bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of transabdominal and transcervical CVS and amniocentesis: Sampling success and risk
Authors: Smidt‐Jensen Steen , Philip John
Published: March 2007

A total of 2931 women randomized to either transabdominal CVS, transceirvical CVS, or amniocentesis were studied. Unless intended or unintended abortion had occurred, they had completed up to 28 weeks of pregnancy. No significant difference was seen between total fetal loss in the transabdominal CVS group and the amniocentesis group (6.5 and 6.8 per cent, respectively, SE difference = 0.92 per cent, p = 0.01). The total fetal loss in the transcervical CVS group was 10.1 per cent. After pooling our data with data from the Canadian randomized study and the American non‐randomized study, the difference in risk between trans‐cervical CVS and amniocentesis was 1.8 per cent (SE difference = 0.64 per cent, p = 0.8). When the number of failed procedures and those cases evaluated as infeasible for the assigned method‐for anatomical reasons‐are compared, the overall sampling efficacy is poorer transcervically than transabdominally.
Chorionic villus sampling: Analysis of fetal losses to delivery, placental pathology, and cervical microbiology
Authors: Wilson R. D. , Cho K. , McGillivray B. , Kalousek D. , Shaw D. , Baldwin V.
Published: March 2007

A population of 1639 patients were seen for chorionic villus sampling (CVS). Embryonic death was identified at ultrasound in 5.3 per cent of patients. The number of patients undergoing CVS was 1551, with 1416 transcervical procedures and 135 transabdominal procedures. The most common indication for CVS was advanced maternal age. Spontaneous pregnancy losses identified by increased risk of pregnancy loss with increasing aspiration attempts. The total fetal loss for this population was 5.4 per cent with the pregnancy loss estimated due to procedure being 1.2 per cent. Analysis of placentae from patients having CVS and amniocen‐tesis showed no differences. Microbiological assessment prior to CVS was similar to previous publications.
Risk of miscarriage after transcervical and transabdominal CVS in relation to bacterial colonization of the cervix
Authors: Baumann P. , Jovanovic V. , Gellert G. , Rauskolb R.
Published: March 2007

Cervieo‐genital colonization with micro‐organisms poses a potential threat to the pregnancy when transcervical (TC) CVS is performed. In order to evaluate this threat, cervical swabs in 478 patients were obtained and cultured for bacteria, yeasts, and mycoplasmas; chlamydias were detected by an enzyme immunology test. Two hundred and seventy‐one patients had CVS (ione transvaginally and 207 underwent transabdominal (TA) CVS. Transvaginal specimens were obtained in 61.6 per cent by forceps biopsy. Overall in 29.9 per cent of patients micro‐organisms were detected, the rate and distribution of different species being the same in both groups. There were 36 (7.5 per cent) miscarriages up to 28 weeks of gestation in the combined groups, 29 (10.7 per cent) in the TC‐CVS group and 7 (3.4 percent) in the TA‐CVS group. When miscarriages occurred after TC‐CVS, bacteria/yeasts were involved in 10.3 per cent cif cases and mycoplasmas in 37.9 per cent, this proportion being almost the same in early (<2 weeks) and late (>2 weeks) miscarriages. After TA‐CVS, in 28.6 per cent only mycoplasmas, and this only in late miscarriages (> 2 weeks), were involved, accounting for 40 per cent of late miscarriages.
Transcervical (TC) and transabdominal (TA) CVS for prenatal diagnosis in rotterdam: Experience with 3611 cases
Authors: Jahoda M. G. J. , Brandenburg H. , Reuss A. , Cohen‐Overbeek T. E. , Wladimiroff J. W. , Los F. J. , Sachs E. S.
Published: March 2007

Data from 3611 consecutive CVS (TC, N= 1780; TA, N= 1831) were analysed with emphasis put on influence of maternal and gestational age at CVS on the fetal loss rate < 28 weeks. For TC‐CVS the gestational age varied from 9.3–11.6 weeks, for TA‐CVS from 9.3–20 weeks. Sampling efficacy at first attempt was 86.5 per cent and 95 per cent respectively. In 4.6 per cent an abnormal result was established. In older mothers (N=2362) the fetal loss rate was significantly higher (p = <0.05) when sampled before 12 weeks (TC‐CVS 6.2 per cent, TA‐CVS 5.8 per cent). When the CVS (TA) was performed after 12 weeks the fetal loss rate decreased to 2.4 per cent.

In 1079 younger women the fetal loss rate remained low (TC 2.8 per cent; TA < 12 weeks 1.8 per cent; TA > 12 weeks 1.7 per cent) and was not influenced by gestational age at the time of sampling. We concluded both methods safe and reliable when the choice of application considers maternal age.
Trisomy 18 in chorionic villus sampling: Problems and consequences
Authors: Wirtz A. , Gloning K.‐Ph. , Murken J.
Published: March 2007

Among 1547 patients undergoing first‐trimester prenatal diagnosis, 100 fetal chromosome aberrations were detected. Thirteen of these involved chromosome 18. In two structural abnormalities of chromosome 18, the aberration could be excluded in amniotic fluid cells and two healthy infants were born. Trisomy 18 was not confirmed in amniotic fluid cells in three trisomy 18 mosaics. In eight non‐mosaic trisomy 18 first‐trimester diagnoses, the diagnosis was excluded by amniotic fluid cells or fetal cultures in four, and confirmed in the remaining four. Diagnosis of chromosome 18 aberrations in the direct preparation should be confirmed in the long‐term culture of the chorionic villus sample or by amniotic fluid cultures.
Uncommon chromosomal mosaicism in chorionic villi
Authors: Kennerknecht I. , Barbi G. , Djalali M. , Just W. , Vogel W. , Terinde R.
Published: March 2007

Three cases of unusual chromosomal mosaicism are reported for which the cytogenetic data show inconsistent findings between CVS and AC or fetal tissue, and which cannot be explained simply by non‐disjunction. For case 1, in CVS the karyotype was 46,XY, whereas lymphocytes and fibroblasts revealed 69,XXY. DNA fingerprinting indicated one paternal and two maternal chromosome sets, the latter most probably due to omission of maternal meiosis II. For case 2, in CVS mos 46,XX/47,XX,+mar de novo was observed. Amniotic fluid cells had the karyotype 46,XX. The origin of the marker chromosome might be explained by at least two events of unknown order (a somatic chromosome/chromatid deletion and non‐disjunction of the homologous chromosome). In case 3 (CVS: mos 46,XY/46,XY,19q+ de novo; amniotic fluid cells, lymphocytes, and fibroblasts: 46,XY), the surplus of chromosome material in 19q+ might be explained on the basis of a somatic translocation. The idea of a chimera is less convincing, as the mosaic finding is restricted to one tissue. Furthermore, there was no hint of a vanishing twin. Hitherto, no case of structural chromosome mosaicism in CVS has been reconfirmed in fetal tissues.
Mosaicism and accuracy of prenatal cytogenetic diagnoses after chorionic villus sampling and placental biopsies
Authors: Miny P. , Hammer P. , Gerlach B. , Tercanli S. , Horst J. , Holzgreve W. , Eiben B.
Published: March 2007

Discrepant chromosome findings in placenta and fetus (false negative and false positive) after chorionic villus sampling (CVS) are mainly due to confined mosaicism. Non‐mosaic normal or abnormal chromosome counts after direct preparation and culture nearly always correctly reflect the fetal chromosome constitution. False‐negative results have almost exclusively been restricted to cytotrophoblast cells not representing a fetal chromosome abnormality. Diagnosis of placental mosaicism definitely requires an adequate follow‐up by amniocentesis, fetal blood sampling, or sonography before a pregnancy is terminated. When direct preparations and cultured cells are used for cytogenetic diagnoses and placental mosaicism is not taken as proof for a chromosomal abnormality in the fetus, CVS is an accurate diagnostic tool.
Proliferation kinetics in native chorionic villus cells
Authors: Kennerknecht I. , Baur‐Aubele S. , Vogel W.
Published: March 2007

In accordance with observations by other groups direct CVS preparations reveal only a few mitoses, whereas semi‐direct cultures (overnight incubation) give good results. By monitoring the BrdU uptake with an immunological method, a delay in the proliferation activity in native villi could be observed up to 7 h after biopsy.
Chorionic villus cDNA library displays expression of butyrylcholinesterase: Putative genetic disposition for ecological danger
Authors: Zakut Haim , Lieman‐Hurwitz Judith , Zamir Ronit , Sindell Lilian , Ginzberg Dalia , Soreq Hermona
Published: March 2007

Gene expression in chorionic villi may be particularly vulnerable to environmental exposure to poisonous substances. To reveal villus gene products which are thus subject to poisoning, molecular cloning was employed. A single sample of apparently normal chorionic villi (approximately 40 mg, from 9 weeks' gestation) was microscopically dissected to ensure purity of fetal tissue. Total RNA was extracted by isothiocyanate and directly employed for reverse transcription. A chorionic villus cDNA library was constructed from this preparation in the phage vector lambda gt10 and contained 60 000 independent recombinants. In the present study, this cDNA library was screened with labelled cDNA probes encoding human butyrylcholinesterase (BCHE) and acetylcholinesterase (ACHE). Nine BCHEcDNA clones were isolated out of 1.6 × 106 phages (5.7 × 10−6 of screened recombinants) and exhibited similar restriction patterns to those observed for BCHEcDNA from other human tissues. In contrast, no ACHEcDNA clones could be found in 4.0 × 106 screened phages (<2.5 × 10−6 of recombinants). These findings demonstrate efficient transcription (similar to fetal brain levels) from the BCHE gene but not from the ACHE gene in chorionic villi, and support the notion that BCHE is involved in chorionic villus growth and development.
Early prenatal diagnosis of the fragile site AT Xq27.3 associated with Martin‐Bell syndrome
Authors: Tommerup N. , Søndergaard F. , Hanauer A. , Oberle I. , Bang J. , Barbi B. , Bech B. , Davies K. , Froster‐Iskenius U. , Gustavson K.‐H. , van der Hagen C. B. , Heiberg A. , Kristoffersen U. , Mikkelsen M. , Miny P. , Nielsen K. B. , Rasmussen K. , Schinzel A. , Tranebjaerg L. , Tønnesen T. , Wahlström1 J.
Published: March 2007

Early prenatal diagnosis of the fragile X was attempted in 44 pregnancies, including one twin pregnancy at risk of Martin‐Bell (MB) syndrome. The sex ratio was 24M:21F. The fragile site was reproducibly demonstrated in cultured chorionic villus (CV) cells in eight male and five female fetuses. Six of the male and three of the female fetuses were terminated. Simultaneous RFLP analysis provided confirmative data with flanking DNA markers in 3 of 13 analysed cases. Recombination and/or non‐informativeness at available distal and/or proximal loci were found in nine cases. In one male fetus, discordance between the haplotype and cyto‐genetics (fragile‐X‐negative) suggested the presence of a normal male transmitter, a double meiotic cross‐over within the region, or a false‐negative cytogenetic diagnosis. However, discordance between prenatal and post‐termination/postnatal cytogenetic findings was not observed in this series. The use of excess thymidine for induction of the fragile X in cultured CV cells provided in the majority of cases a safe and rapid method for cytogenetic diagnosis, with options for early induced termination in fragile‐X‐positive pregnancies, for simultaneous RFLP analysis, and for subsequent second‐trimester analysis of fetal blood in complicated cases.
First‐trimester screening for fetal chromosomal abnormalities. Preliminary results
Authors: van Lith J. M. M.
Published: March 2007

We have started a multicentre trial to study the possibilities of first‐trimester maternal serum screening for fetal chromosomal abnormalities. Maternal blood samples were obtained before 13 weeks of gestation. We present the preliminary results of the first 950 patients on alpha‐fetoprotein (AFP). Results on cancer antigen 125 (CA 125) in Down's syndrome and normal pregnancies are also presented. We conclude that the results on AFP are promising and that CA 125 might be predictive for fetal Down's syndrome.
Prenatal diagnosis of fetal anomalies during the second trimester of pregnancy: Their characterization and delineation of defects in pregnancies at risk
Authors: Dallaire L. , Michaud J. , Melancon S. B. , Potter M. , Lambert M. , Mitchell G. , Boisvert J.
Published: March 2007

During a follow‐up study of 19 790 pregnancies at risk for a genetic disease, from 1968 to 1989, 1083 fetuses were found to have an anomaly during the second trimester, leading to 977 terminations of pregnancy. Neural tube defects (31.4 per cent), chromosomal disorders (27.1 per cent), and Mendelian or multifactorial diseases (10.6 per cent) were the main causes of fetal anomaly. More than half (52.9 per cent) of the fetal anomalies were detected by routine ultrasound examination. Forty‐two per cent of cystic hygromas were secondary to a chromosomal defect. We stress the importance of a comprehensive fetal and newborn examination to ensure an accurate diagnosis so that subsequently accurate counselling can be provided.
Incidence of abortion after genetic amniocentesis in twin pregnancies
Authors: Pruggmayer M. , Baumann P. , Schütte H. , Osmers R. , Bartels I. , Jovanovich V. , Rauskolb R.
Published: March 2007

Fetal outcome after genetic amniocentesis (AC) in viable twin pregnancies was analysed in a retrospective study at three centres in order to estimate the rate of fetal loss after AC. The maternal age ranged from 33 to 45 years (mean 36.7 years). The gestational age varied between 15 and 20 weeks of gestation (mean 17.1). In 98 viable twin pregnancies with complete follow‐up, spontaneous abortion of both fetuses occurred within 28 completed weeks of gestation in eight pregnancies and six women aborted within 20 completed weeks of gestation after AC, corresponding to a rate of fetal loss of 8.1 and 6.1 per cent, respectively (excluding the loss of five twins with viable outcome of the co‐twin in five pregnancies).
Vitamins, folic acid and neural tube defects: Comments on investigations in the United States
Authors: Simpson Joe Leigh , Mills James L. , Rhoads George G. , Cunningham George C. , Hoffman Howard J. , Conley Mary R.
Published: March 2007

No clear answer concerning whether multivitamin/folate supplementation prevents neural tube defects (NTDs) is provided by three studies in the United States. All these studies are occurrence in nature, no recurrence studies having been conducted. The Atlanta Birth Defects Study is subject to pronounced memory and recall biases, the length between event and interview being as long as 16 years. In a second study (Boston University), objections can be raised to certain aspects of the experimental design, and the claim that 22 per cent of women started vitamins sufficiently early after pregnancy diagnosis to influence NTD formation is suspicious. Our NICHD case control study of 541 women in California and Illinois revealed no evidence for multivitamins or folic acid preventing NTDs. U.S. public policy‐makers face difficulties in applying results of recurrence or occurrence studies in high‐risk areas to low‐risk areas in the U.S.
Diagnosis of polyhydramnios in early gestation: Indication for prenatal diagnosis?
Authors: Hendricks Susan K. , Conway Lael , Wang Keith , Komarniski Cathy , Mack Lawrence A. , Cyr Dale , Uhrich Stefanie
Published: March 2007

Previously published reports have indicated that idiopathic polyhydramnios may be associated with trisomies 18 and 21 and that chromosomal analysis is indicated. Furthermore, the natural history and fetal outcome of polyhydramnios diagnosed in early gestation have not been well delineated.

We identified 138 pregnancies with polyhydramnios prior to 26 weeks' gestation. Of 131 complete cases, 21 were diagnosed as severe, 18 as moderate, and 92 as mild polyhydramnios. Congenital abnormalities were noted in 18 of 21 severe cases (86 per cent). Two of the remaining three cases were twin‐to‐twin transfusion. Thirteen of 18 cases with moderate polyhydramnios (72 per cent) were associated with anomalies; six of the remaining cases were twin‐to‐twin transfusion. Sixteen of 92 cases of mild polyhydramnios (17 per cent) were associated with congenital abnormalities.

In 69 of 76 cases of mild hydramnios not associated with anomalies (91 per cent), the hydramnios resolved prior to delivery. Only 2 of 16 (13 per cent) associated with anomalies resolved. In 4 of 5 cases (80 per cent) with moderate hydramnios and no anomalies, the amniotic fluid volume was normal on subsequent ultrasound. No case of moderate polyhydramnios associated with anomalies or maternal conditions nor any case of severe polyhydramnios resolved.

There were seven cases of chromosomal abnormalities in this series; all were associated with sonographic findings in addition to the presence of polyhydramnios. On the basis of these data, we doubt the benefit of amniocentesis following the early diagnosis of idiopathic polyhydramnios in the absence of other ultrasound findings.
Ultrasound diagnosis of fetal abnormalities and cytogenetic evaluation
Authors: van Zalen‐Sprock M. M. , van Vugt J. M. G. , Karsdorp V. H. M. , Maas R. , van Geijn H. P.
Published: March 2007

Over a 65½ year period, in 288 pregnancies a variety of fetal malformations were detected by ultrasound. Two hundred and ten fetuses (73 per cent) were karyotyped. Gestational age at detection ranged from 11 to 38 weeks. The incidence of an abnormal karyotype in the total series was 14 per cent and 14.7 per cent in the 210 pregnancies in which a karyotype was performed. Single structural anomalies were found in 149 cytogenetically investigated fetuses, of which 25 had a chromosomal abnormality (17 per cent). Multiple structural malformations were present in 61 fetuses, of which 16 had an abnormal karyotype (26 per cent). Trisomy 18 was the most frequent finding. The most constant ultrasound finding in cases of an abnormal karyotype was polyhydramnios and severe IUGR in combination with structural defects. There is a need for extensive detailed ultrasound examination in high‐risk pregnancies.
Ethical and legal implications in IVF and prenatal diagnosis in the U.K.
Authors: Ferguson‐Smith Marie E.
Published: March 2007

The natural desire for couples to be parents and the medical practitioner's inability to treat most genetic diseases have been responsible for some of the most exciting research into infertility and genetic disorders. This has led in the United Kingdom to the establishment of the Warnock Committee of Inquiry into Human Fertilization and its report in 1984, and to a Review of the guidance on Research Use of Fetuses and Fetal Material published in 1989 and known as the Polkinghorne Report. The Warnock Report, among other ethical issues, considers the most fundamental question which has been debated for thousands of years, namely, What is life and when does it begin? More recently, the report has been responsible for new legislation which imposes ethical and legal restrictions on the scientific and medical community. The Polkinghorne Report recommends a voluntary code of practice which is morally and ethically acceptable within our society. We are also fortunate in the U.K. to have a parliamentary structure which allows debate on such important human issues and is prepared to impose ethical restrictions.
The vanishing twin: An explanation for discordance between chorionic villus karyotype and fetal phenotype
Authors: Reddy K. S. , Petersen M. B. , Antonarakis S. E. , Blakemore K. J.
Published: March 2007

One ‘erroneous’ diagnosis occurred in 200 first‐trimester chorionic villus samples (CVS) analysed. In direct preparations following 24 h incubation as well as in long‐term cultures, a 46.XX karyotype was observed in the villi (28 and 25 cells, respectively). At 20 weeks of gestation, labour was induced because of fetal death in utero. An autopsy performed on the fetus revealed a male phenotype. Placenta and fetal tissues were not submitted for cytogenetic studies. The discordant CVS karyotype (46,XX), in view of the male fetal phenotype, prompted further cytogenetic and molecular studies. Chromosome marker studies on the parents' blood and chorionic villi confirmed both maternal and paternal inheritance of chromosomes in the CVS. DNA studies on formalin‐fixed skin using a Y‐specific probe, DYZ1, confirmed the presence of a Y chromosome in the fetus. The most likely cause of the discrepant CVS karyotype is the presence of an undetected degenerating dizygotic twin.
Eleventh week amniocentesis for prenatal diagnosis of some metabolic diseases
Authors: Kamoun P. P. , Chadefaux B.
Published: March 2007

We report the results of 23 prenatal diagnoses performed at the 11th or 12th week of gestation by the simultaneous analysis of chorionic villi (for direct or indirect enzymatic analysis) and cell‐free amniotic fluid (for search of accumulated catabolites). For six cases of citrullinaemia, four cases of argininosuccinic aciduria, seven cases of propionic acidaemia, and six cases of methylrnalonic acidaemia, three discrepancies were observed between the two methods used. The amniotic fluid analysis for accumulated catabolites seems to be a safe method and should always be used in conjunction with the enzymatic assays performed for the prenatal diagnosis of these diseases.
Heterochromatin decondensation in chromosomes from chorionic villus samples
Authors: Pérez M. M. , Míguez L. , Fuster C. , Miró R. , Genescà A. , Egozcue J.
Published: March 2007

The spontaneous decondensation of constitutive heterochromatic regions of chromosomes 1, 9, 16, and Y has been observed in 46.6 per cent of chorionic villus samples. This type of decondensation is occasionally observed in amniotic fluid cells (9 per cent) and has never been found in fetal lymphocytes. The phenomenon is similar to that described in spermatogonial metaphases, in primary and secondary spermatocytes and in human sperm chromosomes, although decondensation of the heterochromatin of chromosome 15 has never been recorded in chorionic villus samples.
Prenatal counselling and diagnosis in progressively deforming osteogenesis imperfecta: A case of autosomal dominant transmission
Authors: Phillips Owen P. , Shulman Lee P. , Altieri Lisa A. , Wilroy R. Sidney , Emerson Donald S. , Dacus John V. , Elias Sherman
Published: March 2007

A 21 ‐year‐old woman with progressively deforming or type III osteogenesis imperfecta (OI) presented for prenatal counselling and diagnosis at 10 weeks' gestation. Family history was non‐contributory. At 14.8 weeks' gestation, ultrasonographic examination revealed fetal skeletal hypomineralization, easily compressible fetal cranium, and thickened long bones, indicating that the fetus was also affected. Confirmation of the prenatal diagnosis of OI type III was made following a Caesarean section birth of a male infant with multiple skeletal deformities and blue sclerae implying, in this case, autosomal dominant inheritance.
Sanfilippo D syndrome: Correction of glucosamine‐6‐sulphatase deficiency following fibroblast culture in chang's media
Authors: Freeman Craig , Hopwood John J.
Published: March 2007

The de‐O‐sulphation of α‐linked glucosamine‐6‐sulphate residues in heparan sulphate requires a specific sulphatase, glucosamine‐6‐sulphatase, which has been shown to be deficient in tissues of Sanfilippo D, or mucopolysaccharidosis type IIID (MPS IIID), patients. MPS IIID fibroblasts cultured in Basal Eagle's medium supplemented with either fetal calf serum or heat‐inactivated fetal calf serum, MDCB or Ultraserg media had residual glucosarnine‐6‐sulphatase activities towards a heparin‐derived trisaccharide substrate, O‐(α‐N‐acetylglucosamine‐6‐sulphate)‐(1→4)‐L‐O‐(α‐iduronic acid‐2‐sulphate)‐(1→4)‐D‐O‐2,5‐anhydro [1‐3H]mannitol‐6‐sulphate, GlcNAc6S‐IdoA2S‐anM6S, which were less than 1 per cent of the normal range for fibroblasts cultured in Basal Eagle's medium supplemented with fetal calf serum. However, the glucosamine‐6‐sulphatase activities of MPS IIID fibroblasts grown in Chang's medium were similar to the activities in normal control fibroblasts which were cultured in Basal Eagle's medium. These results indicate that caution is required for prenatal diagnosis of MPS IIID patients using chorionic villi or amniotic cells cultured in Chang's medium.
In utero sonographic diagnosis of diaphragmatic hernia with hepatic protrusion into the pericardium mimicking an intrapericardial tumour
Authors: Aré Evelyne , Fouron Jean‐Claude , Lessard Manon , Boisvert Jacques , Grignon Andrée , Van Doesburg Nicolaas H.
Published: March 2007

A case of right‐sided congenital diaphragmatic hernia was detected at 33 weeks of gestation. Fetal echocardiography revealed the presence of an intrapericardial mass (3.5 × 3 cm) localized at the right of the heart and surrounded by a massive pericardial effusion. This mass had the same echogenicity as the liver, with which it shared vascular channels. The diagnosis of right diaphragmatic hernia with protrusion of hepatic tissue into the pericardial sac and secondary pericardial effusion was made and confirmed after birth. In utero diagnosis of this anomaly enabled correct assessment of perinatal risk, and optimal fetal and infant management.
First‐trimester diagnosis of hypophosphatasia. Importance of gestational age and of purity of CV samples
Authors: Muller F. , Ouryß J. F. , Bussière P. , Lewin F. , Boué Joëlle
Published: March 2007

Prenatal diagnosis of hypophosphatasia was made by alkaline phosphatase (ALP) assay on a chorionic villous sample taken in the first trimester. Very low activities of the LBK isoenzyrnes indicated an affected fetus. Diagnosis was confirmed at 12 weeks of gestation by measurement of LBK isoenzyme activities in fetal bone tissue. In control chorionic villous samples an inverse relation was observed between LBK and placental ALP percentage during gestational age. High LBK ALP activities are observed in decidual tissue. Chorionic villous tissue must not be sampled after 12 weeks of gestation and decidual tissue must be excluded from the sample.
First‐trimester diagnosis of hunter syndrome: Very low iduronate sulphatase activity in chorionic villi from a heterozygous female fetus
Authors: Cooper A. , Thornley M. , Wraith J. E.
Published: March 2007

Iduronate sulphatase activity was determined in uncultured chorionic villi from four fetuses at risk for Hunter syndrome. AH fetuses were shown to be female by chromosome analysis. Biopsy material from three fetuses showed iduronate sulphatase activity within normal limits whilst the fourth fetus showed activity reduced to 7 per cent of our control mean. The importance of fetal sexing in prenatal diagnosis of this condition is emphasized as female carrier fetuses may show iduronate sulphatase activity reduced to levels observed in affected males.
First‐trimester prenatal diagnosis in quintuplets: A practical approach using step‐by‐step embryo reduction
Authors: Dumez Y. , Dommergues M. , Lyonnet S. , Tada K. , Kaplan J. , Mandelbrot L.
Published: March 2007

A multiple pregnancy of high rank may occur in a couple at risk for a Mendelian disorder. Prenatal diagnosis is hampered by the difficulty of (1) obtaining chorionic villi from each zygote arid (2) unequivocally relating each sample to the corresponding embryo. The calculation of the genetic risk according to the number of zygotes led us to propose a diagnostic strategy based on embryo reduction, a technique initially designed to improve the perinatal outcome of multiple pregnancies with normal embryos. We report a case in which this approach allowed rational use of first‐trimester chorionic villus sampling in a quintuplet pregnancy at risk for non‐ketotic hyperglycinaemia, resulting in the selective birth of unaffected twins.
Confirmation of CVS mosaicism in term placentae and high frequency of intrauterine growth retardation association with confined placental mosaicism
Authors: Kalousek D. K. , Howard‐Peebles P. N. , Olson S. B. , Barrett I. J. , Dorfmann A. , Black S. H. , Schulman J. D. , Wilson R. D.
Published: March 2007

About 2 per cent of specimens from chorionic villus sampling (CVS) analysed either on direct preparation of cytotrophoblast cells or afterculture of mesenchymal stroma reveal confined placental mosaicism (CPM), most commonly involving chromosomal trisomy. A significantly higher rate of prenatal loss (22 per cent) as well as the presence of intrauterine growth retardation (IUGR) has been reported among pregnancies with CPM. To evaluate more precisely the effect of these aneuploid cell lines confined to the placenta on intrauterine fetal growth and fetal survival, we have studied 34 term placentae from pregnancies with CPM diagnosed on CVS and confirmed identical mosaicism in 17 of these placentae. There was a direct correlation between a high number of aneuploid cells present at CVS and a high likelihood of their detection in term placenta. Also, the proportion of aneuploid cells in the mosaic term placentae correlated with that observed in CVS specimens. Among 17 gestations with confirmed CPM at delivery, there were six cases of IUGR identified, five in liveborns and one associated with intrauterine death.
First‐trimester aneuploidy screening using serum human chorionic gonadotropin (hCG), free ahCG, and progesterone
Authors: Kratzer Paul G. , Golbus Mitchell S. , Monroe Scott E. , Finkelstein David E. , Taylor Robert N.
Published: March 2007

Immunochemical serum assays for human chorionic gonadotropin (hCG), the free ohCG subunit, and progesterone (P) were considered separately and in combination for their ability to screen for chromosomally abnormal pregnancies in the first trimester. Maternal serum was collected from 141 women undergoing chorionic villus sampling at 9–12 menstrual weeks. Trisomy 21 pregnancies had significantly higher hCG levels, while trisomy 18 and 13 pregnancies had markedly lower hCG and progesterone levels than those of chromosomally normal pregnancies. However, the discrimination of normal from aneuploid pregnancies was poor with either hCG alone, progesterone alone, or free ahCG alone. Much improved discrimination was obtained by combining hCG, free ahCG, and P into an aneuploidy index [(P/hCG)(free ahCG/hCG)]. This index distinguished 9 out of 17 (53 per cent) of the trisomy 21 pregnancies, while only misidentifying 5 out of 112 (4.5 per cent) of the normal pregnancies. The aneuploidy index thus appears promising as a first‐trimester biochemical screen for aneuploid pregnancies.
First‐trimester genetic diagnosis in multiple pregnancy: Principles and potential pitfalls
Authors: Brambati Bruno , Tului Lucia , Lanzani Alessandro , Simoni Giuseppe , Travi Maurizio
Published: March 2007

Both the principles of first‐trimester genetic diagnosis in multiple pregnancy and the special considerations required to avoid potential diagnostic pitfalls are presented. The experience consisted of 65 cases of twins and one case of quadruplets. Dichorionic twins were recognized by sonography in 54 cases. Transabdominal aspiration was generally preferred to trans‐cervical for obtaining chorionic tissue, although in two cases both approaches were used. Diagnostic error following erroneous sampling was reported in 3 out of 54 sets of dichorionic twins (5.5 per cent). When like‐sex dichorionic twins cannot be differentiated by cytogenetic or DNA polymorphism studies, amniocentesis should be recommended to confirm the reliability of the result on chorionic tissue.
An approach to preimplantation diagnosis of β‐thalassaemia
Authors: Varawalla N. Y. , Dokras A. , Old J. M. , Sargent I. L. , Barlow D. H.
Published: March 2007

Using the polymerase chain reaction (PCR), it was possible to amplify a single copy fragment of the β‐globin gene from 2–32 human embryonic cells obtained from arrested preimplantation embryos. For the detection of β‐thalassaemia mutations, allele specific priming of the PCR using nested primers was employed using approximately 10 pg of DN A from individuals known to carry these mutations. This approach was successful in detecting the presence or absence of five Asian Indian β‐thalassaemia mutations that were selected for this study. In spite of meticulous precautions against contamination, false‐positive amplification was observed, a problem that will have to be overcome before this approach can be used in clinical practice.
Intraplacental sonolucent spaces: Incidences and relevance to chorionic villus sampling
Authors: Liu David T. Y. , Agbaje Remi , Preston Christine , Savage Julie
Published: March 2007

Detailed ultrasound examination of the placentae from 293 consecutive women requesting first‐trimester chorionic villus sampling (CVS) showed evidence of intraplacental sonolucent spaces with varying density in 42.3 per cent of these placentae. Their presence, however, did not complicate the subsequent course of these women's pregnancies. Their prime significance relates to CVS, where inadvertent entry into these areas can lead to bleeding and contamination of the villus specimens with blood. A search for these spaces should be made before sampling, and when present, they should be avoided wherever possible.
Recurrent congenital chylothorax
Authors: King P. A. , Ghosh A. , Tang Mary H. Y. , Lam S. K.
Published: March 2007

Congenital chylothorax is an uncommon but well‐described condition. Recurrent congenital chylothorax is extremely rare. Yancy and Spock (1967) reviewed 31 reported cases of spontaneous chylothorax which occurred in the first 2 months of life and noted that male infants were affected twice as commonly as females. Two other cases of recurrent congenital chylothorax in male offspring (Defoort and Thiery, 1978; Reece et al., 1987) led to the suggestion of possible X‐linked recessive inheritance. We describe a case of recurrent congenital chylothorax in which two consecutive female infants in a sibship were affected. The underlying cause of this disorder remains unknown. Inheritance as an X‐linked recessive is not possible and this case is suggestive of autosomal recessive inheritance. The case also serves to emphasize the need for caution in counselling for recurrence risks when the underlying aetiology of the disorder is unknown.
False‐negative prenatal exclusion of Wiskott‐Aldrich syndrome by measurement of fetal platelet count and size
Authors: Lorenz Peter , Bollmann Rainer , Hinkel Georg Klaus , Mächler Marco , Siegert Gabriele , Stamminger Gudrun , Wendisch Jörg , Ziemer Sabine
Published: March 2007

The study of the fetal platelet count and size can, according to the literature, be used for the prenatal diagnosis of the Wiskott‐Aldrich syndrome (WAS). So far, no affected fetuses have been identified by this method. All pregnancies in which this method had been applied to resulted, as correctly predicted, in the birth of normal children. Here we report on a familial case of WAS where the haematological parameters failed to reveal the affected second child. Hence we assume that the platelet count and size of platelets remain normal in fetuses with WAS to the gestational age of 22 weeks and cannot be used for prenatal diagnosis.
Clinical and pathological factors in spontaneous abortion following chorionic villus sampling
Authors: McCormack M. J. , MacKenzie W. E. , Rushton D. I. , Newton R.
Published: March 2007

Twenty‐nine cases of spontaneous abortion following first‐trimester chorionic villus sampling (CVS) were reviewed out of a series of 722 patients. Of the 29 cases, there were only four abnormal CVS results. Pathological examination was performed in 79 per cent of cases, and this did not identify any characteristic pathological feature associated with spontaneous abortion after CVS. There was no obvious difference in the pathological features following the transabdominal (TA) or the transcervical (TC) methods. The majority of miscarriages occurred within 4 weeks of the procedure, but 38 per cent of cases aborted between 7 and 14 weeks after CVS. The TC method was used in 22 patients; the TA in 6; and both methods in 1 patient. The TA method was associated with a significantly lower fetal loss rate than the TC method (TA 2 per cent, TC 9 per cent, p < 0.001).
Estimating the risk of a fetal autosomal trisomy at mid‐trimester using maternal serum alpha fetoprotein and age: A retrospective study of 142 pregnancies
Authors: Zeitune M. , Aitken D. A. , Crossley J. A. , Yates J. R. W. , Cooke A. , Ferguson‐Smith M. A.
Published: March 2007

Risks appropriate for mid‐trimester prenatal screening for autosomal trisomies have been estimated from a combination of maternal age and maternal serum (MS) alpha‐fetoprotein (AFP) levels at 16–20 weeks gestation. Published data on the frequency of Down's syndrome births relative to maternal age were modified to include the additional age‐related frequency of trisomy 18 and trisomy 13 cases to provide an overall risk for an autosomal trisomy at midtrimester. MSAFP results from a retrospective study of 142 affected (114 trisomy 21, 19 trisomy 18, and 9 trisomy 13)and 113 000 unaffected pregnancies were converted to multiples of the appropriate gestational median (MOM). The AFP levels in the autosomal trisomy pregnancies were found to be significantly reduced at 0.72 MOM of the unaffected pregnancies. Risks (likelihood ratios) were derived from the overlapping log Gaussian distributions for affected and unaffected pregnancies and combined with maternal age risks to give the overall odds of an affected pregnancy.

A mid‐trimester cut‐off risk of 1:280 gave an estimated 37 per cent detection rate for autosomal trisomies in the west of Scotland population for a follow‐up (false‐positive) rate of 6.6 per cent. These figures compare with a 30 per cent detection and 6.7 per cent false‐positive rate if age 35 years and over is used as the sole criterion for selection of at‐risk pregnancies.
Prenatal diagnosis of PIBIDS
Authors: Savary J. B. , Vasseur F. , Vinatier D. , Manouvrier S. , Thomas P. , Deminatti M. M.
Published: March 2007

In a well‐documented PIBIDS family, two investigations of DNA excision repair showed a severe defect in lymphocytes from the index case (residual repair activities were 10.6–12.1 per cent). The values for the mother, father, and sister were within the normal range when compared with a healthy control. In the pregnant mother, a prenatal diagnosis of PIBIDS was made by measuring UV‐induced unscheduled DNA synthesis in cultivated amniotic fluid cells. Results ranged between 12.5 and 26.1 per cent depending on the UV doses applied and were consistent with an affected fetus. The parents opted for a termination of pregnancy. Following a therapeutic abortion, fetal skin fibroblasts were tested and showed a severe DNA excision‐repair defect of 9.2–13.5 per cent of residual activity.
Prenatal diagnosis of a fetus with terminal deletion of chromosome 1 (q41)
Authors: Rotmensch Siegfried , Liberati Marco , Luo Jia‐Sen , Tallin Giovanni , Mahoney Maurice J. , Hobbins John C.
Published: March 2007

Many authors have suggested that individuals affected by a terminal 1q deletion display a phenotypically definable and recognizable syndrome. In all of the 27 cases reported to date, the breakpoints were at band q42 or distally to it. To our knowledge, we report the first case of a terminal 1q41 deletion. Diagnosis was made prenatally by amniocentesis, following ultrasonographic diagnosis of omphalocele, cerebral ventriculomegaly, and increased nuchal fold thickness in a 19‐week female fetus. Multiple facial and extremity features were consistent with the proposed distal 1q deletion syndrome; omphalocele, however, has not been reported previously. The absence of liver herniation into the omphalocele sac in this case supports the previously reported association of this finding with chromosomal anomalies.
A case of mosaicism involving an unstable 13/14 Robertsonian translocation
Authors: Wells Sue , Gregson Nina , Porter R. J.
Published: March 2007

Prenatal diagnosis of mosaicism involving an apparently unstable 13/14 Robertsonian trans‐location is reported. This illustrates the difficulties encountered in counselling when mosaicism is ascertained prenatally. Other reported examples of apparently unstable Robertsonian translocations are discussed.
Prenatal diagnosis of haemoglobin disorders by cordocentesis at 12 weeks' gestation
Authors: Di Trapani F. , Marino M. , D'Alcamo E. , Abate I. , D'Agostino S. , Lauricella S. , Musicò M. , Orlandi F. , Sammarco P. , Maggio A. , Modell B.
Published: March 2007

Prenatal diagnosis of haemoglobin disorders is accepted to be a useful procedure to avoid births of infants with homozygous diseases. Advances in sampling and molecular techniques, such as polymerase chain reaction (PCR) and chorionic villus sampling (CVS), have made earlier and safer first‐trimester prenatal diagnosis possible. However, these procedures need previous studies of at‐risk couples, which can be very time‐consuming when a number of different β‐thalassaemia mutations occur in the region. We describe the possibility of making a first‐trimester prenatal diagnosis by cordocentesis and fetal blood analysis at the 12th week of gestation. We found no statistically significant difference (p>0.05) between β/γ values in fetuses at the 12th and 18th weeks of gestation. In seven affected fetuses aborted at the 12th week of gestation, the diagnosis was confirmed in all cases by PCR analysis. These findings suggest that early cordocentesis could be an alternative procedure to CVS and PCR analysis.
A fetal cystic neck mass associated with maternal tuberous sclerosis. Case report and literature review
Authors: van Oppen A. C. C. , Breslau‐Siderius E. J. , Stoutenbeek Ph. , Gunne A. J. Pull Ter , Merkus J. M. W. M.
Published: March 2007

Tuberous sclerosis is a single gene autosomal‐dominant disorder, characterized by multiple hamartoma formation. It shows a wide variability of expression. Prenatal diagnosis by means of a DNA or biochemical marker is not yet possible. Ultrasound offers the only way to detect possible antenatal hamartoma formation, which is most commonly found in the central nervous system, the renal system, and the heart. We report a case of fetal involvement that appears unique because of the unusual location of a tumour in the neck of the fetus.
Nature and frequency of chromosomal abnormalities in pregnancies with abnormal ultrasound findings: An analysis of 117 cases with review of the literature
Authors: Gagnon Sylvie , Fraser William , Fouquette Bertrand , Bastide Adrien , Bureau Marc , Fontaine Jean‐Yves , Huot Céline
Published: March 2007

During a 7‐year period, 117 fetal karyotypes were available from 131 genetic amniocenteses. These procedures were performed between 14 and 37 weeks' gestation for the following abnormal ultrasound findings: (1) intrauterine growth retardation (IUGR)—61 cases; (2) fetal malformation—71 cases; and (3) amniotic fluid volume (AFV) abnormality—60 cases. Chromosomal abnormalities were identified in 19 cases (16.2 per cent). Aneuploidy was 2.5 times as frequent in the presence of malformations than in their absence. No correlation was demonstrated between specific fetal malformations and specific chromosomal abnormalities. Aneuploidy was also twice as frequent in the presence of symmetrical IUGR than in its absence. No chromosomal abnormalities were found among eight cases of asymmetrical IUGR. Four cases of aneuploidy presented with isolated IUGR, three of these involving the X chromosome. The frequency of aneuploidy was the same with or without abnormalities of AFV (14.3 versus 16.4 per cent). No chromosomal abnormality was found associated with isolated AFV abnormalities.
Prenatal diagnosis and investigation of a fetus with chondrodysplasia punctata, ichthyosis, and Kallmann syndrome due to an Xp deletion
Authors: Bick David P. , Schorderet Daniel F. , Price Paul A. , Campbell Leslie , Huff Robert W. , Shapiro Larry J. , Moore Charleen M.
Published: March 2007

We report the prenatal diagnosis of a male fetus with X‐linked recessive chondrodysplasia punctata (CDPX), steroid sulphatase (STS) deficiency, X‐linked Kallmann syndrome (KAL), and a chromosome deletion at Xp22.31. Biochemical analysis of bone from this case indicates that CDPX is not a defect of vitamin K metabolism. Immunocytochemical study of the brain suggests that KAL is a defect in neuronal migration.
An infant with trisomy 9 mosaicism presenting as a complete trisomy 9 by amniocentesis
Authors: Sherer David M. , Wang Nancy , Thompson Howard O. , Peterson Jeanne C. , Miller Marvin E. , Metlay Leon A. , Abramowicz Jacques S.
Published: March 2007

We present a case in which amniocentesis performed at 33 weeks' gestation because of symmetrical intrauterine growth retardation and decreased amniotic fluid volume led to the prenatal diagnosis of a fetus with a karyotype of 47,XX,+9, t(1;20)(q42;p11.2) pat, i.e., with an extra chromosome 9 and a balanced translocation between chromosomes 1 and 20. At delivery, the baby showed clinical features of trisomy 9, yet chromosome analysis of the cord blood revealed no trisomy 9 cells, a finding confirmed by neonatal blood karyotyping. The balanced translocation was present in all cells. A skin biopsy confirmed trisomy 9 mosaicism with 10 per cent trisomy 9 cells. The baby died at 6 weeks and an autopsy was obtained. Chromosome analysis of different organs demonstrated different frequencies of the mosaicism of trisomy 9. The possible underlying mechanism for the discrepancy between the karyotype results by amniocentesis and those of other tissues is discussed.
Origin of raised maternal serum alpha‐fetoprotein levels in second‐trimester oligohydramnios
Authors: Los F. J. , Beekhuis J. R. , Marrink J. , Hagenaars A. M. , Reuss A. , Sachs E. S. , Jahoda M. G. J. , Wladimiroff J. W.
Published: March 2007

Concanavalin A (Con A) subtyping of alpha‐fetoprotein (AFP) revealed higher concentrations of AFP non‐reactive with Con A in sera of 12 pregnant women with second‐trimester oligohydramnios and raised total serum AFP levels than in sera of 42 pregnant women with raised total serum AFP levels and a normal amniotic fluid volume. This suggests that in oligohydramnios the origin of excess AFP in the maternal compartment is amniotic fluid. It is proposed that oligohydramnios and the associated raised maternal serum AFP levels are caused by damage of the fetal membranes prior to 16 weeks of gestation resulting in leakage of amniotic fluid to the decidual tissue and resorption in the maternal circulation.
Placental mosaicism in a case of 46,XY, −22, +t(22;22)(p11;q11) or i(22q) diagnosed at amniocentesis
Authors: Spinner Nancy B. , Gibas Zenon , Kline Rochelle , Berger Bruce , Jackson Laird
Published: March 2007

46,XY, −22,+t(22;22)(p11;q11) or i(22q) was diagnosed in 15/15 cells from two cultures from the amniotic fluid culture of a 31‐year‐old patient whose fetus demonstrated cystic hygroma on ultrasound. Cytogenetic studies performed on fetal skin from the abortus revealed the same karyotype as that seen on amniocentesis, but the placenta demonstrated a 46,XY,46,XY, −22,+t(22;22) or i(22q) mosaicism, with 65 per cent of the cells being 46,XY. This case provides an example of placental mosaicism for a normal male karyotype, while the fetus demonstrated non‐mosaic trisomy 22.
Chorionic villus metaphase chromosomes and interphase nuclei analysed by chromosomal in situ suppression (CISS) hybridization
Authors: Klever Martin , Grond‐Ginsbach Caspar J. , Hager Hans‐Dieter , Schroeder‐Kurth Traute M.
Published: March 2007

Metaphase chromosomes and interphase nuclei of chorionic villus samples (CVS) in five cases were studied after treatment with trypsin and post‐fixation in formaldehyde by chromosomal in situ suppression (CISS) hybridization. Our modified protocol enables the use of in situ hybridization. techniques on CVS preparations after 42 h ofculture. A balanced translocation and trisomy 13 were identified with the aid of CISS hybridization.