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Affected Fetuses (affected + fetuse)
Selected AbstractsA recurrent ITGA9 missense mutation in human fetuses with severe chylothorax: possible correlation with poor response to fetal therapyPRENATAL DIAGNOSIS, Issue 11 2008Gwo-Chin Ma Abstract Objectives To assess the possible correlations between the reported candidate genes (VEGFR3, FOXC2, ITGA9 and ITGB1) and the clinical response in fetuses with severe congenital chylothorax (CC) treated by prenatal OK-432 pleurodesis. Methods We studied 12 unrelated fetuses with severe CC, receiving fetal therapy by OK-432 pleurodesis. Genotyping of the candidate genes and the clinical parameters of these 12 fetuses were investigated. Additional 96 control individuals were enrolled to evaluate the possible polymorphisms at these candidate genes in population. Results A recurrent heterozygous missense mutation (c.1210G > A, p.G404S) was identified in the beta-propeller domain of integrin ,9 (ITGA9), a cell adhesion receptor, in four of the five fetuses who failed to respond to the OK-432 treatment. Computer modeling of the p.G404S substitution supported the deleterious nature of this mutation. Family analyses in three affected fetuses demonstrated that the heterozygous mutant allele is of parental origin, suggesting an autosomal recessive inheritance of this genetic defect. Conclusions To the best of our knowledge, this is the first insight into the possible link between ITGA9 and CC in human fetuses. The identification of pathogenetic mutations and their possible link to the clinical responses of particular treatments may contribute to better pregnancy counseling and management. Copyright © 2008 John Wiley & Sons, Ltd. [source] Amniocentesis in the third trimester of pregnancyPRENATAL DIAGNOSIS, Issue 11 2007Keelin O'Donoghue Abstract Background Amniocentesis in the third trimester, which reduces risks of procedure-related miscarriage but still allows termination of affected fetuses, may be applicable in some pregnancies. The implications of deferring amniocentesis include complications, delivery before the test and increased amniotic fluid culture failure rates. We investigated the indications, complications, karyotype results and laboratory failure rates of third-trimester amniocentesis. Methods We studied all women who underwent third-trimester amniocentesis from 2000 to 2006. Data were collected from ultrasound databases, computerised records and individual chart review. Results We reviewed 165 pregnancies that underwent amniocenteses after 28 weeks. Median maternal age at amniocentesis was 32 years and median gestation, 32+2 weeks. Indications included malformation (60/165), soft markers (37/165), maternal request (12/165), and positive screening test (11/165). Of the 49 women(29.7%) who declined second-trimester amniocentesis, 24.5% had twins and 38.8%, malformations. Amniocentesis was not offered to 116 women: 57/116 (49.1%) third-trimester referrals, 25/116 (21.5%) diagnosed late and the remainder, low-risk indications. Fetal karyotype was abnormal in 17 cases (10.3%). Seven women who initially declined amniocentesis had abnormal results compared with one advised to have late amniocentesis. Culture failure rate was 9.7%, however results were obtained by Quantitative fluorescent polymerase chain reaction (QF-PCR) from 164/165 samples. Complication rate was 1.2%. Conclusion For late diagnoses and for low-risk indications, third-trimester amniocentesis is an acceptable option, especially when utilising QF-PCR with cytogenetic culture. Copyright © 2007 John Wiley & Sons, Ltd. [source] Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemiaPRENATAL DIAGNOSIS, Issue 3 2006Wim J. Kleijer Abstract Background In the course of 25 years, we have experienced a high rate of affected fetuses in the prenatal diagnosis of citrullinemia. Methods and Results Ninety-one pregnancies at 1 in 4 risk were tested; 36 were diagnosed as affected (39.5%; P = 0.0015). The high rate of positive diagnoses was found both after chorionic villus sampling (24/68 = 35.3%) and amniocentesis (12/23 = 52.2%) despite the completely different and independent techniques used. Using exactly the same (indirect) enzyme assay for argininosuccinic aciduria on chorionic villi and a similar method on amniotic fluid, the expected rate of affected fetuses was found: 13/53 = 24.5%. Technical and genetic causes for the unexpected results were excluded by confirmatory studies performed on independent fetal material, which was available for 27 of the 36 fetuses affected with citrullinemia. Biochemical confirmation was obtained in the 27 cases, whereas in 18 fetuses homozygosity or compound heterozygosity for disease-causing mutations were retrospectively demonstrated in the stored fetal cells. Conclusion The results suggest the occurrence of preferential transmission of the mutant allele. An explanation for this phenomenon may be found in a protective role of argininosuccinic acid synthetase deficiency in mutant sperm cells against the possibly detrimental or apoptotic effect of nitric oxide produced normally from arginine by nitric oxide synthase. Copyright © 2006 John Wiley & Sons, Ltd. [source] First-trimester maternal serum PAPP-A, SP1 and M-CSF levels in normal and trisomic twin pregnanciesPRENATAL DIAGNOSIS, Issue 2 2003N. A. Bersinger Abstract Objective To study PAPP-A and SP1 for biochemical trisomy screening in twin pregnancies and to investigate the role of maternal and placental compartments in marker production by comparing the levels of the decidual cytokine M-CSF with the PAPP-A and SP1 from the placenta. Methods Thirteen twin pregnancies with at least one chromosomally abnormal fetus were compared with 68 normal twin pregnancies. Sera were obtained between 11 + 3 and 13 + 6 weeks of gestation, and PAPP-A, SP1 and M-CSF levels were determined by immunoassay. These concentrations were also compared with gestation-matched groups of 18 singleton normal pregnancies and 18 singleton Down syndrome pregnancies. Results PAPP-A and SP1, but not M-CSF, levels were higher in normal twin pregnancy than in normal singleton pregnancy. SP1 levels, but not PAPP-A, correlated to M-CSF. PAPP-A, but not SP1, levels were reduced in abnormal twin pregnancies, with an increasing effect according to the number of affected fetuses, and were more pronounced in pregnancies with trisomy 18 or 13 than in trisomy 21 fetuses. M-CSF was inconsistent, with a trend towards increased levels in trisomy 21. Conclusion PAPP-A remains the best biochemical screening marker for fetal trisomies 21, 18 or 13, in singleton as well as in twin pregnancy. In contrast to SP1, its site of production is not likely to be restricted to the placenta. The role of the (maternally produced) M-CSF remains to be further investigated. Copyright © 2003 John Wiley & Sons, Ltd. [source] Population-based carrier screening for cystic fibrosis in Victoria: The first three years experienceAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 5 2009John MASSIE Background: Cystic fibrosis (CF) is the most common inherited, life-shortening condition affecting Australian children. The carrier frequency is one per 25 and most babies with CF are born to parents with no family history. Carrier testing is possible before a couple has an affected infant. Aims:, To report the outcomes of a carrier screening program for CF. Method: Carrier screening was offered to women and couples planning a pregnancy, or in early pregnancy, through obstetricians and general practitioners in Victoria, Australia. Samples were collected by cheek swab and posted to the laboratory. Twelve CFTR gene mutations were tested. Carriers were offered genetic counselling and partner testing. Carrier couples were offered prenatal testing by chorionic villous sampling (CVS) if pregnant. The number of people tested, carriers detected and pregnancy outcomes were recorded from January 2006 to December 2008. Results: A total of 3200 individuals were screened (3000 females). One hundred and six carriers were identified (one per 30, 95% confidence interval one per 25, one per 36). All carrier partners were screened, and nine carrier couples identified (total carriers 115). Ninety-six individuals (83%) were carriers of the p.508del mutation. Of the nine carrier couples, six were pregnant at the time of screening (five natural conception and one in vitro fertilisation) and all had CVS (mean gestation 12.5 weeks). Two fetuses were affected, three were carriers and one was not a carrier. Termination of pregnancy was undertaken for the affected fetuses. Conclusion: Carrier screening for CF by obstetricians and general practitioners by cheek swab sample can be successfully undertaken prior to pregnancy or in the early stages of pregnancy. [source] The use of nuchal translucency measurement and second trimester biochemical markers in screening for Down's SyndromeBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2001G.D. Michailidis Objective To assess the effectiveness of antenatal screening for trisomy 21 by first trimester sonography followed by second trimester biochemical screening. Design Retrospective five-year review. Setting Maternity unit of a university hospital. Population An unselected group of 7447 pregnant women who had a first trimester scan and nuchal translucency measurement in our unit after January 1995 and had an estimated date of delivery before 1 January 2000. 11.9% were , 37 years old. A subgroup (n=4864) also had second trimester biochemical testing by alpha-fetoprotein and free ,-human chorionic gonadotrophin. Main outcome measures Prenatal and postnatal diagnosis of trisomy 21. Results There were 23 fetuses affected with trisomy 21. The overall prenatal detection rate was 87% (20/23; 95% CI 66% to 97%) and we performed invasive procedures in 8.5% of our population. First trimester sonography identified 74% (95% CI 51.6% to 89.8%) of affected fetuses. Second trimester biochemical screening detected half of the fetuses with trisomy 21 which were missed by first trimester screening, increasing the sensitivity to 90.5% (19/21; 95% CI 69.6% to 98.8%) for an invasive procedure rate of 4.2% performed in screened positive women. However, the positive predictive value of the biochemical test was very low (0.5%). In screen negative women, karyotyping for advanced maternal age did not detect any affected fetuses. Conclusion First trimester nuchal translucency measurement is an effective screening test for the prenatal detection of fetuses with Down's Syndrome. Although the measurement of biochemical markers in the second trimester can detect additional affected fetuses this may be outweighed by the delay in diagnosis, the extra visits and cost so that the right time for biochemical screening is most likely to be in the first trimester. [source] | ||||||||||