Showing papers on "Amniocentesis published in 1985"

Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus

Abstract: Deficiency of ornithine transcarbamylase (OTC; EC 2.1.3.3), a hepatic mitochondrial enzyme involved in the detoxification of ammonia1,2, is a severe inborn error of metabolism. It is an X-linked disorder2–4 which results characteristically in ammonia intoxication, protein intolerance and mental retardation. Early death of affected hemizygous male infants is common, while clinical manifestations in heterozygous females are variable due to random X-chromosome inactivation2–5. Prenatal diagnosis by amniocentesis has not been feasible because OTC is not expressed in amniocytes and because no unusual metabolites can be detected in amniotic fluid. Fetal liver biopsy has been performed for some families at risk6, but the dangers inherent in this procedure severely limit its usefulness. In this report, we describe the use of a nearly full-length cloned human cDNA7 to begin to characterize normal and mutant human OTC genes. One of 15 affected males was found to have a partial deletion of the OTC gene. Two distinct restriction fragment length polymorphisms (RFLPs) were identified at the OTC locus using the restriction endonuclease MspI; 69% of women tested were heterozygous for one or both polymorphisms. Identification of these common polymorphisms makes it possible to offer prenatal diagnosis to a large fraction of obligate carriers and to provide information on carrier status to some females at risk.

Discordance Between Prenatal Cytogenetic Diagnosis after Chorionic Villi Sampling and Chromosomal Constitution of the Fetus

Abstract: Discordance between the prenatal cytogenetic diagnosis at amniocentesis and the outcome of pregnancy was found in nine of 5580 amniocenteses by Loft and Tabar (1984), who estimated that the cytogenetic accuracy rate ranges from 99.2% to 99.9%. These estimates are based on the discordances and errors recorded in the literature, including contamination by maternal cells and mosaicism.

Prenatal diagnosis by chorionic villus sampling: lessons of the first 600 cases.

Abstract: Chorionic villus sampling (CVS) has emerged as a first trimester alternative to amniocentesis for the prenatal detection of genetic disorders. We report our experience in 600 consecutive CVS procedures to better delineate the safety, efficacy and reliability of this new method of prenatal diagnosis. Adequate samples were obtained at the initial visit in 97 per cent of the cases, and successful cultures were established in 98.7 per cent of these patients. Chromosome abnormalities were detected in 5.9 percent of those pregnancies tested because of advanced maternal age (greater than or equal to 35 years). A discrepancy between the villus karyotype and that of the fetus was found in 2.0 per cent of cases, and most commonly consisted of mosaicism in the villus sample for a chromosomal abnormality that was not found in fetal samples. The risk of spontaneous abortion following the procedure was 6.3 per cent. We conclude that chorionic villus sampling is an acceptably safe and reliable procedure, but further investigation is needed before it can become an established technique in prenatal diagnosis.

Prenatal diagnosis of cystic fibrosis. II. Meconium ileus in affected fetuses

Abstract: Meconium ileus was the presenting feature of cystic fibrosis in 46 per cent of the couples which have been referred for prenatal diagnosis. In fetuses which have been aborted on the basis of alkaline phosphatase isoenzymes assays, meconium ileus represented the only pathological feature of cystic fibrosis, and was observed in three fourths of the cases. Real-time sonographic examination of fetuses at the time of amniocentesis was able to show an echogenic mass in the abdomen corresponding to the meconium ileus, and thus may afford a complementary means of diagnosis.

First trimester fetal diagnosis of genetic disorders: clinical evaluation of 250 cases.

Abstract: Chromosome and enzyme determinations were performed in 250 pregnancies between the 7th and the 12th week of gestation. The majority of the tests were performed for risk of chromosomal abnormalities and 75% of the women were 35 years old or more. We describe a chorionic villi sampling (CVS) technique which proved to be highly efficient, with a diagnostic success rate of 97.7%. In the light of our experience we suggest that CVS is best performed between the 9th and 10th weeks of pregnancy. The average weight of the aspirated specimen was 20 mg with a lower limit of 5 mg which proved sufficient for diagnostic purposes. No major maternal complications were encountered and the slight bleeding observed in 14% of the cases during the days following the CVS should be considered a harmless effect of the aspiration technique. The proportion of fetal losses may lie between 4 and 7%. Paediatric monitoring of the 93 infants born so far and ultrasound examination of the pregnancies still in progress at the time of writing did not reveal any negative effect of CVS. Fetal-maternal transfusion and intrauterine infection are problems which need further basic investigations.

Factors influencing maternal estimates of genetic risk.

Abstract: The relationship between the objective and subjective estimates of genetic risk was studied in 202 women accepting and 50 women not accepting amniocentesis. All women were at risk of having a child with congenital anomalies either because of maternal age at pregnancy or family history of Down syndrome (DS) or other congenital anomalies. Only 28.6% of the women rejecting and 44.4% of the women accepting amniocentesis remembered correctly their objective odds. The correlations between the objective risk estimates and the subjective risk estimates were low overall (r = 0.089, p = 0.08); for women rejecting (r = 0.024, p = 0.44) or accepting (r = 0.082, p = 0.12) amniocentesis. The psychosocial and sociodemographic variables relating to either objective or subjective risk estimates were different for both groups of women. The study provides information on variables that should be taken into consideration in formulating a general theory to predict individual perceptions of genetic risk.

The centralized prenatal genetics screening program of New York City III: The first 7,000 cases

Abstract: The Prenatal Diagnosis Laboratory of New York City (PDL) is a regional program for the prevention of genetic diseases. The administrative aspects of the establishment of the laboratory were described in papers I [Hsu, 1981] and II [Hsu and Benn, 1981] in this series. We now report our experience of the first 7,000 referrals to the laboratory. The laboratory achieved a success rate of 99.5% in obtaining a diagnosis. The frequency with which a repeat amniocentesis was required was 1.9%, usually attributable to inadequate initial amniotic fluid volume or condition. Cases were completed in an average time of 20.82 days. A total of 149 (2.13%) cytogenetic abnormalities were detected. There were 59 nonmosaic autosomal trisomies and 29 sex chromosome abnormalities. The incidence of unbalanced structural abnormalities (0.186%) was much higher than that reported in surveys of newborn infants largely because of the prenatal detection of cases with supernumerary chromosomes. The incidence of balanced structural abnormalities was also considerably higher than that found in surveys of the newborn population, in part because of the detection of subtle familial pericentric inversions of common chromosome regions (inv(Y)(p11q11), inv(2) (p11q13), and inv(1)(p11q13)). The incidence of cases with multiple independent chromosome abnormalities was no higher than expected by chance. A high incidence of mosaicism, pseudomosaicism, and maternal cell contamination was found. Screening for neural tube defects accounted for the detection of a further 16 abnormalities. Nearly all women with severely abnormal fetuses (trisomy 13, 18, 21) elected to terminate their pregnancy whereas only 62% of patients with a prenatally diagnosed sex chromosome abnormality elected to terminate their pregnancies. Full details of follow-up and confirmatory studies for unusual diagnoses are reported. Utilization of prenatal diagnosis in the New York City area has increased sharply since PDL became operational. The laboratory's success illustrates the role of a prenatal diagnosis laboratory that provides a service independent of the patient's financial status. The experience further shows the high degree of acceptance of prenatal diagnosis by individuals at high risk for a child with a genetic disorder.

Prenatal diagnosis of tetrasomy 21

Abstract: Amniocentesis and prenatal diagnosis were done for late maternal age and an abnormality consistent with Tetrasomy 21 (47,XX, + t(21;21] was found in every cell examined of the initial amniotic fluid. Clinical examination revealed a fetus with many of the signs of Down Syndrome and pathological examination revealed gross abnormalities of the internal structures. Follow-up tissues showed mosaic Tetrasomy 21.

Chorionic villi sampling: Women's attitudes

Abstract: To determine the acceptability of chorionic villi sampling (CVS) to women eligible for prenatal diagnosis, we undertook a survey to identify aspects of this new procedure that made it more or less preferable than amniocentesis. All women greater than or equal to 35 years scheduled for amniocentesis were asked to read some detailed descriptive material about amniocentesis and CVS, to rate the importance of the specific differences between procedures, and to indicate which procedure they would prefer, first considering each difference between them independently and then considering all the factors jointly. In the absence of precise estimates of CVS-associated risk at the time of the survey, almost equal proportions preferred amniocentesis and CVS (50.2 and 45.1%, respectively). Risk information was the most important factor to women preferring amniocentesis; the timing of the test or nature of the termination procedure was most important to those preferring CVS. In the hypothetical case where CVS was stipulated to have the same attributable risk as amniocentesis, 82% of respondents would prefer it. However, if the spontaneous abortion rate following CVS was stipulated to be 5% more than the amniocentesis risk, preferences reversed and only 22% would still prefer it. Thus, the data suggest that the ultimate acceptability of the new procedure for women over 35 years seeking prenatal diagnosis will depend on the risk associated with it and underscore the importance of ongoing trials aimed at establishing this risk.

Evaluation of amniotic fluid in preterm labor with intact membranes

Abstract: Amniotic fluid was obtained from 35 pregnant women in preterm labor with intact membranes Their gestational ages ranged from 24 to 34 weeks Bacteria were detected in only 1 (3%) of the 35 amniotic fluid samples The anaerobic culture grew Bacteroides corrodens and Fusobacterium nucleatum The L/S ratio was greater than 40 in six patients (17%), 25-40 in two (6%) and less than 25 in 23 (66%); the quantity of fluid was inadequate for L/S analysis in four (11%) None of the 35 newborns developed evidence of infection in the neonatal period Only two women (6%) were febrile postpartum, and none experienced a prolonged hospital stay Seven (20%) of the infants developed respiratory distress syndrome Five (14%) developed hyaline membrane disease, and two (6%) had transient tachypnea of the newborn Intrauterine infection may play a lesser role in preterm labor with intact membranes than previously postulated Amniocentesis may provide useful information for directing management by permitting one to assess fetal pulmonary maturity and the presence of meconium

Temporal changes in the utilization of amniocentesis for prenatal diagnosis by women of advanced maternal age, 1976–1983

Abstract: Utilization of amniocentesis for prenatal diagnosis because of the indication of advanced maternal age (≥ 35 years at delivery) was examined in the population of B.C. over an 8-year period (1976–1983). As of 1983, approximately one out of three eligible women (≥ 35 years at delivery) is having the test. In the older group (≥ 38 years at delivery) approximately one out of two eligible women is having the test. The data do not indicate that the proportion of eligible women having amniocentesis has reached a plateau; utilization is continuing to increase. It appears that prenatal diagnosis is an ethically acceptable alternative for a large proportion of the population.

Prenatal diagnosis of cystic fibrosis: I. Prospective study of 51 pregnancies

Abstract: A prenatal diagnosis was performed in 51 pregnancies with a 1-in-4 risk of having a child with cystic fibrosis. The criteria for determining an affected fetus were based on the results of alkaline phosphatase (ALP) residual activity after inhibition by phenylalanine and by homoarginine, of total ALP activity, and of gamma-glutamyltranspeptidase (GGTP) activity in the amniotic fluid taken between 16 and 19 weeks of pregnancy. The chromosomal analysis of amniotic fluid cells showed trisomy 13 in one case which was excluded from the analysis of biochemical assays. The biochemical assays were in the normal ranges in the amniotic fluid of 35 pregnancies: 26 have reached term and a normal infant has been born, 9 are still in progress. A deficiency of the ALP phenylalanine-inhibitable form, depressed values of total ALP and GGTP were observed in the amniotic fluid of 15 pregnancies: one pregnancy went to term and the infant had CF, in 14 cases the pregnancy was terminated, and meconium ileus was observed in ten of these cases. It was observed that the changes towards abnormal values became more significant with advancing gestational age and that 18 weeks appeared to be the optimum time for diagnostic amniocentesis.

Comparative study of 15 lysosomal enzymes in chorionic villi and cultured amniotic fluid cells. Early prenatal diagnosis in seven pregnancies at risk for lysosomal storage diseases.

Abstract: A large number of chorionic villi samples obtained from women undergoing elective first trimester termination of pregnancy was analysed by enzyme assays similar to those applied to cultured amniotic cells. The levels of 15 lysosomal enzymes were compared to those observed in tissue cultures of amniotic cells obtained through amniocentesis at 16-18 weeks of pregnancy and the results were discussed in order to assess the usefulness of trophoblast biopsy for first trimester diagnosis of hereditary lysosomal diseases. The data suggest the applicability of this source of fetal cells for prenatal diagnosis of fifteen respective genetically determined enzyme deficiencies with the probable exception of α-L-iduronidase deficiency. Enzyme determinations were performed on chorionic villi samples of two pregnancies at risk for Tay-Sachs disease, three pregnancies for GM1 gangliosidosis type 1, one for mucopolysaccharidosis type VI and one for Wolman's disease.

Genetic amniocentesis: a twelve years' experience.

Abstract: The first 2,013 fetuses in 2,000 patients undergoing genetic amniocentesis at our institution were analyzed for the incidence of abnormal findings and for the safety and accuracy of the procedure. One percent of the patients were found to have aneuploid fetuses and another 1% were found to have elevated amniotic fluid concentrations of alpha-fetoprotein. Advanced maternal age was the indication for amniocentesis in 84% of the women with aneuploid fetuses. Thirty-two (1.6%) of the pregnancies ended in spontaneous abortion and 35 (1.7%) were terminated because of abnormal results of the prenatal diagnostic procedure. Our error rate was 0.15%, and tissue culture was successful in 97.7% of the procedures. During the latter part of our experience concurrent ultrasonography was utilized with the amniocentesis, resulting in a reduction in blood-tinged specimens from 15.0% to 5.2%. In experienced hands, midtrimester amniocentesis for the purpose of prenatal diagnosis of genetically determined defects is a safe, accurate, and valuable procedure for the identification of fetal abnormalities.