Clinical analysis of monochorionic-diamniotic twins with genetic discordance / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of 5 cases of monochorionic-diamniotic (MCDA) with genetic discordance.@*METHODS@#148 cases of MCDA twins who were diagnosed by amniocentesis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 2016 to June 2020 were selected as the study subjects. Relevant clinical data of the pregnant women were collected, and amniotic fluid samples of the twins were collected separately. Chromosomal karyotyping analysis and single nucleotide polymorphism array (SNP array) assay were carried out.@*RESULTS@#The results of chromosomal karyotyping analysis showed that 5 of the MCDA twins had inconsistent chromosome karyotypes, with an incidence of 3.4% (5/148). SNP array assay showed that 3 fetuses were mosaics.@*CONCLUSION@#Genetic discordance occurs among MCDA twins, and prenatal counseling for such cases should be given by doctors with experience in medical genetics and fetal medicine, and personalized clinical management should be recommended.

Genetic analysis of a fetus with mosaic trisomy 12 and severe heart defects and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with severe heart defect and mosaic trisomy 12, and the correlation between chromosomal abnormalities and clinical manifestations and pregnancy outcome.@*METHODS@#A 33-year-old pregnant woman who presented at Lianyungang Maternal and Child Health Care Hospital on May 17, 2021 due to abnormal fetal heart development revealed by ultrasonography was selected as the study subject. Clinical data of the fetus were collected. Amniotic fluid sample of the pregnant women was collected and subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). The CNKI, WanFang and PubMed databases were searched with key words, with the retrieval period set as from June 1, 1992 to June 1, 2022.@*RESULTS@#For the 33-year-old pregnant woman, ultrasonography at 22+6 gestational weeks had revealed abnormal fetal heart development and ectopic pulmonary vein drainage. G-banded karyotyping showed that the fetus has a karyotype of mos 47,XX,+12[1]/46,XX[73], with the mosaicism rate being 1.35%. CMA results suggested that about 18% of fetal chromosome 12 was trisomic. A newborn was delivered at 39 weeks of gestation. Follow-up confirmed severe congenital heart disease, small head circumference, low-set ears and auricular deformity. The infant had died 3 months later. The database search has retrieved 9 reports. Literature review suggested that the liveborn infants with mosaic trisomy 12 had diverse clinical manifestations depending on the affected organs, which had included congenital heart disease and/or other organs and facial dysmorphisms, resulting in adverse pregnancy outcomes.@*CONCLUSION@#Trisomy 12 mosaicism is an important factor for severe heart defects. The results of ultrasound examination have important value for evaluating the prognosis of the affected fetuses.

Genetic analysis of a fetus with mosaicism of 13q inversion duplication / 中华医学遗传学杂志

OBJECTIVE@#To report on a case of mosaicism 13q inversion duplication, analyze its mechanism, and discuss the correlation between its genotype and phenotype.@*METHODS@#Amniotic fluid and umbilical cord blood were collected at 23 and 32 weeks of gestation, respectively. Combined with G-banding chromosome karyotyping analysis, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) were used to confirm the result.@*RESULTS@#The karyotype of the fetus was determined as 47,XY,+inv dup(13)(q14.3q34)/46,XY. After careful counseling, the couple decided to continue with the pregnancy, and had given birth to a boy at 40 weeks' gestation. Except for a red plaque (hemangioma) on the nose bridge, no obvious abnormality (intelligence to be evaluated) was discovered.@*CONCLUSION@#To provide reference for clinical genetic counseling and risk assessment, the location and proportion of new centromere formation should be fully considered in the case of mosaicism 13q inversion duplication.

Preterm premature rupture of membranes: management between 28 and 34 weeks of pregnancy / Ruptura prematura de membranas pré-termo: conduta entre 28 e 34 semanas de gestação

INTRODUCTION: Premature rupture of membranes remains a challenge for professionals due to the high rates of maternal and neonatal morbidity and mortality, mainly related to complications resulting from prematurity. OBJECTIVE: To analyze the scientific production about premature rupture of membranes in pregnancies above 28 weeks and below 34 weeks. METHODS: Integrative literature review carried out in the Lilacs, SciELO, Medline and Cochrane Library databases, between 2014 and 2018, in Portuguese, English and Spanish, including original articles, available in full online, with free access, that addressed the study theme, using the keywords "premature rupture of ovular membranes", "premature labor" and "pregnancy complications" combined using the Boolean operators "AND" and "OR". RESULTS: Fourteen studies were included. It was possible to highlight the main recommendations regarding preterm premature rupture of membranes, divided into six categories for discussion, namely: indications for expectant management and delivery induction, prophylactic antibiotic therapy, prenatal corticosteroids, use of tocolytics, recommendations regarding the use of magnesium sulfate and amniocentesis. CONCLUSION: It was identified that expectant management is the ideal approach, with constant monitoring of the pregnant woman and the fetus, in addition to the administration of prophylactic antibiotics and prenatal corticosteroids, in the face of premature rupture of membranes in pregnancies between 28 and 34 weeks in order to provide the best maternal and perinatal results, guiding health professionals to evidence-based practice.

INTRODUÇÃO: A ruptura prematura de membranas continua a ser um desafio para os profissionais devido às altas taxas de morbimortalidade materna e neonatal, relacionada principalmente às complicações decorrentes da prematuridade. OBJETIVO: Analisar a produção científica acerca das evidências frente a ruptura prematura de membranas em gestações acima de 28 semanas e abaixo de 34 semanas. MÉTODOS: Revisão integrativa da literatura realizada nas bases de dados Lilacs, SciELO, Medline e Cochrane Library, entre 2014-2018, em português, inglês e espanhol, incluídos artigos originais, disponíveis completos online, com acesso livre, que abordassem a temática do estudo, utilizando os descritores "ruptura prematura de membranas ovulares", "trabalho de parto prematuro" e "complicações na gravidez" combinados por meio dos operadores booleanos "AND" e "OR". RESULTADOS: Foram incluídos 14 estudos, nos quais foi possível evidenciar as principais recomendações frente a ruptura prematura de membranas fetais pré-termo, divididos em seis categorias para discussão, sendo elas: indicações para o manejo expectante e indução do parto, antibioticoterapia profilática, corticosteroides pré-natais, uso de tocolíticos, recomendações quanto ao uso de sulfato de magnésio e realização de amniocentese. CONCLUSÃO: O estudo possibilitou identificar que o manejo expectante é a conduta ideal, com monitorização constante da gestante e do feto, além da administração de antibióticos profiláticos e corticosteroides pré-natais, frente a ruptura prematura de membranas em gestações entre 28 e 34 semanas a fim de proporcionar os melhores resultados maternos e perinatais, guiando os profissionais da saúde para uma prática baseada em evidências.

Non-invasive prenatal detection of ocutaneous albinism type I based on cfDNA barcode-enabled single-molecule test / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing based on cfDNA barcode-enabled single-molecule test (cfBEST) for the prenatal diagnosis of oculocutaneous albinism type I in a family.@*METHODS@#Prenatal genetic diagnosis was carried out by using the cfBEST-based method as well as invasive prenatal diagnosis through amniocentesis. The outcome of the pregnancy was followed up.@*RESULTS@#Non-invasive prenatal testing based on cfBEST showed a fetal DNA concentration of 6.6%, with the proportion of c.929_930insC (p.Arg311Lysfs*7) and c.1037-7T>A mutations being 45.7% and 0%, respectively. The posterior frequency of the negative results was 1, suggesting that the fetus carried neither of the two mutations. The result was consistent with that of invasive prenatal diagnosis, and the follow-up found that the fetus was normal.@*CONCLUSION@#Non-invasive prenatal testing based on cfBEST can be used to detect maternal and fetal genotypes in maternal cell-free DNA, which is clinically feasible.

Prenatal cytogenetic and molecular genetic analysis of a fetus with confined placenta mosaicism for trisomy 16 / 中华医学遗传学杂志

OBJECTIVE@#To review the clinical data of a fetus with false positive result of non-invasive prenatal testing (NIPT) due to confined placental mosaicism (CPM).@*METHODS@#Amniotic fluid sample was taken from a pregnant women with high risk for chromosome 16 aneuploidy for karyotyping analysis, single nucleotide polymorphism array (SNP array) and interphase fluorescence in situ hybridization (FISH). Genetic testing was also conducted on the fetal and maternal surface of the placenta, root of umbilical cord and fetal skin tissue after induced abortion.@*RESULTS@#Cytogenetic analysis of the amniotic fluid sample yielded a normal karyotype. SNP array revealed mosaicism (20%) of trisomy 16 in the fetus. FISH confirmed the presence of mosaicism (25%) for trisomy 16. After induced labor, all sampled sites of placenta were confirmed to contain trisomy 16 by SNP array, while the analysis of fetal skin tissue yielded a negative result.@*CONCLUSION@#CPM is an important factor for false positive NIPT result. Prenatal identification of CPM and strengthened pregnancy management are important to reduce adverse pregnancy outcomes.

Trisomía 9, trisomía 13 y trisomía 18: resultados del análisis citogenético prenatal, Hospital Clínico Universidad de Chile, años 2000-2017 / Trisomy 9, trisomy 13 and trisomy 18: results of the prenatal cytogenical analysis, Hospital Clínico Universidad de Chile, years 2000-2017

INTRODUCCIÓN: En Chile, la norma técnica de la Ley N° 21.030 de 2017 considera tres aneuploidías como letales; las trisomías 9, 13 y 18, cuyo diagnóstico se confirma con un cariograma. No existe a la fecha registro nacional de frecuencia prenatal de estas patologías. OBJETIVO: Determinar la frecuencia de trisomías 9, 13 y 18 en los estudios citogenéticos prenatales en muestras de células obtenidas con amniocentesis y cordocentesis, procesados en el Laboratorio de Citogenética del Hospital Clínico Universidad de Chile. MATERIALES Y MÉTODOS: Estudio descriptivo y retrospectivo de los resultados de cariograma de líquido amniótico (LA) y sangre fetal (SF), procesados desde enero de 2000 a diciembre de 2017. RESULTADOS: Se incluyeron 2.305 muestras (402 de SF y 1.903 de LA), de ellas 442 (19%) fueron trisomías letales (TL), dentro de ellas fueron TL libres 416 (95%), TL estructurales 15 (2,7%) y mosaicos 11 (2,3%). La trisomía 18 fue en ambos tipos de muestra la más frecuente (73,5%), seguida de trisomía 13 (24,2%) y trisomía 9 (2,3%). Se desglosan resultados conforme al tipo de TL, muestra, motivo de derivación, edad materna y edad gestacional. CONCLUSIONES: El cariograma confirma el diagnóstico de aneuploidías y aporta datos relevantes para el consejo genético. La cromosomopatía letal más frecuente fue la trisomía 18. Se observó que uno de cada cinco cariogramas referidos por anomalías congénitas y/o marcadores de aneuploidía revelaban una TL.

INTRODUCTION: In Chile, the technical standard of Law No. 21,030 of 2017 considers three aneuploidies as lethal; trisomies 9, 13 and 18, whose diagnosis is confirmed with a Karyotype. To date there is not a national registry of prenatal frequency of these pathologies. OBJECTIVE: To determine the frequency of trisomies 9, 13 and 18 in prenatal cytogenetic studies in samples of cells obtained with amniocentesis and cordocentesis, processed in the Cytogenetics Laboratory of the Universidad de Chile Clinical Hospital. MATERIALS AND METHODS: Descriptive and retrospective study of the results of karyotypes of amniotic fluid (LA) and fetal blood (SF) processed from January 2000 to December 2017. Results: 2,305 samples (402 of SF and 1,903 of LA) were included, of which 438 (19%) were lethal trisomies (TL), corresponding to free TL 416 (95%), structural TL 12 (2,7%) and mosaics 10 (2.3%). Trisomy 18 was the most frequent in both types of sample (73,5 %), followed by trisomy 13 (24,2%) and trisomy 9 (2.3%). RESULTS are shown according to the type of TL, sample, reason for referral, maternal age and gestational age. CONCLUSIONS: The karyotype confirms the diagnosis of aneuploidies and provides relevant data for genetic counseling. The most frequent lethal chromosomopathy was trisomy 18. It was observed that one in five karyotypes referred for congenital anomalies and / or aneuploidy markers revealed a TL.

Hemorragia intracraniana en un feto con trisomia 21 y rabdomiomas cardiacos: diagnostico diferencial de esclerosis tuberosa: estudio antenatal a propósito de un caso / Intracranian hemorrhage in a fetus with trisomy 21 and cardiac rhabdomyomas: differential diagnosis of tuberous sclerosis: antenatal study regarding a case

INTRODUCCIÓN: El Síndrome de Down (SD) es una de las aneuploidías más frecuentes. En Chile, la incidencia es de 2.2 por 1000 nv. La esclerosis tuberosa (ET) es una enfermedad genética autosómica dominante con una prevalencia de 1:600 a 1:10.000 nacidos vivos (nv) que se sospecha prenatalmente por la presencia de rabdomiomas cardiacos. Los tumores cardiacos fetales tienen una prevalencia de 1:10000 nv, los más prevalentes son los Rabdomiomas. El hallazgo de tumores intracraneanos son infrecuentes, dentro del diagnóstico diferencial es necesario descartar la Hemorragia Intraventricular (HIV). CASO CLÍNICO: Paciente de 29 años, M2, Derivada a nuestro centro a las 27+4 semanas para evaluación ecográfica. Entre los hallazgos se encuentran tumores intracardiacos en ventrículo derecho y marcadores blandos para alto riesgo de aneuploidía, por lo que se realiza cariotipo (amniocentesis genética: 47, XX+21). A las 32+0 semanas en una nueva evaluación presenta imagen hiperecogénica sugerente de tumor intracerebral. Se solicita resonancia magnética fetal que informa hemorragia intraventricular (HIV). El parto ocurre con un recién nacido de término, fenotipo concordante con Trisomía 21, ecocardiograma confirma dos tumores intracardiacos (Rabdomiomas) y ecografía cerebral confirma el diagnóstico de HIV Grado III derecho. Ante el diagnóstico diferencial de ET, se realiza ANGIO-TAC que resulta negativo para ET. DISCUSIÓN: En la evaluación ecográfica antenatal, la presencia de tumores intracardiacos asociados a tumor cerebral hace plantear el diagnóstico de una ET. El diagnóstico antenatal de tumores cerebrales vs HIV por ultrasonido es difícil. La resonancia es un examen complementario de gran ayuda, permitiendo un diagnóstico de certeza. La HIV fetal es un diagnóstico poco frecuente de diagnostico prenatal asociado a feto con trisomia 21.

INTRODUCTION: Down Syndrome (DS) is one of the most frequent aneuploidies. In our country its incidence is 2.2 every 1000 newborns. Tuberous sclerosis (TS) is a dominant autosomal genetic disease with a prevalence of 1:6000 to 1:10.000 newborns, this disease is suspected by the finding of cardiac rhabdomyomas. Rhabdomyomas are the most prevalent fetal heart tumors. Intracranial tumors are a rare prenatal finding in ultrasound the main differential diagnosis is Intraventricular Hemorrhage (IVH). The Objective of this paper is present a case report of a fetus with trisomy 21 plus rhabdomyomas and cranial tumors. CASE REPORT: 29 years old patient, referred for ultrasound at 27+4 week. Cardiac tumors and aneuploidy soft markers are found. Genetic amniocentesis is performed (Result: 47, XX+21). At 32+0 weeks ultrasound finding of intracranial tumor. Fetal MRI was performed which reports suspected IVH. Confirmed postnatally. Baby was delivered at term. Neonatal findings: Trisomy 21 phenotype, Echocardiogram with two cardiac tumors (Rhabdomyomas), neonatal brain ultrasound confirms Grade III - IVH. To rule out TS, an Angio-CT is performed which is negative for the disease. DISCUSSION: Cardiac Tumors associated to brain tumors in antenatal period make TS a possible diagnosis. Differentiate brain tumors and IVH by ultrasound is very difficult. MRI is a very helpful tool for an accurate diagnostic. IVH is a rare antenatal diagnosis. Not reported before in a baby with trisomy 21.

Detección de un mosaico de trisomía 21 en líquido amniótico / Detection of a mosaicism of trisomy 21 in amniotic liquid

Resumen Se analizó un resultado con alteración cromosómica tomado de una base de datos conformada por un total de 4755 muestras de líquido amniótico extraídos mediante amniocentesis con indicación de su médico tratante, riesgo sérico y edad materna avanzada. En este reporte se presenta la detección de un mosaico de trisomía 21 en líquido amniótico, mediante la técnica de Banda G donde se analizaron 20 metafases. Los resultados obtenidos documentan una composición cromosómica 47, XY+21 y 46, XY con una relación 9:11 respecto a las metafases analizadas, confirmándose así el diagnóstico del Síndrome de Down secundario a mosaico.

Abstract A result with chromosomal alteration was analyzed from a database consisting of a total of 4755 samples of amniotic fluid extracted by amniocentesis with indication of the attending physician, serum risk and advanced maternal age. This report presents the detection of a mosaicism of trisomy 21 in amniotic fluid, using G- Banding where 20 metaphases were analyzed. The results obtained document a chromosomal composition 47, XY + 21 and 46, XY with a 9:11 ratio with respect to the metaphases analyzed, confirming the diagnosis of Down syndrome secondary to mosaicism.

Hipoplasia de timo con trisomía del cromosoma10 / Thymus hypoplasia with chromosome 10 trisomy

INTRODUCCIÓN: La hipoplasia de timo es una entidad que puede asociarse a múltiples patologías fetales de ahí la importancia de su diagnóstico y su manejo. OBJETIVO: Utilidad y métodos de evaluación del timo en la ecografía morfológica y valor de la interpretación del análisis genético de los microarrays. CASO CLÍNICO: Se presenta el caso clínico de una gestante en la que se detecta una glándula tímica hipoplásica utilizando para su medición el índice timo-torácico en un plano de tres vasos. Ante estos hallazgos se realiza una amniocentesis para análisis genético usando la QF-PCR y un análisis ARRAY-CGH. RESULTADOS: En el análisis de ARRAY-CGH se observa una duplicación patológica en mosaico compatible con una trisomía del cromosoma 10, alteración genética infrecuente de la que se han reportado unos 50 casos en recién nacidos vivos. Esta alteración presenta un rango muy amplio de alteraciones, desde malformaciones graves a niños completamente normales. En los controles posteriores la gestación es normoevolutiva y finaliza en la semana 40 mediante un parto eutócico de inicio espontáneo naciendo un bebé fenotípicamente normal con un timo de menor tamaño del habitual siendo pronto para saber las consecuencias de esta alteración en su inmunidad. CONCLUSIONES: Por un lado, el timo es una estructura fácil de visualizar en la ecografía morfológica de la semana 20 y su medición mediante el índice timo-torácico nos aporta información útil acerca de posibles patologías fetales. Por otro, tener en cuenta que debemos ser muy cautelosos con la interpretación de resultados de pruebas genéticas cuando éstas no tienen un significado clínico claro.

INTRODUCTION : Thymus hypoplasia can associate many different pathologies so is highly important the diagnosis and the management. OBJECTIVE: Utility and methods in the evaluation of the fetal thymus in the morphological ultrasound and interpretation of microarray results. CLINICAL CASE: We present a case of fetal hypoplastic thymus gland in a pregnant woman. We measure it using the thymus-torax index in a three vessel view. A genetical analysis was made using QF-PCR and Array-CGH. RESULTS: In the ARRAY-CGH analysis it is found a pathological mosaicism that match with chromosome 10 trisomy, a very uncommon genetical alteration with only 50 reported cases. This trisomy can traduce from serious malformations to complete normal children. The parents decide to continue with the pregnancy and in week 40 it finishes with an uncomplicated delivery of a healthy child. In the newborn pediatrics remark a thymus gland smaller than expected but it is early to say if it will have or not consequences in its immunity. CONCLUSION: On one hand the thymus is a structure that we can easily display in the morphological ultrasound in the 20 week of pregnancy and its measure, using the thymus-torax index, can be very helpful in the detection of fetal pathologies. On the other hand, is important being careful when we interpret a genetical alteration without a clear clinical significance.

Síndrome de Edwards con cardiopatía congénita de larga supervivencia: reporte de caso y revisión de literatura / Prolonged survival in Edwards syndrome with congenital heart disease: a case report and literature review

El síndrome de Edwards o trisomía 18 es una entidad compleja, con afectaciones en los sistemas musculoesquelético, craneofacial, cardiovascular y neurológico. Su genética es variada, presentándose tanto de manera completa como en mosaicismo. Es infrecuente que la supervivencia supere el primer año de vida. Su caracterización fenotípica no es patognomónica, por lo cual el cariotipo es fundamental para el diagnóstico prenatal por medio de amniocentesis y cordocentesis mediante técnica de hibridación fluorescente in situ. Se presenta el caso de una paciente de ocho años que ha sobrevivido con esta condición, a pesar de presentar tetralogía de Fallot acompañada de malformaciones cardíacas graves. El diagnóstico comenzó por ecografía de tamizaje prenatal a las 16 semanas y ecografía de detalle, con amniocentesis y cariotipo de líquido amniótico, con resultado 47 XX+18. Ha sido tratada por múltiples especialidades médicas, debido a complicaciones osteomusculares, articulares, neurológicas, metabólicas y cardiovasculares que han limitado su calidad de vida. El manejo de estos pacientes requiere un equipo médico multidisciplinario. La consejería a los padres debe incluir aspectos relativos a la sobrevida, complicaciones frecuentes y riesgo-beneficio a evaluar antes de someter al menor a intervenciones quirúrgicas complejas o correctivas.

Edwards syndrome or trisomy 18 is a complex entity that involves the musculoskeletal, craniofacial, cardiovascular, and neurological systems. Its genetics are varied, presenting both in a complete and mosaic type. Survival rarely exceeds the first year of life. Its phenotype characterization is not pathognomonic, so karyotype is essential for diagnosis, prenatally by amniocentesis and cordocentesis by FISH technique. We present the case of an eight-year-old girl who has survived with this condition despite presenting tetralogy of Fallot and serious cardiac malformations. Diagnosis began with prenatal screening ultrasound at 16 weeks and detailed ultrasound, with amniocentesis and amniotic fluid karyotype, with a result of 47 XX+18. She has been treated by multiple medical specialties, due to musculoskeletal, joint, neurological, metabolic, and cardiovascular complications that have limited her quality of life. The management of these patients requires a multidisciplinary medical team, and counseling for parents should include aspects related to survival, frequent complications, and risk-benefit to be evaluated before subjecting the minor to complex or corrective surgical interventions.

The Identification of Immune-Related Plasma Proteins Associated with Spontaneous Preterm Delivery and Intra-Amniotic Infection in Women with Premature Cervical Dilation or an Asymptomatic Short Cervix

BACKGROUND: We aimed to investigate whether various immune-related plasma proteins, alone or in combination with conventional clinical risk factors, can predict spontaneous preterm delivery (SPTD) and intra-amniotic infection in women with premature cervical dilation or a short cervix (≤ 25 mm).METHODS: This retrospective study included 80 asymptomatic women with premature cervical dilation (n = 50) or a short cervix (n = 30), who underwent amniocentesis at 17–29 weeks. Amniotic fluid (AF) was cultured, and maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and complements C3a and C5a, using enzyme-linked immunosorbent assay (ELISA) kits. The primary outcome measures were SPTD at < 32 weeks and positive AF cultures.RESULTS: The plasma levels of IL-6, C3a, and C5a, but not of MMP-9 and TIMP-1, were significantly higher in women with SPTD at < 32 weeks than in those who delivered at ≥ 32 weeks. The women who delivered at < 32 weeks had more advanced cervical dilatation, and higher rates of antibiotic and tocolytic administration and were less likely to be given vaginal progesterone than those who delivered at ≥ 32 weeks. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma IL-6 and C3a levels, and cervical dilatation (area under the curve [AUC], 0.901). The AUC for this model was significantly greater than that for any single variable included in the predictive model. In the univariate analysis, plasma IL-6 level was the only significant predictor of intra-amniotic infection.CONCLUSION: In women with premature cervical dilation or a short cervix, maternal plasma IL-6, C3a, and C5a levels could be useful non-invasive predictors of SPTD at < 32 weeks. A combination of these biomarkers and conventional clinical factors may clearly improve the predictability for SPTD, as compared with the biomarkers alone. An increased plasma level of IL-6 predicted intra-amniotic infection.

Resultados después de la implementación del test de DNA fetal libre circulante en sangre materna (DNA-lc) para cribado de cromosomopatías fetales / Results after the implementation of the cell-free fetal DNA test in maternal plasma (cfDNA) in screening for fetal aneuploidies

Objetivo: Evaluar la disminución de la tasa de técnicas invasivas de diagnóstico prenatal tras la introducción del cribado contingente de cromosomopatías con test de DNA fetal libre circulante (DNA-lc)y demostrar que este método de cribado es coste-efectivo. Método: estudio observacional prospectivo y estudio de coste efectividad. Primero se describen los resultados del cribado combinado en dos tiempos de primer trimestre desde febrero de 2008 a junio 2018 diez primeros años del hospital): 21744 cribados realizados de un total de 23000 partos. En abril de 2016 se implementa un modelo de cribado contingente de cromosomopatías con test de DNAlc (se oferta el test a pacientes con resultado de riesgo intermedio en el cribado combinado). En segundo lugar se analizan los resultados tras la implementación del test y se comparan dos períodos de tiempo con y sin cribado contingente (año 2015 con el período abril 2016 hasta marzo de 2019). Resulta-dos: disminución total de las técnicas invasivas del 54% por disminución de la tasa de amniocentesis, manteniéndose constante la tasa de biopsias coriales. La tasa de pérdidas fetales por técnica invasiva alcanza el 0%. Usamos seis indicadores de calidad para evaluar el test. Se hanahorrado 70200 euros con la implementación del test de DNA-lc. Discusión: el test de DNAlc resulta útil en el cribado contingente de cromosomopatías porque reduce la tasa de amniocentesis por indicación de alto riesgo y además es coste efectivo. El cribado combinado de primer trimestre es la técnica de elección para el cribado de aneuploidias. El test de DNAlc no puede sustituir al cribado combinado porque es caro, pero resulta muy útil si se realiza cribado contingente a la población seleccionada de riesgo intermedio.

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)

Salud respiratoria y del sueño infantil tras una amniocentesis en el segundo trimestre / Child's respiratory and sleep health following mid-trimester amniocentesis

Objetivo. Investigar las tasas de trastornos respiratorios y del sueño en los niños cuyas madres se sometieron a una amniocentesis. Materiales y métodos. Se incluyó a niños cuyas madres se sometieron a una amniocentesis en el segundo trimestre (entre las 16 y las 20 semanas) y otros sin procedimiento invasivo (controles). Resultados. Se anallizó a 50 niños en el grupo de amniocentesis y a 47 controles. Hubo mayor incidencia de trastornos del sueño en el grupo de amniocentesis: 30 casos (60 %) frente a 11 controles (23,4 %) (p = 0,001). En el grupo de amniocentesis, 7 niños (14%) tenían asma; en el grupo de referencia, 1 niño (2,1 %) (p = 0,032).Conclusión. Podría haber una asociación entre la amniocentesis en el segundo trimestre, el asma y los trastornos del sueño en los niños. Se requieren estudios futuros y analizar los efectos a largo plazo de las pruebas invasivas.

Objective. The aim was to investigate the rates of respiratory and sleep disturbances in infants whose mothers experienced amniocentesis.Material and methods. Infants whose mothers have undergone midterm amniocentesis (between 16 and 20 weeks) and no invasive procedure (controls) were enrolled.Results. The study analyzed 50 infants whose mothers have undergone amniocentesis (amniocentesis group) and 47 controls. Amniocentesis group had higher incidence of sleep disturbances: 30 cases (60 %), compared with 11 controls (23.4 %) (P = 0.001). In the amniocentesis group there were 7 children (14 %) with asthma, while in the control group, asthma was confirmed in 1 child (2.1 %) (P = 0.032).Conclusion. Our data triggers the hypothesis that associations between midterm amniocentesis, child's asthma and sleep isturbances may exist. These preliminary results reveal the importance of further studies and the need for the analysis of long term effects of invasive testing.

Amniocentesis para estudio citogenético y sus principales indicaciones en La Habana, Cuba (2007 - 2016) / Amniocentesis for Cytogenetic Study and Its Main Indications in Havana, Cuba (2007 - 2016)

RESUMEN Introducción: El diagnóstico prenatal de alteraciones cromosómicas en Cuba se inició en La Habana en 1984, mediante análisis del líquido amniótico obtenido por amniocentesis en el segundo trimestre del embarazo. En 1987 se introdujo el diagnóstico por análisis de vellosidades coriónicas en el primer trimestre, como parte de un subprograma dentro del Programa Nacional de Diagnóstico y Prevención de Enfermedades Genéticas dirigido por el Centro Nacional de Genética Médica. Objetivo: Demostrar que la edad materna avanzada sigue siendo la principal indicación de estudio citogenético en las gestantes de alto riesgo en la provincia de La Habana. Métodos: Se realizó un estudio descriptivo, retrospectivo y de corte longitudinal que abarcó 12 909 historias clínicas de gestantes a las que se realizaron amniocentesis, indicadas en la consulta del Centro Provincial de Genética Médica de la Habana, en el período comprendido entre enero 2007 y diciembre 2016. Se analizaron diferentes parámetros relacionados con la cantidad de casos por años según diferentes criterios y se calculó la sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo de la edad materna como predictor de la ocurrencia de anomalías cromosómicas. Resultados: El principal criterio de indicación del estudio invasivo lo constituyó la edad materna avanzada con 82 por ciento de los casos, mostrando una sensibilidad de 86 por ciento y una tasa de falsos positivos que alcanzó el 95,85 por ciento. Sería de utilidad actualizar el subprograma de diagnóstico prenatal mediante herramientas que permitan recalcular el riesgo a priori, a un riesgo individualizado y reclasificar la población de alto riesgo genético. Conclusiones: A partir del estudio realizado se puede concluir que la avanzada edad materna constituye el principal criterio de indicación para estudio citogenético por amniocentesis en las gestantes de alto riesgo de La Habana(AU)

ABSTRACT Introduction: The prenatal diagnosis of chromosomal abnormalities in Cuba began in Havana in 1984, by analyzing the amniotic fluid by amniocentesis in the second trimester of pregnancy. In 1987, diagnosis by chorionic villus analysis was introduced in the first trimester, as part of a subprogram within the National Program for the Diagnosis and Prevention of Genetic Diseases led by the National Center for Medical Genetics. Objective: To validate that advanced maternal age continues to be the main feature to propose a cytogenetic study in high-risk pregnant women in the province of Havana. Methods: A descriptive, retrospective, longitudinal-section study was conducted in 12,909 medical records of pregnant women who underwent amniocentesis, proposed in the consultation of Havana Provincial Center for Medical Genetics, from January 2007 to December 2016. Different parameters related to the number of cases per year were analyzed according to different criteria and sensitivity, specificity, positive predictive value and negative predictive value of maternal age were calculated as a predictor of the occurrence of chromosomal abnormalities. Results: The main criterion for indicating this invasive study was the advanced maternal age in 82 percent of cases, showing 86 percent of sensitivity and 95.85 percent false positive rate. It would be useful to update the prenatal diagnosis subprogram using tools that allow the risk to be recalculated a priori to an individualized risk and to reclassify the population in high genetic risk. Conclusions: From this study it can be concluded that advanced maternal age constitutes the main criterion for indicating amniocentesis cytogenetic study in high-risk pregnant women in Havana(AU)

Follow-up of toxoplasmosis during pregnancy: ten-year experience in a University hospital in southern Brazil / Acompanhamento da toxoplasmose durante a gravidez: uma década de experiência em um hospital universitário no Sul do Brasil

Abstract Objective To describe a population of pregnant women diagnosed with toxoplasmosis and their respective newborns, describing the hospital protocol for treatment and follow-up. Methods Retrospective cohort of pregnant women with acute toxoplasmosis infection and risk of transplacental transmission who were sent to the Fetal Medicine Group of Hospital de Clínicas de Porto Alegre (HCPA) between - January 1, 2006 and December 31, 2016. All patients with confirmed disease were included. The diagnostic protocol and treatment were applied; a polymerase chain reaction (PCR) analysis of the amniotic fluid was used to diagnose toxoplasmosis and determine the treatment. The newborns were followed up at the pediatric outpatient clinic specializing in congenital infection. The patients who were not followed up or were not born in the HCPA were excluded. Results A total of 65 patients were confirmed to have gestational toxoplasmosis; 40 performed amniocentesis, and 6 (15%) were identified as having positive PCR in the amniotic fluid. In five of those cases, this result associated with the gestational age defined the triple therapy during pregnancy, and in one case, it defined the monotherapy (advanced gestational age). A total of 4 of these newborns were treated from birth with triple therapy for 10months, 1 was not treated (due to maternal refusal), and 1 progressed to death within the first 54 hours of life due to complications of congenital toxoplasmosis. Of the 34 remaining cases with a negative PCR, 33 were treated with monotherapy and 1 was treated with triple therapy (ultrasound findings); of these children, 9 (26.5%) presented negative immunoglobulin G (IgG), 24 (70.6%) presented positive IgG (but none presented positive immunoglobulin M [IgM]), and 1 (2,9%) presented alterations compatible with congenital disease and started treatment with the triple therapy soon after birth. Out of the total sample of 60 patients, among the 25 who did not perform amniotic fluid PCR, 5 were treated with triple therapy (ultrasound findings/prior treatment) and 20 patients were submitted to monotherapy; only two newborns underwent treatment for congenital toxoplasmosis. Among the 65 cases of gestational toxoplasmosis, 6 (9,2%) children had a diagnosis of congenital toxoplasmosis, and 2 patients with triple therapy felt severe adverse effects of the medications. Conclusions The present study suggests that research on PCR screening of the amniotic fluid may be useful to identify patients with a higher potential for fetal complications, who may benefit from the poly-antimicrobial treatment. Patients with negative PCR results must continue to prevent fetal infection with monotherapy, without risk of fetal or maternal impairment.

Resumo Objetivo Descrever uma população de pacientes diagnosticadas com toxoplasmose na gestação e seus respectivos recém-nascidos, relatando o protocolo do hospital durante o tratamento e seguimento. Métodos Coorte retrospectiva de gestantes com infecção aguda por toxoplasmose e risco de transmissão transplacentária, encaminhadas para acompanhamento pelo Grupo deMedicina Fetal doHospital de Clínicas de Porto Alegre (HCPA) entre 1o de janeiro de 2006 e 31 de dezembro de 2016. Todas as pacientes comdoença confirmada foram incluídas. O protocolo de diagnóstico e tratamento foi aplicado; uma análise da reação em cadeia da polimerase (RCP) no líquido amniótico foi utilizada para diagnosticar a toxoplasmose e determinar o tratamento. Os recém-nascidos foram acompanhados no ambulatório de pediatria especializadoeminfecções congênitas. Pacientes que não foramseguidas ou cujo parto não foi feito no hospital foram excluídas. Resultados A toxoplasmose gestacional foi confirmada em 65 pacientes; 40 realizaram amniocentese, e 6 (15%) foram identificadas com RCP positiva no líquido amniótico. Este resultado associado à idade gestacional definiu a terapia tríplice durante a gestação em 5 casos, e a monoterapia em 1 caso (por idade gestacional avançada). Quatro destas crianças foram tratadas desde o nascimento com terapia tríplice por 12 meses, 1 não foi tratada (por recusa materna), e 1 evoluiu com óbito dentro das primeiras 54 horas de vida devido a complicações da toxoplasmose congênita. Dos 34 casos remanescentes com RCP negativa, 33 foram tratados com monoterapia, e 1 foi tratado com terapia tríplice (por achados ultrassonográficos); destes recém-nascidos, 9 (26,5%) tiveram imunoglobulina G (IgG) negativa, 24 (70,6%) tiveram IgG positiva, mas nenhum apresentou imunoglobulina M (IgM) positiva, e 1 (2,9%) apresentou alterações compatíveis comdoença congênita e iniciou a terapia tríplice logo após o nascimento. Entre as 25 pacientes que não fizeram RCP no líquido amniótico, 5 foram tratadas com terapia tríplice (por achados ultrassonográficos/ tratamento prévio) e 20 receberam monoterapia; somente 2 recém-nascidos receberam tratamento para toxoplasmose congênita. Entre os 65 casos de toxoplasmose gestacional, 6 (9,2%) recém-nascidos tiveram o diagnóstico de toxoplasmose congênita. Um total de 2 pacientes submetidas à terapia tríplice apresentaram efeitos adversos severos das medicações utilizadas. Conclusão Este estudo sugere que a triagem da RCP para toxoplasmose do líquido amniótico pode ser útil no rastreamento de pacientes com maior potencial para complicações fetais, que podem se beneficiar do tratamento poli antimicrobiano. Pacientes com RCP negativa devem continuar a prevenir a infecção fetal com monoterapia, sem risco de comprometimento fetal ou materno.

Prenatal diagnosis of monochorionic-diamniotic twins discordant for 45,X/46,XX mosaicism / 中华医学遗传学杂志

OBJECTIVE@#To explore the prenatal screening and diagnosis for a pair of monochorionic-diamniotic (MCDA) twins discordant for 45,X/46,XX mosaicism.@*METHODS@#Amniotic fluid samples were taken from both twins for whom non-invasive prenatal testing has signaled a high risk for sex chromosomal abnormality. Uncultured amniotic fluid was analyzed by fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array). Conventional G-banded karyotyping analysis was performed on the cultured amniotic fluid.@*RESULTS@#Metaphase chromosome analysis showed that one of the twins had a mos 45,X[11]/46,XX[26] karyotype, while the other had a normal karyotype. FISH and SNP-array applied on uncultured amniotic fluid revealed about 30% mosaicism in one of the twins. The twins were confirmed to be monozygotic by SNP-array analysis.@*CONCLUSION@#To avoid confusion arising from discordant karyotypes in MCDA twins with abnormal non-invasive prenatal testing (NIPT) results, dual amniocentesis should be carried out to obtain amniotic fluid samples for chromosomal as well as molecular analysis. To determine the ratio of 45,X and 46,XX cells in Turner syndrome can provide valuable information for prenatal genetic counseling.

Exploration of the process of prenatal screening and diagnosis for women with advanced maternal age based on results of 351 cases of fetal chromosomal abnormalities / 中华医学遗传学杂志

OBJECTIVE@#To explore the suitable process for prenatal screening and diagnosis for women with advanced maternal age.@*METHODS@#From January 2014 to November 2017, the indications and distributions of prenatal diagnosis for women with advanced maternal age only or accompanying with positive maternal serum test screening and non-invasive prenatal testing (NIPT), abnormal fetal ultrasound, one harboring chromosomal abnormalities or anomalous reproductive history were analyzed. The rate of fetal chromosomal abnormalities was compared between different groups.@*RESULTS@#The 351 pregnant women with fetal chromosomal abnormalities have included 196 cases with advanced maternal age, 26 with positive maternal serum test, 96 with high-risk by NIPT, 14 with abnormal fetal ultrasound, 15 with one partner harboring chromosomal abnormalities, and 4 with anomalous reproductive history. Assuming that all pregnant women had undergone maternal serum test screening or NIPT without amniocentesis, the detection rate of fetal chromosome abnormality would be 51.0% and 69.2%, respectively. However, should these women have received both tests, the detection rate would be as high as 84.6%. Should those with one partner harboring chromosomal abnormalities undergone maternal serum test screening or NIPT without amniocentesis, the detection rate of fetal chromosomal abnormality would only be 6.7%.@*CONCLUSION@#Should pregnant women with advanced maternal age undergo both maternal serum test and NIPT, the detection rate of fetal chromosomal abnormality will be higher than those receiving only maternal serum test screening or NIPT. Couples with one partner harboring chromosomal abnormalities should undergo prenatal diagnosis by amniocentesis.