[Discordant Down syndrome risk calculation with low maternal serum markers: About five cases of digynic triploidies]. / Risque de trisomie 21 discordant en cas de marqueurs sériques très bas : à propos de cinq cas de triploïdie digynique.

OBJECTIVE: We compare the risk of Down syndrome among five patients carrying a foetus with digynic triploidy and suggest a course of action for these particular serological profiles. METHODS: The concentrations of the different markers used are transformed into multiples of the median by using each of the three software types present on the French market which then determine the risk of Down syndrome. RESULTS: For comparable biochemical and ultrasound profiles, the risk of Down syndrome turns out to be vastly different depending on the type of software employed. The relevance of an immediate diagnostic procedure, of a cell free DNA test or of a basic ultrasound follow-up then arises, leading to a potentially variable care pathway for the patient. CONCLUSIONS: This study confirms that for this type of biochemical profile, the laboratory's advisory service is fundamental, that a control ultrasound is essential and that an invasive procedure must be used almost invariably due to the extremely substantial risk factors.

[Genetics, diagnosis and characteristics of trisomy 21]. / Génétique, diagnostic et caractéristiques de la trisomie 21.

Trisomy 21 remains relevant today. As patients' life expectancy increases, medical monitoring shows the importance of screening for associated complications such as epilepsy and sleep apnoea. For caregivers, it constitutes a care model for intellectually disabled people notably with regard to anxiety, poor expression of pain and family suffering. Scientific advances raise hope of progress in therapeutic practices.

[Trisomy 21, the ethics between the right to life and a possible termination of pregnancy for medical reasons]. / Trisomie 21, quelle éthique entre le droit à la vie et une possible interruption médicale de grossesse ?

The antenatal diagnosis tools now available feed the fantasy of the 'perfect baby'. In this context and in parallel to a whole range of other foetal pathologies, trisomy 21 represents an emblematic situation which acts as a reminder that it is ethically essential to keep open the question of terminating or continuing with a pregnancy. Multidisciplinary team work remains the best safeguard against possible abuses.

[Support for families through a Disability Resource Unit]. / L'accompagnement des familles par une Cellule Ressource Handicap.

The Disability Resource Unit of the mother and infant welfare protection centre aims to facilitate the care of children with a disability in day care centres or at school. Thanks to the creation of a doctor-children's nurse partnership, the unit provides families with personalised support. Listening, availability and empathy are essential in order to meet as best as possible the specific needs of the child and the parents' expectations. Interview with Véronique Labidoire, child care worker and technical advisor in the Disability Resource Unit of the Gironde's mother and infant welfare protection centre.

[The announcement of the diagnosis of trisomy 21]. / L'annonce du diagnostic de trisomie 21.

The announcement of trisomy 21 in a child, either in the prenatal or postnatal period, is a difficult moment for the parents as well as for the caregivers. The latter must be skilled in the general principles of communication and be able to adapt to each specific situation while providing the necessary medical care, support and empathy.

[Social representations of trisomy 21]. / Les représentations sociales de la trisomie 21.

Social representations of trisomy 21 have evolved considerably since its first descriptions in France in the 19th century. Today contradictory trends are at work. Some convey alarmist and stereotypical images while others favour greater understanding of life with trisomy 21.

[The multidisciplinary and specific care of children with trisomy 21]. / La prise en charge pluridisciplinaire des enfants porteurs de trisomie 21.

A centre for early medico-social action supports children aged between 0 and 6 with a disability or likely to present a developmental disorder. One such centre has put in place a specific multidisciplinary follow-up of children with trisomy 21 and their family, with the added support of a wide network of partners. Particular attention is paid to providing early guidance and support for the parents.

[Feelings of caregivers faced with trisomy 21]. / Ressentis des soignants face à la trisomie 21.

Caregivers' practices with children with trisomy 21 can be influenced by many factors. The issues of antenatal diagnosis and the termination of pregnancy for medical reasons can cause contradictory feelings. Collective and individual defence strategies can however be put in place to support the children and their families along their care and life pathway.

[A specialised consultation for children and young adults with trisomy 21]. / Une consultation spécialisée pour l'enfant et le jeune adulte atteints de trisomie 21.

The life expectancy of people with trisomy 21 has increased over recent decades. More than half live over 55 years today, compared to just 9 years in 1929. This progress is thanks to easier access to care and improved medical diagnoses as well as greater physical and psychological stimulation. Continued monitoring remains essential but it becomes less systematic as children grow up, despite the risk of certain complications increasing from puberty. Consultations devoted to trisomy 21 aim to facilitate access to care through an adapted care pathway.

[Overview of feelings and practices of gynecologists and obstetricians for the noninvasive prenatal testing in France]. / État des lieux du ressenti et des pratiques des gynécologues-obstétriciens face au dépistage prénatal non invasif en France.

OBJECTIVES: To evaluate the feelings and practices of French obstetrician-gynecologists in prescribing the noninvasive prenatal testing (NIPT) before the release of the French High Authority of Health recommendations. METHODS: Descriptive, declarative and transversal study, analyzing the feelings and practices of obstetrician-gynecologists, members of the French College of Gynecologists and Obstetricians (CNGOF) between February and May 2017 using an online questionnaire. Practitioners' feedback was self-assessed for several clinical situations using a numerical scale ranging from 1 to 10. This experience was rated as "good" (grades 6 to 10) or "bad" (grades 1-5). RESULTS: Overall, 529 practitioners (29.2%) of 1812 CNGOF members, answered the online questionnaire. A "good" feeling was found for more than 65% of the practitioners audited. Feelings were significantly better for obstetricians, sonographers (P<0.05) and CPDPN members (P=0.003) compared to other practitioners. Situations where the DPNI was proposed "systematically" were risks greater than 1/250 (70.9%), between 1/250 and 1/500 (59.4%), greater than 1/250 associated with history of spontaneous miscarriages and/or fetal death in utero (66%), greater than 1/250 associated with pregnancy resulting from PMA (68.3%), history of fetal aneuploidy (54%) and a parent carrying a Robertsonian translocation (51.6%). CONCLUSION: This study highlights a good overall feeling of the practitioners with the NIPT.

[Analysis of prenatal follow-up strategies for trisomy 21 affected pregnancies in France]. / Analyse du parcours de dépistage prénatal des femmes ayant donné naissance en France à un enfant atteint de trisomie 21.

OBJECTIVE: The main objective of this study was to screen the prenatal follow-up of women with live birth trisomy 21 child in order to evaluate the proportion of prenatal screening failure versus cases where the women refused either the screening or the prenatal diagnosis of Down syndrome. This study covers the period of time from 2009 to 2012 when the national prenatal screening policy changed from second to first trimester and allows for a comparative assessment of the nationwide efficiency of the various maternal serum marker based strategies. METHOD: All authorized cytogenetic laboratories sent required data for all cases of trisomy 21 diagnosed in FRANCE in new-borns (less than 1-year-old) from January 2010 to July 2013. RESULTS: A total of 1253 cases of trisomy 21 were diagnosed before 1 year of age whose mother did not had prenatal diagnosis. For 861 of them, information on the prenatal follow-up was available, with 72% of cases where a prenatal screening was organized either by maternal serum marker or by ultrasound. Results of the screening strategy was positive with maternal serum marker in 28% of cases (calculated risk≥1/250), positive because of abnormal ultrasound in 5% and negative with maternal marker screening (whatever the strategy used) in 67% of cases. Detection rate over the period of the study was 82%, with similar efficiency of first and second trimester strategies (83%) but significantly lower with sequential association of first trimester Nuchal translucency measurement and second trimester serum screening (70%). CONCLUSION: Switching from second trimester to first trimester screening strategy, with as many trisomy 21 foetuses diagnosed with half invasive procedures fulfilled national health policy objectives. Analysis of these data gives useful insights to elaborate a future screening policy involving cell-free foetal DNA sequencing.

[Assessment of screening for Down syndrome in Martinique from 2011 to 2013: An island location favoured]. / Évaluation du dépistage de la trisomie 21 en Martinique de 2011 à 2013 : une situation insulaire privilégiée.

OBJECTIVES: The aim of this study is to evaluate the screening for trisomy 21 (T21) between 2011 and 2013 on Martinique French West Indies after the decree of 23 June 2009. MATERIALS AND METHODS: Were used the prenatal data provided by accredited laboratories and the data from the Registry of Congenital French West Indies (REMALAN). RESULTS: A total of 85.9 % of patients underwent screening: 60.5 % on a combined calculation of risk (CRC), 14.6 % on a sequential calculation of risk (CRS) and 10.8 % on serum markers 2nd trimester (MST2). Overall 5.4 % of the patients were placed in a risk group. During this period, 47 trisomy 21 were identified by the REMALAN which 38 (80.1 %) were detected prenatally: 24 of CRC, 3 on MST2 and 11 on signs of ultrasound at the 1st and 2nd trimester. The sensitivity of the CRC was 88 % for a false positive rate of 3.87 %. The overall sensitivity of screening (CRC, CRS and MST2) was 87 % for a false positive rate of 5.21 %. CONCLUSION: These data show that the coverage rate in Martinique is satisfactory and the screening fir Down syndrome meet expectations.

[The noninvasive prenatal testing for Down's Syndrome. Retrospective study of 8821 patients]. / Le dépistage prénatal non invasif de la trisomie 21. Étude rétrospective à propos de 8821 patientes.

OBJECTIVE: To demonstrate the decrease in intrauterine invasive procedures through analysis of DNA fetoplacental free circulating in maternal blood: Non Invasive Prenatal Test (NIPT), in Prenatal Diagnosis Center of American Hospital of Paris (AHP). MATERIALS AND METHODS: Retrospective descriptive study of 8821 patients in Prenatal Diagnosis Center at the AHP between 01/01/2012 and 09/25/2014. The NIPT is available to patients since 1st January 2013. RESULTS: The number of invasive procedures decreased significantly (P<0.0001) between 2012 (n=1177, i.e. 42 % of the global activity of the Prenatal Diagnosis Center at the AHP in 2012) and 2013 (n=987 or 28.5 %) and between 2013 and 2014 (n=599 or 23.4 %). The NIPT calculated performance statistics are: sensitivity≥99.9 %; specificity=99.8 %; Positive Predictive Value=90.4 %; Negative Predictive Value≥99.9 %; False Positives=3. While the actual screening statistic values are: sensitivity≥95.4 %; specificity=82.5 %; Positive Predictive Value=6.5 %; Negative Predictive Value=99.9 %; False Positives=1197. The NIPT has reduced the number of invasive procedures at the Prenatal Diagnosis Center at the AHP. The NIPT performances are superior to those of the actual screening.

[Trisomy 21 and breast cancer: A genetic abnormality which protects against breast cancer?]. / Cancer du sein et trisomie 21 : une anomalie génétique qui protège contre le cancer du sein ?

INTRODUCTION: Trisomy 21 (T21) is the most common chromosomal abnormality and one of the main causes of intellectual disability. The tumor profile of T21 patients is characterized by the low frequency of solid tumors including breast cancer. METHODS: The objective of this work was to analyze the literature to find possible clues for the low frequency of breast cancer in T21 persons with a focus on one hand to the various risks and protective factors against breast cancer for women T21, and on the other hand to changes in the expression of different genes located on chromosome 21. RESULTS: T21 women have hormonal and societal risk factors for breast cancer: frequent nulliparity, lack of breastfeeding, physical inactivity and high body mass index. The age of menopause, earlier in T21 women, has a modest protective effect against breast cancer. The low rate of breast tumors in T21 women is probably mainly linked to the reduced life expectancy compared to the general population (risk of death before the age of onset of the majority of breast cancers) and the presence of a third chromosome 21, characterizing the disease. It might lead to the increased expression of a number of genes contributing directly or undirectly to tumor suppression, decreased tumor angiogenesis and increased cell apoptosis. Moreover, changes in the mammary stroma of persons T21 could have an inhibitory role on the development of breast tumors. CONCLUSION: The low frequency of breast cancers for T21 patients may not only be explained by hormonal and societal factors, but also by genetic mechanisms which could constitute an interesting axis of research in breast cancer.

[First trimester screening for Down syndrome at Prima facie. A 6-year survey]. / Dépistage de la trisomie 21 au premier trimestre. Bilan de 6 années à Prima facie.

OBJECTIVE: To evaluate the results of screening for trisomy 21 by the combined risk of first trimester (as defined by the decree of June 23, 2009) in the Prima facie structure. METHODS: Single center study involving all patients that were seen for first trimester screening at Prima facie with singleton living pregnancy, not obtained by embryo donation, between 1 January 2009 and 31 December 2014. RESULTS: Eighteen thousand two hundred and fifty-one patients were included, of which underwent screening for trisomy 21 by the combined risk. One thousand and forty-six (6.1%) had a calculated risk higher than 1/250. Seventy-five were affected by trisomy 21, of whom 65 in the high risk group. The sensitivity and specificity of screening are 86.7% and 94.4%. The median nuchal translucency was 0.98 MoM. CONCLUSIONS: Screening for trisomy 21 by calculating the combined risk of first trimester enabled to detect 86.7% of trisomy 21 with a false positive rate of 5.6%.

[Analysis of cell-free DNA in maternal blood for detection of fetal trisomy 21 in high-risk population: Couples acceptance and grounds for refusal]. / Étude de l'ADN fœtal dans le sang maternel pour la détection de la trisomie 21 en population à risque accru : adhésion des couples et motifs de refus.

OBJECTIVES: To assess the determinants associated with the use of analysis of cell-free DNA in maternal blood for detection of trisomy 21 in high-risk women. MATERIALS AND METHODS: Prospective study conducted in a single center between July 15, 2014 and December 15, 2014 on 99 consecutive women with increased risk of trisomy 21 above 1/250. RESULTS: Analysis of cell-free DNA in maternal blood for detection of fetal trisomy 21 was proposed to 95 women out of 99, among them, 43 women (45.3%) required the test. Among these 43 women, 17 (38.6%) had a higher socio-economic status versus 10 (19.2%) among the women who did not request the test (P=0.03). The most common reason given by the 52 women who did not request the analysis of cell-free DNA was the cost, for 30 of them (57.7%), then because the test was not providing certainty for the diagnostic of trisomy 21 for 23 women (44.2%). CONCLUSION: Analysis of cell-free DNA on maternal blood for detection of trisomy 21 does not seem accepted by the majority of women. The cost is probably the main reason for not using this test, but it seems that the lack of diagnostic certainty is also an obstacle for some women.

[Assessment of patients' knowledge of first-trimester combined Down syndrome screening at the time of their first trimester ultrasonographic evaluation: Results of a prospective study about 201 women]. / Évaluation des connaissances des patientes concernant le dépistage de la trisomie 21 lors de l'échographie du premier trimestre : résultats d'un sondage prospectif sur un échantillon de 201 femmes.

OBJECTIVE: Assess pregnant women's knowledge on first-trimester combined Down syndrome screening, at the time of their first trimester ultrasound scan. MATERIALS AND METHODS: A questionnaire was submitted to the patients coming for their 12-week pregnancy ultrasonographic evaluation in a University Hospital prenatal clinic between May 2012 and May 2013. Correct and incorrect statements on Down syndrome screening were proposed to the mothers who were asked to rate them. Each patient was questioned on her prior exposition to Down syndrome screening, the category of medical of professional she previously consulted, and the information she received. Patients' knowledge was evaluated according to these criteria. RESULTS: Two hundred and one patients were included in this study. The average correct answer rating was 4.6 (out of 8 questions). The average incorrect answer rating was 2.4 (out of 6 questions). No difference was found between the different social and demographic groups, nor according to the category of professional consulted before the first ultrasound scan. Higher correct answer ratings were observed when the patient had already been submitted to a Down syndrome screening (P=0.039), when they had previously received explanations about the screening (P=0.003); and when they stated that they had been sufficiently informed (P=0.042). CONCLUSION: These results show that patients' knowledge on Down syndrome screening is inadequate and depends on their experience of previous screening and information. It is deemed necessary to improve information especially to young women who are pregnant for the first time.

[Birth of a child with Down syndrome: parental choice or failure of screening policy?]. / Naissance d'un enfant porteur de trisomie 21: choix parental ou défaut de la politique de dépistage ?

OBJECTIVES: Birth of a child with Down syndrome (DS) can follow parental choice or failure of screening. The objective of this work is to describe the circumstances of births of children with DS in a French perinatal health network. METHODS: Retrospective multicentric study, with prospective trial registration of all children born alive with DS, between 2010 and 2013. RESULTS: Sixty-three children were born with DS. Complete screening was performed by 61 % of patients, incomplete screening by 29 % of patients and no screening test by 10 %. Among these births, 50 % occurred following parental choice, 40 % following failure of screening and for 10 %, parental choice concerning screening was unknown. False negative had often calculating risk close to 1/1000. CONCLUSION: In this study, the birth of a child with DS occurred following parental choice in half of cases. It's necessary, to optimize the follow-up, to document in medical records the medical information and parental choice concerning DS screening and data of screening when this was done.