RESUMEN
France has decided to add to the national neonatal screening program (Phenylketonuria, Hypothyroidism, Congenital Adrenal Hyperplasia, Sickle cell disease) the screening of cystic fibrosis (CF). The screening of CF will be implemented in all regions of France by the end of 2002 and will cover all newborn (near 800,000/year). Based on the recommendation of the French Screening Foundation, the project has been approved by the Health Ministry and will be financed by the social security. CF neonatal screening is now technically feasible and reliable. The proposed methodology includes: immunoreactive trypsin (IRT) dosage on all newborns at day 3 (by radioimmunology "Cis Bio" or immunofluorescence "Delfia") followed by genotype CFTR analysis if IRT level is above 60 micrograms/L. Screening for 29 mutations is planned. If genotype is negative, control of IRT at day 21 will be obtained. Several requirements are included in the program: a protocol of care for the newly diagnosed CF in a specialised CF center; information to all parents of newborns; results of CFTR genotype has to be given during a clinical visit, even if negative. This screening program should allow to screen 98% of the cystic fibrosis patients before the age of 1 month. In order to ensure perfect efficacy, the CF screening program will be evaluated and modified if necessary.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/análisis , Fibrosis Quística/diagnóstico , Tamizaje Neonatal , Fibrosis Quística/genética , Francia , Genotipo , Política de Salud , Humanos , Inmunoensayo , Recién Nacido , TripsinaRESUMEN
Recent European studies have shown that growth retardation is com-mon in people with phenylketonuria (PKU) during the first years of life while they receive a low-phenylalanine (Phe) diet. The aims of the present study were to assess the growth of our PKU patients and to search for nutritional and hormonal explanations for the growth delay. Twenty PKU patients aged 8 months to 7 years entered the study. The design was cross-sectional, a longitudinal study having already been performed in our centre. The following data were recorded: weight/height (W/H), height/age (H/A), and weight/age (W/A) Z-scores; fat-free mass (measured from bioelectrical impedometry (FFM1), and skinfold thickness (FFMA). Thyroid hormones, insulin-like growth factor I (IGF1), insulin-like growth factor binding protein (IGFBP3), selenium, zinc, and Phe blood levels were measured. Dietary intake was also recorded over 4 days. PKU patients were moderately but significantly shorter (H/A Z-score varied from -2.12 to 1.61; mean -0.49) and lighter (W/A Z-score varied from -2.58 to 1.49; mean -0.71) than the French reference population. Body composition was not different from that of controls matched for age and sex. IGF1, IGFBP3, and thyroid hormone levels were within normal range. All children received more than two-thirds of the recommended daily allowances for energy (91% +/- 18%) and for proteins (146% +/- 26%). The mean daily intake of our patients was sufficient in selenium, but markedly deficient in zinc (2.4 +/- 2.2 mg/day). No correlation was found between zinc daily intake or zinc plasma levels and growth retardation. Moreover, no relation was found between the plasma Phe concentrations, protein or caloric intake and the presence of growth retardation. Our results show that growth retardation in PKU patients is not related to hormonal or caloric deficiencies. Further studies are needed to investigate the effect of various nutrient supplementation regimens (especially zinc) on the growth of PKU patients.
Asunto(s)
Trastornos del Crecimiento/etiología , Estado Nutricional , Fenilcetonurias/diagnóstico , Fenilcetonurias/fisiopatología , Envejecimiento/fisiología , Antropometría , Composición Corporal , Estatura/fisiología , Peso Corporal/fisiología , Niño , Preescolar , Cromatografía de Gases , Estudios Transversales , Dieta , Eritrocitos/metabolismo , Femenino , Hormonas/sangre , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Fenilalanina/sangre , Fenilcetonurias/complicaciones , Hormonas Tiroideas/sangre , Oligoelementos/metabolismo , Tirosina/sangreRESUMEN
Neonatal screening for cystic fibrosis was decided by the national medical authorities after a common investigation conducted by the French association ADPHE and national health insurance fund. Based on therapeutic progress and the proposed method using determination of blood immunoreactive trypsin then study of the main CF mutations, there is strong hope of effective CF detection and clinical benefit for the patients.
Asunto(s)
Fibrosis Quística/diagnóstico , Programas de Gobierno , Tamizaje Neonatal , Fibrosis Quística/genética , Fibrosis Quística/terapia , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Francia , Programas de Gobierno/organización & administración , Humanos , Recién Nacido , Mutación , Tamizaje Neonatal/organización & administración , Tripsina/sangreRESUMEN
This paper describes the adjustments to the French neonatal screening programme required by the introduction of systematic screening for cystic fibrosis (CF), taking into account both the legal and statutory framework and the lessons of a pilot study carried out 10 years ago. The French association for the screening and prevention of infant handicaps (AFDPHE) has been mandated by its regulatory agencies to organize screening for CF in France (metropolitan and overseas territories). During the year 2001, expert groups (Technical Aspects, Information, Ethics and Genetics, Criteria for CF Centres, Protocol for the Care of a Newborn with CF) issued recommendations for the establishment of a national programme that would guarantee efficiency and adequate patient care from the time of diagnosis onward. The programme is based on a strategy combining immunoreactive trypsin (IRT) assay and the analysis of DNA mutations in dried blood samples obtained at 3 days of age. When an elevated IRT value is found, DNA analysis is performed on the same sample. Owing to the relative regional heterogeneity existing in France, 30 selected mutations are used, which provide 85% coverage. The Ethics and Genetics Committee recommended that, in order to avoid arousing anxiety by a recall, informed consent, according to the French legislation on bioethics, should be obtained for all neonates at birth by having the parents sign directly on the sampling paper. Information brochures for parents and health professionals have been designed. A new organization of patient care, involving the creation of CF centres recognized by the Ministry of Health, has been decided; all children diagnosed are to be referred to such centres, where they can be well cared for by a trained staff with sufficient means. The programme was implemented region by region in France, from the beginning of the year 2002 to early 2003. The expert groups still meet periodically to evaluate the implementation of the programme and to check that the terms of the agreement between the AFDPHE and the Social Security Agency are complied with.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/diagnóstico , Mutación , Tamizaje Neonatal , Tripsina/sangre , Francia , Humanos , Recién Nacido , Padres , Tripsina/inmunologíaRESUMEN
A neonatal screening allows a preclinical diagnosis of major sickle cell syndromes and an early management of the affected children. That would improve their life quality and expectancy. The preliminary program was set up on 518 senegalese newborn aged from 1 to 4 days, and coming from all the country ethnic groups. Isoelectrofocalisation is the test used on dried blood eluate and the positive control on citrate agar gel. 478 samples out of 518 (92.5%) have been analysed. Haemoglobinopathy have been found in 11.1% of cases, distributed as follow: heterozygoty FAS and FAC: 9%, double heterozygoty FSC: 0.2% and homozygoty FSS: 1.9%. Sickle cell neonatal screening should be imperatively implemented, with regards in economical considerations. It would be relevant to integrate it in a larger program including information, training and genetic counselling in order to avoid homozygotes birth and to lower the spread of this disease.
Asunto(s)
Anemia de Células Falciformes/diagnóstico , Tamizaje Neonatal/métodos , Anemia de Células Falciformes/genética , Femenino , Asesoramiento Genético , Humanos , Recién Nacido , Masculino , Pronóstico , Calidad de Vida , Senegal , Sensibilidad y EspecificidadRESUMEN
The concept of neonatal screening for metabolic disorders was launched by Robert Guthrie in 1963. A filter paper blood sample and a cheap and rapid analytical technique were factors that paved the road to success. Mass screening for phenylketonuria soon started to spread. Various additional screening procedures for other metabolic or endocrine conditions were subsequently developed. Most of developed countries have set up systematic neonatal screening programs and million of babies are screened each year. This review presents the main milestones of the fantastic history of neonatal screening but also the questions risen by many temptations to extend the screening to other disorders which not necessarily fulfil classic criteria for systematic search. Ethical and health economical aspects will be the most important issues for the development of neonatal screening in the next millennium.
Asunto(s)
Enfermedades Metabólicas/historia , Tamizaje Neonatal/historia , Historia del Siglo XX , Humanos , Recién Nacido , Enfermedades Metabólicas/diagnósticoRESUMEN
AIM: To determine whether pancreatitis associated protein (PAP) is a marker for cystic fibrosis which could be used in neonatal screening for the disease. METHODS: PAP was assayed on screening cards from 202,807 neonates. Babies with PAP > or = 15 ng/ml, or > or = 11.5 ng/ml and immunoreactive trypsinogen (IRT) > or = 700 ng/ml were recalled for clinical examination, sweat testing, and cystic fibrosis transmembrane regulator (CFTR) gene analysis. RESULTS: Median PAP value was 2.8 ng/ml. Forty four cases of cystic fibrosis were recorded. Recalled neonates (n = 398) included only 11 carriers. A receiver operating characteristic curve analysis showed that PAP above 8.0 ng/ml would select 0.76% of babies, including all those with cystic fibrosis, except for one with meconium ileus and two with mild CFTR mutations. Screening 27,146 babies with both PAP and IRT showed that only 0.12% had PAP > 8.0 ng/ml and IRT > 700 ng/ml, including all cases of cystic fibrosis. CONCLUSION: PAP is increased in most neonates with cystic fibrosis and could be used for CF screening. Its combination with IRT looks promising.
Asunto(s)
Proteínas de Fase Aguda/análisis , Antígenos de Neoplasias , Biomarcadores de Tumor , Fibrosis Quística/diagnóstico , Lectinas Tipo C , Tamizaje Neonatal/métodos , Biomarcadores/sangre , Fibrosis Quística/sangre , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Humanos , Recién Nacido , Proteínas Asociadas a Pancreatitis , Valor Predictivo de las Pruebas , Estudios Prospectivos , Tripsinógeno/sangreRESUMEN
AIM: The results of the neonatal screening of congenital adrenal hyperplasia due to 21-hydroxylase deficiency by 17-hydroxyprogesterone measurement from blood spot on blotting-paper in 408,138 newborns in the French Nord-Pas-de-Calais region from 1980 to 1996 are reported. METHODS: This measurement successively used a tracer tritium labelled (RIA H3), 125 iodine (RIA I125), then immunofluorometric method (Delfia). From 1992, sampling was systematically performed at the third day of life. RESULTS: Thirty-three cases were detected and confirmed (20 boys and 13 girls). Diagnosis was made before recalling on a clinical basis in three boys and eight girls. In 22 cases (17 boys and five girls) when diagnosis was not made before recalling, it could have been suspected in three girls because of a sex ambiguity once associated with dehydration and in eight boys because of failure to thrive (six times) or a marked dehydration (twice). Lack of sex ambiguity in two girls characterized non classical form of the illness. These two patients benefited from the early detection of the illness on growth data. Out of 49 subjects who died before recall, three could be suspected of bearing 21-hydroxylase deficiency. One single false negative case was found, which led to decrease cut-off value. On the other hand, false positive cases were frequent (0.37%), mainly in premature newborns (88% of cases). CONCLUSION: Although decrease of median age for recall at 7 days did not prevent the occurrence of two cases of dehydration, neonatal screening of 21-hydroxylase deficiency appears to be efficient, as far as diagnostic strategy is considered.
Asunto(s)
Hiperplasia Suprarrenal Congénita/diagnóstico , Tamizaje Neonatal , 17-alfa-Hidroxiprogesterona/sangre , Factores de Edad , Reacciones Falso Positivas , Femenino , Fluoroinmunoensayo , Francia , Humanos , Recién Nacido , Masculino , Radioinmunoensayo , Factores SexualesRESUMEN
Blau syndrome (MK186580) comprises granulomatous arthritis, iritis, and skin rash, and is an autosomal-dominant trait with variable expressivity. So far it was described in 5 families. We report on a sixth family with severe progression of eye involvement and discuss the nosology with similar diseases, such as early-infantile sarcoidosis.
Asunto(s)
Artritis/patología , Exantema/patología , Granuloma/patología , Iritis/patología , Adolescente , Adulto , Artritis/genética , Ceguera/genética , Niño , Preescolar , Cromosomas Humanos Par 16 , Exantema/genética , Femenino , Retardo del Crecimiento Fetal , Genotipo , Granuloma/genética , Humanos , Lactante , Iritis/genética , Masculino , Linaje , Sarcoidosis/patología , Síndrome , Sinovitis/genética , Sinovitis/patología , Gemelos MonocigóticosRESUMEN
BACKGROUND: In adults, Helicobacter pylori infection is always associated with gastritis or ulcer. However, very active gastritis and ulcers are rarely seen in children. The aim of the present work was to study the relationships between H. pylori and gastric mucosa in children. METHODS: Eighty infected children and adolescents including 48 (60%) neurologically impaired institutionalized patients, aged 2 months-22 years (mean 11.7 +/- 5.2 years) were studied retrospectively. All the patients underwent gastroscopy, and three antral and two fundic biopsy specimens were taken for histology and bacteriology. RESULTS: A normal gastric mucosa was found in 22 of 80 patients (27.5%), whereas the others had gastritis (n = 58, 72.5%). There were no statistical differences between patients with normal histology and those presenting with gastritis for age, sex, ethnic background, symptoms, and the degree of bacterial colonization. The macroscopic aspect of gastritis was less frequently found in children with a normal histology compared with those with histological gastritis (p < 0.001). CONCLUSIONS: These data show that H. pylori infection can be associated with a normal gastric histology in children.
Asunto(s)
Mucosa Gástrica/patología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Adolescente , Adulto , Biopsia , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Mucosa Gástrica/microbiología , Gastroscopía , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Humanos , Lactante , Masculino , Valores de Referencia , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the short term effects on nutritional status of home intravenous anti-pseudomonas antibiotic courses in cystic fibrosis (CF) patients chronically colonised with Pseudomonas aeruginosa. DESIGN: A prospective study involving 38 CF patients, mean age 10.9 (SD 4.3) years (range 4.3 to 22.2 years), presenting with pulmonary exacerbations of P aeruginosa infection. The patients received a 14 day antibiotic course of intravenous ceftazidime (200 mg/kg/day) and either amikacin (35 mg/kg/day) or tobramycin (15 mg/kg/day). Nutritional evaluation on days 1 and 14 involved measurements of weight, weight/height ratio (per cent of predicted value), energy intake (per cent of recommended daily allowances), serum prealbumin, and body composition assessed by two methods: bioelectrical analysis (BIA) and skinfold anthropometry. The non-parametric Wilcoxon t test was used for statistical analysis, with a Bland-Altman plot to assess the degree of agreement between the two methods of evaluating body composition. RESULTS: Weight increased by 1.0 (0.8) kg (p < 0.001); weight/height increased from 94.4(12.2)% to 98(12.7)% (p < 0.001), energy intake from 107(32)% to 119(41)% (p < 0.02), and prealbumin from 183 (63) to 276 (89) mg/l (p < 0.001). Fat mass increased by 0.8 (1.0) kg (p < 0.001), without any significant change in fat-free mass. The limits of agreement between BIA and anthropometry were -0.7 kg and +1.1 kg. CONCLUSIONS: Antibiotic courses allow an improvement in nutritional status in CF patients, with a gain in fat mass.
Asunto(s)
Fibrosis Quística/complicaciones , Quimioterapia Combinada/uso terapéutico , Estado Nutricional , Infecciones Oportunistas/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Adolescente , Adulto , Amicacina/uso terapéutico , Antropometría , Composición Corporal , Ceftazidima/uso terapéutico , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Masculino , Infecciones Oportunistas/complicaciones , Estudios Prospectivos , Infecciones por Pseudomonas/complicaciones , Tobramicina/uso terapéuticoRESUMEN
UNLABELLED: Upper gastrointestinal endoscopy is frequently used in the neonatal period. The aim of this study was to assess the frequency of the different lesions occurring as well as to precise indications of upper gastrointestinal endoscopy in neonates. POPULATION AND METHODS: A retrospective study including 107 neonates referred between October 1986 and April 1995 has been achieved in the pediatric gastroenterology unit of the Lille University Hospital. Various factors were analysed: gestational age, sex, reasons for endoscopy and macroscopic lesions observed. Three groups were constituted according to macroscopic findings; group I: normal aspect (n = 22); group II: isolated esophagitis (n = 27); group III: esogastritis or gastroduodenitis or esogastroduodenitis (n = 38). Chi 2 test was performed for statistical analysis. RESULTS: Signs recalling esophagitis (cry during feeding) were more frequent in group II than in group III: 37% vs 13% (P < 0.03). The neonates undergoing endoscopy for life-threatening events were more frequent in group I than in group II or III, respectively: 59% vs 15% (P < 0.01) and 59% vs 8% (P < 10(-4). Upper gastrointestinal endoscopy led to a precise diagnosis in 80% of the neonates. However 95% of those examined for hematemesis presented macroscopic lesions. CONCLUSIONS: Hematemesis and suspicion of esophagitis are good indications for upper gastrointestinal endoscopy in neonatal period. In life-threatening events and suspicion of pyloric stenosis, upper gastrointestinal endoscopy is only complementary of more contributive other examinations.
Asunto(s)
Enfermedades del Esófago/diagnóstico , Recien Nacido Prematuro , Duodenoscopía/estadística & datos numéricos , Enfermedades del Esófago/epidemiología , Esofagitis/diagnóstico , Esofagitis/epidemiología , Unión Esofagogástrica/patología , Esofagoscopía/estadística & datos numéricos , Femenino , Francia/epidemiología , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/epidemiología , Gastroscopía/estadística & datos numéricos , Humanos , Recién Nacido , Masculino , Estudios RetrospectivosAsunto(s)
Enfermedades de los Conductos Biliares/etiología , Colestasis Intrahepática/etiología , Enfermedad de Hodgkin/complicaciones , Fosfatasa Alcalina/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aspartato Aminotransferasas/sangre , Enfermedades de los Conductos Biliares/sangre , Enfermedades de los Conductos Biliares/patología , Bilirrubina/sangre , Biopsia con Aguja , Preescolar , Colestasis Intrahepática/sangre , Colestasis Intrahepática/patología , Resultado Fatal , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Hígado/patología , Fallo Hepático/etiología , Fallo Hepático/patología , Ganglios Linfáticos/patología , Masculino , Síndrome , gamma-Glutamiltransferasa/sangreRESUMEN
UNLABELLED: The adequate L-thyroxine dosage for the initial treatment of infants with congenital hypothyroidism is a subject of controversy. Some recommend higher dosages (> 10 micrograms/kg/day) to ensure adequate levels, while others advocate lower dosages to permit normalisation of thyroid status. The aim of this study was to evaluate the results of a treatment strategy using an initial dosage of 7.5-8.0 micrograms/kg per day, TSH measurements being taken at 15 and 30 days of treatment. Fifty one newborns infants with primary congenital hypothyroidism detected by neonatal screening were treated with the same therapeutic strategy. A mean L-thyroxine dosage of 7.9 micrograms/kg per day at the onset of treatment and 6.6 micrograms/kg/d at 2 months, normalised the FT4 and FT3 levels at 15 days in 100% and TSH levels at 2 months in 90% of cases. Many patients showed elevated levels of FT4 and a systematic higher initial dosage could expose many infants to a dangerous hyperthyroidism. Patients with abnormal TSH levels at 2 months already had higher TSH levels in the first 8 weeks of life and, despite higher L-thyroxine dosage, also exhibited lower FT4 and FT3 levels. These patients who needed an early increase in dosage had already shown a more profound ante and neonatal hypothyroidism. This subgroup of patients require a higher dosage of thyroxine and early assessment of FT4, FT3 and TSH levels are required for optimum dosage choice. CONCLUSION: Even though a subgroup of patients may require a higher dosage of L-thyroxine, an initial dosage of 7.5-8.0 micrograms/kg per day, with an early assessment of FT4, FT3, and TSH levels, is adequate for the treatment of the majority of infants with congenital hypothyroidism.