RESUMO
Celiac disease is strongly associated with HLA DQ, specifically with haplotypes. DRB1*03-DQA1*05:01/DQB1*02:01 (DQ2.5),DRB1*07-DQA1*02:01/DQB1*02:02 (DQ2.2), DRB1*11-DQA1*05:05/DQB1*03:01 (DQ7.5), and DRB1*04-DQA1*03:01/DQB1*03:02 (DQ8). The distribution of these risk haplotypes in patients with celiac disease is different in the geographical areas investigated. A high frequency of DRB1*07- DQA1*02:01/DQB1*02:02 (DQ2.2) and DRB1*11-DQA1*05:05/DQB1*03:01 (DQ7.5), has been described in Southern Europe. We analyzed 2102 confirmed CD cases with information on both DQB1* alelles and their distribution by geographical area in Spain. According to the presence of this haplotype in one or two chromosomes, the genotype is classified in: DQ2 homozygous, DQ2 heterozygous (cis or trans), DQ8 homozygous, DQ8/DQ2.5, DQ 2.2 homozygous and genotype known as "half DQ2". Two different patterns of risks related to CD were identified. In the Basque Country and Navarre, the Mediterranean Area (Aragon, Catalonia, Valencia, Balearic Islands, and Murcia), the South of Spain (Andalucía and Extremadura), and the Canary Islands, higher frequency of DQ2.5 trans, and more than 80% of DQ2.5/DQ2.2 homozygosis were described. The Cantabrian Coast (Cantabria, Asturias, and Galicia) and Central Areas (Castilla-León and Castilla-La Mancha) showed a higher percentage of DQ2.5/DQ2.5 homozygosis and a lower DQ2.5 in trans frequency, as in Northern Europe. Madrid has an intermediate model between the two described above. 17 cases (0.8%) did not carry any CD risk haplotypes.
Assuntos
Doença Celíaca , Antígenos HLA-DQ , Humanos , Criança , Espanha/epidemiologia , Antígenos HLA-DQ/genética , Doença Celíaca/genética , Predisposição Genética para Doença , Alelos , Genótipo , Haplótipos , Cadeias beta de HLA-DQ/genética , Cadeias alfa de HLA-DQ/genéticaRESUMO
OBJECTIVES: The objective of this study was to assess the association between serological markers and changes of the intestinal mucosa in children with celiac disease (CD). METHODS: Clinical data from CD patients under 15 years old were collected from the participating centers in an on-line multicenter nationwide observational Spanish registry called REPAC-2 (2011-2017). Correlation between anti-tissue transglutaminase antibodies (t-TGA) levels and other variables, including mucosal damage and clinical findings (symptoms, age, and gender), was assessed. RESULTS: A total of 2955 of 4838 patients had t-TGA and a small bowel biopsy (SBB) performed for CD diagnosis. A total of 1931 (66.2%) patients with normal IgA values had a Marsh 3b-c lesion and 1892 (64.9%) had t-TGA Immunoglobulin A (IgA) ≥ 10 times upper limit of normal (ULN). There is a statistically significant association between t-TGA IgA levels and the degree of mucosal damage ( P < 0.001), the higher the t-TGA IgA levels the more severe the mucosal damage. Those patients who reported symptoms had more severe mucosal damage ( P = 0.001). On the contrary, there was a negative association between age and changes of the intestinal mucosa ( P < 0.001). No association was found with gender. Regarding the IgA-deficient patients, 47.4% (18 cases) had t-TGA Immunoglobulin A (IgA) ≥ 10 times ULN and a Marsh 3b-c lesion was observed in 68.4% (26 patients). No statistical relation was found between t-TGA IgG levels and the changes of the intestinal mucosa, neither a relation with age, gender, or symptoms. CONCLUSIONS: There is a positive correlation between t-TGA IgA levels and the severity of changes of the intestinal mucosa. Such correlation was not found in IgA-deficient patients who had positive t-TGA IgG serology. The results in this group of patients support the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition recommendations about the need of performing a SBB in IgA-deficient individuals despite high t-TGA IgG levels.
Assuntos
Doença Celíaca , Adolescente , Criança , Humanos , Autoanticorpos , Biópsia , Doença Celíaca/diagnóstico , Imunoglobulina A , Imunoglobulina G , TransglutaminasesRESUMO
BACKGROUND: Maternal iodine deficiency is related to high neonatal thyroid-stimulating hormone (TSH) values, with the threshold of 5 mIU/L recommended as an indicator of iodine nutrition status. The objective of this study was to analyse possible risk factors for increased TSH that could distort its validity as a marker of iodine status. The clinical relevance of this research question is that if the factors associated with iodine deficiency are known, iodine supplementation can be introduced in risk groups, both during pregnancy and in newborns. METHODS: A case-control study was carried out in a sample of 46,622 newborns in 2002-2015 in Spain. Of these, 45,326 had a neonatal TSH value ≥5 mIU/L. The main variable was having TSH ≥5 mIU/L and the secondary variables were: sex, gestational age, day of sample extraction and maternal origin. Associated factors were analysed through a logistic regression model, calculating the odds ratio (OR). RESULTS: The factors associated with this outcome were: male sex (OR = 1.34, 95% CI: 1.20-1.50, p<0.001), originating from an Asian/Oceanic country (OR = 0.80, 95% CI: 0.54-1.20, p = 0.536) or Europe (OR = 0.80, 95% CI: 0.66-0.96, p = 0.285) (including Spain, OR = 1) [p<0.001 for America (OR = 0.54, 95% CI: 0.44-0.68) and p = 0.025 for Africa (OR = 0.78, 95% CI: 0.62-0.97)] and fewer days from birth to sampling (OR = 0.80, 95% CI: 0.77-0.82, p<0.001). CONCLUSIONS: The risk of high neonatal TSH without congenital hypothyroidism is higher in males, decreases with a greater number of days from birth to extraction, and is dependent on maternal ethnicity but not on gestational age.
Assuntos
Hipertireoxinemia/diagnóstico , Hipertireoxinemia/etiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hipertireoxinemia/metabolismo , Recém-Nascido , Doenças do Recém-Nascido , Masculino , Triagem Neonatal , Razão de Chances , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Tireotropina/metabolismoRESUMO
BACKGROUND: Dual-energy X-ray absorptiometry (DXA) provides separate measurements of fat mass, fat-free mass and bone mass, and is a quick, accurate, and safe technique, yet one that is not readily available in routine clinical practice. Consequently, we aimed to develop statistical formulas to predict fat mass (%) and fat mass index (FMI) with simple parameters (age, sex, weight and height). METHODS: We conducted a retrospective observational cross-sectional study in 416 overweight or obese patients aged 4-18 years that involved assessing adiposity by DXA (fat mass percentage and FMI), body mass index (BMI), sex and age. We randomly divided the sample into two parts (construction and validation). In the construction sample, we developed formulas to predict fat mass and FMI using linear multiple regression models. The formulas were validated in the other sample, calculating the intraclass correlation coefficient via bootstrapping. RESULTS: The fat mass percentage formula had a coefficient of determination of 0.65. This value was 0.86 for FMI. In the validation, the constructed formulas had an intraclass correlation coefficient of 0.77 for fat mass percentage and 0.92 for FMI. CONCLUSIONS: Our predictive formulas accurately predicted fat mass and FMI with simple parameters (BMI, sex and age) in children with overweight and obesity. The proposed methodology could be applied in other fields. Further studies are needed to externally validate these formulas.
RESUMO
BACKGROUND: Others have described a relationship between hemoglobin A levels and gestational age, gender and ethnicity. However, studies are needed to determine normal cut-off points considering these factors. To address this issue we designed a study to determine the percentiles of normality of neonatal hemoglobin A levels taking these factors into account. METHODS: This cross-sectional study involved 16,025 samples for sickle cell disease screening in the province of Alicante, Spain, which has a high immigration rate. The primary variable was hemoglobin A, and the secondary variables were gender, gestational age (preterm and full term) and maternal origin (Spain, the rest of Europe, North Africa, Sub-Saharan Africa, Latin America and Asia). Percentiles of normality (1 and 99) were obtained by origin, gender and gestational age using quantile regression models and bootstrap samples. The association between these percentiles of normality and altered levels (≥1%) of hemoglobin E was analyzed. We obtained the percentiles of normality (1 and 99) for each maternal origin, gender and gestational age. RESULTS: Of a total of 88 possible E carriers, 65 had above-normal hemoglobin A levels (74%). The levels of normality for hemoglobin A varied greatly according to the maternal origin and gestational age. CONCLUSION: With the levels of normality that we established it is possible to discard samples with unrecorded blood transfusions. Our methodology could be applied to other diseases in the neonatal screening.
Assuntos
Anemia Falciforme/diagnóstico , Emigração e Imigração , Recém-Nascido Prematuro , Triagem Neonatal , Anemia Falciforme/epidemiologia , Estudos Transversais , Feminino , Idade Gestacional , Hemoglobina A , Humanos , Recém-Nascido , Masculino , Programas de Rastreamento , Espanha/epidemiologia , Espanha/etnologiaRESUMO
OBJECTIVES: The aim of this study was to assess the incidence and clinical pattern of celiac disease (CD) presently diagnosed in Spanish children. METHODS: A prospective, multicenter, nationwide registry of new cases of CD in children <15 years was conducted from June 1, 2006 to May 31, 2007. The parameters studied were age at diagnosis, sex, clinical symptoms, associated diseases, nutritional status, CD serology, histological lesions, and HLA-DQ2/-DQ8. The crude incidence rate of CD was calculated as new cases per 1000 live births and as new cases per 100,000 person-years <15 years of age. RESULTS: A total of 974 new cases of CD were included. The median age at diagnosis was 2.3 years; 39.5% of CD diagnoses occurred in the first 2 years, 42% between 2 and 6, and 18.4% from 6 to 15. Total number of cases in each age group was 385, 409, and 180, respectively. Regarding clinical presentation 70.9% showed classical symptoms, 21.9% were nonclassical, and 7% were asymptomatic. A total of 95.7% of 931, 94.7% of 611, and 86.7% of 651 children tested positive, respectively, for immunoglobulin A (IgA) anti-transglutaminase type 2 antibodies, IgA endomysial antibodies, and IgA anti-gliadin antibodies. Villous atrophy was observed in 92.4% and increased intraepithelial lymphocytes with crypt hyperplasia in 3.3%. Of the children, 55% had normal growth, and 3.4% were overweight. The HLA phenotype was DQ2: 88.3%, DQ2/DQ8: 8.4%, and DQ8: 2.3%. The incidence rate was 7.9 cases of CD per 1000 live births and 54 cases per 100,000 person-years. CONCLUSIONS: In Spain, the most frequent clinical presentation of CD is the classical form, mainly diagnosed during the first 2 years of life. The observed incidence of CD in Spanish children is much higher than the present CD incidence rates observed in other European countries.
Assuntos
Anticorpos/sangue , Doença Celíaca/epidemiologia , Mucosa Intestinal , Linfócitos/metabolismo , Peso Corporal , Doença Celíaca/sangue , Doença Celíaca/complicações , Doença Celíaca/patologia , Criança , Pré-Escolar , Feminino , Antígenos HLA-DQ/sangue , Humanos , Incidência , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Fenótipo , Sistema de Registros , Espanha/epidemiologiaRESUMO
OBJECTIVES: Exclusive enteral nutrition (EEN) is one of the therapeutic strategies used to induce remission in pediatric Crohn's disease (CD). Although its use is recommended in clinical practice guidelines and consensus documents, the frequency of this practice in Spain is unknown. METHODS: A 70-item questionnaire ( PRESENT: PREScription of Enteral Nutrition in pediaTric Crohn's disease in Spain) was drafted and distributed through the SEGHNP (Spanish Society for Pediatric Gastroenterology, Hepatology and Nutrition) e-mail list. RESULTS: We received information from 51 Pediatric Gastroenterology Units. Of the 287 patients newly diagnosed with CD in 2011-2012 at these centres (139 in 2011, 148 in 2012), 182 (63%) received EEN (58% in 2011 and 68% in 2012). 26% of the patients who received EEN in the period studied (64/246) did so during relapses. All the physicians (100%) who responded to the questionnaire believe that EEN is effective in inducing clinical remission in mild to moderate CD. However, 24.5% of respondents never use EEN during relapses. The enteral formulas used most often used were polymeric formulas specific for CD (70.6%) and the preferred administration route was oral, with 60.8% using flavouring and 9.3% allowing a variable percentage of calories in the form of other foods. 65% use 5-ASA together with EEN, 69% use antibiotics and 95% immunomodulators (thiopurines). The duration of EEN tends to be 8 weeks (47.1%), and transition to regular diet was achieved sequentially over a variable period of time. Regarding barriers and limiting factors for the use of EEN, those most frequently reported include lack of acceptance by the patient and/or family (71%), lack of time and/or ancillary staff (69%) and difficulty in convincing the patient and/or family of the suitability of treatment (43%). CONCLUSIONS: EEN use rates are similar to those of other European questionnaires. Tools that facilitate acceptance by the patient and family are needed. Increasing the time dedicated to this therapeutic modality is likewise important. Given the disparity of criteria for indicating treatment with EEN, it would be useful to have widely accepted clinical practice guidelines or protocols that facilitate the decision to use it.
Objetivos: La nutrición enteral exclusiva (NEE) es una de las estrategias terapéuticas empleadas para inducir la remisión en niños con enfermedad de Crohn (EC). Pese a que la NEE se recomienda en las guías de práctica clínica y en los documentos de consenso, la frecuencia real de su empleo en España es desconocida. Métodos: Encuesta compuesta por 70-items (PRESENT: PREScription of Enteral Nutrition in pediaTric Crohn's disease in Spain) que se distribuyó a través de la lista de distribución de Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP). Resultados: Se recibieron los datos de 51 unidades de Gastroenterología Pediátrica del territorio español. De los 287 pacientes recién diagnosticados de EC durante los años 2011-12 en esos centros (139 en 2011 y 148 en 20212), 182 (63%) recibieron NEE (58% en 2011 y 68% en 2012). El 26% de los pacientes que recibieron NEE estaban en recaída. Todos los facultativos que respondieron pensaban que la NEE es efectiva para inducir la remisión clínica en los brotes leves-moderados. El 24,5% no emplean la NEE durante las recaídas. Las formulas enterales empleadas más frecuentemente fueron las específicas para EC (70,6%), la vía oral fue la más utilizada, el 60,8% utilizaron saborizantes y el 9,8% de las unidades permitían un porcentaje variable de calorías en forma de otros alimentos durante el periodo de NEE. El 65% emplearon 5-ASA junto con la NEE, el 69% antibióticos y hasta un 95% inmunomoduladores. La duración de la NEE fue de 8 semanas en el 47,1% de los casos, la transición hacia una dieta normal se realizó de forma secuencial. En relación a las barreras y factores limitantes encontrados por los respondedores para instaurar la NEE destacaban la falta de aceptación por el paciente y/o la familia (71%), falta de tiempo o de personal auxiliar (69%) y la dificultad para convencer al paciente o su familia de la idoneidad del tratamiento (43%). Conclusiones: La frecuencia de empleo de la NEE en pacientes con EC es similar a la de otros cuestionarios europeos. Se precisan herramientas y recursos que faciliten la aceptación por parte del paciente y de su familia así como disponer de más tiempo a dedicar para instaurar esta modalidad terapéutica. Dada la disparidad de criterios para la indicación de la EEN, sería útil disponer de guías de práctica clínica ampliamente aceptadas o protocolos que facilitan la decisión de utilizarla.