Le dépistage de la mucoviscidose en période néonatale a d\e'buté il y a plus de 40 ans. Après la possibilité d'un test de dépistage par recherche de l'albumine méconiale, le dosage de la trypsine ...immunoréactive san- guine sur papier buvard couplé à la recherche des principales mutations du gène CFTR est utilisé de façon courante avec une bonne sensibilité et spécificité du test. Ce dépistage a Iongtemps fait l'objet de controverses, mais ses avantages au moins à moyen terme et, notamment sur le plan nutritionnel, sont bien démontrés dès lors que le suivi de l'enfant dépisté est réalisé dans des centres spécialisés. C'est la raison pour laquelle la généralisation du dépistage néonatal sur l'ensemble de la France en 2002 s'est accompagnée de recommandations de suivi de I'enfant dépisté dans des centres de soins que les autorités de santé ont officialisé et dénommé centres de ressources et de compétences de la mucoviscidose. La France est ainsi devenue le premier pays au monde à effectuer ce dépistage sur I'ensemble de son territoire, dont l'organisation a été confiée à l'Association française de dépistage et de prévention des handicaps de I'enfant. Depuis le début du programme jusqu'au 31 décembre 2005, 625 nouveau-nés ont été ainsi repérés, soit une incidence de 1/4348, avec de fortes variabilités régionales. Le problème actuel, qui se produit dans 14 % des cas, est celui de la révélation de cas dont les tests de la sueur intermédiaires ou normaux sont associés à au moins une mutation dite modérée et pour lesquels on ignore le pronostic clinique qui peut rester pauci symptomatique.
Cystic fibrosis newborn screening : implemen- tation, laboratories involvement and national results CF neonatal screening programs began over than 40 years ago. Initially a meconium albumin screening test measurement was performed; more recently it moved to immunoreactive trypsin measurements on dried blood samples collected on filter paper combined to molecular analysis for the main CFTR mutations with good test sensitivity and specifity. CF neonatal screening has been controversial for many years; the long term benefit on pulmonary function test is not yet demonstrated but its median term benefits on nutritional parameters are esta- blished as soon as the CF screened infant follow-up is done in a specialized centre. That is the reason why the systematic newborn screening program implemented in France in 2002, was combined with a follow-up care for CF patients in CF care centres (CRCMs) created by the health regulatory agency. France became the first country in the world to per- form the CF neonatal screening all over its territory, and the French Association for the Screening and Prevention of Infant Handicaps (AFDPHE) has been mandated. From 2002 to December 2005, 625 CF cases were detected.The incidence is 1/4348 with a wide range of regional variations. Among these, 14% of the infants with positive CF NBS results have a dilemma case presentation with a borderline or normal sweat test results and at least one mild mutation whose prognosis re- mains unknown.
To assess the efficiency of the French national screening program for 21-hydroxylase deficiency (21-OHD). Neonatal screening for congenital adrenal hyperplasia due to 21-OHD is mainly intended to ...prevent death due to salt wasting but remains controversial because of the number of false-positive results and the ease with which most female cases can be identified by virilized genitalia at birth.
Population-based study.
National neonatal screening program, pediatric endocrinologists nationwide, and reference center for genotyping.
All neonates screened for 21-OHD in mainland France between January 1, 1996, and December 31, 2003.
Screening efficiency indicators, disease severity, contribution of screening to early diagnosis, and disease-specific mortality before and during the study period.
A total of 6,012,798 neonates were screened; results in 15,407 were considered positive for 21-OHD. Three hundred eighty-three cases were identified, giving a prevalence of 1 for every 15,699 births. The positive predictive value of screening was 2.3% (95% CI, 2.1%-2.6%), with a sensitivity of 93.5% (90.9%-95.9%) and a specificity of 99.7% (99.7%-99.7%). The false-positive rate was particularly high in preterm infants, for which the positive predictive value was 0.4% (95% CI, 0.2%-0.5%). Screening allowed clinical diagnosis in 162 of 383 cases (42.3%), with the others being detected clinically or through family history. There was a trend toward declining neonatal mortality due to 21-OHD.
In this large population-based study, the efficiency of routine 21-OHD screening was moderate in neonates born at term and very low in preterm neonates. We recommend the discontinuation of screening, as currently performed in France, in preterm neonates.
We investigated the physicochemical and transport properties of sputum samples collected in physiotherapy from a well-documented group of 27 cystic fibrosis (CF) patients with identified CF ...genotypes. Sputum samples were characterized ex vivo for their water content, surface properties (surface tension and contact angle), rheologic properties (viscosity and elastic modulus), and transport properties (mucociliary and cough transport). These data were analyzed in relation to the clinical status of the patients (FEV1, FVC, Shwachman score, Brasfield score, nutritional status), their genotype, and the degree of infection of their sputa (leukocyte and Pseudomonas aeruginosa counts). We observed negative and significant correlations between mucociliary transport and elastic modulus of the patients' sputum (r = -0.63, p < 0.01), and between the cough transport and contact angle of the sputum (r = -0.81, p < 0.0001), respectively. The P. aeruginosa count was also significantly correlated with the sputum water content (r = -0.53, p < 0.02) as well as with the cough transport of the sputum (r = -0.62, p < 0.01). In CF patients with a sputum leukocyte count > 2,000/mm3, the sputum water content (p < 0.02), FEV1 (p < 0.05) and FVC (p < 0.02) were significantly lower than those of CF patients with a leukocyte count < or = 2,000/mm3. CF patients with a homozygous delta F 508 genotype had significantly greater values of sputum water content (p < 0.05), and cough-transport capacity (p < 0.05) than did heterozygous patients. No correlation was observed between the sputum properties and any of the clinical data. These results suggest that the control of infection should be emphasized in CF, since it can directly or indirectly modulate the degree of hydration, and therefore the physicochemical and transport properties, of airway secretions.
Liver disease in patients with cystic fibrosis (CF) is inconstant and has not yet been clearly related to any specific risk factor. While the expression of cystic fibrosis transmembrane conductance ...regulator (CFTR) is restricted to the biliary epithelium in the liver, recent findings indicate that CFTR modulates reduced glutathione (GSH) transport and that CFTR dysfunction creates an imbalance in the antioxidant defense. Among liver detoxifying enzymes, the glutathione S-transferases (GSTs) play a key role in the protection against oxidative stress. Because oxidative injury contributes to the development of liver disease, we hypothesized that 2 members of the GST superfamily, GSTM1 and GSTP1, which are expressed in the biliary epithelium, could influence the hepatic status in patients with CF. The potential impact of GSTM1 and GSTP1 gene polymorphisms was assessed in 106 children with CF (mean age, 11.5 years). Based on polymerase chain reaction/restriction fragment length polymorphism analysis, we found that the frequency of GSTP1-Ile(105)/Ile(105) genotype was significantly higher in patients with CF with liver disease than in those without (P <.03). Among the youngest patients, aged 6 years, GSTP1-Ile(105)/Ile(105) genotype was associated with a 8-fold increase in the risk of liver disease compared with other GSTP1 genotypes (P =.002). No association between the GSTM1 genotype and liver status was documented. In conclusion, GSTP1-Ile(105)-encoding allele contributes to hepatic dysfunction in CF. Identification of this polymorphism may have prognostic value and prompt early treatment in patients with CF with an increased risk of liver disease.
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 ⩾ 15 ng/ml, or ⩾ 11.5 ng/ml and immunoreactive trypsinogen (IRT) ⩾ 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. Key messages CF neonatal screening with PAP is technically feasible in the same environment as other neonatal screenings (PKU, hypothyroidism) CF neonatal screening with PAP alone performs similarly to screening with IRT alone, with less carrier detection Combining PAP with IRT for CF neonatal screening could be as efficient as the IRT/DNA strategy, but would be cheaper and incur limited carrier detection If a legal requirement for informed consent before DNA testing has expired, the PAP/IRT strategy would be an alternative to the IRT/DNA strategy
To provide an overview of non-specific modifications on whole-body post-mortem computed tomography (PMCT) images of infants and children.
69 infants and children underwent a whole-body PMCT scan at ...our institution following sudden unexpected death. Two paediatric radiologists reviewed the PMCT images, specifically focusing on non-specific postmortem modifications unrelated to the presumed cause of death.
Iatrogenic post-mortem modifications included focal infiltration of the legs (n=15) and hemopericardium (n=2). Vascular postmortem modifications included hypostasis (density in the posterior sagittal sinus was correlated with density in the dependent portion of the heart (p<0.001)), portal vein thrombosis (n=56, 75.3%), hyperattenuating aortic wall and reduced abdominal aortic diameter (n=69, 100%). Intravascular gas was detected in 40 subjects (57.9%). Ligamentum arteriosum calcification was seen in 42 children and was not correlated with age (p=0.68). Umbilical artery calcification was found in 30 children and was correlated with age (p<0.005). Gaseous distension of the stomach (n=45, 65.2%) and bowels (n=44, 63.7%) was a frequent finding. Mean liver density was 49.6±7.5HU and mean spleen density was 43.2±5.9HU. Ground-glass opacity was observed in 63 cases (91.3%) and mild bilateral consolidation in 16 cases (23.1%).
Non-specific post-mortem signs are rare and new to clinical paediatric radiologists. They should be aware of these signs when interpreting whole-body PMCT images in cases of sudden unexpected death in infancy or childhood in order to avoid pitfalls that may have a critical impact.
•Clinical paediatric radiologists should be aware of non-specific post-mortem signs.•Some non-specific post-mortem modifications in children are the same as in adults.•Whole-body PMCT has paediatric specificities.
PURPOSE Antibiotic prophylaxis is administered to children at risk of a urinary tract infection (UTI). However proof of its effectiveness in children with low grade vesicoureteral reflux (VUR) is ...lacking. Our objective was to determine whether antibiotic prophylaxis reduced the incidence of a UTI . MATERIAL AND METHODS Children, 1-month to 3-years-old, with low grade VUR, were assigned randomly to receive daily cotrimoxazole or not and then followed up for 18 months. Clinical examination and renal ultrasound were carried out at 9 and 18 months, and a voiding cystourethrogram at 18 months. A UTI constituted an exit criteria. Survival curves without infection were compared with a log-rank test. RESULTS 223 children were enrolled, 102 in the cotrimoxazole group and 121 in the control group. Sex, age at inclusion and grade of reflux were similar in the two groups. There was no significant difference for the occurrence of UTI or pyelonephritis between the two groups. Considering pyelonephritis, there was no significant difference for girls, whatever the grade of VUR. However, prophylaxis tended to reduce pyelonephritis only for boys with grade III VUR. CONCLUSIONS These data suggested that antibiotic prophylaxis did not reduce the incidence of UTI in young children with low grade VUR. However, it may prevent further pyelonephritis in boys with grade III VUR.
À propos de la mort subite du nourrisson Sénécal, Jean; Roussey, Michel; Bouvier-Colle, Marie-Hélène ...
Population (France),
07/1998, Volume:
53, Issue:
4
Journal Article
À propos de la mort subite du nourrisson Sénécal, Jean; Roussey, Michel; Bouvier-Colle, Marie-Hélène ...
Population (France),
07/1998, Volume:
53, Issue:
4
Journal Article
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