This review summarises the trajectory of neonatal screening strategies for the detection of cystic fibrosis (CF) using the measurement of Immunoreactive Trypsin (IRT) in dried blood spots (DBS) from 1979 until the beginning of the 21st century when newborn screening (NBS) programmes started to spread throughout many countries, using IRT measurement combined with a CF genotype analysis of DBS.

There is wide agreement on the benefits of NBS for CF in terms of lowered disease severity, decreased burden of care, and reduced costs. Risks are mainly associated with disclosure of carrier status and diagnostic uncertainty. When starting a NBS programme for CF it is important to take precautions in order to minimise avoidable risks and maximise benefits.In Europe more than 25 screening programmes have been developed, with quite marked variation in protocol design. However, given the wide geographic, ethnic, and economic variations, complete harmonisation of protocols is not appropriate. There is little evidence to support the use of IRT alone as a second tier, without involving DNA mutation analysis. However, if IRT/DNA testing does not lead to the desired specificity/sensitivity ratio in a population, a screening programme based on IRT/IRT may be used.Sweat chloride concentration remains the gold standard for discriminating between NBS false and true positives, but age-related changes in sweat chloride should be taken into account. CF phenotypes associated with less severe disease often have intermediate or normal sweat chloride concentrations. Programmes should include arrangements for counselling and management of infants where the diagnosis is not clear-cut.All newborns identified by NBS should be managed according to internationally accepted guidelines. CF centre care and the availability of necessary medication are essential prerequisites before the introduction of NBS programmes.Clear explanation to families of the process of screening and of implications of normal and abnormal results is central to the success of CF NBS programmes. Effective communication is especially important when parents are told that their child is affected or is a carrier. When establishing a NBS programme for CF, attention should be given to ensuring timely and appropriate processing of results, to minimise potential stress for families.

The earlier in gestation the infant is born, the lower neonatal FT4 concentrations will be. Although the first studies showed a relationship between thyroxine levels and neurodevelopmental outcome, recent studies are less conclusive. Objective To attempt to show a relationship between neonatal FT4 levels and neurodevelopmental outcome at age 5 years in children Methods Retrospective study; serum FT4 levels measured by radioimmunoassay (FT4 at day 3, mean FT4 between days 4 and 15, 16 and 30 and 4 and 30) in preterm neonates Results 176 premature infants born between March 1998 and December 2001 were enrolled. 121 were tested at 5 years of age. The group of non-examined children and the group of examined children were similar in regard to major prognostic factors. In univariate analyse, walking age was correlated to mean FT4 values between day 4 and day 15 (p = 0.04) but not to the other FT4 values. Touwen and KABC scores were not correlated to FT4 values at any time. Multivariate analysis taking in account the most important neurological outcome factors showed no correlation between walking age and FT4 values at either period. Conclusion Our results suggest that there may not be any benefit in supplementing hypothyroxinemic preterms with T4 hormone.

La thyroxinémie libre (T4l) du prématuré est d’autant plus basse que l’âge gestationnel (AG) est plus bas. Si les premières études montraient une corrélation entre les valeurs néonatales de T4 et le devenir neurodéveloppemental, des études plus récentes sont moins catégoriques. Objectifs Rechercher, chez les prématurés d’AG < 31 SA, une corrélation entre les valeurs de la T4l en période néonatale et le devenir neurodéveloppemental à 5 ans. Sujets et Méthodes dosage de T4l (technique RIA) chez les prématurés d’AG < 31 SA (valeurs à J3, valeurs moyennes entre J4 et J15, entre J16 et J30 et entre J4 et J30) ; âge de la marche obtenu auprès du médecin traitant aux 2 ans de l’enfant ; puis convocation à l’âge de 5 ans pour la passation d’un test de Touwen et du KABC ; comparaison de l’âge de la marche, du Touwen et du KABC selon le quartile de T4l Résultats 176 prématurés, nés entre mars 1998 et décembre 2001, ont été inclus. 7 enfants ont été exclus de l’étude à 2 ans (5 décès et 2 perdus de vue). 121/169 enfants ont été explorés à l’âge de 5 ans (Touwen et KABC). Parmi les 48 enfants restant, 1 est décédé après 2 ans, 31 ont été perdus de vue et 16 enfants ne sont pas venus à la convocation. Le groupe des enfants explorés est similaire au groupe des enfants non explorés pour les principaux facteurs du pronostic neurologique. En analyse univariée, l’âge de la marche est corrélée à la valeur de la T4l entre J4 et J15 (p = 0,04) mais pas aux autres périodes ; le Touwen n’est corrélé à aucune valeur de la T4l, ni le KABC, même s’il est plus bas dans le groupe du premier quartile de T4l entre J4 et J15 (p = 0,08). En analyse multivariée, il n’existe aucune corrélation pour ces 3 données et les valeurs de T4l aux 4 différentes périodes. Conclusion contrairement à van Wassenaer, nous n’avons pas trouvé de corrélation entre le Touwen et les valeurs moyennes de T4l de J3 à J30 en univarié ; en revanche comme lui nous n’avons pas retrouvé de corrélation entre les valeurs moyennes de T4l de J3 à J30 et le développement cognitif. Nos résultats semblent aller à l’encontre de l’intérêt d’une supplémentation en thyroxine des prématurés avec basse T4, mais seule une étude adaptée, basée sur les valeurs néonatales de la T4l, permettrait une conclusion formelle.

Annually these programmes screen approximately 1,600,000 newborns for CF and over 400 affected infants are recognised. The findings of this survey will guide the development of European evidence based guidelines and may help new regions or nations in the development and implementation of NBS for cystic fibrosis.

People with autism spectrum disorders (ASD) have pervasive impairments in social interactions, a diagnostic component that may have its roots in atypical social motivation and attention. One of the brain structures implicated in the social abnormalities seen in ASD is the amygdala. To further characterize the impairment of people with ASD in social attention, and to explore the possible role of the amygdala, we employed a series of visual search tasks with both social (faces and people with different postures, emotions, ages, and genders) and non-social stimuli (e.g., electronics, food, and utensils). We first conducted trial-wise analyses of fixation properties and elucidated visual search mechanisms. We found that an attentional mechanism of initial orientation could explain the detection advantage of non-social targets. We then zoomed into fixation-wise analyses. We defined target-relevant effects as the difference in the percentage of fixations that fell on target-congruent vs. target-incongruent items in the array. In Experiment 1, we tested 8 high-functioning adults with ASD, 3 adults with focal bilateral amygdala lesions, and 19 controls. Controls rapidly oriented to target-congruent items and showed a strong and sustained preference for fixating them. Strikingly, people with ASD oriented significantly less and more slowly to target-congruent items, an attentional deficit especially with social targets. By contrast, patients with amygdala lesions performed indistinguishably from controls. In Experiment 2, we recruited a different sample of 13 people with ASD and 8 healthy controls, and tested them on the same search arrays but with all array items equalized for low-level saliency. The results replicated those of Experiment 1. In Experiment 3, we recruited 13 people with ASD, 8 healthy controls, 3 amygdala lesion patients and another group of 11 controls and tested them on a simpler array. Here our group effect for ASD strongly diminished and all four subject groups showed similar target-relevant effects. These findings argue for an attentional deficit in ASD that is disproportionate for social stimuli, cannot be explained by low-level visual properties of the stimuli, and is more severe with high-load top-down task demands. Furthermore, this deficit appears to be independent of the amygdala, and not evident from general social bias independent of the target-directed search.

Vingt-neuf patients ont bénéficié de transfert nerveux : 15 simples transferts et 14 doubles transferts. L’âge moyen des patients était de 30,2 ans, le délai moyen préopératoire était de 6 mois et le suivi postopératoire moyen était de 34,2 mois. Pour le simple transfert, 60 % des patients ont récupéré un stade M4 à un délai postopératoire moyen de 13,2 mois. Pour le double transfert, 85 % des patients ont récupéré un stade M4 à un délai postopératoire moyen de 11 mois. Il n’y avait pas de différence significative entre les deux groupes, notamment pour la force stade M4. L’évaluation clinique au dernier recul trouvait un déficit moteur ou sensitif dans 7 cas sur 29, déficit considéré comme non gênant par le patient. Les résultats de notre série sont comparables à ceux de la littérature. Les patients avec une atteinte C5-C6 présentaient de meilleurs résultats dans le délai de récupération et dans la force contre résistance que ceux souffrant d’une atteinte C5-C6-C7. La restauration d’une fonction au niveau de l’épaule est un objectif à atteindre afin d’améliorer le résultat final, notamment pour la flexion du coude. Cette amélioration peut en partie être attribuée à la stabilisation de la racine du membre thoracique.Twenty-nine patients underwent single (n = 15) or double (n = 14) nerve transfer for post-traumatic elbow flexion palsy. Patients averaged 30.2 years, with a mean preoperative delay of six months and postoperative follow-up of 34.2 months. Sixty per cent of the single transfer patients recovered to BMRC grade M4 after an average of follow-up of 13.2 months. Eighty-five percent of double nerve transfer patients reached grade M4 after an average follow-up of 11 months. There were no significant differences between groups. Clinical assessment revealed motor or sensory deficit in seven cases, which did not cause any impairment. Patients with a C5-C6 injury had shorter recovery times and better strength in comparison with those with C5-C6-C7 injury. By restoring shoulder function, elbow flexion will be indirectly improved. This improvement can be partially attributed to the base of the arm being more stable.

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.

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 much less thanCis Biomuch greater than or immunofluorescence much less thanDelfiamuch greater than) followed by genotype CFTR analysis if IRT level is above 60 pg/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 I month. In order to ensure perfect efficacy, the CF screening program will be evaluated and modified if necessary. (C) 2003 Elsevier SAS. All rights reserved.

The neonatal screening programme in Normandy (France) allowed the formation of a homogenous cystic fibrosis (CF) cohort of 750 children diagnosed between 1980 and 1997. At the time of this retrospective study, 11 were deceased, out of which nine had meconium ileus (eight deaths after surgery, one at 5 years of age). Sixty children born between 1980 and 1993 in the Basse-Normandie region were followed up during a mean 80 months following similar protocols. The mean age at diagnosis was 47 days (SD = 27 d) for infants without meconium ileus. The occurrence of Pseudomonas aeruginosa (P. aeruginosa) infection and chronic colonization was studied using a monovariate followed by a multivariate analysis including the following variables: sex; meconium ileus; anthropometric data at birth and at diagnosis; pancreatic insufficiency; radiological data (Brasfield score); microbiology data at diagnosis; and genetic data. P. aeruginosa infection appeared earlier in children with pancreatic insufficiency (OR=2.2; p<0.05) or with radiological abnormalities (Brasfield score <21) at diagnosis (OR=3.9; p<0.05). Meconium ileus (OR=5.3; p<0.01), pancreatic insufficiency (OR=3.8; p<0.01) and Brasfield score <21 at diagnosis (OR=5.6; p<0.001) were prognosis factors for early chronic P. aeruginosa colonization. In CF children without meconium ileus, the major risk factor found through multivariate analysis for earlier infection and for earlier chronic colonization by P. aeruginosa was a diagnosis delay >40 days (respectively OR=4.6; p<0.001 and OR=10.4; p<0.005). These results must be compared with the lower Brasfield score at diagnosis in infants diagnosed after 40 days of life (p<0.01). (C) 2001 Editions scientifiques et medicales Elsevier SAS.

Cent cinquante enfants atteints de mucoviscidose ont été dépistés en période néonatale en Normandie entre 1980 et 1997, 36 enfants étaient porteurs d'un ileus méconial. Au moment de cette étude rétrospective, 11 enfants étaient décédés, neuf d'entre eux avaient eu un ileus méconial (huit décès après intervention chirurgicale et un décès à cinq ans). À partir d'une cohorte de 60 enfants dépistés de 1980 à 1993 et suivis régulièrement en Basse-Normandie, dans le même centre de soins, sur une durée moyenne de 80 mois, des facteurs pronostiques précoces de la survenue de la première infection à Pseudomonas aeruginosa (P. aeruginosa) et du passage à la chronicité ont été recherchés. L'âge moyen au diagnostic des enfants sans ileus (n = 44) était de 41 jours (déviation standard égale à 27 jours). L'analyse statistique a été effectuée selon une approche univariée puis multivariée pour les variables explicatives suivantes : présence d'un ileus méconial ; sexe ; données anthropométriques à la naissance et au diagnostic ; anomalies pulmonaires radiologiques (score de Brasfield), insuffisance pancréatique et données bactériologiques au moment du diagnostic ; mutations génétiques. Pour ces 60 enfants, les facteurs pronostiques mis en évidence ont été pour la précocité de la première atteinte à P. aeruginosa : l'insuffisance pancréatique au diagnostic (odds ratio [OR] égal à 2,2 ; p < 0,05) et un score de Brasfield initial inférieur à 21 (OR = 3,9 ; p < 0,05). Pour la précocité du portage chronique à P. aeruginosa : la présence d'un ileus (OR = 5,3 ; p < 0,01), l'insuffisance pancréatique (OR = 3,8 ; p < 0,01), et un score de Brasfield initial inférieur à 21 (OR = 5,6 ; p < 0,001). Pour les enfants sans ileus méconial, le facteur significatif défavorable majeur, pour la première atteinte et pour l'infection chronique à P. aeruginosa, en analyse multivariée, était un âge au diagnostic excédant 40 jours de vie (respectivement OR = 4,6 ; p < 0,001 et OR = 10,4 ; p < 0,005), à rapprocher de la valeur du score de Brasfield, significativement plus basse lorsque le délai de prise en charge était supérieur à 40 jours (p < 0,01).