (1,10 and 15 d:P<0.05, 5d: P<0.001), and lower in mitochondria (P<0.05). The expression of AIF in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.001), and significantly lower in mitochondria (1, 5d: P<0.001, 10, 15 d: P<0.01). he expression of caspase-3 P20 in the cytosol of hypothyroid pups was significantly higher as compared with that of the age-matched controls (1, 15d: P<0.01, 5,1 0 d: P<0.001). CONCLUSION: The intrinsic death pathway in mitochondria may be one of the mechanisms with which hypothyroid induces apoptosis of hippocampus neuron in developing rats.
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Apoptose/fisiologia , Hipocampo/patologia , Hipotireoidismo/patologia , Complicações na Gravidez/patologia , Animais , Animais Recém-Nascidos , Feminino , Hipotireoidismo/induzido quimicamente , Neurônios/patologia , Gravidez , Propiltiouracila , Ratos , Ratos WistarRESUMO
OBJECTIVE: To analyze the data of screening for congenital hypothyroidism (CH) newborns in Zhejiang Province during 1999-2004. METHODS: The dried blood samples were collected on filter paper. The levels of thyroid-stimulating hormone (TSH) were measured by time-resolved fluoroimmunoassay, and the serum levels of TSH, triiodothyronine (T(3)) and thyroxine (T(4)) were detected by chemiluminescence. Infants with CH confirmed by neonatal screening were treated with levothyroxine (L-T(4)) initiated with 4-6 g/kg x d(-1 )for 2-3 years. Growth, development and intelligence status, scintigraphy or ultrasonography of thyroid, and bone age were investigated to evaluate the efficacy of therapy during follow-ups. RESULT: A total of 1112784 neonates were screened for CH during 1999-2004 with a coverage rate of 63.5%. Of the 6750 suspected CH cases, 6335 (93.8%) were recalled. 764 cases of CH were confirmed with an average incidence rate of 1 case CH per 1457 newborns (1/1457). 244 of 764 patients were followed-up for more than 1.5-2 years. All of them received thyroid by scintigraphy or ultrasonography. Among them 189 cases were found with normal gland, 35 with hypogenetic gland, 11 with ectopic gland, and the remaining 9 didn't show any image of thyroid. The average score of development quotient (DQ) was 106. 9. Among them, the DQ score was less than 85 in 2 cases, less than 90 in 9 cases, less than 100 in 28 cases, and in 68 cases the DQ was greater than 100. The bone age of 122 CH infants was evaluated with the X-ray radiography. In 90 cases of them,the bone age was normal, and 32 cases had progressed from development delay to normal. The height and weigh measured in all 106 cases had reached the related age criteria. The evaluation indicated that 55 cases were found with primary CH, 169 with temporary CH and 20 with subclinical CH. CONCLUSION: Neonatal screening for CH and regular treatment for CH patients are important for attaining normal body development and intelligence development of patients.