[Characteristics and challenges of the antenatal diagnosis]. / Caractéristiques et enjeux du diagnostic anténatal.

The period of antenatal diagnostic testing is fraught with emotions for the parents. Screening ultrasound scans often constitute the indication of an antenatal diagnostic consultation in a multidisciplinary centre. There then follows a period of diagnosis, prognosis and decisions. Parents must be given specific support throughout this time.

[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.

[Toxoplasmosis in pregnancy: Practical Management]. / Toxoplasmose pendant la grossesse : proposition actuelle de prise en charge pratique.

The burden of congenital toxoplasmosis has become small in France today, in particular as a result of timely therapy for pregnant women, fetuses and newborns. Thus, the French screening and prevention program has been evaluated and recently confirmed despite a decline over time in the incidence of toxoplasmosis. Serological diagnosis of maternal seroconversion is usually simple but can be difficult when the first trimester test shows the presence of IgM, requiring referral to an expert laboratory. Woman with confirmed seroconversion should be referred quickly to an expert center, which will decide with her on treatment and antenatal diagnosis. Although the level of proof is moderate, there is a body of evidence in favor of active prophylactic prenatal treatment started as early as possible (ideally within 3 weeks of seroconversion) to reduce the risk of maternal-fetal transmission, as well as symptoms in children. The recommended therapies to prevent maternal-fetal transmission are: (1) spiramycin in case of maternal infection before 14 gestational weeks; (2) pyrimethamine and sulfadiazine (P-S) with folinic acid in case of maternal infection at 14 WG or more. Amniocentesis is recommended to guide prenatal and neonatal care. If fetal infection is diagnosed by PCR on amniotic fluid, therapy with P-S should be initiated as early as possible or continued in order reduce the risk of damage to the brain or eyes. Further research is required to validate new approaches to preventing congenital toxoplasmosis.

[Training of residents in amniocentesis: Effectiveness of a craft simulator]. / Formation des internes à l'amniocentèse : intérêt d'un simulateur artisanal.

OBJECTIVE: This prospective study aims to assess a low fidelity simulation device for learning amniocentesis to gynecology-obstetrics residents. METHODS: From 2013 to 2016, gynecology-obstetrics residents of all levels, from the maternity of Nancy hospital, which have already performed amniocentesis or not, participated in amniocentesis training on an artisanal simulator. Residents were evaluated on the amniocentesis simulator according to seven quality criteria. Three scores were assigned: the first (S1) at the beginning of the first training session, the second (S2) at the end of the first session after individualized personal training and the third (S3) two months after the first simulation. RESULTS: A total of 40 residents were included. The scores obtained by the residents were 3.2±1.8 points for S1 versus 6.2±0.9 points for S2 (P<0.001). Two months after, the residents' performances remained significantly improved compared to the initial assessment with a score (S3) of 5.8±1.3 points at S3 (P<0.001). CONCLUSION: Amniocentesis craft simulator is effective for performance improvement and allows a persistence of acquired skills two months after the training. At the time of "never the first time on the patient", it should be part of the curriculum of gynecology-obstetrics residents in order to guarantee patients quality care and optimum safety.

[Hepatitis B and pregnancy. Part 1. Thirteen practical issues in antenatal period]. / Hépatite B et grossesse. Partie 1. Treize questions pratiques en période anténatale.

In France, the prevalence of chronic hepatitis B is about 1% in pregnant women (usually asymptomatic carriers of HBsAg). The risk of maternal-fetal transmission of hepatitis B is particularly high when viral load measured by PCR is higher in mothers (above 7 log) or HBeAg is present. In case of maternal-fetal transmission of hepatitis B, the risk to the newborn of developing subsequent chronic hepatitis B is very high (90%), with long-term complications such as cirrhosis and hepatocellular carcinoma. The prevention of maternal-fetal transmission is based on systematic testing for hepatitis B during pregnancy, followed by serovaccination of the newborn at birth. If necessary, amniocentesis can be realised but will avoid the realization of a transplacental gesture. In case of high viral load, the establishment of a maternal antiviral treatment with lamivudine or tenofovir from 28SA can further reduce the risk of transmission. Given the low resistance it induces, tenofovir should be used preferentially.

[Clubfoot's prenatal ultrasound diagnosis: is amniocentesis always warranted? About 124 cases]. / Diagnostic anténatal de pied bot : la réalisation d'une amniocentèse est-elle toujours justifiée ? À propos de 124 cas.

OBJECTIVES: Analyze factors leading to isolated clubfoot's occurrence, identify clubfeet associated pathologies, and discuss the opportunity of performing an amniocentesis in cases of isolated clubfoot. PATIENTS AND METHODS: Between January 2007 and December 2011, all patients diagnosed with clubfoot in our prenatal diagnostic center were retrospectively included. We then defined and analyzed idiopathic or isolated talipses equinovarus (ITEV) and clubfeet associated with others morphologic abnormalities or syndromic talipses equinovarus (STEV). RESULTS: One hundred and twenty-four clubfeet were analyzed. Forty-seven cases of ITEV, for which 34 caryotypes were performed with a normal result. Risk factors of ITEV in our series were male gender (P=0.0017), a family history of clubfoot (P=0.001) and primiparity (P=0.04). Seventy-seven cases of STEV were diagnosed, 14 of which had chromosomal abnormalities, 18 spina bifida and 10 musculo-skeletal abnormalities. Among the 124 cases of clubfeet, 25 were unilateral and 99 were bilateral. Bilateral talipses equinovarus do not constitute a risk factor of STEV (P=0.8). DISCUSSION AND CONCLUSION: We did not find any chromosomic abnormalities in cases of ITEV. The results of our study could lead to defer systematic amniocentesis in cases of primiparous women diagnosed with an ITEV, with a familial history of clubfoot and a male fetus. A referent echographist in prenatal diagnosis should still perform a systematic morphologic echography.

Condução da toxoplasmose gestacional / Management of gestational toxoplasmosis

A toxoplasmose é uma doença proveniente do Toxoplasma gondii, um protozoário que tem os felinos como seu hospedeiro definitivo e os mamíferos e aves como seu hospedeiro intermediário. Tem um curso benigno e autolimitado quando acomete um indivíduo imunocompetente, no entanto a infecção durante a gestação acarreta até 50% de chance de toxoplasmose congênita, podendo causar danos severos ao feto. A virulência dos genótipos encontrados nas Américas Central e do Sul é a mais alta, comparada a Europa e América do Norte, tendo a doença um comportamento mais agressivo. Os estudos relatam a diminuição da infecção fetal em até 60% com o uso da espiramicina, usada ainda na profilaxia. Este artigo discute sobre a triagem materna pré-natal e sua necessidade, a profilaxia e o tratamento da infecção fetal ainda intraútero, com o objetivo de diminuir a transmissão vertical e as sequelas neonatais com suas implicações ao longo da vida.(AU)

Toxoplasmosis it is a disease originating from Toxoplasma gondii, a protozoan that has felines at as ultimate host and mammals and birds at as intermediate host. Has a benign and self-limiting course when affects immunocompetent individual, however, infection during pregnancy leads 50% chance of congenital toxoplasmosis and can cause severe damage to the fetus. The virulence of genotypes found in Central and South America is the highest compared to Europe and North America, having the disease a more aggressive behavior. Studies report a reduction in fetal infection 60% with the use spiramycin still used for prophylaxis. This article discusses prenatal maternal screening, prophylaxis and treatment of fetal infection still in utero with the objective of decreasing vertical transmission and neonatal sequelae with their lifelong implications.(AU)

Alteraciones citogenéticas en gestantes con edad avanzada. Granma. 2016-2018 / Cytogenetic alterations in pregnant women with advanced age. Granma 2016-2018 / Alterações citogenéticas em gestantes com idade avançada. Granma 2016-2018

RESUMEN Uno de los riesgos asociados al embarazo es la edad materna avanzada, la cual es considerada en nuestro país, a partir de los 35 años de edad. En la actualidad, constituye el principal motivo de indicación para el diagnóstico prenatal citogenético (DPC). Se realizó un estudio descriptivo transversal, con el objetivo de describir la frecuencia de las alteraciones citogenéticas en gestantes con avanzada edad en la provincia Granma en el período de 2016 a 2018. La muestra estuvo constituida por 803 gestantes de 37 años y más a las que se le realizó el diagnóstico prenatal citogenético por amniocentesis entre las 16 y 20 semanas de acuerdo a la fecha de la última menstruación (FUM) o por ultrasonido del primer trimestre en las gestantes con FUM dudosa. Los estudios citogenéticos en el líquido amniótico dirigidos a mujeres de edad materna avanzada están establecidos en nuestro país a las gestantes que tengan≥ 37 años ya que se considera el grupo poblacional de mayor riesgo. En el período estudiado se realizaron 803 estudios citogenéticos. Durante estos tres años de trabajo se obtuvo un 2,6% de resultados positivos, dentro de ellos 57,1% corresponden a aberraciones numéricas y 42,9% a estructurales. Bayamo (52,4%) resultó el municipio con mayor número de casos positivos.

ABSTRACT One of the risks associated with pregnancy is advanced maternal age, which is considered in our country, from 35 years of age. At present, it constitutes the main reason for indication for cytogenetic prenatal diagnosis (CPD). A descriptive cross-sectional study was carried out, with the objective of describing the frequency of cytogenetic alterations in pregnant women with advanced age in the province of Granma in the period from 2016 to 2018. The sample consisted of 803 pregnant women aged 37 years and older at whom the cytogenetic prenatal diagnosis was made by amniocentesis between 16 and 20 weeks according to the date of the last menstruation (FUM) or by ultrasound of the first trimester in pregnant women with doubtful FUM. Cytogenetic studies in amniotic fluid aimed at women of advanced maternal age are established in our country to pregnant women who are ≥ 37 years old since it is considered the population group with the highest risk. In the period studied, 803 cytogenetic studies were performed. During these three years of work, 2.6% of positive results were obtained, 57.1% of which correspond to numerical aberrations and 42.9% to structural ones. Bayamo (52.4%) was the municipality with the highest number of positive cases.

RESUMO Um dos riscos associados à gravidez é a idade materna avançada, considerada em nosso país a partir dos 35 anos de idade. Atualmente, constitui o principal motivo de indicação para o diagnóstico pré-natal citogenético (DPC). Foi realizado um estudo transversal descritivo, com o objetivo de descrever a frequência de alterações citogenéticas em gestantes com idade avançada na província de Granma no período de 2016 a 2018. A amostra foi composta por 803 gestantes com 37 anos ou mais de idade, nas quais o diagnóstico citogenético pré-natal foi realizado por amniocentese entre 16 e 20 semanas, de acordo com a data da última menstruação (FUM) ou por ultrassom do primeiro trimestre em gestantes com FUM duvidoso. Estudos citogenéticos em líquido amniótico direcionados a mulheres em idade materna avançada são estabelecidos em nosso país para gestantes com idade ≥ 37 anos, uma vez que é considerado o grupo populacional de maior risco. No período estudado, foram realizados 803 estudos citogenéticos. Durante esses três anos de trabalho, foram obtidos 2,6% de resultados positivos, 57,1% dos quais correspondem a aberrações numéricas e 42,9% a estruturais. Bayamo (52,4%) foi o município com o maior número de casos positivos.

[Managing and identifying the causes of IUGR]. / Bilan étiologique du retard de croissance intra-utérin (RCIU).

INTRODUCTION: The management and identification of the causes for a small for gestational age (SGA) and/or an intrauterine growth restriction (IUGR) fetus is a common but complex problem in Obstetrics. MATERIALS AND METHODS: The Medline, Embase and the Cochrane Library databases were examined over the last 15 years, with no language restrictions, using a combination of the words PAG (SGA), IUGR (IUGR), fetal weight (Fetal weight), sonography (ultrasound), management, cause (etiology), examinations (examinations). Some references not selected by this strategy, but associated with these publications or suggested by members of the working group were also added. The relevant articles were used to establish the text of recommendation following discussion between experts of the working group. RESULTS: Once the diagnosis of SGA is raised (whether on clinical, echocardiographic or Doppler), a management strategy to look for potential causes must be proposed and discussed with parents (Expert reviews). The extent of additional explorations varies depending on the exact presentation of the case (term at diagnosis, severity of anomalies). Additional explorations only make sense if they are likely to change the management of the current pregnancy and particularly to reduce perinatal morbidity and mortality. Explorations have two main objectives: (i) assess fetal vitality and possibilities for continuing the pregnancy in terms of safety for the mother and the foetus; (ii) establish the origin of SGA. The latter is detailed in this chapter recommendation. The earlier and the more severe the biometric anomalies, the more comprehensive the investigations. Maternal symptoms or fetal Doppler anomalies also require urgent management. CONCLUSION: Explorations to establish the origin of SGA and/or IUGR must follow a rigorous and systematic approach. In all cases, the practitioner will provide clear information to parents and collect information including detailed clinical and ultrasound examinations. Additional tests and in particular fetal invasive testing must be performed in some cases after parental consent and according to clinical and sonographic guidance elements.

[Fetal taking in some particular circumstances]. / Prélèvements fœtaux : à propos de quelques situations problématiques.

Fetal takings still concern about 6 to 7% of the pregnancies. If, in the majority of the cases, the taking does not present difficulty for a trained operator, particular circumstances related to maternal context (anticoagulating treatment, vaginal bleeding, fever…) may make the taking become more difficult. From a questionnaire sent to the French multidisciplinary centers for prenatal diagnosis and a review of the literature, we establish guidelines for fetal taking in these circumstances.

Reporte de 4 casos de inversión de cromosoma 9 en una muestra de 4755 líquidos amnióticos en una población venezolana

La inversión del cromosoma 9, inv (9), es una reordenación cromosómica relativamente común y generalmente se considera como una variante normal. No obstante, varios estudios han sugerido una posible asociación con síndrome metabólico, obesidad, galactosemia, diabetes mellitus y aborto espontáneo recurrente. Este estudio tiene como objetivo describir cuatro casos con la misma inversión cromosómica 9, inv (9) (p12; q12), y compararlo con lo que ha sido expuesto en la literatura. Se realizaron una serie de casos retrospectivos. Se evaluó una gran base de datos de informes de amniocentesis realizados en el centro Policlínica Metropolitana de Caracas entre 2005 y 2016. Como parte del protocolo del centro, todas las muestras de líquido amniótico recuperadas se centrifugaron a 800 rpm. Finalmente, se realizó un análisis de 20 bandas en metafase G para el cariotipo. Se recuperaron todos los cariotipos que informaron inv (9) (p12; q12). De 4755 informes de amniocentesis, se identificaron un total de 4 casos de inv (9) (p12; q12) pericéntrico. Según la literatura, este tipo de reordenamiento se ha asociado a algunas enfermedades metabólicas. Este hallazgo está respaldado por el hecho de que esta región cromosómica contiene el factor 1 promotor de insulina y el factor iniciador para la alfa quinasa 3 del factor de iniciación de traducción eucariótico, ambos implicados en la diabetes transitoria. Existe escasa literatura sobre este tipo de inversión, y se necesitan más estudios para un análisis de correlación adecuado. Los resultados de esta breve serie y los hallazgos de la literatura respaldan la importancia de los primeros estudios de cariotipo para identificar posibles asociaciones.

The inversion of chromosome 9, inv (9), is a relatively common chromosomal rearrangement and is commonly considered as a normal variant. However, several studies have suggested a possible association with metabolic syndrome, obesity, galactosemia, diabetes melli-tus and recurrent spontaneous abortion. This study aims to describe four cases with the same chromosome inversion 9, inv (9) (p12; q12), and compare them with what has been shown in the literature. A set of retrospective cases were carried out. A large database of amniocentesis reports made at the Policlinica Metropolitana of Caracas between 2005 and 2016 were analyzed. As part of the protocol of the Center, all recovered amniotic fluid samples were centrifuged at 800 rpm. Finally, an analysis of 20 metaphase G bands was performed for the karyotype. All the karyotypes that reported inv (9) (p12; q12) were recovered. According to 4755 reports of amniocentesis, a total of 4 cases of inv (9) pericentric (p12; q12) were identified. Based on the literature, this type of rearrangement has been associated with some metabolic diseases. This finding is supported by the fact that this chromosomal region contains the insulin promoter factor-1 and the initiating factor for alpha kinase 3 of the eukaryotic translation initiation factor, both involved in transient diabetes. There is not enough literature on this type of inversion, and more and more studies are needed to perform an adequate correlation analysis. The findings of this brief series and the literature review support the importance of the first karyotype studies to identify possible associations.

A inversão do cromossomo 9, inv (9), é um rearranjo cromossômico relativamente comum e é geralmente considerada como uma variante normal. No entanto, vários estudos sugeriram uma possível associação com a síndrome metabólica, obesidade, galactosemia, diabetes mellitus e aborto espontâneo recorrente. Este estudo tem como objetivo descrever quatro casos com a mesma inversão cromossômica 9, inv (9) (p12q12), e compará-lo com o exposto na literatura. Uma série de casos retrospectivos foi feita. Avaliara-se uma grande base de dados de relatórios de amniocentese realizada no centro Policlínica Metropolitana de Caracas entre 2005 e 2016. Como parte do protocolo do centro, todas as amostras de líquido amniótico recuperadas foram centrifugadas a 800 rpm. Finalmente, uma análise de 20 bandas G foi realizada para o cariótipo. Todos os cariótipos com inv (9) (p12q12) foram recuperados. Dos 4.755 relatos de amniocentese, foram identificados 4 casos de inv (9) pericêntricos (p12q12). Segundo a literatura, esse tipo de rearranjo tem sido associado a algumas doenças metabólicas. Esta conclusão é apoiada pelo facto de que esta região cromossómica contém o fator promotor de insulina 1 e o fator iniciador para a 3-quinase alfa do fator de início de tradução de euca-riotos, ambos envolvidos na diabetes transitória. Há escassa literatura sobre este tipo de inversão, e mais estudos são necessários para uma análise de correlação adequada. Os resultados desta breve série e os resultados encontrados na literatura corroboram a importância dos primeiros estudos de cariótipos para identificar possíveis associações.

Impacto do diagnóstico pré-natal (DPN) citogenético e ansiedade materna sobre a interação precoce mãe-bebê / The impact of cytogenic prenatal diagnosis (PND) and maternal anxiety on early mother-child interaction / Impacto del diagnóstico prenatal (DPN) citogenético y ansiedad maternal sobre la interacción precoz madre-bebé

O presente estudo de natureza longitudinal teve como objetivo estudar a influência que o diagnóstico pré-natal citogenético pode exercer sobre a ansiedade materna, a adaptação à gravidez e a relação precoce mãe-bebê, particularmente em grávidas de idade materna avançada. A amostra incidiu sobre 3 grupos de gestantes: G1 selecionadas para amniocentese (≥35 anos); G2 selecionadas para amniocentese por rastreio (<35 anos); G3 gestantes (20-34 anos) não selecionadas, e decorreu entre Março de 2008 e Maio de 2009. Os resultados revelaram que a expectativa de realização do exame citogenético conduz a um aumento da ansiedade-estado mais significativo entre as mulheres propostas para teste após rastreio positivo; a ansiedade-estado evidenciada pelas mães é mediadora da relação entre a interação mãe-bebê e os sentimentos face à gravidez. Estes resultados permitem fundamentar recomendações no sentido de efetuar uma intervenção profilática entre as mães que, durante a gravidez, reagiram com maior ansiedade ao exame.

The objective of this longitudinal study was to study the influence of cytogenic prenatal diagnosis on maternal anxiety, her adaptation to pregnancy and on early mother-child relation, particularly in pregnant women at a mature age. The sample was formed by three groups of pregnant women: G1selected for amniocentesis (≥35 years old); G2 selected for amniocentesis through screening (<35 years old); G3 pregnant women not selected (20-34 years old). The study was performed between March of 2008 and May of 2009. The results revealed that the expectation to take the cytogenic test increases anxiety-state more significantly among women referred to tests after a positive screening; the anxiety-state evidenced by mothers is a mediator of the mother-child interaction and feelings towards the pregnancy. These results permit to found recommendations in the sense of making a prophylactic intervention among mothers who, during pregnancy, reacted to the test with greater anxiety.

Este estudio longitudinal objetivó identificar la influencia del diagnóstico prenatal citogenético en la ansiedad maternal, la adaptación al embarazo y la relación precoz madre-bebé, particularmente en embarazadas de edad materna avanzada. La muestra incidió sobre tres grupos de gestantes: G1 seleccionadas para amniocentesis criterios etarios (≥35 años); G2 seleccionadas para amniocentesis por rastreo (<35 años); G3 gestantes (20-34 años) no seleccionadas, y transcurrió entre marzo 2008 y mayo 2009. Los resultados expresaron que la expectativa de realización del examen citogenético lleva a un aumento de la ansiedad-estado, más significativo entre las mujeres propuestas para el test luego de rastreo positivo; la ansiedad-estado expresada por las madres es mediadora de la relación entre la interacción madre-bebé y los sentimientos frente al embarazo. Estos resultados permiten fundamental recomendaciones en el sentido de efectuar una intervención profiláctica entre las madres que, durante el embarazo, reaccionaron con mayor ansiedad al examen.

Diagnóstico pré-natal das genodermatoses / Prenatal diagnosis of genodermatoses

O diagnóstico pré-natal está indicado para algumas genodermatoses graves, como a epidermólise bolhosa distrófica recessiva e a epidermólise bolhosa juncional. A biópsia de pele fetal foi introduzida em 1980, mas não pode ser realizada antes da 15a semana de gestação. A análise do DNA fetal é método preciso e pode ser realizado mais precocemente na gestação. No entanto, deve-se conhecer a base molecular da genodermatose, e é essencial determinar a mutação e/ou marcadores informativos nas famílias com criança previamente afetada. O DNA fetal pode ser obtido pela biópsia da vilosidade coriônica ou amniocentese. O diagnóstico genético pré-implantação tem surgido como alternativa que dispensa a interrupção da gestação. Essa técnica, que envolve fertilização in vitro e teste genético do embrião. vem sendo realizada para genodermatoses em poucos centros de referência. A ultra-sonografia é exame não invasivo, mas tem uso limitado no diagnóstico pré-natal de genodermatoses. A ultrasonografia tridimensional geralmente estabelece o diagnóstico tardiamente na gestação, e há apenas relatos anedóticos de diagnóstico pré-natal de genodermatoses usando esse método.

Prenatal diagnostic testing is indicated for some severe genodermatoses, such as recessive dystrophic epidermolysis bullosa and junctional epidermolysis bullosa. Fetal skin biopsy was introduced in 1980, but it cannot be performed before 15th gestational week. Fetal DNA analysis is a precise method and can be performed earlier in pregnancy. However, the molecular basis of the genodermatoses must be known and it is essential to determine the gene mutations and/or informative markers in the families with a previously affected child. Fetal DNA can be obtained by chorionic villus sampling or amniocentesis. Preimplantation genetic diagnosis is an alternative approach obviating the need for termination of pregnancy. It involves in vitro fertilization and genetic testing of embryos. However, this technique has been performed for genodermatoses in only a few reference centers. Ultrasonography is a non-invasive test, but has a limited use in prenatal diagnosis of genodermatoses. Tridimensional ultrasonography usually establishes diagnosis late in pregnancy and there are only anecdotal reports of prenatal diagnosis of genodermatoses using this method.