RESUMEN
We have developed a two-colour immunocytochemical staining method for the detection of fetal and embryonic haemoglobin in erythroid cells. The method was applied to study these haemoglobin types in fetal red cells. Specimens from fetal blood (10 weeks), cord blood and fetal liver (14 weeks) as well as chorionic villus samples (10-13 weeks) were stained for gamma and epsilon chains using CY3 and FITC labelled antibodies. Morphometric analysis was applied to determine cell size. Samples from organs involved in early embryonic development contained relatively large erythroblasts expressing the epsilon globin chain (megaloblasts); later in gestation the gamma chain was co-expressed by the same cells which ultimately became smaller and contained HbF (alpha 2 gamma 2) only. This phenomenon was confirmed in CVS samples in which all cell types were abundantly present. Since fetal erythroblasts are considered candidate cells for non-invasive prenatal diagnosis using FISH, we studied the phenotype of erythroblasts circulating in the maternal blood. The majority of erythroblasts in maternal blood appeared to be of the relatively small gamma globin-containing cell type. However, careful screening of the same maternal blood samples also revealed erythroblasts expressing epsilon or epsilon and gamma globins simultaneously, although at low frequency. Control specimens from non-pregnant women did not show nucleated red cells expressing either of the haemoglobin types. These observations may contribute to the better recognition of fetal cells in the maternal blood for prenatal diagnosis.
Asunto(s)
Eritrocitos/química , Sangre Fetal/citología , Globinas/análisis , Inmunohistoquímica/métodos , Coloración y Etiquetado , Muestra de la Vellosidad Coriónica , Eritroblastos/química , Femenino , Edad Gestacional , Humanos , Hibridación Fluorescente in Situ , Hígado/citología , Hígado/embriología , EmbarazoRESUMEN
Latin and Asian-Pacific immigrants are the fastest growing new-comer groups in the U.S. contributing to 85% of immigration totals. New immigrants experience multiple barriers to accessing genetic counseling resulting from cultural, linguistic, financial, and educational factors as well as having unique perceptions on health, illness, reproduction, and life as a whole. In addition, new immigrants lack familiarity with Western medical practices as well as genetic risk and available interventions. We provided perinatal genetic services to 2430 clients, mostly new immigrants of Latin and Asian-Pacific descent over a period of 6 years. Counseling aides sharing the clients' cultural backgrounds were employed. A study assessing the efficacy of cross-cultural education regarding advanced maternal age risk and amniocentesis was implemented and linked to a database containing demographic and clinical information. Practical observations relating to cultural beliefs in the two groups relevant to perinatal genetic counseling were made.
RESUMEN
We studied the efficacy of in utero hematopoietic stem cell transplantation and the ability of such transplantation to induce tolerance in a fetal normal mouse allogeneic model. In 9 of the 162 surviving recipients (5.6%), cells of donor origin were detected after birth. The highest engraftment rate was achieved by transplanting fetal liver cells in a relatively high dose (> 10(6) cells/fetal gram). Skin grafting was performed to determine the presence of prenatally induced tolerance. Only those mice which showed evidence of chimerism became tolerant to skin derived from the prenatal donor's strain while remaining competent to reject a skin transplant from a third strain. Tolerant mice could have significant chimerism reestablished by utilizing monoclonal antibody specific for the recipient H-2 antigen as conditioning for IV fetal stem cell retransplantation.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Tolerancia Inmunológica , Animales , Anticuerpos Monoclonales/inmunología , Transfusión de Sangre Intrauterina , Quimera , Supervivencia de Injerto , Antígenos H-2/inmunología , Focalización Isoeléctrica , Hígado/embriología , Trasplante de Hígado , Ratones , Ratones Endogámicos C57BL , Trasplante de Piel , Trasplante HomólogoRESUMEN
Prenatal testing of 12 pregnancies at risk for argininosuccinic aciduria due to argininosuccinate lyase (ASAL) deficiency and three pregnancies at risk for citrullinaemia due to argininosuccinate synthatase (ASAS) deficiency was performed by metabolite detection in amniotic fluid and measurement of enzyme activity in uncultured and cultured chorionic tissue and in cultured amniocytes. From our data and those of previous studies, amniotic fluid argininosuccinate measurement alone is clearly a reliable and rapid diagnostic test for both severe and mild ASAL deficiency if maternal ASAL deficiency can be excluded. For prenatal diagnosis of ASAS deficiency, however, both measurement of the amniotic fluid citrulline level and enzyme assay should be employed.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Líquido Amniótico/química , Argininosuccinato Sintasa/deficiencia , Ácido Argininosuccínico/análisis , Aciduria Argininosuccínica , Citrulina/análisis , Enfermedades Fetales/diagnóstico , Aminoacidurias Renales/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/enzimología , Amniocentesis , Líquido Amniótico/citología , Líquido Amniótico/enzimología , Argininosuccinatoliasa/metabolismo , Argininosuccinato Sintasa/metabolismo , Ácido Argininosuccínico/química , Radioisótopos de Carbono , Células Cultivadas , Vellosidades Coriónicas/química , Vellosidades Coriónicas/enzimología , Muestra de la Vellosidad Coriónica , Citrulina/sangre , Femenino , Enfermedades Fetales/enzimología , Fibroblastos/química , Fibroblastos/enzimología , Humanos , Lactante , Recién Nacido , Embarazo , Segundo Trimestre del Embarazo , Aminoacidurias Renales/enzimología , TritioRESUMEN
OBJECTIVE: Our purpose was to develop fluorescence in situ hybridization to repetitive chromosome-specific sequences to detect chromosome aneuploidy faster than hybridization to unique targets or karyotyping. STUDY DESIGN: Aneuploidy involving chromosomes 13, 18, 21, X, and Y comprises 70% of chromosome abnormalities in 10- to 12-week fetuses, 95% of the phenotypically significant newborn chromosome abnormalities. Our improved 8-hour protocol used repetitive probes to label and count the number of these centromeric chromosome domains. RESULTS: This protocol correctly determined chromosome 13, 18, and 21 status in 50 of 50 unselected direct amniocyte samples and found abnormal patterns in 27 of 27 archived trisomy 21 cases. Altogether karyotyping confirmed 744 of 745 chromosome-specific repetitive sequence test results. CONCLUSION: This protocol rapidly tests abnormal fetuses and newborn infants in whom diagnosis is made at the initiation of labor or before urgent surgery when a cytogenetic result cannot be completed.
Asunto(s)
Aneuploidia , Enfermedades Fetales/diagnóstico , Diagnóstico Prenatal , Aberraciones Cromosómicas/diagnóstico , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Cromosomas Humanos Par 13 , Cromosomas Humanos Par 18 , Cromosomas Humanos Par 21 , ADN/análisis , Femenino , Enfermedades Fetales/genética , Humanos , Hibridación Fluorescente in Situ/métodos , Embarazo , Embarazo de Alto Riesgo , Secuencias Repetitivas de Ácidos Nucleicos/genética , Cromosoma X , Cromosoma YRESUMEN
OBJECTIVE: To develop the most up-to-date, complete data base of multifetal pregnancy reduction (MFPR) from cases, and to provide the best counseling for couples with multifetal pregnancies. METHODS: From nine centers in five countries, 1789 completed MFPR cases were collected and outcomes evaluated. Pregnancy losses were defined as through 24 weeks and deliveries categorized in groups of 25-28, 29-32, 33-36, and 37 or more weeks. RESULTS: Overall, the pregnancy loss rate was 11.7% but varied from a low of 7.6% for triplets to twins and increased with each additional starting number to 22.9% for sextuplets or higher. Early premature deliveries (25-28 weeks) were 4.5% and varied with starting number. Loss rates by finishing number were highest for triplets and lowest for twins, but gestational age at delivery was highest for singletons. CONCLUSIONS: Multifetal pregnancy reduction has been shown to be a safe and effective method to improve outcome in multifetal pregnancies. Outcomes are worse with higher-order gestations and support the need for continued vigilance of fertility therapy.
Asunto(s)
Aborto Espontáneo/epidemiología , Recien Nacido Prematuro , Reducción de Embarazo Multifetal , Parto Obstétrico , Femenino , Edad Gestacional , Humanos , Recién Nacido , Estudios Multicéntricos como Asunto , Embarazo , Resultado del Embarazo , Reducción de Embarazo Multifetal/efectos adversos , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Medición de Riesgo , Trillizos , GemelosRESUMEN
OBJECTIVES: Our purposes were (1) to compare the safety of transabdominal and transcervical chorionic villus sampling with the use of a consistent technique at one center and (2) to determine whether the training of fellows can be accomplished without an increase in the loss rate. STUDY DESIGN: We performed a retrospective comparison of transabdominal and transcervical chorionic villus sampling loss rates from procedures performed by three principal operators between 1984 and 1992. The type of procedure was chosen by the operator at the time of the procedure on the basis of placental location. RESULTS: Procedures 1 through 2573 were performed solely by transcervical chorionic villus sampling and had an overall fetal loss rate of 5.12%. With the addition of transabdominal chorionic villus sampling the overall fetal loss rate dropped to 3.07% (p < 0.0001). Three and one half years after the start of transabdominal chorionic villus sampling (about 1300 transabdominal chorionic villus sampling procedures), the transabdominal chorionic villus sampling loss rate was significantly better than the transcervical loss rate (p = 0.035), and the difference widened steadily after that. During the same time period seven fellows performed 716 procedures for a fetal loss rate among fellows of 2.72%. CONCLUSIONS: (1) Under optimal circumstances (one center, large numbers, few operators, consistent technique, operator choice of best approach), transabdominal chorionic villus sampling may be inherently safer than transcervical chorionic villus sampling. (2) The addition of transabdominal chorionic villus sampling decreases overall chorionic villus sampling loss rates. (3) Although the number of procedures performed by fellows is small, it appears that with close supervision by experienced operators successful training of fellows can be accomplished without adverse effects on loss rates.
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Muestra de la Vellosidad Coriónica/efectos adversos , Muerte Fetal/etiología , Distribución de Chi-Cuadrado , Muestra de la Vellosidad Coriónica/métodos , Becas , Femenino , Humanos , Obstetricia/educación , Oportunidad Relativa , Embarazo , Análisis de Regresión , Estudios RetrospectivosRESUMEN
OBJECTIVE: To develop a fetal muscle biopsy technique for immunohistochemical diagnosis of Duchenne and Becker muscular dystrophies. METHODS: Data from two clinical centers and one reference laboratory were combined to show 12 completed cases, ten at risk for Duchenne muscular dystrophy, one for Becker muscular dystrophy, and one for mitochondrial myopathy. Samples of fetal gluteal muscle were obtained percutaneously under ultrasound guidance (some with endoscopic assistance) with a biopsy gun. The samples were frozen and assayed for dystrophin by immunohistochemical techniques. RESULTS: Samples were obtained in 11 of 12 (92%) cases, and spontaneous abortion after the procedure occurred in two of 12 (17%) cases. Laboratory diagnoses were possible on small samples, and four of 12 fetuses (33%) were affected. Endoscopy with direct visualization might aid in the procedure. CONCLUSIONS: The development of fetal muscle biopsy allows for an expansion of the diagnostic possibilities for myopathies. The experiences of our two clinical centers show that the procedure can be done with accuracy and acceptable safety. The evolving laboratory experience has reduced the amount of tissue necessary for the diagnosis, increased the sophistication of the immunohistochemical analysis, allowed the diagnosis of abnormalities in different parts of the dystrophin gene, and expanded the indications for the use of fetal muscle biopsy. Fetal muscle biopsy can be used successfully for the diagnosis in otherwise uninformative cases, and there is a wide variety of indications beyond traditional Duchenne muscular dystrophy possible, including female fetuses at risk because of X-autosomal translocations.
Asunto(s)
Biopsia con Aguja/métodos , Enfermedades Fetales/diagnóstico , Músculo Esquelético/química , Distrofias Musculares/diagnóstico , Diagnóstico Prenatal , Aborto Espontáneo/etiología , Biomarcadores/análisis , Biopsia con Aguja/efectos adversos , Biopsia con Aguja/instrumentación , Distrofina/análisis , Femenino , Fetoscopía , Técnica del Anticuerpo Fluorescente , Humanos , Immunoblotting , Masculino , Músculo Esquelético/patología , Embarazo , Diagnóstico Prenatal/efectos adversosRESUMEN
To further characterize the clinical, radiographic and chondro-osseous morphologic changes in the Desbuquois syndrome, 7 patients from three sibships are described. They all had prenatal onset severe rhizomelic and mesomelic shortness with marked joint laxity and marked micrognathia. Radiographic changes were distinct, consisting of a supernumerary ossification center between the proximal phalanx of the index finger and the second metacarpal, and variable thumb changes. The femoral necks showed enlargement of the lesser trochanter with metaphyseal breaking, producing a characteristic "monkey wrench" (Swedish key) appearance. Growth plate cartilage showed dilated cisterns of rough endoplasmic reticulum in reserve zone chondrocytes. Three of the 7 cases were diagnosed prenatally by second trimester ultrasound and one case by fetoscopy. This syndrome exhibits significant phenotypic variability and must be differentiated from the Catel-Manzke syndrome which exhibits similar radiographic changes in the hands.
Asunto(s)
Huesos/anomalías , Enanismo/patología , Inestabilidad de la Articulación/patología , Adolescente , Preescolar , Enanismo/diagnóstico por imagen , Femenino , Placa de Crecimiento/patología , Humanos , Cuerpos de Inclusión/patología , Lactante , Inestabilidad de la Articulación/diagnóstico por imagen , Masculino , Radiografía , SíndromeRESUMEN
OBJECTIVE: Our goal was to develop the most comprehensive database possible to counsel patients about selective termination for fetal abnormalities, because no one center has sufficient data to assess much more than crude loss rates. STUDY DESIGN: A total of 183 completed cases of selective termination from 9 centers in 4 countries were combined (169 twins, 11 triplets, 3 quadruplets). Variables included indications, methods, (potassium chloride, exsanguination, air embolus), gestational age at procedure, pregnancies lost (< or = 24 weeks), gestational age at delivery, and neonatal outcome. RESULTS: Indications for selective termination were 96 chromosomal, 76 structural, and 11 mendelian. Selective termination was technically successful in 100% of cases. In 23 of 183 (12.6%) miscarriage occurred before 24 weeks; 2 of 37 (5.4%) occurred when the procedure done at < or = 16 weeks and 21 of 146 (14.4%) when it was done thereafter. Air embolization had a higher loss rate: 10 of 24 (41.7%) compared with 13 of 156 (8.3%) by potassium chloride (chi 2 = 117, p < 0.0001). Three cases of selective termination performed in monochorionic pregnancies all resulted in pregnancy loss. Among 183 potentially viable deliveries, 7 occurred before 28 weeks, 19 at 29 to 32 weeks, 41 at 33 to 36 weeks, and 93 at > or = 37 weeks. Gestational age at delivery was not influenced by the technique used or the indication but was negatively correlated with gestational age at the time of selective termination. No coagulopathy or ischemic damage was observed in survivors. There was no maternal morbidity. CONCLUSIONS: (1) Selective termination in experienced hands for a dizygotic abnormal twin is safe and effective when done with potassium chloride. A total of 83.8% of viable deliveries occurred after 33 weeks and only 4.3% at 25 to 28 weeks. (2) Gestational age at the procedure correlated positively with loss rate and inversely with gestational age at delivery; this emphasizes the need for early diagnosis in multifetal pregnancies. (3) Coagulopathy tests are probably unnecessary.
Asunto(s)
Aborto Terapéutico , Feto/anomalías , Embarazo Múltiple , Aborto Terapéutico/métodos , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Embolia Aérea , Femenino , Enfermedades Fetales , Humanos , Cloruro de Potasio/uso terapéutico , Embarazo , Resultado del Embarazo , Segundo Trimestre del EmbarazoRESUMEN
While analyzing 280 hemoglobinopathy kindreds with prescribed molecular tests, 3 unusual mutations were observed that required additional characterization. In the first case, the hypervariable region flanking the alpha-globin genes generated an intermediate length 8.2 kb psi zeta-globin gene fragment on a Southeast Asian chromosome with two deleted alpha-globin genes. Rehybridization of the Southern blot with alpha-globin probe distinguished the mutation unambiguously. In the second case, restriction enzyme analysis of a PCR amplified black beta-globin gene detected a novel beta-83 point mutation adjacent to a promoter element. In the third case, which was uninformative with available allele specific oligonucleotides (ASOs), total genomic PCR amplification and sequencing identified a single basepair insertion in codon 36/37 of an Iranian beta-globin gene that shifted the reading frame and obliterated gene activity. Developing additional region-specific ASOs will further diminish the number of cases that must be characterized by genomic PCR sequencing.
Asunto(s)
Muestra de la Vellosidad Coriónica , Enfermedades Fetales/diagnóstico , Hemoglobinopatías/genética , Mutación , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/genética , Secuencia de Bases , Análisis Mutacional de ADN , Cartilla de ADN , Femenino , Enfermedades Fetales/genética , Mutación del Sistema de Lectura , Eliminación de Gen , Haplotipos , Hemoglobinopatías/diagnóstico , Humanos , Masculino , Datos de Secuencia Molecular , Sondas de Oligonucleótidos , Linaje , Mutación Puntual , Reacción en Cadena de la Polimerasa , Talasemia alfa/diagnóstico , Talasemia alfa/genética , Talasemia beta/diagnóstico , Talasemia beta/genéticaRESUMEN
The finding of a 'faint-positive' acetylcholinesterase band in amniotic fluid samples of women at 15 weeks' gestation or above is associated with an increased risk of fetal abnormalities, most commonly gastroschisis. This finding warrants a targeted sonographic evaluation, in order to rule out significant fetal malformations.
Asunto(s)
Acetilcolinesterasa/análisis , Líquido Amniótico/enzimología , Anomalías Congénitas/diagnóstico , Femenino , Humanos , Valor Predictivo de las Pruebas , Embarazo , Segundo Trimestre del Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Gastroschisis is a rare congenital anomaly characterized by the herniation of fetal intestines directly through an abdominal wall defect. It is associated infrequently with chromosomal or other nonbowel defects and can be treated surgically after delivery, with survival rates reported to be between 87 and 100%. We reviewed 21 cases of prenatally diagnosed gastroschisis to ascertain the effect of fetal growth retardation on perinatal outcome. Ten of the 21 fetuses (48%) were identified prenatally as growth retarded, although only seven of these ten truly had birth weights less than the 10th percentile. Three additional fetuses that had not been identified prenatally as growth retarded did, in fact, have birth weights less than the 10th percentile, for a total frequency of growth retardation at birth of 48% (10/21 fetuses). When compared to non-growth-retarded fetuses with gastroschisis, fetuses who were growth retarded, although more likely to have been delivered by emergency cesarean section, had shorter hospitalization times, were more likely to have undergone primary closure on the first day of life, and had fewer major complications. We conclude that growth retardation is common in fetuses with gastroschisis and the postnatal outcome in gastroschisis is not poorer for fetuses who are growth retarded.
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Músculos Abdominales/anomalías , Músculos Abdominales/diagnóstico por imagen , Retardo del Crecimiento Fetal/diagnóstico por imagen , Hernia/diagnóstico por imagen , Ultrasonografía Prenatal , Femenino , Retardo del Crecimiento Fetal/complicaciones , Hernia/embriología , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Embarazo , PronósticoRESUMEN
Our Factor VIII and RFLP analyses identified previously unreported grandpaternal hemophilia A mosaicism in a male who transmitted the disease allele to 2 of 4 daughters and 2 of 4 grandsons. An uncommon flanking polymorphic DXS52 allele cosegregated with this grandpaternal mutant allele. This and other reports of mosaic hemophilia A carriers indicate that parental mosaicism can explain unusual segregation of low Factor VIII activities and DNA polymorphisms in about 1% of hemophilia A pedigrees.
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Factor VIII/genética , Enfermedades Fetales/diagnóstico , Hemofilia A/diagnóstico , Mosaicismo , Análisis Mutacional de ADN , Femenino , Enfermedades Fetales/genética , Haplotipos/genética , Hemofilia A/embriología , Hemofilia A/genética , Heterocigoto , Humanos , Masculino , Linaje , Polimorfismo de Longitud del Fragmento de Restricción , Factor de von Willebrand/genéticaRESUMEN
Modern physicians desire not only to treat but to cure congenital diseases. In a wide variety of diseases, bone marrow transplantation can be the tool of final cure. The limitations and risks of this procedure have motivated researchers to search for an earlier and safer method of treatment. Special features of fetal immune systems make it possible to perform the transplantation during fetal life using fetal hematopoietic stem cells, thus avoiding many of the side effects of bone marrow transplantation in neonatal life. We review the experimental work done with animal models in this field and the human trials that have been published recently.
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Enfermedades Fetales/cirugía , Trasplante de Células Madre Hematopoyéticas , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Síndromes de Inmunodeficiencia/cirugía , EmbarazoRESUMEN
Invasive prenatal testing has become an important way to evaluate fetuses at increased risk for hereditary disorders. In utero sampling of fetal skin, liver, and muscle may be required to diagnose before-birth disorders that cannot be diagnosed by analysis using chorionic villi or amniotic fluid. In the next few years, many of these conditions will be detected by DNA analysis, and the need for these procedures may decrease dramatically. First performed by fetoscopy, fetal tissue sampling is now most frequently done by inserting a biopsy needle under continuous ultrasonographic guidance. We describe the indications, techniques, complications, and experience with obtaining fetal skin, liver, and muscle biopsy specimens.
Asunto(s)
Enfermedades Fetales/diagnóstico , Enfermedades Genéticas Congénitas/diagnóstico , Diagnóstico Prenatal/métodos , Biopsia con Aguja/métodos , Femenino , Humanos , Hígado/patología , Errores Innatos del Metabolismo/diagnóstico , Músculos/patología , Embarazo , Piel/patologíaRESUMEN
All current methods of fetal karyotyping are invasive and carry a definite, albeit small, procedure-related risk. Because of this and testing costs, only women older than 35 years who have a greater risk for fetal aneuploidy are currently offered prenatal testing. But this detects only 20% to 25% of fetuses with Down syndrome. It would be a tremendous advance to find a noninvasive technique for prenatal diagnosis that carries no procedure-related risk and could be offered to all pregnant women. We describe a possible technique for noninvasive prenatal diagnosis that aims to identify fetal cells in the peripheral maternal circulation and successfully garner them for prenatal testing. Early attempts at fetal karyotyping were hampered by inaccurate diagnostic methods and cumbersome cell-counting techniques. Today, improved capabilities of identifying and enriching for fetal cells, coupled with sensitive methods of analysis such as the polymerase chain reaction, bring renewed enthusiasm to this task. Many technical issues, as well as serious questions regarding the test's utility, still exist, however, and must be explored and answered before the capture of fetal cells in the maternal circulation translates into reality for noninvasive prenatal diagnosis.
Asunto(s)
Embarazo/sangre , Diagnóstico Prenatal/métodos , Anticuerpos Monoclonales , Femenino , Humanos , Hibridación Fluorescente in Situ , Reacción en Cadena de la Polimerasa , Trofoblastos/citologíaRESUMEN
From 1978 to 1990, 263 fetuses with an elevated level of amniotic fluid alpha-fetoprotein (AF-AFP) (> 2.0 multiples of the median) were examined with targeted fetal sonography. All cases of AF-AFP elevation among 22,355 genetic amniocenteses were represented. Sonography correctly showed 32 open neural-tube defects, including 20 myelomeningoceles, and depicted 94% (63 of 67) of the anomalous fetuses. Two of five anomalous fetuses with normal sonograms, however, had extremely high AF-AFP levels leading to prospectively correct diagnoses of congenital nephrosis. Therefore, programmatically, 97% (65 of 67) of the anomalous fetuses were recognized. The three programmatic misdiagnoses were all detected in the neonatal period and surgically corrected; subsequent development was normal. The combination of an elevated AF-AFP level and a detailed sonogram allowed distinction between a normal and an anomalous fetus in 99% of cases. When elevated levels are noted, AF-AFP analysis followed by detailed sonography is highly successful for the detection and characterization of anomalous fetuses and the recognition of normal fetuses with physiologic increases of this protein in the amniotic fluid.
Asunto(s)
Líquido Amniótico/química , Anomalías Congénitas/diagnóstico , Ultrasonografía Prenatal , alfa-Fetoproteínas/análisis , Acetilcolinesterasa/análisis , Amniocentesis , Reacciones Falso Negativas , Femenino , Humanos , Defectos del Tubo Neural/diagnóstico , Valor Predictivo de las Pruebas , Embarazo/sangre , Sensibilidad y Especificidad , Ultrasonografía Prenatal/métodosRESUMEN
X-linked ichthyosis results from steroid sulfatase (STS) deficiency; 90% of affected patients have a complete deletion of the entire 146 kb STS gene on the distal X chromosome short arm (Xp22.3). In these families prenatal diagnosis and carrier testing can be completed in 2 days by hybridizing simultaneously 2 different cosmid probes labeled with fluorescein or Texas red and counterstaining interphase nuclear DNA with DAPI. An STS gene probe labeled with Texas red hybridizes specifically to the steroid sulfatase gene on the X chromosome. A second flanking probe labeled with fluorescein hybridizes to both the normal Y chromosome and normal and STS deleted X chromosomes. In this fashion the interphase nuclei of normal males, affected males, normal females, and carrier females can be distinguished unambiguously. Because normal males and carrier females each show two yellow-green fluorescein spots and one Texas red STS spot, use of this test prenatally requires determining fetal sex independently with repetitive X and Y chromosome-specific probes. This procedure can be used with lymphocytes, direct and cultured chorionic villus cells, direct and cultured amniocytes, and fibroblasts. Similar methods are anticipated to be useful for rapid diagnostic assessment of other aneuploid gene disorders.
Asunto(s)
Arilsulfatasas/genética , Eliminación de Gen , Ictiosis Ligada al Cromosoma X/diagnóstico , Hibridación in Situ/métodos , Diagnóstico Prenatal , Femenino , Humanos , Ictiosis Ligada al Cromosoma X/genética , Masculino , Embarazo , Esteril-SulfatasaRESUMEN
OBJECTIVE: To evaluate the safety and efficacy of transabdominal multifetal pregnancy reduction (MFPR) in the management of iatrogenic and spontaneous multifetal pregnancies. METHODS: Data were combined from 463 completed pregnancies that underwent MFPR at major worldwide centers. RESULTS: Multifetal pregnancy reduction was performed with a 100% technical success rate (there were no failed procedures); 83.8% had delivery of potentially viable fetuses (defined as 24 weeks' gestation or later), and 83.5% of these viable pregnancies delivered at 33 weeks or later. The risk of fetal loss was 3.9% at 2 weeks or less post-procedure, 4.6% at 4 weeks or less, and 16.2% at less than 24 weeks of gestation. Gestational age at delivery varied principally with the number of fetuses remaining, with 7.1% delivering prematurely at less than 28 weeks, and 9.4% at 29-32 weeks. The incidence of obstetric and medical complications appeared to be unaffected, and there was no increase in congenital malformations. CONCLUSIONS: Multifetal pregnancy reduction is an efficient and safe way of improving outcome in multifetal pregnancies, unambiguously for quadruplets or more, and arguably for triplets. However, particularly at higher starting numbers, there are still suboptimal outcomes. We cannot answer the question of whether MFPR should be offered to women with triplets or twins. The only major risk appears to be fetal loss per se, and because the procedure itself does not damage the survivors, parental autonomy should be given a higher priority in the decision process than previously. However, to obviate the need for this procedure, infertility specialists must continue to be vigilant in the use of fertility drugs.