Detection of chromosome aberrations during prenatal genetic testing for single gene disorders.
Explore the source record for details and available documents.
Adult↗
SEARCH · Search PubMed
Results for “prenatal testing”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Policy analysis for prenatal genetic diagnosis.
Consideration of the analytic difficulties faced in estimating the benefits and costs of prenatal genetic diagnosis, coupled with a brief review of existing benefit-cost studies, leads to the conclusion that public subsidy of prenatal testing can yield benefits substantially in excess of costs. The practical obstacles to such programs include the attitudes of prospective parents, a lack of knowledge, monetary barriers, inadequately organized medical resources, and the political issue of abortion. Policy analysis can now nevertheless formulate principles and guide immediate actions to improve present utilization of prenatal testing and to facilitate possible future expansion of these diagnostic techniques.
Abortion, Induced↗
Changing their minds with time: a comparison of hypothetical and actual reproductive behaviors in parents of children with cystic fibrosis.
OBJECTIVE: Newborn screening for cystic fibrosis, with appropriate counseling, enables carrier parents to be informed early about future reproductive choices. Previous studies have assessed attitudes toward reproductive decisions in a hypothetical pregnancy or have measured reproductive behaviors. We aimed to measure parent attitudes to reproductive technologies and to compare prospectively these attitudes with later reproductive behaviors. METHODS: Parents of children who had cystic fibrosis and were aged 2 to 7 years were surveyed at baseline using a written questionnaire that explored attitudes to prenatal testing and termination of pregnancy in a hypothetical pregnancy. Parent knowledge and access to genetic counseling services also were assessed. Five years later, we compared attitudes with actual reproductive behaviors. RESULTS: Fifty-six mothers participated at baseline, and 43 were resurveyed 5 years later. Parent knowledge of cystic fibrosis and genetics was very good. A total of 93% had met a genetic counselor at the time of diagnosis, and more than half had on at least 1 subsequent occasion. At baseline, 82% reported that they would be likely to have prenatal diagnosis in a subsequent pregnancy, and 56% reported that they would be likely to terminate an affected pregnancy. Twenty-seven mothers since had been pregnant, with prenatal diagnosis used in 33 of the 55 pregnancies. In 67%, the hypothetically reported behavior regarding use of prenatal testing was the same as their actual behavior. Five of the 33 tested pregnancies were affected; all ended in termination. Reproductive choices in relationship to the number of children wanted, together with attitudes toward prenatal diagnosis and termination of pregnancy, were dynamic over time, with decisions having changed in both directions. CONCLUSIONS: This cohort of parents has actively used reproductive technologies since the birth of a child who has cystic fibrosis that was diagnosed by newborn screening. The dynamic aspect of reproductive choices highlights the importance of ongoing access to genetic counseling beyond the initial period of diagnosis and education, regardless of whether parents report that they expect to use reproductive technologies.
Abortion, Induced↗
How and why parents change their attitudes to prenatal diagnosis.
Parents who know they are carriers of a genetically transmitted disease because they gave birth to an affected child are being offered a number of reproductive options in a subsequent pregnancy. We describe the attitudes and motives of parents of children with cystic fibrosis (CF) who were initially determined to use prenatal testing but eventually refused it. Based on our observations and clinical impressions we built a model of change that entails a series of stages and depicts change as a process. This begins with the provision of comprehensive information and emotional support through health professionals (Stage 1). The parents then engage in intense confrontation with the impact of prenatal testing and are exposed to influences from many sides. The repeated comparing of the arguments results in uncertainty and distress (Stage 2). When pregnancy occurs a decision must be made and the process culminates in participating in a life-or-death decision. If the parents cannot cope with that responsibility then a change towards rejection of prenatal diagnosis is likely (Stage 3). This phenomenon seems to be the most decisive factor. A case vignette is used to illustrate this model which may be applicable to many individuals who face major and emotionally fraught decisions.
Adaptation, Psychological↗
Effect of androgens on the germ cell-depleted testes of prenatally irradiated rats.
To study the effect of androgens on somatic testicular cells, rats were rendered germ cell depleted by prenatal irradiation (RX). Adult RX rats were treated with a desensitizing dose of a GnRH agonist (GnRHa; Zoladex), combined with an antiandrogen (Nilutamide) to preclude all androgen effects, or combined with testosterone or hCG to restore androgen action. The effect of these treatments for 3 weeks on the weight of testes and accessory sex glands, hormones (LH, FSH, testosterone, inhibin), testicular proteins, the pattern of incorporation of [35S]-methionine into testicular proteins (studied by two dimensional gel electrophoresis) and steady state mRNA levels for transferrin and androgen-binding protein (ABP) were evaluated. Combined treatment with GnRHa and antiandrogen virtually eliminated gonadotrophins, androgens and androgen effects. Testicular weight was reduced to 50% of that observed in RX controls. Treatment with GnRHa and testosterone resulted in supraphysiological levels of testosterone and testicular weights comparable to those observed in RX controls. FSH levels in these animals, however, were in the normal range. A low dose of hCG also restored testicular weight in the presence of low concentrations of serum testosterone and low normal levels of FSH. Neither polyacrylamide gel electrophoresis of total testicular proteins nor two dimensional gel electrophoresis of [35S]-methionine labelled proteins revealed striking changes in distinct testicular proteins as a result of androgen withdrawal or androgen treatment. Dot blot hybridization showed a three-fold increase in the mRNA level for ABP (expressed per microgram total RNA) in the Sertoli cell enriched testes of RX rats. This level was barely influenced by androgen withdrawal or androgen administration. The mRNA level for transferrin was increased six-fold in RX rats. A 50% reduction of this level was observed after combined treatment with GnRHa and antiandrogen. It is concluded that, in the germ cell-depleted testis, the major effect of androgens is an overall increase in protein and RNA synthesis rather than a very important and selective increase of a few gene products.
Androgen Antagonists↗
Dealing with the prenatal diagnosis of clefting: a parent's perspective.
OBJECTIVES: Prenatal testing and information is available on an increasing basis for a variety of reasons. There are conflicting standards of care in the delivery of this type of evaluation and even more confusion around access to such services. As physicians and patients evaluate which tests will generate useful information with acceptable levels of risk, the rules of the game constantly shift. Presenting the situation from the viewpoints of both a professional and a parent, issues revolving around uncertainty and reassurance are evaluated. A description of the personal experience of the impact of the discovery of a cleft prenatally is provided. CONCLUSIONS: Finally, efforts are made to raise questions about our motivations behind conducting prenatal testing and also developing some suggestions about how to support families better in our regular clinical work. A challenge is made to providers and patients to do more work prior to examination to explore how the unexpected will be handled. The dilemma about how to facilitate informed consent through full disclosure without overwhelming the patient is also discussed.
Attitude to Health↗
Attitudes towards bipolar disorder and predictive genetic testing among patients and providers.
Attitudes about bipolar disorder (manic depressive disorder) and genetic testing were investigated. Three groups of subjects were surveyed including members of a manic depressive support group, medical students, and psychiatry residents. The questionnaire was intended to elicit impressions and attitudes about bipolar disorder (BP) from mental health consumers and health care providers with varying levels of personal and professional familiarity with the disorder. Attitudes towards prenatal testing and pregnancy termination were also assessed. The intention hypothetically to terminate a pregnancy was influenced by the likelihood of developing BP a well as the projected course and severity of illness. Nearly half of the total sample would terminate pregnancy if the fetus were definitely to develop an unspecified form of bipolar disorder. Presumed severity of illness was also found to be a modifying factor in the decision, with a low percentage of subjects electing to terminate for a mild course of bipolar disorder and a majority opting for termination in the case of an extremely severe presentation. Support group members were the least likely to terminate a hypothetical pregnancy in the case of a positive prenatal test and were the most likely to desire childhood testing in the absence of preventive or treatment options. The possible implications of these findings, as well as avenues of future research, are discussed.
Abortion, Spontaneous↗
New rapid test for prenatal detection of trisomy 21 (Down's syndrome): preliminary report.
OBJECTIVE: To devise and evaluate a rapid screening method for detecting trisomy 21 (Down's syndrome) in samples of uncultured amniotic fluid cells. DESIGN: Non-radioactive in situ hybridisation with HY128, a 500,000 base pair yeast artificial chromosome probe specific for chromosome 21. Blinded study of 12 karyotypically normal amniotic fluid samples and eight samples trisomic for chromosome 21. SETTING: Cytogenetic and obstetric services at a tertiary referral centre, Copenhagen. MAIN OUTCOME MEASURES: Time necessary to complete the test. Proportion of cell nuclei containing two and three hybridisation signals in karyotypically normal and abnormal amniotic fluid samples. RESULTS: The test could be completed within three to four days after amniocentesis. In the normal samples a mean of 73% (range 61-82%) of the amniotic cell nuclei showed two hybridisation signals and 6% (0-18%) showed three signals. By contrast, among the trisomic samples 29% (19-38%) of the nuclei exhibited two signals and 48% (31-60%) showed three signals. CONCLUSION: The technique clearly distinguished between normal and trisomic samples. Prenatal diagnosis with in situ hybridisation with chromosome specific probes was fast and may make it possible to screen for selected, aneuploidies. However, the technique is still at a preliminary stage and needs further evaluation and refinement.
Amniocentesis↗
Molecular analysis of 4q35 rearrangements in fascioscapulohumeral muscular dystrophy (FSHD): application to family studies for a correct genetic advice and a reliable prenatal diagnosis of the disease.
In the majority of facioscapulohumeral muscular dystrophy (FSHD) families (about 95%) the genetic defect has been identified as a deletion of a variable number of KpnI repeats in the 4q35 region, although no specific transcripts from this locus have been isolated so far. Molecular diagnosis is based on the detection by probe p13E-11 of EcoRI small fragments, in the range 10-28 kb, that are resistant to BlnI digestion. In family studies this probe is used with other 4q35 polymorphic markers to assign the haplotype associated with the disease. So far, we performed DNA analysis in 145 FSHD families and identified the 4q35 DNA rearrangement not only in affected individuals, but also in healthy subjects at risk of transmitting the disease, such as non-penetrant gene carriers and somatic mosaics. In addition we applied prenatal tests to 19 fetuses, using DNA extracted from chorionic villi samples (CVS) at 10-11 weeks of gestation. The FSHD status, as determined by the presence of BlnI-resistant small fragments associated with the at risk haplotype, was assessed in nine fetuses; in the remaining 10 cases the disease was excluded. Our results show that molecular analysis of 4q35 rearrangements is a reliable indirect method to perform diagnostic, predictive and prenatal tests in FSHD.
Chromosomes, Human, Pair 4↗
Early prenatal diagnosis of cartilage-hair hypoplasia (CHH) with polymorphic DNA markers.
Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder resulting in short stature and hypoplasia of hair. Associated features include impaired T-cell-mediated immunity, deficient erythropoiesis, gastrointestinal dysfunction, and an increased risk of malignancies. As the condition may, in some cases, be severe or even fatal during childhood, families with a previous history of CHH may wish to have prenatal diagnosis. We have previously assigned the gene for CHH to the proximal 9p by linkage analysis using several polymorphic DNA markers. Here we report the prenatal testing for CHH in three Finnish and one Australian family using three DNA markers closely linked to the CHH gene. In three cases a fetus unaffected with CHH was predicted at the probability level of more than 94 per cent. In one case, an affected fetus was predicted. The results were in concordance with ultrasonography performed for all fetuses. The three children born to date were unaffected as predicted. The DNA marker-based analysis thus provides a useful method for early prenatal testing for CHH.
Base Sequence↗
Impaired performance on odor-aversion testing following prenatal aspartame exposure in the guinea pig.
Pregnant guinea pigs were administered aspartame (500 mg/kg) in sesame oil by gavage or sesame oil alone between the day of conception and parturition. A nontreated control group was also maintained. There were no statistically significant effects of the treatment on maternal weight gain, litter size, or birth weight of the pups. Newborn pups were weighed daily and on day 15 were injected with either LiCl or saline and placed in a cage with vanilla odor for 30 min. Twenty-four hr later the pups were permitted to choose between vanilla and lemon odors in a preference test. While both the vehicle-treated control and nontreated control groups injected with LiCl showed a conditioned aversion to vanilla, the aspartame-treated pups injected with LiCl did not. These data indicate that aspartame exposure at 500 mg/kg throughout gestation disrupts odor-associative learning in 15-day-old guinea pigs.
Animals↗
Genetic counseling and prenatal diagnosis: a multicultural perspective.
More and more women are using prenatal tests to obtain specific information on the health of the developing fetus. The objective of genetic counseling is not to decrease the occurrence of genetic disease, it is to help individuals and families adjust to their genetic risks and make their own decisions in line with their reproductive goals and world views. Choices made by parent(s) will reflect their own intrapsychic processes as well as their own cultural and social understanding of genetic risk and disease. As prenatal testing continues to diagnose an ever growing number of genetic disorders, genetic counseling faces greater and greater challenges. Now more than ever before, genetic counseling must incorporate both psychological counseling and multiculturalism in order to serve diverse individuals and families at risk for genetic disease.
Attitude to Health↗
[Frequency and practice of prescribing prenatal HIV tests during pregnancy].
BACKGROUND: To assess frequency and practices of antenatal HIV testing. METHODS: Cross-sectional study. Site: obstetric units of San Paolo Hospital, Milan (teaching, public, 60 beds, 1500 deliveries/years, reference centre for HIV and pregnancy) and of Sandro Pertini Hospital, Rome (public, urban, 36 beds, 1500 deliveries/year). PARTICIPANTS: parturients consecutively admitted for delivery, in the last three months of 1997. INTERVENTION: interview by a structured questionnaire. Out-comes: frequency and practices of antenatal HIV testing. RESULTS: About 79% of the 500 parturients admitted at the San Paolo Hospital and 57% of the 300 at the Pertini Hospital had been tested for HIV during the current pregnancy (p < 0.001). Overall, in 91% of cases (507/555) the test has been requested by the woman's gynecologist with other antenatal tests. Discussion on HIV testing, infection and pregnancy lasted less than 5 minutes in 92% of San Paolo parturients, and in almost all (99.4%) of the Pertini women. Women in the San Paolo hospital had HIV information available by leaflets in 47% of cases in comparison to 35% of those at the Pertini hospital. CONCLUSIONS: In Italy, HIV testing seems to be routinely included in the management of pregnancy, although the uptake and practices of offering the test seem not always appropriate. The higher uptake and the better practice seem to correlate with the higher involvement of San Paolo hospital in the fields of HIV infection in pregnancy. However, the reported overall 71% of tested parturients suggests that in Italy we are still far away from a universal antenatal HIV testing. Specific guidelines should be issued in order to implement and to uniform universal antenatal HIV testing, and to optimize the management of infected women.
Adolescent↗
Screening tests in prenatal care: a national study in Israel.
BACKGROUND: Prenatal care in Israel is established as a universal service, but the degree of compliance with care recommendations may vary with the healthcare provider or the characteristics of the population. OBJECTIVES: To study referral to and compliance with the performance of ultrasound, alpha-fetoprotein and amniocentesis and the factors associated with them in a national sample. METHODS: The sampling frame consisted of women who gave birth during March 2000. The sample included 1,100 Israeli Jewish and Arab women who resided in localities with over 50,000 and 20,000 inhabitants respectively. They were interviewed by phone 3 months after delivery. RESULTS: In both population groups 30% reported having seven or more ultrasounds during pregnancy. The performance of fetal body scans was relatively low. Factors associated with non-performance among Jewish women were: lower education, religiousness, and attending Mother and Child Health services as compared to all other services. Seventy-seven percent of Jewish women and 84% of Arab women reported that they had been referred for alpha-protein tests. For women aged 35 and over, 55% of Jewish women were referred for amniocentesis and 63% complied, whereas 39% of Arab women were referred but none complied. CONCLUSIONS: Ultrasound is almost universally performed among Jewish and Arab women, however fetal body scans, alpha-fetoprotein and amniocentesis (for women over the age of 35) are not. The reasons for the lower coverage may be due to under-referral and/or lack of compliance of the women, perhaps due to sociocultural barriers. In both population groups considerable out-of-pocket money is paid for the tests.
Amniocentesis↗
Prenatal diagnosis for thalassaemia in a multicultural society.
The provision of a prenatal diagnosis service for thalassaemia is becoming more demanding. In an ethnically-diverse community, the number of mutations has increased. Requests for prenatal testing continue to come at advanced stage in pregnancy, often without the underlying mutation having been identified. Although controls are included in PCR assays, errors can still occur. The alternative to DNA testing, i.e., an alpha/beta globin chain synthesis ratio on a fetal blood sample, is now less readily available. In the circumstances described, the laboratory must adopt a more efficient and reliable approach to DNA mutation analysis. With currently available technology, this improvement is more likely to come through increased automation. To achieve this aim, we have moved to capillary electrophoresis. With capillary electrophoresis we are able to use a PCR-based screening strategy which can detect up to 11 beta thalassaemia mutations. The actual prenatal test is undertaken using two independent PCRs thereby reducing the potential for error. Despite the advantages of PCR, approximately 12 per cent of beta thalassaemia and about nine per cent of alpha thalassaemia cases require further study in our experience. In this situation, capillary electrophoresis has again proven helpful since a DNA scanning approach, such as single strand conformation polymorphism, can be automated to identify the region of DNA to be sequenced.
Asia, Southeastern↗
First trimester maternal serum lysosomal enzymes: implications for carrier testing and prenatal diagnosis.
Carrier detection for lysosomal storage diseases is sometimes possible by evaluating maternal serum levels of specific enzymes. However, lysosomal enzymes (LE) can be modified by maternal hormonal changes in pregnancy or embryonic contributions. Maternal serum was obtained prospectively in the follicular phase and at 2-5 and 7-11 weeks after conception from 13 infertility patients with precisely known ovulation dates. Eleven enzyme activities were determined fluorimetrically using 4-methylumbelliferyl substrates. Using repeated measures ANOVA, alpha-N-acetyl-glucosaminidase (p less than 0.05), hexosaminidase A (p less than 0.005) and hexosaminidase A and B (p less than 0.005) increased during the first trimester, and 8 enzymes did not change significantly. Our data show differing patterns of LE in the first trimester. These may be explained by: (1) variability of maternal reaction to hormonal changes of pregnancy, or (2) variable embryonic contributions suggesting differential ontogeny and placental transfer of these enzymes. The increase in levels of the 3 specific LE in maternal serum may interfere with the accuracy of carrier testing in early pregnancy, but pregnancy should not interfere with the other 8.
Adult↗
Prenatal diagnosis of haemoglobinopathies: A status report.
An international registry of prenatal tests for haemoglobinopathies has been kept since July, 1974. Up to March, 1981, 1856 tests had been done with fetal blood and 70 with amniotic fibroblast DNA in 21 centres. Of the tests on fetal blood 92% were for the diagnosis of thalassaemia and 8% for that of sickle disorders. Blood was sampled via fetoscopy in 67% of cases and by placental aspiration in 33%. Adequate samples were obtained in 97% of cases. With fetoscopy the proportion of red cells obtained that were of fetal origin was 92%, and with aspiration it was 57%. In the most recent year of the registry the fetal loss rate was 3.9% (of 725 cases); and the rate was 5.6% overall (5.2% by fetoscopy and 6.5% by aspiration). Affected fetuses were detected in 23% of cases at risk for thalassaemia, and in 15% at risk for sickle disorders. The error rate was 0.9% and consisted mostly of false negatives. Fibroblast DNA analyses were used to assess the risk of sickle disorders in 61 (87%) of the 70 cases studied. 24% were affected. 26% had exclusion diagnoses only. The use of prenatal tests, together with genetic screening and counselling, has considerably reduced the rate at which new homozygous thalassaemics are born in several regions of the world.
Anemia, Sickle Cell↗
[Treacher Collins syndrome: case report and literature review].
OBJECTIVE: To study the genetic background, clinical features, diagnosis, management, and prenatal testing and counseling of Treacher Collins syndrome (TCS). METHOD: The clinical data of a patient and his mother suffering from TCS was reported and the relevant literatures were also reviewed. RESULT: TCS is an autosomal dominant disorder characterized by craniofacial mal-development, including antimongoloid slant of the eyes, micrognathia, microtia and other deformity of the ears. TCS results from the mutation in TCOF1 gene (Treacher Collins-Franceschetti Syndrome gene), located in 5q32-q33.1. Diagnosis of TCS is made through clinical evaluation, radiographic examination, and molecular genetic analysis. Treatment is tailored to the specific needs of each individual by a multidisciplinary craniofacial management team. The choosing of optimal operation time and method is very important. Prenatal testing and genetic counseling for risky pregnancy is necessary. CONCLUSION: The stepwise regimen of treatment is craniofacial reconstruction, orthognathic procedures, orthodontic alignment of the teeth, nasal reconstruction, external ear reconstruction and external auditory canal and middle ear reconstruction.
Female↗