RESUMO
Objetivo: Determinar el grupo RhD fetal a través del estudio del gen RHD en ADN fetal que se encuentra libre en plasma de embarazadas RhD negativo. Método: Se analizó la presencia de los genes RHD, SRY y BGLO en ADNfl obtenido de plasma de 51 embarazadas RhD negativo no sensibilizadas, utilizando una qPCR. Los resultados del estudio genético del gen RHD se compararon con el estudio del grupo sanguíneo RhD realizado por método serológico en muestras de sangre de cordón, y los resultados del estudio del gen SRY fueron cotejados con el sexo fetal determinado por ecografía. Se calcularon la sensibilidad, la especificidad, los valores predictivos y la capacidad discriminativa del método estandarizado. Resultados: El gen RHD estaba presente en el 72,5% de las muestras y el gen SRY en el 55,5%, coincidiendo en un 100% con los resultados del grupo RhD detectado en sangre de cordón y con el sexo fetal confirmado por ecografía, respectivamente. Conclusiones: Fue posible deducir el grupo sanguíneo RhD del feto mediante el estudio del ADN fetal que se encuentra libre en el plasma de embarazadas con un método molecular no invasivo desarrollado y validado para este fin. Este test no invasivo puede ser utilizado para tomar la decisión de administrar inmunoglobulina anti-D solo a embarazadas RhD negativo que portan un feto RhD positivo.
Objective: To determine the fetal RhD group through the study of the RHD gene in fetal DNA found free in plasma of RhD negative pregnant women. Method: The presence of the RHD, SRY and BGLO genes in fetal DNA obtained from plasma of 51 non-sensitized RhD negative pregnant women was analyzed using qPCR. The results of the genetic study of the RHD gene were compared with the RhD blood group study performed by serological method in cord blood samples, and the results of the SRY gene study were compared with the fetal sex determined by ultrasound. Sensitivity, specificity, predictive values and discriminative capacity of the standardized method were calculated. Results: The RHD gene was present in 72.5% of the samples and the SRY gene in 55.5%, coinciding 100% with the results of the RhD group detected in cord blood, and with the fetal sex confirmed by ultrasound, respectively. Conclusions: It was possible to deduce the RhD blood group of the fetus through the study of fetal DNA found free in the plasma of pregnant women with a non-invasive molecular method developed and validated for this purpose. This non-invasive test can be used to make the decision to administer anti-D immunoglobulin only to RhD-negative pregnant women carrying an RhD-positive fetus.
Assuntos
Humanos , Feminino , Gravidez , Sistema do Grupo Sanguíneo Rh-Hr/genética , DNA , Eritroblastose Fetal/diagnóstico , Eritroblastose Fetal/genética , Fenótipo , Diagnóstico Pré-Natal , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Imunoglobulina rho(D) , Genes sry/genética , Eritroblastose Fetal/sangue , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Doenças Fetais/sangue , GenótipoRESUMO
INTRODUCTION: Neonatal hyperthyroidism is a disease that can cause mortality and sequelae. To date, there is no clinical series of cases that allows us to know the local reality of this condition. OBJECTIVE: to charac terize the children of mothers with Graves' disease (GD) from a clinical and biochemical point of view. SUBJECTS AND METHOD: A prospective follow-up of all newborns (NB) of mothers with history of GD was performed in two public hospitals in Santiago, during 5 years. Clinical and laboratory variables of mother-child pairs and thyroid-stimulating hormone receptor antibodies (TRAbs) le vels were analyzed looking for associations between these variables and the development of neonatal hyperthyroidism. RESULTS: Seventy-six mother-child pairs were included (0.2% of all deliveries). Five neonates (6.6%) presented biochemical hyperthyroidism, and 3 of them developed clinical disease and required treatment. All 5 NBs who developed hyperthyroidism had mothers with positive or indeterminate TRAbs. No child of TRAbs-negative mothers developed the disease. TRAbs could be determined in only 65% of the mothers and 72% of the NBs. There was a significant correlation bet ween maternal TRAbs titers (p < 0.03), neonatal TRAbs titers (p < 0.008), and neonatal TSH between days 2-6 (p < 0.006), with the subsequent development of hyperthyroidism. All cases of neonatal hyperthyroidism were transient. There was no mortality in our series. CONCLUSIONS: This is the first national case series of children of mothers with GD. Maternal and neonatal TRAbs and TSH between days 2-6 of life were predictors of neonatal hyperthyroidism.
Assuntos
Doenças Fetais/sangue , Doença de Graves/sangue , Hipertireoidismo/diagnóstico , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/terapia , Tireotoxicose , Biomarcadores/sangue , Filho de Pais com Deficiência , Feminino , Doenças Fetais/etiologia , Doenças Fetais/imunologia , Doença de Graves/complicações , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/congênito , Recém-Nascido , Doenças do Recém-Nascido , Mães , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Estudos Prospectivos , Testes de Função Tireóidea , TireotropinaRESUMO
Dyslipidaemia occurs in pregnancy to secure foetal development. The mother shows a physiological increase in plasma total cholesterol and Triglycerides (TG) as pregnancy progresses (i.e. maternal physiological dyslipidaemia in pregnancy). However, in some women pregnancy-associated dyslipidaemia exceeds this physiological adaptation. The consequences of this condition on the developing fetus include endothelial dysfunction of the foetoplacental vasculature and development of foetal aortic atherosclerosis. Gestational Diabetes Mellitus (GDM) associates with abnormal function of the foetoplacental vasculature due to foetal hyperglycaemia and hyperinsulinaemia, and associates with development of cardiovascular disease in adulthood. Supraphysiological dyslipidaemia is also detected in GDM pregnancies. Although there are several studies showing the alteration in the maternal and neonatal lipid profile in GDM pregnancies, there are no studies addressing the effect of dyslipidaemia in the maternal and foetal vasculature. The literature reviewed suggests that dyslipidaemia in GDM pregnancy should be an additional factor contributing to worsen GDM-associated endothelial dysfunction by altering signalling pathways involving nitric oxide bioavailability and neonatal lipoproteins.
Assuntos
Doenças da Aorta/sangue , Aterosclerose/sangue , Glicemia/metabolismo , Diabetes Gestacional/sangue , Dislipidemias/sangue , Doenças Fetais/sangue , Lipoproteínas/sangue , Circulação Placentária , Efeitos Tardios da Exposição Pré-Natal , Animais , Doenças da Aorta/diagnóstico , Doenças da Aorta/fisiopatologia , Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/fisiopatologia , Dislipidemias/diagnóstico , Dislipidemias/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/fisiopatologia , Humanos , Gravidez , Fatores de RiscoRESUMO
Several changes occur in lipid metabolism during gestation due to hormonal and metabolic changes, which are essential to satisfy the nutritional demands of the maternal-fetal unit development. The gestation shows two distinct periods that begin with fat accumulation, mainly in maternal adipose tissue, and the late phase, characterized by accelerated catabolism, with the increase of fatty acids in the circulation that causes hyperlipidemia, especially the one characterized as hypertriglyceridemia. Maternal hyperlipidemia may be associated with the development of maternal-fetal complications (preterm birth, preeclampsia, vascular complications) and the development of long-term cardiovascular disease. The cardiovascular risk may not only be related to lipoproteins cholesterol content, but also to the number and functionality of circulating lipoprotein particles. This review reports the major changes that occur in lipoprotein metabolism during pregnancy and that are associated with the development of dyslipidemias, lipoprotein atherogenic phenotype, and maternal-fetal unit complications.
Diversas mudanças ocorrem no metabolismo lipídico durante a gestação em função das alterações hormonais e metabólicas, que são essenciais para satisfazer a demanda nutricional ocasionada pelo desenvolvimento da unidade feto-placentária. O período da gestação apresenta dois momentos distintos que iniciam com acúmulo de gordura principalmente no tecido adiposo materno, e a fase tardia, caracterizada por catabolismo acelerado, com aumento de ácidos graxos na circulação causando hiperlipidemia, principalmente a aquela caracterizada como hipertrigliceridemia. A hiperlipidemia materna pode estar associada ao desenvolvimento de complicações materno-fetais (parto prematuro, pré-eclâmpsia, complicações vasculares) e de doenças cardiovasculares, a longo prazo. O risco pode estar relacionado não apenas ao teor de colesterol contido nas frações lipoprotéicas, mas também ao número e a funcionalidade das partículas lipoproteicas. Esta revisão aborda as principais mudanças que ocorrem no metabolismo lipoproteico durante a gravidez, e que estão associadas ao desenvolvimento de dislipidemias, fenótipo aterogênico e complicações materno-fetais.
Assuntos
Doenças Fetais/sangue , Lipoproteínas/sangue , Complicações Cardiovasculares na Gravidez/sangue , Complicações na Gravidez/sangue , Biomarcadores/sangue , Feminino , Humanos , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Medição de RiscoRESUMO
Abstract Several changes occur in lipid metabolism during gestation due to hormonal and metabolic changes, which are essential to satisfy the nutritional demands of the maternal-fetal unit development. The gestation shows two distinct periods that begin with fat accumulation, mainly in maternal adipose tissue, and the late phase, characterized by accelerated catabolism, with the increase of fatty acids in the circulation that causes hyperlipidemia, especially the one characterized as hypertriglyceridemia. Maternal hyperlipidemia may be associated with the development of maternal-fetal complications (preterm birth, preeclampsia, vascular complications) and the development of long-term cardiovascular disease. The cardiovascular risk may not only be related to lipoproteins cholesterol content, but also to the number and functionality of circulating lipoprotein particles. This review reports themajor changes that occur in lipoprotein metabolismduring pregnancy and that are associated with the development of dyslipidemias, lipoprotein atherogenic phenotype, and maternal-fetal unit complications.
Resumo Diversas mudanças ocorrem no metabolismo lipídico durante a gestação em função das alterações hormonais e metabólicas, que são essenciais para satisfazer a demanda nutricional ocasionada pelo desenvolvimento da unidade feto-placentária. O período da gestação apresenta dois momentos distintos que iniciam com acúmulo de gordura principalmente no tecido adiposo materno, e a fase tardia, caracterizada por catabolismo acelerado, com aumento de ácidos graxos na circulação causando hiperlipidemia, principalmente a aquela caracterizada como hipertrigliceridemia. A hiperlipidemia materna pode estar associada ao desenvolvimento de complicações materno-fetais (parto prematuro, pré-eclâmpsia, complicações vasculares) e de doenças cardiovasculares, a longo prazo. O risco pode estar relacionado não apenas ao teor de colesterol contido nas frações lipoprotéicas, mas também ao número e a funcionalidade das partículas lipoproteicas. Esta revisão aborda as principais mudanças que ocorrem no metabolismo lipoproteico durante a gravidez, e que estão associadas ao desenvolvimento de dislipidemias, fenótipo aterogênico e complicações maternofetais.
Assuntos
Humanos , Feminino , Gravidez , Complicações na Gravidez/sangue , Complicações Cardiovasculares na Gravidez/sangue , Doenças Fetais/sangue , Lipoproteínas/sangue , Complicações Cardiovasculares na Gravidez/epidemiologia , Biomarcadores/sangue , Medição de RiscoRESUMO
OBJETIVO: Evaluar la efectividad del cribado combinado de primer trimestre para la detección prenatal de aneuploidías tras 6 años de implantación en nuestro servicio y su repercusión en la disminución de pruebas diagnósticas invasivas. Se propone establecer un protocolo para incorporar el estudio de ADN fetal en sangre materna a partir de las revisiones bibliográficas publicadas. MÉTODO: Se evaluó el riesgo de anomalía cromosómica fetal en 3177 gestaciones mediante cribado combinado de primer trimestre entre enero de 2011 y diciembre de 2014. Se revisaron las amniocentesis realizadas desde que se instauró el cribado combinado en 2008 comparándolas con las de los 5 años anteriores. RESULTADOS: La tasa de detección del cribado para trisomía 21 fue del 94,4% y la tasa de falsos positivos de 6,4%. En el año 2005 estábamos realizando 194 amniocentesis, tras 6 años de implantación del cribado, en el año 2013 se realizaron 35 amniocentesis lo que implica una disminución del 70%. CONCLUSIONES: El cribado combinado de primer trimestre ha demostrado una mayor tasa de detección para trisomía 21 que el cribado de segundo trimestre y/o la edad materna, además de que ha llevado a una importante reducción en el número de pruebas invasivas. En los próximos años la incorporación del estudio de ADN fetal mejorará la detección de aneuploidías, con una drástica disminución de las pruebas invasivas por lo que se hace necesario la implantación de nuevos protocolos.
AIMS: To evaluate the effectiveness of first trimester combined screening in the prenatal detection of aneuploidy after 6 years of implantation in our service and its impact in reducing invasive diagnostic tests. It is proposed to establish a protocol to incorporate the study of fetal DNA in maternal blood from published literature reviews. METHODS: The risk of fetal chromosomal anomalies was assessed in 3177 pregnancies with first trimester combined screening between January 2009 and December 2014. The amniocenteses performed were checked against those of the previous 5 years. RESULTS: The detection rate of screening for trisomy 21 was 94.4% and the false-positive rate was 6.4%. In 2005 there were 194 amniocenteses. In 2013, 5 years after the introduction of screening, 68 amniocenteses were performed, representing a 70% reduction in invasive procedures. CONCLUSIONS: First trimester combined screening has shown a higher detection rate for trisomy 21 that the second trimester screening and/or maternal age, and has substantially reduced the use of invasive prenatal diagnostics procedures. In the coming years, the incorporation of the study of fetal DNA improve the detection of aneuploidys with a drastic reduction of invasive tests so that, the implementation of new protocols is necessary.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Doenças Fetais/diagnóstico , Testes para Triagem do Soro Materno/métodos , Aneuploidia , Segundo Trimestre da Gravidez/sangue , Primeiro Trimestre da Gravidez/sangue , Diagnóstico Pré-Natal/métodos , DNA/sangue , Testes Genéticos , Ultrassonografia Pré-Natal/métodos , Aberrações Cromossômicas , Medição de Risco , Doenças Fetais/sangue , Teste Pré-Natal não Invasivo , AmniocenteseRESUMO
AIM: The aim of this study was to evaluate the passage of fetal erythrocytes into the maternal circulation after invasive obstetric procedures, using the Kleihauer-Betke test, flow cytometry and α-fetoprotein concentration in maternal blood. MATERIAL AND METHODS: This was a prospective descriptive study on patients who underwent: amniocentesis, cordocentesis, chorionic villus sample, amniotic infusion, bladder drainage and ventricular-amniotic shunt to investigate the karyotype; treatment for hydrocephalus, oligohydramnios, obstructive uropathy and polyhydramnios; and investigation of lung maturity. Maternal blood samples were collected before and 60 min after the invasive obstetric procedure in order to evaluate the passage of fetal erythrocytes using the Kleihauer-Betke test, flow cytometry and α-fetoprotein concentration. RESULTS: In total, 43 invasive obstetric procedures were performed. The procedures performed were: 27 cases of amniocentesis (62.7%), seven cases of cordocentesis (16.2%), four chorionic villus samples (9.4%), two amniotic infusions (4.7%), two ventricular-amniotic shunts and one bladder drainage (2.3%). After one case of cordocentesis with two puncture attempts via the placenta, a significant increase in fetal erythrocytes was detected using the three methods. After another cordocentesis with one puncture via the placenta, a significant increase in fetal erythrocytes was detected using flow cytometry and α-fetoprotein concentration, but not through the Kleihauer-Betke test. The other 41 samples did not show any significant increase in fetal erythrocytes in the maternal blood. CONCLUSION: Invasive obstetric procedures performed during prenatal care are safe when performed by experienced professionals with the proper technique, with minimal chance of passage of fetal erythrocytes into the maternal compartment.
Assuntos
Amniocentese/efeitos adversos , Amostra da Vilosidade Coriônica/efeitos adversos , Cordocentese/efeitos adversos , Doenças Fetais/diagnóstico , Transfusão Feto-Materna/etiologia , Troca Materno-Fetal , Complicações na Gravidez/diagnóstico , Adolescente , Adulto , Eritrócitos , Feminino , Doenças Fetais/sangue , Transfusão Feto-Materna/sangue , Humanos , Gravidez , Complicações na Gravidez/sangue , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: To study the effect of fetal anemia on fetal cardiac troponin T (cTnT) in pregnancies complicated by RhD alloimmunization. METHOD: Twenty pregnant women complicated by RhD alloimmunization who underwent intrauterine transfusion (IUT) for treatment of fetal anemia were studied. Immediately before IUT, fetal blood was obtained for hemoglobin and cTnT measurements. RESULTS: Complete measurements of hemoglobin and cTnT before IUT were obtained in 49 procedures, of which 20 were first-time. The regression analysis between hemoglobin z-score and cTnT values in 49 procedures showed significant negative correlation (r = -0.43, p = 0.002, Regression equation Log(cTnT) = -1.5057 + -0.07563 Hb z-score). Cardiac TnT values before first IUT were significantly associated with perinatal death. In the group with elevated cTnT (n = 7), fetal or neonatal death was more frequent (2 IUD and 2 NND) when compared to normal cTnT group (n = 13, 1 IUD) (57.1 vs. 7.7%, p = 0.031, Fisher's exact test). CONCLUSION: Fetal blood concentration of cTnT before IUT was negatively correlated to hemoglobin z-score, and levels of cTnT help to manage the pregnancies complicated by RhD alloimmunization.
Assuntos
Doenças Fetais/metabolismo , Coração Fetal/metabolismo , Miocárdio/metabolismo , Isoimunização Rh/metabolismo , Troponina T/sangue , Adulto , Anemia , Transfusão de Sangue Intrauterina , Estudos de Coortes , Eritroblastose Fetal/sangue , Eritroblastose Fetal/metabolismo , Eritroblastose Fetal/terapia , Feminino , Doenças Fetais/sangue , Doenças Fetais/terapia , Coração Fetal/química , Hemoglobinas/análise , Humanos , Miocárdio/química , Concentração Osmolar , Gravidez , Isoimunização Rh/sangue , Isoimunização Rh/terapia , Adulto JovemRESUMO
INTRODUCTION: the leading cause of fetal anemia is Rh isoimmunization. The timely diagnosis by ultrasound and intravascular transfusion improves the prognosis. OBJECTIVE: to evaluate the increase in hemoglobin in the fetus and correlate the red cell transfusion volume with elevation of hemoglobin and perinatal outcome. PATIENTS AND METHODS: prospective, case series study. We included 17 patients with fetal anemia detected by measuring the peak systolic velocity of middle cerebral artery and determination of fetal hemoglobin before and after cordocentesis. After confirmation of fetal anemia (Hb <10 g/dL), was held fetal transfusion with 50 mL/kg estimated fetal weight, with packed red blood cells type O Rh negative. RESULTS: In 17 cases fetal anemia was diagnosed, of which 11 (64%) had Rh isoimmunization and 6 (36%) were not immune. The 17 cases received 27 intravascular transfusions, in 75% hemoglobin rose to 10 g/dL, 45% in the first transfusion, 25% in the second and 10% in the third transfusion. Fetal hemoglobin between before and after transfusion was 6.5 and 12.9 g/dl, respectively (p<0.001) and allowed to continue the pregnancy from 3 to 12 weeks from the first transfusion. There were 4 deaths (2 stillbirths and 2 neonatal), but only one was related to the procedure. the survival rate was 76%, mortality in the presence of hydrops was 30% and no deaths in patients without hydrops. CONCLUSIONS: Mortality in fetal anemia was 23.6% and only one case was related to intravascular transfusion. In cases of survival to birth, pregnancy lasted >30 weeks gestation. Hemoglobin rose from 27 to 300% of the initial fetal hemoglobin. The presence of fetal hydrops significantly increases mortality.
Assuntos
Anemia Hemolítica/terapia , Transfusão de Sangue Intrauterina/estatística & dados numéricos , Doenças Fetais/terapia , Resultado da Gravidez , Isoimunização Rh , Anemia Hemolítica/epidemiologia , Anemia Hemolítica/etiologia , Velocidade do Fluxo Sanguíneo , Transfusão de Sangue Intrauterina/efeitos adversos , Transfusão de Sangue Intrauterina/métodos , Cordocentese , Eritroblastose Fetal/epidemiologia , Eritroblastose Fetal/etiologia , Feminino , Sangue Fetal/química , Morte Fetal/epidemiologia , Morte Fetal/etiologia , Doenças Fetais/sangue , Doenças Fetais/epidemiologia , Doenças Fetais/etiologia , Hemoglobinas/análise , Humanos , Hidropisia Fetal/etiologia , Hidropisia Fetal/mortalidade , Recém-Nascido , Artéria Cerebral Média , Gravidez , Estudos Prospectivos , Natimorto/epidemiologiaRESUMO
As anomalias cromossômicas apresentam grande incidência entre os nativivos e natimortos, constituindo a maior causa de morte fetal em países desenvolvidos, no período perinatal. Tradicionalmente, o diagnóstico dessas cromossomopatias é feito por procedimentos invasivos, que não são isentos de complicações materno-fetais. O desenvolvimento de técnicas que permitem identificação e o isolamento de células fetais e de DNA fetal livre no sangue periférico materno tem permitido o diagnóstico precoce das anomalias cromossômicas, tornando-se, desse modo, uma área de intensas pesquisas. Estudos mais recentes também envolvem a identificação e quantificação de mRNA fetal na circulação materna, o que torna possível a análise da expressão gênica fetal durante a gestação. O resgate de material fetal em sangue periférico materno e sua utilização no diagnóstico de várias doenças fetais é uma área de grande interesse na medicina fetal atual. Estudos são necessários para se avaliar melhor o papel propedêutico dessas novas técnicas, assim como sua aplicabilidade na prática clínica rotineira.
Chromosomal abnormalities show great incidence among live birth and stillbirth, becoming the major fetal death cause during the perinatal period in developed countries. Traditionally, the diagnosis of these chromosomal abnormalities is performed through invasive techniques which are not free from maternal-fetal complications. The development of techniques that allows identification and isolation of fetal cells and free fetal DNA in peripheral maternal blood has afforded the early diagnosis of chromosomal abnormalities and, therefore, become an intensive area of research. Recent studies describe the identification and qualification of fetal mRNA in the maternal circulation, which makes possible fetal gene expression analysis during pregnancy. The identification of fetal material in maternal circulation and its value on the diagnosis of several fetal diseases is a great area of interest in the current fetal medicine. Studies are necessary to evaluate the best propedeutic role of these new techniques, as well as their applicability in the routine clinical practice.