Urine tests for Down's syndrome screening

Background Down's syndrome occurs when a person has three copies of chromosome 21, or the specific area of chromosome 21 implicated in causing Down's syndrome, rather than two. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life. The risk of a Down's syndrome affected pregnancy increases with advancing maternal age. Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have. Objectives To estimate and compare the accuracy of first and second trimester urine markers for the detection of Down's syndrome. Search methods We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), EMBASE (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2011, Issue 7), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (archived 2007), Health Services Research Projects in Progress database (25 August 2011). We studied reference lists and published review articles. Selection criteria Studies evaluating tests of maternal urine in women up to 24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. Data collection and analysis We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC (receiver operating characteristic) meta-analytical methods to analyse test performance and compare test accuracy. We performed analysis of studies allowing direct comparison between tests. We investigated the impact of maternal age on test performance in subgroup analyses. Main results We included 19 studies involving 18,013 pregnancies (including 527 with Down's syndrome). Studies were generally of high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Twenty-four test combinations were evaluated formed from combinations of the following seven different markers with and without maternal age: AFP (alpha-fetoprotein), ITA (invasive trophoblast antigen), ß-core fragment, free ßhCG (beta human chorionic gonadotrophin), total hCG, oestriol, gonadotropin peptide and various marker ratios. The strategies evaluated included three double tests and seven single tests in combination with maternal age, and one triple test, two double tests and 11 single tests without maternal age. Twelve of the 19 studies only evaluated the performance of a single test strategy while the remaining seven evaluated at least two test strategies. Two marker combinations were evaluated in more than four studies; second trimester ß-core fragment (six studies), and second trimester ß-core fragment with maternal age (five studies). In direct test comparisons, for a 5% false positive rate (FPR), the diagnostic accuracy of the double marker second trimester ß-core fragment and oestriol with maternal age test combination was significantly better (ratio of diagnostic odds ratio (RDOR): 2.2 (95% confidence interval (CI) 1.1 to 4.5), P = 0.02) (summary sensitivity of 73% (CI 57 to 85) at a cut-point of 5% FPR) than that of the single marker test strategy of second trimester ß-core fragment and maternal age (summary sensitivity of 56% (CI 45 to 66) at a cut-point of 5% FPR), but was not significantly better (RDOR: 1.5 (0.8 to 2.8), P = 0.21) than that of the second trimester ß-core fragment to oestriol ratio and maternal age test strategy (summary sensitivity of 71% (CI 51 to 86) at a cut-point of 5% FPR). Authors' conclusions Tests involving second trimester ß-core fragment and oestriol with maternal age are significantly more sensitive than the single marker second trimester ß-core fragment and maternal age, however, there were few studies. There is a paucity of evidence available to support the use of urine testing for Down's syndrome screening in clinical practice where alternatives are available

Contribution a l'identification des dynamiques de production des pristinamycines et a la mise au point de nouvelles procedures de fabrication

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Logistic regression model to estimate the risk of viable unbalanced offspring in reciprocal translocations

International audienceThe aim of this study was to estimate the risk of viable unbalanced offspring for a parental carrier of reciprocal translocation. On a large computerized database of reciprocal translocations we used logistic regression to model this risk. The status of the progeny is the outcome variable. Explanatory covariates are cytogenetic characteristics of the translocation, age and sex of the parental carrier, and potential viability of the gametes. The results obtained by the logistic model demonstrate the important role of certain variables such as the sex of the parental carrier and the R band length of the translocated segments. Within the group of lower risk (risk of viable unbalanced offspring less than 5%), 97% of the individuals are correctly classified with this model. For this group, the choice prenatal diagnosis can be best discussed by considering both the risk for viable unbalanced offspring and the risk of induced abortion following prenatal diagnosis

Stillbirth classification in population-based data and role of fetal growth restriction: the example of RECODE

International audienc

Déficiences et handicaps d'origine périnatale : dépistage et prise en charge

Les progrès réalisés dans le domaine de l’obstétrique et de la néonatalogie ontété importants ces trente dernières années. Ils ont été initiés dans les années1970 par le programme national périnatal (1970-72), dont les objectifsétaient de réduire les décès et handicaps imputables à la grossesse et àl’accouchement. Les principales mesures mises en place ont permisd’améliorer l’équipement des établissements accueillant les femmes enceinteset des services de réanimation néonatale, la formation des personnels, lasurveillance prénatale et de l’accouchement. Plus tard, dans le cadre du planpérinatalité (1993-2000), la réforme des établissements accueillant lesfemmes enceintes et les enfants à la naissance est venue compléter le dispositifexistant. Parallèlement, des progrès ont été accomplis dans la prise encharge des populations à haut risque : mise en réseau des établissements,orientation des femmes à haut risque vers des maternités disposant d’unservice de réanimation néonatale, diffusion de nouveaux traitements (corticothérapieanténatale, surfactant) et développement de la réanimation néonatale.L’ensemble de ces mesures s’est accompagné d’une baisse importantede la mortalité périnatale, qui est passée de 21 pour 1 000 naissances en 1972à 7 pour 1 000 en 1998, et de la mortalité néonatale, passée de 14 pour1 000 naissances vivantes en 1969 à 3 pour 1 000 en 1997. La diminution dela mortalité néonatale a été de 25-35 % chez les enfants prématurés et de30-55 % chez les enfants grands prématurés dans les quinze dernières années.Ces évolutions ont rendu nécessaire la prise en compte de nouveaux indicateurspour évaluer de la prise en charge périnatale, en particulier en ce quiconcerne les conditions de survie des enfants et la survenue d’un handicap(infirmité motrice cérébrale, déficiences auditives et visuelles, déficiencesintellectuelles, troubles psychiatriques{). Si l’étude des handicaps de l’enfants’est peu à peu imposée, elle n’en soulève pas moins de nombreuses questions.Ces questions concernent la définition du handicap et ses spécificités chezl’enfant. Elles portent aussi sur les sources d’informations disponibles enFrance. En effet, bien que le programme national périnatal de 1970 fasseexplicitement référence aux handicaps, il n’existait pas de moyens de lesmesurer à l’époque. Depuis, des travaux ont porté sur les enfants handicapés,mais ces travaux sont peu nombreux en France. Nous verrons dans quellemesure ils permettent de dresser un bilan des principales déficiences, de leurévolution et de leurs causes.La loi d’orientation du 30 juin 1975 en faveur des personnes handicapéesencadre un ensemble de dispositifs. La nouvelle loi qui entrera en vigueur au1er janvier 2005 après examen parlementaire prévoit la création d’un droit àcompensation qui permettra la prise en charge par la collectivité des dépenses d’aide humaine et technique correspondant aux besoins de chaquepersonne handicapée. Le projet de loi a également pour objectif d’améliorerl’intégration scolaire des enfants handicapés. Il pose le principe de leur scolarisationdans l’établissement le plus proche du domicile parental, les établissementset services spécialisés intervenant en complément. Des plansd’actions devraient conduire à créer d’ici 2007 des places en établissements etservices pour enfants et adultes et à apporter des réponses spécifiques auxbesoins des personnes souffrant de handicaps lourds (autistes, polyhandicapés{).L’analyse des données nationales et internationales à propos de la prévalence,des facteurs étiologiques ou de risque, des dispositifs de dépistage et d’interventionprécoce, des programmes et de l’organisation de la prise en chargedoit contribuer à la connaissance indispensable pour la mise en place despolitiques publiques. (...