bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal serum CA 125 levels in pregnancies with chromosomally‐normal and ‐abnormal fetuses
Authors: Van Lith J. M. M. , Mantingh A. , De Bruijn H. W. A. ,   For the Dutch Working Party on Prenatal Diagnosis
Published: March 2007

We measured the maternal serum cancer antigen 125 (MS‐CA 125) levels in 98 nonpregnant women, 765 first‐ and second‐trimester pregnancies with chromosomally‐normal fetuses, and 54 chromosomally‐abnormal pregnancies. To determine the MS‐CA 125 concentration, we used a new automated microparticle enzyme immunoassay with low inter‐assay variability. The median MS‐CA 125 level decreased from the first to the second trimester of pregnancy and was higher than that in non‐pregnant women. We found no difference between normal and Down's syndrome (n = 29) pregnancies ( t‐test: t = 0·57, p >0·5). The MS‐CA 125 levels in pregnancies with other chromosomal abnormalities showed no difference either, compared with the normals. We conclude that MS‐CA 125 is not a useful marker for fetal Down's syndrome, nor for other chromosomal disorders in pregnancy.
Asymptomatic carrier of two CFTR mutations: Consequences for prenatal diagnosis?
Authors: Verlingue C. , David A. , Audrezet M. P. , Le Roux M. G. , Mercier B. , Moisan J. P. , Ferec C.
Published: March 2007

The cystic fibrosis (CF) gene has been observed to have the highest frequency of mutations in the Caucasian population. Prenatal diagnosis can now be performed with a high degree of accuracy since the identification of most of the gene's mutations, as well as the characterization of intragenic markers. However, the observation of a distribution of clinical phenotypes increases the need to identify a mild phenotype and avoid false‐negative diagnosis. By screening most of the exons of the CFTR gene, we showed that a supposed obligate carrier of CF was in fact an asymptomatic affected woman.
Prenatal diagnosis of sanfilippo disease type C using a simple fluorometric enzyme assay
Authors: He Wang , Voznyi Ya. V. , Huijmans J. G. M. , Geilen G. C. , Karpova E. A. , Dudukina T. V. , Zaremba J. , van Diggelen O. P. , Kleijer W. J.
Published: March 2007

A new fluorogenic substrate, 4‐methylumbelliferyl β‐D‐glucosaminide, was used for the assay of acetyl CoA:glucosaminide N‐acetyltransferase in chorionic villi, cultured villus cells, and amniocytes. Optimal conditions for the assay and the ranges of enzyme activity were established for the various types of fetal cells. This simple fluorometric assay provides a reliable method for early prenatal diagnosis of Sanfilippo disease type C which is more convenient than current methods using radiolabelled substrates. The method was applied to amniotic fluid cells and fetal fibroblasts from an at‐risk pregnancy in which an affected fetus was diagnosed by two‐dimensional electrophoresis of glycosaminoglycans in the amniotic fluid.
Prenatal diagnosis of X‐linked hydrocephalus in a Chinese family with four successive affected pregnancies
Authors: Ko Tsang‐Ming , Hwa Hsiao‐Ling , Tseng Li‐Hui , Hsieh Fon‐Jou , Huang Shiu‐Feng , Lee Tzu‐Yao
Published: March 2007

We report on a woman with four successive pregnancies affected with X‐linked hydrocephalus (XLH). The first child had prenatal craniocentesis and died in utero. The second child had a postnatal shunting operation, but suffers from severe growth and mental retardation at 5 years of age. In the third pregnancy, prenatal ultrasound detected hydrocephalus at the 16th and 20th weeks of gestation and the pregnancy was terminated. In the fourth pregnancy, ultrasound scanning at the 17th and 20th weeks of gestation revealed no remarkable findings, but hydrocephalus was detected at the 24th week. Autopsy confirmed the prenatal diagnosis. DNA polymorphism analysis of the Bell site of exons 17–18 of factor VIII gene of the woman and her last two fetuses seemed to be compatible with a linkage between the XLH locus and factor VIII gene. Although XLH has a variable presentation of ventriculomegaly, ultrasound scanning is still a useful tool for prenatal diagnosis at present. Earlier and more accurate prenatal diagnosis will be feasible with molecular analysis of the XLH locus or its flanking regions.
Fluorescence in situ hybridization with a chromosome 21‐specific cosmid contig: 1‐day detection of trisomy 21 in uncultured mesenchymal chorionic villus cells
Authors: Bryndorf Thue , Christensen Britta , Xiang Yang , Philip John , Yokobata Kathy , Bui Nga , Gaiser Candy
Published: March 2007

We present a modified, fast trisomy 21 detection assay using fluorescence in situ hybridization (FISH) on uncultured mesenchymal chorionic villus cells. The whole test takes about 24 h. We used a cosmid contig as a probe and modified an in situ sample preparation method first described by Klinger et al. (1992). The assay saves time and cost of culture in comparison with a previously described trisomy 21 detection FISH assay (Bryndorf et al., 1993). A small blind clinical study comparing the modified and the previously described FISH assays using mesenchymal chorionic villus cells showed comparable results and concordance with conventional cytogenetic analysis. The frequency of nuclei with three hybridization signals from samples disomic for chromosome 21 ranged from 0 to 8 per cent with both assays, while trisomic samples had 60–80 and 54–90 per cent of the mesenchymal nuclei with three signals in the modified and previously described assays, respectively. Normal (disomic) and trisomic mesenchymal chorionic villus samples can be distinguished clearly and rapidly without culture in the modified assay.
Tertiary centre referral of small‐for‐gestational age pregnancies: A 10‐year retrospective analysis
Authors: Heydanus R. , van Splunder I. P. , Wladimiroff J. W.
Published: March 2007

Between 1981 and 1991, 461 pregnant women between 15 and 40 weeks of gestation (mean 30 weeks) with completed follow‐up were referred to our centre for prenatal diagnosis because of a small‐for‐gestational age (SGA) fetus or combined SGA and structural abnormality. The referral diagnosis was based either on biparietal diameter measurements or on measurement of the upper‐abdominal circumference. SGA in our centre was defined as a fetal upper‐abdominal circumference below the tenth centile. SGA was confirmed by ultrasound in 75 per cent of the fetuses, whilst combined SGA and fetal structural abnormality was substantiated in only 16 per cent of the fetuses. However, in our centre structural abnormality was detected in 34 fetuses who were referred because of SGA alone. Nearly half of the structurally normal SGA fetuses displayed a normal head‐to‐abdomen (H/A), ratio, whereas an increased H/A ratio was found in 13/15 fetuses with an abnormal karyotype. An abnormal karyotype was present in 20 fetuses, which is 7 per cent of the total SGA population. Nearly 50 per cent represented triploidy associated with oligohydramnios. SGA was confirmed by a birth weight below the tenth centile in 89 per cent, below the fifth centile in 77 per cent, and below the 2·3rd centile in 55 per cent of infants. Structural abnormality was confirmed in 65 per cent of infants, whereas in 19 per cent of infants the abnormality was missed or a misclassification was made. Perinatal mortality was 31 per cent for all SGA fetuses, 27 per cent for SGA fetuses without anomalies, and 64 per cent for SGA fetuses with structural abnormality.
Maternal contamination of amniotic fluid demonstrated by DNA analysis
Authors: Rebello M. T. , Abas A. , Nicolaides K. , Coleman D. V.
Published: March 2007

DNA from 16 sets of samples comprising DNA from uncultured amniotic fluid cells, cultured amniotic fluid cells, fetal tissue, and maternal blood was analysed by the polymerase chain reaction (PCR) with AC‐repeat primers. The analysis was performed to investigate the presence of contaminating maternal cells in amniotic fluid which would affect the reliability of DNA studies for prenatal diagnosis. In three sets, maternal contamination of uncultured amniotic fluid cells was detected. In one of the three sets, maternal contamination was present in both uncultured and cultured amniotic fluid cells. The use of amniotic fluid cells as a source of DNA for prenatal diagnosis should be limited to cases where the purity of the DNA can be demonstrated prior to the diagnostic test being performed. This limitation in the use of amniotic fluid DNA also extends to other forms of diagnosis relying on the purity of amniotic fluid samples, particularly the new in situ hybridization methods currently being developed.
Six years' experience with rapid karyotyping in prenatal diagnosis: Correlations between phenotype detected by ultrasound and fetal karyotype
Authors: Claussen Uwe , Ulmer Renate , Beinder Ernst , Voigt Hans‐Joachim
Published: March 2007

From September 1985 to March 1992, 804 amniotic fluid samples from 64 different diagnostic centres of the Federal Republic of Germany were sent to our laboratory exclusively for rapid karyotyping. The average time needed for notification of the analysed karyotype was 4·65 days when the ‘pipette method’ was used for chromosome harvesting and 5·97 days when the ‘in situ’ technique was used. The overall incidence of chromosome aberrations was 15·3 per cent. Data are presented about the likelihood of abnormal ultrasound findings being caused by chromosome aberrations. These findings include polyhydramnios, oligohydramnios, growth retardation, fetal effusions, neural tube defects, craniofacial defects, heart defects, gastroschisis and omphalocele, gastrointestinal tract defects, urinogenital defects, and limb defects. In future, such data need to contain larger numbers of cases for each week of gestation. This will improve the risk evaluation for each case with abnormal ultrasound findings, which should lead to better management during pregnancy, delivery, and postnatal care for those who require rapid karyotyping.
Screening of monoclonal antibodies recognizing oncofetal antigens for isolation of trophoblasts from maternal blood for prenatal diagnosis
Authors: Durrant L. G. , McDowell K. M. , Holmes R. A. , Liu D. T. Y.
Published: March 2007

Many monoclonal antibodies have been produced against tumour‐associated cell surface antigens for cancer therapy. They have therefore been selected for minimal reactivity with normal tissues and in particular for lack of binding to blood cells or serum components. Many of the antigens recognized are of fetal origin. These monoclonal antibodies may therefore be ideal candidates to recognize and sort fetal trophoblasts from maternal blood for prenatal diagnosis of genetic abnormalities. A panel of 19 anti‐tumour antibodies were therefore screened for reactivity with early trimester placenta and two, 340 and 154, were shown to stain trophoblasts. If MAb 340 is linked to magnetic beads, it can efficiently sort trophoblast cell lines from whole blood.
Meckel‐Gruber syndrome: Prenatal diagnosis at 10 menstrual weeks using embryoscopy
Authors: Dumez Yves , Dommergues Marc , Gubler Marie‐Claire , Bunduki Victor , Narcy Francoise , Lemerrer Martine , Mandelbrot Laurent , Berkowitz Richard
Published: March 2007

A case of Meckel—Gruber syndrome was diagnosed by embryoscopy at 10 menstrual weeks, allowing for early termination of pregnancy. Post‐mortem examination confirmed the presence of polydactyly and bilateral cystic lesions of the mesonephros and metanephros. Both the forming nephrons and the collecting ducts were involved in the formation of renal cysts.
Prenatal exclusion of stickler syndrome
Authors: Zlotogora Joel , Granat Menachem , Knowlton Robert G.
Published: March 2007

Stickler syndrome is an autosomal dominant disorder of the connective tissue which includes ocular and systemic manifestations. We report on a large kindred in which we were able to demonstrate very tight linkage between the disease and the type II collagen gene (COL2A1) (LOD score 3·91 at θ=0). In a family in which the father and one of his daughters were severely affected, DNA analysis from a chorionic villus sample demonstrated that the fetus possessed the normal allele of COL2A1. Thereafter a normal child was born.
Mosaic triple trisomy in amniocytes from a phenotypically and karyotypically normal fetus
Authors: Mascarello J. T. , Jones M. C. , Catanzarit V. A. , Brown Kathryn H.
Published: March 2007

We report the detection of a mosaic triple trisomy, 46, XY/49, XY, + 13, +20, +21, in two amniotic fluid specimens obtained from a pregnancy that yielded a normal infant. Traditional cytogenetic methods failed to detect the abnormal cell lineage in fetal blood, foreskin, amnion, umbilical cord, and three different biopsies of the chorion. In addition, fluorescence in situ hybridization study of cells from a buccal smear showed no evidence of cells with three copies of chromosome 20.
Early genetic amniocentesis and its relationship to respiratory difficulties in paediatric patients: A report of findings in patients and matched controls 3–5 years post‐procedure
Authors: Calhoun Byron C. , Brehm Walter , Bombard Allan T.
Published: March 2007

This study evaluates the long‐term pulmonary complications of 25 children from a prospective, matched‐control, pilot study evaluating short‐term complications of early (11–14 weeks' gestation) versus traditional (15 weeks' gestation and later) genetic amniocentesis. Five children in the early amniocentesis group were found to have various respiratory difficulties, a morbidity rate comparable to that of paediatric patients in the general population. These data identify the need for larger, multicentre trials.
Re‐evaluation of the colorimetric assay for cytidine deaminase activity
Authors: Okamura Takashi , Kigasawa Kazuko
Published: March 2007

This study re‐evaluated the colorimetric assay for cytidine deaminase (CTD), and showed that the optimum conditions were pH 7·5, 37°C, and up to 24 h. In addition, this method was found to require protein precipitation. Following these modifications, intra‐assay and inter‐assay coefficients of variation were below 5 per cent, indicating that the assay was highly reliable. CTD activity was determined in 282 serum samples from 206 normal pregnant women by the incubation of 100 μl of serum and 400 μl of 1·4 mmol/l cytidine substrate for 16 h at 37°C. Following protein precipitation, the ammonia liberated during conversion was measured by a colorimetric procedure. The mean (±SD) CTD activity was 7·31 ± 2·50 U at 3–12 weeks of gestation, 8·70 ± 2·12 U at 13–24 weeks, 7·59 ± 2·25 U at 25–36 weeks, and 7·29 ± 2·16 U at 37–42 weeks. High levels of CTD activity were found in patients with abruptio placentae and amnionitis associated with intrauterine fetal death (IUFD). The increase in CTD activity was noted from 3 days to 1 week before the confirmation of IUFD. The placenta contains extremely high levels of CTD, but cord serum does not. Thus, the excessive elevation of CTD activity was probably derived from progressive placental damage. This modified CTD assay was concluded to be simple and reliable, and may perhaps be useful in detecting pregnancy disorders.
Prenatal diagnosis of werdnig‐hoffmann disease: DNA analysis of a mummified umbilical cord using closely linked microsatellite markers
Authors: Matilla T. , Corral J. , Miranda M. , Troyano J. , Morrison K. , Volpini V. , Estivill X.
Published: March 2007

We present a case of prenatal diagnosis of Werdnig‐Hoffmann disease, the most severe type of spinal muscular atrophy (SMA). DNA obtained from a mummified umbilical cord of a deceased affected brother of the index case was analysed with four closely linked microsatellite markers [EF1/2a and EF13/14 (D5S125), MAP1B, and JK53CA (D5S112)], flanking theSMAgene, on chromosome 5q11·2‐13·3. The fetus was diagnosed as homozygous for the deleteriousSMAgene.
Prenatal detection of X‐linked ichthyosis by maternal serum screening for down syndrome
Authors: Bartels Iris , Caesar Julius , Sancken Ulrich
Published: March 2007

Maternal serum unconjugated oestriol (uE3) was measured in 15 375 pregnancies during 2 years of second‐trimester risk assessment for Down syndrome using biochemical markers. Very low levels of uE3 (<0·1 MOM) were detected in 22 serum samples (0·14 per cent). Very low uE3 was associated with an adverse outcome in 13 pregnancies including fetal death and miscarriage (N=11), anencephaly (N=1), and Meckel—Gruber syndrome (N=1). Dry scales on the skin appeared in the first year of life in four boys. From dermatological diagnosis, prenatal uE3 levels, and pedigree analysis, it is concluded that at least 5 in approximately 7500 male births in the study population are affected by steroid sulphatase deficiency, which is the biochemical defect in X‐linked ichthyosis. Very low uE3 levels in the second trimester are indicative of this disease in pregnancies with normal ultrasound findings.
Prenatal exclusion of duchenne muscular dystrophy by fetal muscle biopsy
Authors: Benzie R. J. , Ray P. , Thompson D. , Hunter A. G. W. , Iwey B. , Salvador L.
Published: March 2007

A fetal thigh muscle biopsy was performed at 18 weeks and 6 days' gestation using an automatic 18‐gauge biopsy needle. A positive immunoreaction with antisera to the amino‐ and carboxy‐terminals of dystrophin excluded Duchenne muscular dystrophy from this at‐risk male.
Abnormal immunological development in fetuses with trisomy 18
Authors: Makrydimas G. , Plachouras N. , Thilaganathan B. , Nicolaides K. H.
Published: March 2007

Flow cytometry was used to enumerate the lymphocyte subpopulations in fetal blood obtained by cordocentesis from eight trisomy 18 fetuses at 20–36 weeks' gestation. Compared with values in chromosomally normal fetuses, in trisomy 18 the mean T‐ and natural killer (NK) cell counts were significantly lower (t= − 7·63, P<0·001 and t= − 3·58, P<0·01, respectively); the mean B‐cell count was not significantly different (t= − 1·32). These findings demonstrate that in trisomy 18 there is abnormal intrauterine development of the immune system.
Prenatal diagnosis and dysmorphic findings in mosaic trisomy 16
Authors: Garber Ann , Carlson Dru , Schreck Rhona , Fischel‐Ghodsian Nathan , Hsu Wei‐Tong , Oeztas Sitki , Pepkowitz Sam , Graham John M.
Published: March 2007

We report two cases of mosaic trisomy 16 diagnosed by amniocentesis, with dysmorphic findings in both cases evident upon delivery. Following elective termination, case 1 demonstrated a trisomy 16 cell line in fetal skin (4 per cent) and placental tissue (64 per cent). Molecular studies on the disomic cell line indicated that both chromosome 16s were maternal in origin, suggesting loss of the paternal chromosome 16 from a trisomic zygote (uniparental heterodisomy). At birth, case 2 demonstrated only disomic cells in skin and blood, with trisomy 16 present in 4 per cent of cells from the amnion. Molecular studies confirmed both maternal and paternal contributions of the chromosome 16s. We analysed DNA from one previously reported case of mosaic trisomy 16 (Williams et al., 1992) and failed to find signs of uniparental disomy in this child with congenital heart defects. These cases had distinctive but different dysmorphic features. We suggest that trisomy 16 embryos may revert to disomy during the course of pregnancy, allowing for longer survival with various abnormalities in growth and morphogenesis. The clinical significance of prenatally detected mosaic trisomy 16 may not be completely defined by additional cytogenetic, molecular, and ultrasound studies.
Comparison of first‐trimester transvaginal amniocentesis with chorionic villus sampling and mid‐trimester amniocentesis
Authors: Shalev E. , Weiner E. , Yanai N. , Shneur Y. , Cohen H.
Published: March 2007

Between August 1989 and December 1991, 356 patients underwent first‐trimester transvaginal amniocentesis (10–12 weeks). The same number of patients referred in the same period for mid‐trimester amniocentesis (14–21 weeks) was matched also for maternal age and indication. A third group consisted of the first 356 cases in which chorionic villus sampling (CVS) was attempted. The overall success rate was 99·7 and 100 per cent for early and mid‐trimester amniocentesis, respectively, and 97·2 per cent for CVS. The mean harvesting time was 12·8, 11, and 7·9 days, respectively. The percentage of patients rescheduled was 3·4 per cent in first‐trimester amniocentesis, 1·7 per cent in mid‐trimester amniocentesis, and 6·2 per cent in the CVS group. The early (less than 2 weeks) pregnancy loss was 1·7 and 0·6 per cent in early and mid‐trimester amniocentesis, respectively, and 1·7 per cent in CVS. The total pregnancy loss was 3·2, 0·9, and 2·9 per cent, respectively. The rate of preterm birth was 6·0, 5·2 and 6·9 per cent, respectively. The results indicate that CVS has the shortest procedure‐result interval, but the highest rescheduling rate. First‐trimester amniocentesis has a higher procedure and laboratory success rate but, until otherwise proved, mid‐trimester amniocentesis is the most efficient and safest procedure.
The early prenatal sonographic diagnosis of renal agenesis: Techniques and possible pitfalls
Authors: Bronshtein M. , Amit A. , Achiron R. , Noy I. , Blumenfeld Z.
Published: March 2007

Out of 13 252 cases in which fetal bilateral echogenic kidneys were detected by transvaginal sonography between 12 and 18 weeks' gestation, there were nine fetuses where oval hypoechogenic masses were detected in the renal bed. In five fetuses where hypoechogenic masses in the renal bed were sonographically visualized, postabortal examination was compatible with renal agenesis and the hypoechogenic masses proved to be enlarged adrenals. In three additional cases, unilateral renal agenesis was accompanied by unilateral enlarged adrenals, radiologically confirmed postnatally. In one case, a false‐positive sonographic diagnosis of Potter syndrome was made because of bilateral hypoechogenic masses in the renal bed. Postabortal examination detected hypoplastic kidneys, but of normal histology, in a dyskaryotic fetus with trisomy 22. In four cases of renal agenesis, the amniotic fluid was of normal volume until the 17th week. In two of the five cases of Potter syndrome, a cystic structure, compatible with the urinary bladder, was detected in the pelvis at 14 weeks. The diagnostic criteria for renal agenesis in the early fetus differ from those used in the second half of gestation.
Simpson—Golabi—Behmel syndrome: Disproportionate fetal overgrowth and elevated maternal serum alpha‐fetoprotein
Authors: Hughes‐Benzie R. M. , Tolmie J. L. , McNay M. , Patrick A.
Published: March 2007

Simpson—Golabi—Behmel (SGB) syndrome is an X‐linked condition with pre‐ and postnatal overgrowth, characteristic facies, and visceral and skeletal anomalies. We report an affected male who presented at 16 weeks' gestation with elevated maternal serum α‐fetoprotein (MSAFP). Fetal measurements at 20 and 31 weeks' gestation were disproportionate, with marked macrosomia but a low head to abdominal circumference ratio and normal femur length. Fetal overgrowth with elevated MSAFP may prove to be useful markers for the prenatal diagnosis of SGB syndrome.
Variation in prenatal cytogenetic diagnosis: Policies in 13 european countries, 1989–1991
Authors: Cornel Martina C. ,   THE EUROCAT WORKING GROUP
Published: March 2007

The livebirth prevalence of autosomal chromosomal anomalies is determined by several factors, including maternal age distribution and the impact of prenatal cytogenetic diagnosis (PCD). The impact of PCD varies between countries, as the indications and the uptake vary. In a previous study we described differences in Down syndrome prevalence and the proportion of older mothers. We have now made a survey of the official PCD policies in 25 regions in 13 European countries for the period 1989–1991. In two countries, termination of pregnancy was not available. In the other 11 countries, international agreement existed on five indications: advanced maternal age, a previous child with a chromosomal anomaly, parents who are carriers of a balanced translocation, mothers who are carriers of an X‐linked disorder, and malformations at ultrasound. The exact limit for advanced maternal age varied from 35 to 38 years. There was a considerable variation for the indications advanced paternal age, amniocentesis for AFP or DNA, parental anxiety, a previous child with a congenital anomaly, abnormal maternal serum markers, and exposure to radiation/chemotherapy. The PCD uptake for mothers above the maternal age limit varied from 10 to 88 per cent. International harmonization of the indications for PCD is not considered feasible at present, because of the rapid changes in PCD policies even within countries.
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

Over 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

We 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

Pyruvate 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

An 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

We 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

The 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

Twenty‐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

Trisomy 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

Prenatal 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

Amniocentesis 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

RFLP 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

This 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

The 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

Cytogenetic 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

We 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

Karyotypic 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

The 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

An 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.