bluuebunny/crossref_metadata_2025_split huggingface dataset:
Second‐trimester maternal serum screening using alpha‐fetoprotein, human chorionic gonadotrophin, and unconjugated oestriol: Experience of a regional programme
Authors: Goodburn S. F. , Yates J. R. W. , Raggatt P. R. , Carr C. , Ferguson‐Smith M. E. , Kershaw A. J. , Milton P. J. D. , Ferguson‐Smith M. A. 
Published: March 2007

AbstractOver a 2‐year period from January 1991 to December 1992, second‐trimester maternal serum screening for Down's syndrome using alpha‐fetoprotein (aFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) was made available to five health districts in East Anglia, with a total population of 1·2 million. Amniocentesis was offered when the risk of Down's syndrome at term was 1:200 or greater. 25359 singleton pregnancies were screened, representing an uptake of 77 per cent. The recall rate for the 24 per cent of women who had not had a dating scan prior to the test was 9·4 per cent compared with 3·9 per cent for those who had been scanned (P<0·0005). Seventy‐five per cent (36/48) of Down's syndrome pregnancies were detected for a false‐positive rate of 4·0 per cent. Twenty‐five out of 36 of detected Down's syndrome pregnancies were dated by scan prior to sampling, and in the 11 remaining cases, the dates were confirmed by scan after a high‐risk result was obtained. The exclusion of uE3 from the screening protocol would have reduced the detection rate to 52 per cent (25/48) for the same false‐positive rate. Eighty‐five per cent of women identified at high risk accepted the offer of an amniocentesis. Other fetal abnormalities detected were trisomy 18 (3), trisomy 13 (2), 45,X (6), 69,XXX (5), other chromosome abnormalities (9), open neural tube defects (26), hydrocephalus (7), abdominal wall defects (4), and steroid sulphatase deficiency (6).
Congenital malformations subsequent to chorionic villus sampling: Outcome analysis of 1048 consecutive procedures
Authors: Silver Richard K. , Macgregor Scott N. , Muhlbach Lydia H. , Knutel Terri A. , Kambich Michelle P. 
Published: March 2007

AbstractWe wished to identify the types and frequencies of malformations among continuing pregnancies exposed to chorionic villus sampling (CVS) and to determine whether selected procedure‐related variables differ between the normal and anomalous cohorts. CVS was performed in 1048 patients between May 1988 and January 1992. Prospective assessment of perinatal outcome was ascertained by (1) physician—patient phone contact within 1 week of sampling, (2) ultrasound evaluation of the fetal anatomy at mid‐gestation, (3) a detailed post‐partum questionnaire completed by the referring obstetrician, and (4) a telephone interview with each patient after the expected date of confinement. Twenty‐seven major malformations were documented among 938 pregnancies (live born, n=934; electively terminated, n=4), and included cardiac malformations (5), hypospadias (5), craniosynostosis (2), pyloric stenosis (2), inguinal hernia (2), polydactyly (2), syndactyly, distal extremely hemimelia, anencephaly, hydrocephalus, cleft lip and palate, omphalocele, diaphragmatic hernia, thanatophoric dysplasia, and unilateral cataract. Normal and anomalous cohorts were similar with respect to sampling method (transabdominal/transcervical ratio), mean gestational age at CVS, single‐pass success rate, and mean total sample weight. No relationship between any procedure‐related variable and the risk of malformation was observed.
Prenatal diagnosis of pyruvate dehydrogenase E1α subunit deficiency
Authors: Brown R. M. , Brown G. K. 
Published: March 2007

AbstractPyruvate dehydrogenase (PDH) E1α subunit deficiency is an X‐linked inborn error of metabolism affecting males and females with equal frequency. The diagnosis is usually based on determination of enzyme activity, although this may present difficulties in some females because of X‐inactivation patterns favouring expression of the normal X chromosome. This is a particular problem for prenatal diagnosis using chorionic villus cells where normal enzyme assay results do not necessarily exclude the diagnosis and confirmatory X‐inactivation analysis may be complicated by variable methylation of active and inactive X chromosomes. We describe prenatal diagnosis in two pregnancies in a family following diagnosis of a PDH E1α deficient male. The first prenatal diagnosis was performed by enzyme assay, but by the time of the subsequent pregnancy, the underlying mutation in the affected male had been identified and direct gene analysis was possible. This study highlights the limitations of diagnosis of PDH E1α deficiency based on measurement of the gene product and illustrates the need for mutation analysis in affected individuals.
Prenatal diagnosis of tyrosinase‐negative oculocutaneous albinism by an electron microscopic dopa reaction test of fetal skin
Authors: Shimizu Hiroshi , Ishiko Akira , Kikuchi Arata , Akiyama Masashi , Suzumori Kaoru , Nishikawa Takeji 
Published: March 2007

AbstractAn electron microscopic DOPA reaction test of fetal skin was used for the prenatal diagnosis of tyrosinase‐negative oculocutaneous albinism (OCA). The subject was a 34‐year‐old Japanese woman in her second pregnancy. Her first child, born in 1982, had been previously examined and confirmed to have tyrosinase‐negative OCA. The parents requested a prenatal diagnosis and we sampled skin from the upper trunk of the fetus. On conventional electron microscopy, the development of melanosomes in interfollicular melanocytes had progressed no further than stage II. Fetal skin samples incubated with L‐DOPA solution indicated a lack of tyrosinase activity and showed that the melanosomes had not progressed beyond stage II. In skin samples from the trunks of three Japanese fetuses aborted for other reasons at 19–20 weeks of gestation, most premature melanosomes were further melanized to stage IV after incubation with L‐DOPA solution. A prenatal diagnosis of tyrosinase‐negative OCA was made. The parents requested a termination and skin biopsies of the abortus confirmed the diagnosis. This study shows that tyrosinase is normally present in melanocytes of the fetal epidermis at 20 weeks' gestation, and that the electron microscopic DOPA reaction test of a fetal skin biopsy specimen is safe and practical, and provides reliable information for making a prenatal diagnosis of tyrosinase‐negative OCA in the second trimester.
Trisomy 8 mosaicism in chorionic villus sampling: Case report and counselling issues
Authors: Klein Jana , Graham John M. , Platt Lawrence D. , Schreck Rhona 
Published: March 2007

AbstractWe report an unusual case involving chorionic villus sampling (CVS) and trisomy 8 mosaicism. CVS showed a normal direct preparation while the culture showed mosaicism for trisomy 8. Subsequent amniocentesis revealed only normal chromosomes. A peripheral blood culture after birth revealed low‐level trisomy 8 mosaicism. The patient appeared phenotypically and developmentally normal at 30 months of age. We conclude that prenatal counselling for similar cases needs to include the rare but real possibility that chromosome mosaicism detected prenatally may be found postnatally with largely unknown consequences. Secondly, low‐level chromosomal mosaicism may be more common than previously recognized. Thirdly, very low‐level trisomy 8 mosaicism may be compatible with a normal phenotype but long‐term follow‐up is required. And lastly, the use of fetal blood sampling is questionable in these cases because the phenotype may not be accurately predicted. Further studies of such cases are needed to address these important and unanswered issues, including the potential implication of mosaicism on academic performance and cognitive functioning.
Screening maternal serum alpha‐fetoprotein levels and human parvovirus antibodies
Authors: Johnson David R. , Fisher Rachel A. , Helwick Jenny J. , Murray Dennis L. , Patterson Maria J. , Downes Frances P. 
Published: March 2007

AbstractThe association between gestational infection with human parvovirus (B19) and fetal loss has increased interest in this virus and demand for diagnostic testing. However, serological assays for B19 are not yet widely available. Maternal serum alpha‐fetoprotein (MSAFP) testing is commonly used during the second trimester to screen for various fetal defects. We attempted to determine whether an elevated level of MSAFP would be an appropriate indication for B19‐specific tests. Over a 26‐month period, MSAFP tests were performed at Michigan State University for 21 392 women. Sera remaining after that testing were stored frozen. Of these, 22 case samples—from women with MSAFP levels greater than 3·0 multiples of the median (MOM) and pregnancies that ended in fetal loss—and 44 matched control samples—from women with MSAFP levels greater than 0·4 and less than 2·2 MOM and live births at term—were tested for B19 antibodies. None of the 66 samples was IgM positive, while 33 (50 per cent) were IgG positive. The presence of IgG was not significantly associated with case or control status (matched odds ratio=0·77, 95 per cent confidence interval 0·28–2·11). These findings are consistent with other studies indicating prior infection in approximately half of adults and suggest that elevated screening MSAFP levels, in the absence of other evidence of B19 infection, should not prompt B19‐specific testing.
First‐trimester prenatal diagnosis of spinal muscular atrophy using microsatellite markers
Authors: Cicero S. Lo , Capon F. , Melchionda S. , Gennarelli M. , Novelli G. , Dallapiccola B. 
Published: March 2007

AbstractTwenty‐five pregnancies at risk for spinal muscular atrophy I (SMA I) have been monitored by first‐trimester prenatal diagnosis. Microsatellite markers were used in all cases to amplify polymorphic regions at the D5S125, D5S435, D5S39, D5S127, and D5S112 loci. All families, including 12 SMA I pedigrees with a deceased index child, were fully informative for DNA analysis. Three fetuses were predicted to be affected and 22 fetuses were predicted to be unaffected. Twenty‐two newborns were unaffected by clinical examination at birth. These results support the accuracy of SMA I prenatal diagnosis based on linkage analysis.
Fetal nuchal oedema and antenatal diagnosis of trisomy 10
Authors: Farrell S. A. , Sue‐Chue‐Lam A. , Miskin M. , Fan Yao‐Shan 
Published: March 2007

AbstractTrisomy 10 was detected at amniocentesis undertaken following observation of fetal nuchal oedema. This is the first report of fetal trisomy 10 in association with nuchal oedema. The physical features of fetal trisomy 10 are described.
Prenatal diagnosis of glutathione synthase deficiency
Authors: Manning N. J. , Davies N. P. , Olpin S. E. , Carpenter K. H. , Smith M. F. , Pollitt R. J. , Duncan S. L. B. , Larsson A. , Carlsson B. 
Published: March 2007

AbstractPrenatal diagnosis for glutathione synthase (EC 6·3.2·3) deficiency in two pregnancies of an at‐risk couple was performed on amniotic fluid taken at 16 weeks' gestation. 5‐Oxoproline (pyroglutamic acid) levels were 970 and 790 μmol/l compared with the normal mean value of 29 μmol/l (range 13–51 μmol/l). The pregnancies were terminated and the diagnosis in one case was subsequently confirmed by assay of glutathione synthase in cultured fetal fibroblasts. In the other, post‐mortem tissue samples failed to grow.
Prenatal diagnosis and post‐mortem study of a fetus with mosaic trisomy 14 due to a dic(14)(p11)
Authors: Lambert I. , Kemp J. , Jackson J. , Joyce H. , Mann S. , Kan A. , Smith A. 
Published: March 2007

AbstractAmniocentesis at 17 weeks' gestation revealed a mosaic karyotype—46,XX/46,XX, — 14,+dic(14)(p11). No abnormalities were detected on ultrasound. Growth and placentation were normal. The fetus was examined after termination of pregnancy and micrognathia and pulmonary hyperlobation were the only abnormalities detected. Several tissues were set up for cytogenetics, including fetal skin, kidney, ovary, and placenta. The diagnosis was confirmed by these studies. The level of mosaicism varied between tissues, with the trisomy 14 cell line highest in amniotic fluid.
Allele frequencies and molecular diagnosis in haemophilia A and B patients from russia and from some Asian Republics of the former U.S.S.R.
Authors: Aseev M. , Surin V. , Baboev K. , Gornostaeva N. , Kuznetzova T. , Kascheeva T. , Ivaschenko T. , Solovyev G. , Mikhailov A. , Lebedev V. , Papaian L. , Andreeva T. , Amoashyi Dm. , Vakharlovsky V. , Baranov V. S. 
Published: March 2007

AbstractRFLP analysis of some intra‐ and extra‐genic polymorphic sites of Factor VIII (FVIII) and Factor IX (FIX) genes with relevant DNA probes or by polymerase chain reaction (PCR) was carried out in Slavic populations from the European part of Russia and also in the native ethnic groups of Uzbekistan and Kazahstan. The allele frequencies for the HindIII (intron 19) and XbaI (intron 22) polymorphic sites (PSs) in the FVIII gene were very similar in the two populations studied, but different for the intron 13 (CA)n repeat. Significant variations in the TaqI (intron d) and DdeI (intron a) polymorphisms of the FIX gene were evident between the Russian and Asian populations. Two unusual alleles (4·35 and 4·2 kb) for the extragenic PS St14/TaqI were registered in Slavs and one new allele (380 bp) for the DdeI polymorphic site of FIX was discovered in both Asian populations. Altogether, 210 haemophilia A (HA) and 24 haemophilia B (HB) families were subjected to molecular studies. So far, 160 HA and 12 HB families have been found to be informative for DNA analysis. Carrier status was ascertained in 42 HA and 6 HB female relatives, and rejected in 52 and 10 of them, respectively. The origin of some HA and HB mutations was traced with relevant polymorphic markers in several at‐risk families. Prenatal diagnosis was accomplished in 28 HA and three HB families, resulting in the identification of 20 affected male fetuses.
Maternal age‐specific risks for trisomies at 9—14 weeks' gestation
Authors: Snijders R. J. M. , Holzgreve W. , Cuckle H. , Nicolaides K. H. 
Published: March 2007

AbstractThis study provides data on the incidence of fetal trisomies 21, 18, and 13 at 9–14 weeks' gestation in women aged 35–45 years and estimates of maternal age‐specific risks in women aged 20–45 years. Our data from 5814 singleton pregnancies undergoing first‐trimester karyotyping for the sole indication of maternal age ⩾ 35 years were combined with those from two previous reports and the incidence of the trisomies was calculated from a total of 15 793 pregnancies. Comparison of incidences at 9–14 weeks' gestation with published data at 15–20 weeks' gestation and in livebirths demonstrated that at birth the maternal age‐specific incidence of trisomy 21 is 33 per cent lower than at 15–20 weeks' gestation and 54 per cent lower than at 9–14 weeks' gestation. Furthermore, the relative frequency of trisomies 18 and 13 decreases from 30 per cent at 9–14 weeks to 22 per cent at 15–20 weeks and 14 per cent at birth.
Maternal serum markers in second‐trimester oligohydramnios
Authors: Los Frans J. , Hagenaars Adriana M. , Cohen‐Overbeek Titia E. , Quartero Hendrik W. P. 
Published: March 2007

AbstractThe levels of the maternal serum markers alpha‐fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) in 35 pregnant women with early second‐trimester oligohydramnios differed from those in a reference population of 1699 singleton pregnancies. Maternal serum AFP levels above the 95th centile of the population distribution were observed in 80 per cent (16/20) of oligohydramnios cases with a normal fetus and in only 20 per cent (3/15) of the cases with a fetus displaying urogenital tract malformations. Elevated levels of hCG (above the 95th centile) and decreased levels of uE3 (below the fifth centile) were encountered in 26 per cent (9/35) and 17 per cent (6/35) of the women, irrespective of the fetal condition. The abnormal profile of the serum markers in early second‐trimester oligohydramnios resulted in 57 per cent (20 out of 35) of screen‐positive cases for either fetal Down's syndrome or neural tube defects, compared with 8·4 per cent (143 out of 1699) in the reference population.
Discrepant karyotypes after second‐ and third‐trimester combined placentacentesis/amniocentesis
Authors: Caspari D. , Bartels I. , Rauskolb R. , Prange G. , Osmers R. , Eiben B. 
Published: March 2007

AbstractCytogenetic data are presented from a total of 1306 consecutive pregnancies with successful diagnosis obtained from both chorionic villi after short‐time culture (CVS‐SC) and amniotic fluid cell cultures (AC); samples had been taken simultaneously at combined placentacentesis (placental biopsy) and amniocentesis during the second (92·8 per cent) and third (7·2 per cent) trimesters. Concordant results were obtained in 1218 pregnancies with a normal karyotype and in 62 pregnancies with an aberrant fetal karyotype. Discrepant, i. e. false‐positive and false‐negative, results were found in 26 cases (2 per cent). From these data the accuracy of CVS‐SC, defined as the proportion of all correct diagnoses, is calculated to be 98 per cent. Three non‐mosaic and 14 mosaic false‐positive results obtained after CVS‐SC could not be confirmed by AC. Related to 1235 true normal fetal karyotypes, the specificity of CVS‐SC, i.e. the proportion of normal karyotypes correctly diagnosed, amounts to 98·6 per cent. In nine pregnancies, an aberrant fetal karyotype detected after AC was missed by CVS‐SC. The sensitivity of CVS‐SC, i.e. the proportion of abnormal fetuses correctly diagnosed (62 out of 71), amounts to 87·3 per cent in our study group.
Characterization of marker chromosomes by microdissection and fluorescence in situ hybridization
Authors: Thangavelu Maya , Pergament Eugene , Iii Rafael Espinosa , Bohlander Stefan K. 
Published: March 2007

AbstractWe characterized by microdissection and fluorescence in situ hybridization (FISH) two marker chromosomes: (1) a de novo, acrocentric marker chromosome detected in 88 per cent of the amniotic fluid cells of one of two physically and developmentally normal twins; and (2) a metacentric marker chromosome present in a phenotypically normal female. Analysis of FISH probes developed from the marker chromosomes indicated that the marker chromosomes in cases 1 and 2 were del(14)(q11) and a derivative chromosome from a Robertsonian translocation, respectively. Microdissection in combination with FISH may prove to be a valuable technique in determining the chromosomal origin of de novo marker chromosomes and unbalanced structural rearrangements detected during prenatal diagnosis.
Complex karyotypic mosaicism as a result of non‐disjunction and subsequent centromere fission
Authors: Prabhakar Gayathri , Schwartz Stuart , Waters Elizabeth , Punzalan Cecile , Cohen Maimon M. 
Published: March 2007

AbstractKaryotypic discrepancy among four different cell types is described in tissues derived from a pregnancy terminated because of chromosomal anomalies. Chorionic villus cells demonstrated 46,XX (direct preparation) and 46, XX/47,XX,+marl (cultured cells) karyotypes, while fetal skin fibroblasts had a karyotype of 47,XX,+ 18 and the placenta showed a triple mosaicism of 47,XX, + 18/47,XX,+mar1/48,XX,+ 18,+mar2. The origin of this complex chromosomal distribution and its significance are discussed in comparison with findings in similar cases.
Repeat maternal serum testing in multiple marker down's syndrome screening programmes
Authors: Cuckle Howard , Densem James , Wald Nicholas 
Published: March 2007

AbstractThe effect of repeat testing in maternal serum multiple marker screening for Down's syndrome was estimated using samples stored in an antenatal serum bank. Human chorionic gonadotropin (hCG) and unconjugated oestriol (uE3) levels were determined in 142 pairs of routinely collected samples which had already been tested for alpha‐fetoprotein (AFP). For each marker, about two‐thirds of the pairs of values were within 20 per cent of each other and most were within 40 per cent. A multivariate Gaussian model was used to estimate the detection and false‐positive rates for different repeat testing policies. A policy of repeat testing those with a high risk of a Down's syndrome term pregnancy given age and marker levels would reduce the false‐positive rate but there would also be a reduction in the detection rate. For example, using all three markers and a 1 in 250 cut‐off risk, the estimated false‐positive rate would fall from 5·3 to 3·8 per cent but the detection rate would decrease from 58 to 55 per cent. A policy of repeating those with either high or borderline risks would produce a modest improvement in screening efficiency. Repeating the 11 per cent with a risk exceeding 1 in 500 yields an estimated false‐positive rate of 5·0 per cent and a detection rate of 60 per cent. A policy of selective repeat testing is not recommended as it would not substantially improve screening efficiency. Nonetheless, if a repeat test has been performed, the parameters given in this paper will enable an unbiased estimate of the Down's syndrome risk to be calculated for individual women.
Adverse perinatal outcome in patients screen‐positive for neural tube defects and fetal down syndrome
Authors: Gross Susan J. , Phillips Owen P. , Shulman Lee P. , Bright N. Lawrette , Dungan Jeffrey S. , Simpson Joe Leigh , Elias Sherman 
Published: March 2007

AbstractAn association between various abnormal mid‐trimester maternal serum analyte values and adverse perinatal outcome has been reported. From an original sample of 14 857 women, we observed five women who were ‘screen‐positive’ for both neural tube defects [maternal serum alpha‐fetoprotein (MSAFP) ≥2·5 multiples of the median] and Down syndrome [risk ≥1/274 using MSAFP, maternal serum unconjugated oestriol (MSuE3), maternal serum human chorionic gonadotropin (MShCG), and maternal age]. The four patients who elected to undergo amniocentesis all demonstrated both normal karyotype and normal amniotic fluid AFP levels. All five cases were associated with intrauterine growth retardation (IUGR) and abnormal pregnancy outcomes. Two cases exhibiting severe IUGR on ultrasound examination were terminated at 19·1 and 21·2 weeks, respectively; the former also exhibited fetal calcifications and positive maternal serology for toxoplasmosis. In another case, fetal demise occurred at 36 weeks' gestation in a patient who had been treated for syphilis in the second trimester. Neither infection was confirmed in fetal tissue studies. Though resulting in live births, the remaining two cases required operative deliveries; emergency Caesarean sections for fetal distress were performed at 38 and 32 weeks, respectively, the latter case being associated with severe pre‐eclampsia. We conclude that elevated mid‐trimester MSAFP levels concurrent with maternal serum analyte values associated with increased risk for fetal Down syndrome may presage a poor perinatal outcome, particularly IUGR and possibly congenital infection.