bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound screening for chromosomal anomalies in the first trimester of pregnancy
Authors: Savoldelli Guido , Binkert Franz , Achermann Josef , Schmid Werner
Published: March 2007

For the last 6 years, sonographic signs for excessive fluid accumulation in the backs of 10‐ to 12‐week‐old fetuses have been looked for prior to transabdominal chorionic biopsy. In 1400 pregnancies, subsequent karyotype analyses revealed 28 cases of Down syndrome. In 15 ( = 54 per cent), a large fluid cushion over most of the back had been documented at the time of biopsy. Only a few chromosomally normal fetuses with the same peculiarity were observed. The cushion was also present in fetuses with trisomies 18 and 13, and in Turner syndrome. Systematic first‐trimester screening for nuchal fluid accumulation seems to be a recommended method for the detection of Down syndrome and other chromosome anomalies in young pregnant women at low risk. It compares favourably with current methods of maternal serum screening performed at 16–18 weeks which require a higher number of invasive procedures.
Achondrogenesis type 2 diagnosed by transvaginal ultrasound at 12 weeks' gestation
Authors: Soothill P. W. , Vuthiwong C. , Rees H.
Published: March 2007

Ultrasound examination at 12 weeks' gestation revealed severe generalised subcutaneous oedema in a pregnancy at risk for achondrogenesis type II. Transvaginal scanning confirmed the oedema and suggested abnormal limb development. The prenatal diagnosis was confirmed by X‐ray examination after transvaginal termination.
First report of prenatal diagnosis of long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency in a pregnancy at risk
Authors: Perez‐Cerda C. , Merinero B. , Jimenez A. , García M. J. , Sanz P. , Ulst L. , Wanders R. J. A. , Ugarte M.
Published: March 2007

Prenatal diagnosis of long‐chain 3‐hydroxyacyl‐CoA dehydrogenase (3‐HAD) deficiency was performed in a family at risk. The diagnosis of an affected fetus was carried out by enzyme assay in cultured chorionic villus cells.
The diagnostic potential of fetal renal biopsy
Authors: Greco P. , Loverro G. , Caruso G. , Clemente R. , Selvaggi L.
Published: March 2007

The feasibility of fetal renal biopsy has been investigated in order to assess the diagnostic value of the histological specimen. Two fetuses with a severe bilateral renal abnormality (multicystic dysplastic kidney, Meckel‐Gruber syndrome with polycystic kidney) and one fetus with Down syndrome (no detectable structural anomaly) were sampled. Histological findings in the biopsy specimens of cases 1 and 2 were diagnostic of an early obstructive renal disease. In case 3, the findings were consistent with normal development for gestational age of the kidney. Fetal renal biopsy is technically feasible; histological examination of the samples showed a good correlation with postnatal findings. Further studies of its diagnostic value are required.
First‐trimester maternal serum schwangerschafts protein 1 (SP1) in pregnancies associated with chromosomal anomalies
Authors: Macintosh M. C. M. , Brambati B. , Chard T. , Grudzinskas J. G.
Published: March 2007

The relationship between first‐trimester maternal serum Schwangerschafts protein 1 (SP1) and the karyotype of the pregnancy was examined in 692 women who underwent chorionic villus biopsy at 6–12 weeks. There were 30 pregnancies with abnormal karyotypes, consisting of 14 Down's syndrome (DS), eight trisomy 18, and eight other anomalies, two of which were mosaics. The normal ranges and medians for gestation were defined from the 662 cases in which the karyotype was normal. The median SP1 (0·5 MOM) of the abnormal group was significantly lower than that of the normal group (10 MOM). This relationship was maintained for the DS pregnancies (0·4 MOM) and for anomalies other than trisomy 18 (0·43 MOM) but not trisomy 18 (1·1 MOM). It is possible that the use of SP1 as a screening test for chromosome anomalies in the first trimester could have a 43 per cent detection rate for a 5 per cent false‐positive rate.
A rare inherited euchromatic heteromorphism on chromosome 1
Authors: Zaslav A. L. , Blumenthal D. , Fox J. E. , Thomson K. A. , Segraves R. , Weinstein M. E.
Published: March 2007

Extra genetic material that is euchromatic is generally regarded to be associated with phenotypic abnormalities. However, recent studies suggest that this is not always the case. Chromosome analysis was performed on amniotic fluid cells from a 37‐year‐old phenotypi‐cally normal patient referred for advanced maternal age. All the cells analysed showed a karyotype of 46, XY, 1p‐K The 1p+ chromosome had extra genetic material of uncertain origin in chromosome band region 1p21 →31. Chromosome analysis on the father revealed a normal 46, XY male karyotype. The mother's karyotype showed the same 1p+ chromosome. C and Q banding, as well as silver staining studies, in both the mother and the fetus support the interpretation that the extra chromosomal material was euchromatic in nature. This 1p + chromosome may be characterized as a euchromatic heteromorphism. Euchromatic hetero‐morphisms not associated with phenotypic abnormalities have been reported for chromosomes 9 and 16. To the best of our knowledge, this is the first report involving this type of cytogenetic anomaly on chromosome number 1 in a phenotypically normal mother and infant.
Prenatal diagnosis by in situ hybridization on uncultured amniocytes: Reduced sensitivity and potential risk of misdiagnosis in blood‐stained samples
Authors: Christensen Britta , Bryndorf Thue , Philip John , Xiang Yang , Hansen Winnie
Published: March 2007

Maternal cell contamination was assessed in 18 macroscopically blood‐stained amniotic fluid samples from male fetuses. The samples were analysed by double‐target fluorescent in situ hybridization (ISH) with Y and X chromosome‐specific probes. The only sample with an aberrant karyotype (47, XY, +18) was also analysed by hybridization with a chromosome 18‐specific probe. An interpretation of extensive maternal cell contamination was made in two samples, one of which was the sample with trisomy 18. ISH with the chromosome 18‐specific probe on this latter sample showed that the sensitivity of the ISH method for chromosome enumeration of uncultured amniotic fluid samples may be reduced in bloodstained samples. It was calculated that by using ISH for chromosome enumeration of the two extensively contaminated samples, a case of trisomy 21 might have been overlooked in both samples, while a case of trisomy 18 might only have been overlooked in one of the samples. It is concluded that ISH should not be used for chromosome enumeration of uncultured amniotic fluid samples that are macroscopically blood‐stained without further technical developments.
Serum PAPP‐A levels are depressed in women with fetal Down syndrome in early pregnancy
Authors: Muller F. , Cuckle H. , Teisner B. , Grudzinskas J. G.
Published: March 2007

The value of maternal serum pregnancy‐associated plasma protein (PAPP)‐A in screening for Down syndrome in early pregnancy was assessed using stored samples. Seventeen cases of Down syndrome and 66 unaffected control pregnancies were studied. The median PAPP‐A level in the cases was 0.42 multiples of the expected value in controls (p <0.0001). Eleven cases (65 per cent) had levels less than half the expected value compared with only six controls (9 per cent). A commercial assay kit is now needed so that prospective screening with this marker can begin.
46,XY/47,XY,+ 17p+ mosaicism in amniocytes associated with fetal abnormalities despite normal fetal blood karyotype
Authors: Kingston Helen M. , Nicolini Umberto , Haslam John , Andrews Tony
Published: March 2007

46,XY/47,XY, + 17p + mosaicism was found in two primary amniotic fluid cultures (AFCs). Fetal blood karyotype was normal, but ultrasonography revealed Dandy‐Walker malformation and bilateral choroid plexus cysts. Following termination of pregnancy, fetal examination revealed post‐axial polydactyly and neuroblastoma‐in‐situ affecting both adrenals in addition to the cerebellar abnormalities. Mosaicism for the aberrant cell line was confirmed in all fetal tissues sampled and in the placenta.
Prenatal diagnosis of the acute form of proximal spinal muscular atrophy: Experience on the acceptance of linkage analyses by the families
Authors: Huschenbett J. , Hanke R. , Pfeifer L. , Speer A.
Published: March 2007

The acute form of proximal spinal muscular atrophy (SMA) is a severe autosomal recessive inherited neuromuscular disorder. It has been mapped to chromosome 5q 11.2‐13.3. Using restriction fragment length polymorphisms (RFLPs) or (CA)n repeats of DNA probes in this region, prenatal diagnosis is, in principle, possible. Misdiagnosis can be due to incorrect diagnosis in the index patient, and crossing‐over events. Using the DNA probes D5S6, D5S112, D5S39, and D5S78, we cover a region of 10.4 mega‐base pairs (Mbp) of partially NotI‐digested genomic DNA without overlap of fragments. The DNA probes D5S6 and D5S112, most likely flanking the SMA gene, cover a distance of about 6.6 Mbp. This corresponds to the genetic distance of 6 cM (Morrison et al., 1992; Daniels et al., 1992). But since the precise localization of the SMA gene is still unknown (Simard et al., 1992), a 10 per cent risk of misdiagnoses due to crossing‐over events cannot be excluded. The acceptance of this 10 per cent risk for prenatal diagnoses differs in SMA families. We observed a case in which a woman accepted a 25 per cent risk because RFLPs and (CA)n repeats were both uninformative. In contrast, another family did not accept the minimal 10 per cent risk and the pregnancy was terminated. In two families, we performed prenatal diagnosis by linkage analysis. One child predicted to be healthy has been born in the meantime and has shown no indication of SMA during her first 8 months.
Successful DNA‐based prenatal exclusion of juvenile neuronal ceroid lipofuscinosis
Authors: Uvebrant Paul , Björck Eva , Conradi Nils , Hökegård Klas‐Henry , Martinsson Tommy , Wahlström Jan
Published: March 2007

A family with two siblings, 10 and 8 years old, both with clinical and ultrastructural evidence of juvenile neuronal ceroid lipofuscinosis is described. The family was found to be informative for the restriction fragment length polymorphisms (RFLPs) detected by the probes pCJ52–95Ml (locus D16S148) and pCJ52‐94Tl (locus D16S159) flanking the juvenile neuronal ceroid lipofuscinosis locus, CLN3. The parents were both heterozygous using these probes, while their two children with juvenile neuronal ceroid lipofuscinosis were both homozygous. Chorionic villi analysis showed that the fetus was heterozygous and had inherited the one allele of the mother which was not found in the two siblings. This suggested that the fetus had derived one healthy allele from the mother, the risk for a double crossing‐over being less than 1 per cent. Electron microscopy showed no fingerprint inclusions in chorionic villi. The child was investigated at 6 months of age and found to be healthy, as new fingerprint inclusions were found at electron microscopy and no vacuolated lymphocytes were found in the blood smear. Due to the risk of heterogeneity, both DNA‐based analysis and electron microscopy on chorionic villi are recommended for prenatal examination for juvenile neuronal ceroid lipofuscinosis.
Fluorescent in situ hybridization (FISH): A new application in the delineation of true vs. pseudomosaicism in prenatal diagnosis
Authors: Schwartz Stuart , Leana‐Cox Julie
Published: March 2007

Metaphase chromosomes and interphase nuclei from nine amniotic fluid cultures were studied with fluorescence in situ hybridization (FISH). The samples were initially analyzed with routine G‐banding and were diagnosed as having true mosaicism (five patients) or pseudomosaicism (four patients). In our study, FISH analysis could provide additional information to distinguish pseudo– from true mosaicism by allowing interphase studies and analysis of an increased number of metaphase spreads. These results suggest a multilinear origin of ‘in situ’ colonies of cells.
Molecular cytogenetic analysis of term placentae suspected of mosaicism using fluorescence in situ hybridization
Authors: Schuring‐Blom G. H. , Keuzer M. , Jakobs M. E. , van den Brande D. M. , Visser H. M. , Wiegant J. , Hoovers J. M. N. , Leschot N. J.
Published: March 2007

In first‐trimester chorionic villus sampling (CVS) for prenatal diagnosis, abnormal chromosomal findings, such as mosaicism, trisomies, or suspect abnormal karyotypes, are found more frequently than at amniocentesis. The fact that these chromosomal abnormalities do not always reflect the fetal karyotype but may be restricted to the placenta is a major problem in diagnosis and counselling. In this paper we present the results of fluorescence in situ hybridization (FISH) studies on interphase nuclei of three term placentae investigated because of false‐positive findings at first‐trimester CVS. The chorionic villi of the first case showed a mosaic chromosome pattern involving a trisomy 10 cell line and a normal cell line, those of the second case a total trisomy 8 cell line, while in the third case a complete monosomy X was found. Follow‐up amniocentesis in each of these three cases revealed a normal karyotype. By using FISH, we were able to confirm the presence of the aberrant cell lines, which were all confined to one part of the placenta. FISH on interphase nuclei allows the investigation of large numbers of cells for the existence of numerical chromosome aberrations in a quick and reliable way.
Is selective abortion for a genetic disease an issue for the medical profession? A comparative study of Quebec and France
Authors: Renaud M. , Bouchard L. , Kremp O. , Dallaire L. , Labadie J. F. , Bisson J. , Trugeon A.
Published: March 2007

This article discusses the results of a study of the stand and attitudes of physicians from the Picardie, Nord‐Pas‐de‐Calais region in France and the province of Quebec (Canada) regarding abortion following the diagnosis of a fetal anomaly by ultrasound, amniocentesis, or chorionic villus sampling. The study examined the degree of acceptability of abortion for several specific conditions as well as the physicians' perceptions of their role in the women's decision to abort. The study shows a consensus (over 75 per cent of the physicians surveyed) for aborting a fetus with trisomy 21. There is a similar consensus, except among Francophones in Quebec, for muscular dystrophy, cystic fibrosis, and Huntington disease. Conversely, there is no consensus (below 60 per cent) for several anomalies. In these cases, Quebec Anglophone physicians find abortion more acceptable than Quebec Francophone or French physicians. Concerning the role of the practitioners in the decision to abort, physicians in France tend to be much more directive than their overseas colleagues. Several hypotheses are suggested to explain the difference between the three groups surveyed.
Attitudes toward abortion for fetal anomaly in the second vs. the third trimester: A survey of Parisian obstetricians
Authors: Geller Gail , Tambor Ellen S. , Papiernik Emile
Published: March 2007

Cross‐cultural differences exist in prenatal diagnosis and abortion for fetal anomaly, stemming from variations in laws, reimbursement policies, litigation, physicians' decision‐making authority, and attitudes toward the prevention of handicaps. The first part of this paper discusses such differences in France and the U.S. The second part describes a survey of practising obstetricians in Paris, designed to assess (1) their attitudes toward pregnancy termination for various conditions, (2) their concern about fetal viability, (3) their desire for diagnostic certainty before justifying a late abortion, and (4) their perceived role in such decision‐making. Among the 64.8 per cent (N = 217) who responded, the majority supported third‐trimester termination (TTT) for diseases such as spina bifida, trisomy 21, microcephaly, and Duchenne muscular dystrophy; 30–59 per cent supported TTT for cystic fibrosis and sickle cell disease; and 22–29 per cent supported TTT for haemophilia, tetralogy of Fallot, limb amputation, and Turner and Klinefelter syndromes. Obstetricians who approved of abortion across trimesters were less concerned with the certainty of diagnosis than its severity, more likely to think that abortion ought to be the parents' choice, but more likely to report making a recommendation to the parents about whether to abort a fetus. Such permissive abortion attitudes might imply more permissive prenatal diagnosis and abortion practice among Parisian obstetricians, which might lead to increased migration of patients from other E.C. countries. Cross‐cultural variation in obstetric practice suggests that an international registry of pregnancies terminated for medical reasons, enabling further study of this issue, would be valuable.
Cytogenetic analysis of 2928 CVS samples and 1075 amniocenteses from randomized studies
Authors: Smidt‐Jensen Steen , Lind Anne‐Marie , Permin Michael , Zachary Julia M. , Lundsteen Claes , Philip John
Published: March 2007

We report cytogenetic results from a randomized Danish chorionic villus sampling (CVS) and amniocentesis (AC) study including 2928 placental and 1075 amniotic fluid specimens processed in the same laboratory. The results are presented in groups comparing CVS with amniocentesis and transabdominal (TA) CVS with transcervical (TC) CVS as randomized. More abnormalities and more ambiguous diagnostic problems were found in placental tissues than in amniotic cells. There were no diagnostic errors and no incorrect sex predictions. Mosaicism was detected in 1 per cent of all cases of CVS (discordancies included). When confirmation studies were done, 90 per cent were found to be confined to the placenta. Eight cases (0.7 per cent) of mosaicism/pseudomosaicism were seen in amniotic fluid specimens, and two cases of five with confirmation studies were confirmed in the fetus. The rate of mosaicism/pseudomosaicism in CVS and AC specimens differed (P <0.05). The rate of pseudomosaicism in cultures of villi and amniotic fluid cells was 0.5 and 0.6 per cent, respectively. Single‐cell aneuploidy was observed in 1.8 per cent of villi and 1.4 per cent of amniotic fluid cell specimens. Maternal cell contamination (MCC) was seen more often after TC sampling (4.5 per cent) compared with TA sampling (1.5 per cent), but posed no problems in interpretation. Compared with the processing of cultured specimens, the short‐term method of preparation of villi in our laboratory doubled the technicians' workload. For practical and economic reasons we have ceased the routine use of short‐term preparations.
Measurement of the fetal mandible—feasibility and construction of a centile chart
Authors: Chitty Lyn S. , Campbell Stuart , Altman Douglas G.
Published: March 2007

The prenatal diagnosis of micrognathia is usually based on a subjective impression of the size of the jaw when examining the fetal profile. We have constructed a centile chart for mandibular length between 12 and 27 post‐menstrual weeks in a cross‐sectional study of 184 fetuses. The application of this chart in clinical practice may permit a more objective diagnosis of micrognathia in the prenatal period.
Verification of carrier status for Becker muscular dystrophy from analysis of a blighted ovum
Authors: Wilton S. D. , Goldblatt J. , Laing N. G.
Published: March 2007

The polymerase chain reaction (PCR) was used on material from a blighted ovum to confirm indirectly the carrier status of a woman with a family history of Becker muscular dystrophy. Conventional testing including creatine kinase levels, muscle biopsy, and EMG had been inconclusive, and on the basis of one elevated creatine kinase level, the woman had been designated a possible carrier. Ultrasound examination at 10 weeks of pregnancy indicated a blighted ovum, from which DNA was subsequently extracted and subjected to PCR testing for determination of sex and genotypic status with respect to the known familial deletion of the dystrophin gene. The blighted ovum was found to have a Y chromosome and also to be deleted for at least exon 6 of the dystrophin gene, indirectly indicating that the mother most likely carried the family mutation for Becker muscular dystrophy.
Magnetic resonance imaging of the fetus: A study of 20 cases performed without curarization
Authors: Revel M. P. , Pons J. C. , Lelaidier C. , Fournet P. , Vial M. , Musset D. , Labrune M. , Frydman R.
Published: March 2007

Twenty patients underwent magnetic resonance imaging (MRI) at a mean gestational age of 32 weeks. There were 12 patients with suspected fetal brain abnormality and four with intrauterine growth retardation (IUGR), while the remaining four cases were studied for other reasons. The MRI examinations were performed on a 0.5 Tesla machine, with surface coils. One minute acquisition time T1 sequences were used. All the studies were performed without fetal curarization, and only under maternal sedation using flunitrazepam given per os 1 h before MRI examination. Three examinations were incomplete because of fetal movement artefacts. In the remaining cases, MRI allowed the examination of fetal brain anatomy. In five cases, it helped to differentiate isolated hydrocephalus and corpus callosum agenesis. Sub‐ependymal nodules were depicted in a case of fetal tuberous sclerosis. One suspected arachnoid cyst was proved to be an ultrasound artefact. Decreased fetal fat on MR images was correlated with low birth weight in cases of IUGR. Due to its better spatial resolution, ultrasonography was more accurate for the diagnosis of facial and lumbar anomalies.

Fetal MRI may be performed without curarization. Surface coils allow the detailed analysis of brain parenchyma, and thus MRI is especially useful in the difficult prenatal diagnosis of fetal brain abnormalities.
Cytogenetic analysis of 1375 amniotic fluid specimens from pregnancies with gestational age less than 14 weeks
Authors: Lockwood David H. , Neu Richard L.
Published: March 2007

Our laboratory has received 1375 early amniotic fluid (EA) specimens during the past 5‐year period for cytogenetics analysis. The gestational ages of the EA specimens were less than 14 weeks as estimated by ultrasound. The average volume of specimen received was 16 ml. Specimens were typically received in two collection tubes and cultured in Chang A and in supplemented MEM media using the in situ technique. Of the 1375 EA specimens received, 1356 were successfully cultured and yielded results. Abnormal results were found in 67 (4.9 per cent) of the cases. Nineteen specimens (1.4 per cent) failed to yield a result. The mean turn‐around time (TAT) for all EA specimens was 8.28 days. In 1991, the average TAT for the EA specimens was 8.00 days compared with a TAT of 6.59 days for all specimens received over 14 weeks gestational age. The number of EA specimens received has increased from 1.5 per month in 1986 to 57 per month in 1991. In summary, our experience with EA specimens for cytogenetic analysis has demonstrated that the success rate is 98.6 per cent and that an increasing number of obstetricians are performing early amniocentesis as they seek to provide their patients with earlier results and an alternative to chorionic villus sampling.
Rapid detection of numerical aberrations of chromosomes 13, 18 and 21 in chorionic mesenchymal cells
Authors: Bryndorf Thue , Christensen Britta , Xiang Yang , Lind Anne‐Marie , Philip John
Published: March 2007

We have devised and evaluated a rapid screening method for the detection of numerical aberrations of chromosomes13, 18 and 21 in chorionic villus cells. We used non‐radioactive in situ hybridization (ISH) with three chromosome‐specific probes on overnight‐attached mesenchymal cells from chorionic villi. A blind study was performed of 47 karyotypically normal samples, one triploid sample, two samples trisomic for chromosome 21, and two samples from a fetus with putative mosaicism (46/47, +21). All samples were hybridized with the chromosome 18‐ and 21‐specific probes. Thirty samples were additionally hybridized with the chromosome 13‐specific probe. The test could be completed within 3‐4 days of sampling. In samples disomic with respect to the probed chromosomes, an average of 2 per cent (range 0‐9 per cent) had three hybridization signals. By contrast, in the samples trisomic for the probed chromosome(s), 57 per cent (chromosome 13), 51 per cent (chromosome 18), and an average of 74 per cent (55‐86 per cent) (chromosome 21) of the nuclei exhibited three signals. In the putative mosaic samples, the number of nuclei with three chromosome 21‐specific signals ranged from 41 to 69 per cent. We conclude that this technique rapidly and clearly distinguishes between normal and trisomic/triploid samples, and consequently may be of use in future prenatal diagnosis.
Fetal tissue involvement in the late infantile type of neuronal ceroid lipofuscinosis
Authors: Chow C. W. , Borg J. , Billson V. R. , Lake B. D.
Published: March 2007

Prenatal diagnosis in a pregnancy at risk for late infantile neuronal ceroid lipofuscinosis (Batten's disease) was undertaken at 17 weeks' gestation by ultrastructural examination of amniotic fluid cells. The presence of curvilinear profiles indicated an affected fetus and the diagnosis was confirmed, after the pregnancy was terminated, by the finding of many typical curvilinear profiles in multiple tissues which included skin, amnion, umbilical vessels, blood, liver, and brain. Comparison between the involved cells in the amniotic fluid and fetal tissues suggests that these cells are probably derived from the periderm, and possibly also from the amnion. The prominent presence of cytosomes in the periderm and intermediate cells of the fetal epidermis and occasionally also in the endothelial cells of the dermis suggests that fetal skin may be a useful alternative site for assessing fetal involvement. Control specimens of the amniotic fluid, fetal skin, amnion, and liver showed no similar cytosomes. However, some control amniotic fluid samples did contain cells with large collections of irregular trilaminar membranes, and these could be open to misinterpretation. It is important that only typical curvilinear profiles are considered as an indication of an affected pregnancy.
Expanding multiple marker screening for Down's syndrome to include Edward'S syndrome
Authors: Barkai G. , Goldman B. , Ries L. , Chaki R. , Zer T. , Cuckle H.
Published: March 2007

Information on maternal age and maternal serum alpha‐fetoprotein, unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was used to investigate retrospectively the effect of estimating Edward's syndrome risk in women having multi‐marker screening for Down's syndrome. The screened population comprised 15 pregnancies affected by Edward's syndrome, 15 with Down's syndrome and 5472 unaffected pregnancies. The use of all three markers to estimate Edward's syndrome risk would have led to the detection of 10–12 (67–80 per cent) cases with a false‐positive rate of 0.3–0.6 per cent depending on the risk cut‐off. A further case would have been detected as a result of screening for Down's syndrome alone. Similar results were obtained when the Edward's syndrome risk was based on uE3 and hCG only. These data suggest that extending Down's syndrome screening to include Edward's syndrome risk will yield a high detection rate with only a small increase in the false‐positive rate.
The early diagnosis of neural tube defects
Authors: Blumenfeld Zeev , Siegler Ephraim , Bronshtein Moshe
Published: March 2007

The sonographic diagnosis of fetal neural tube defects (NTDs) has been enhanced by the recognition of associated brain and skull anomalies. Previous reports have found these anomalies to be accurate in predicting spina bifida after 16 weeks' gestation, and an inverse correlation was suggested between the presence of these sonographic markers and gestational age. Therefore, we assumed that early second‐trimester sonography would be at least as accurate as that performed after 16 weeks' gestation. To examine this hypothesis, we looked for the presence of these cranial sonographic markers suggestive of open NTDs in 8011 low‐risk cases, using transvaginal sonography (TVS), between the 12th and 17th week of gestation (menstrual age). Fetal NTDs were identified in ten cases (l.25%o). The NTDs were cervico‐cranial in three, lumbo‐sacral in six, and thoracal in one of the ten cases. None of the seven cases examined was dyskaryotic. Cerebellar dysmorphism, ‘banana’ sign, cerebellar absence, and hypoplasia were detected in all the low NTDs, usually before the detection of the spinal lesion. All the sonographically diagnosed malformations were confirmed by post‐abortal examination except in one case, where the patient decided to continue the pregnancy and refused follow‐up. We therefore conclude that transvaginal sonographic examination of the fetal skull before the 17th week of gestation is an accurate method for the detection of low NTDs.
Polymerase chain reaction analysis of the cystic fibrosis ΔF508 mutation in human blastomeres following oocyte injection of a single sperm from a carrier
Authors: Liu Jiaen , Lissens Willy , Devroey Paul , Van Steirteghem Andre , Liebaers Ingeborg
Published: March 2007

The efficiency of the polymerase chain reaction (PCR) in detecting the cystic fibrosis (CF) ΔF508 mutation (which is the most common mutation of CF) was assessed in single human blastomeres. Twenty‐one human immature oocytes (germinal‐vesicle‐stage oocytes) that had been donated for research were matured in vitro and a single spermatozoon from a carrier of the CF ΔF508 mutation was injected into the ooplasm. Fourteen embryos were obtained after intracytoplasmic sperm injection (ICSI). PCR analysis was carried out on 70 single blastomeres isolated from these 14 embryos. The results showed that the efficiency of DNA amplification by PCR in single nucleate blastomeres was 94 per cent (59/63). There were no false‐positive results since none of the blank samples or the blastomeres without a nucleus showed an amplified signal. We found that nine embryos were homozygous for the unaffected genotype and that four embryos were heterozygous since they contained both the unaffected and the ΔF508 genotype. In a four‐cell embryo, we observed the homozygous unaffected genotype in one blastomere and a heterozygous ΔF508/unaffected genotype in the other three blastomeres.
Familial congenital diaphragmatic hernia: Prenatal diagnosis, management, and outcome
Authors: Narayan Harini , De Chazal Richard , Barrow Margaret , McKeever Patricia , Neale Edmund
Published: March 2007

Congenital diaphragmatic hernia (CDH) is a developmental defect of as yet unknown aetiology which accounts for 8 per cent of all major congenital anomalies and is associated with up to 80 per cent mortality despite optimal postnatal treatment. The risk of recurrence of CDH for future sibs after one affected infant is about 2 per cent. A multifactorial/threshold inheritance pattern with an observed high male:female sex ratio is currently favoured for the rare occurrence of familial CDH, although other modes of inheritance have also been described. We report three cases of familial CDH, two of whom were brother and sister sibs and the third was a first cousin, born within 18 months of each other. The diagnosis was by ultrasound and there were several factors predicting a poor outcome. The mortality in this group was 100 per cent. The prenatal diagnosis, treatment options, the unusual genetic aspects, outcome, and the pathology involved are discussed.
Serum PAPP‐A measurements in first‐trimester screening for Down syndrome
Authors: Hurley P. A. , Ward R. H. T. , Teisner B. , Iles R. K. , Lucas M. , Grudzinskas J. G.
Published: March 2007

Serum PAPP‐A measurements taken from 254 women in the first trimester are reported. Eleven chromosomal abnormalities were detected. The mean serum PAPP‐A levels in cases of Down syndrome were 0.44 MOM at 9 weeks gestation, 0.15 MOM at 10 weeks, and 0.29 MOM at 11 weeks. The PAPP‐A level at 10 weeks was below those of pregnancies which aborted spontaneously. At 11 weeks, the pregnancies with Down syndrome recorded the lowest PAPP‐A levels at that gestation. On this small sample, offering chorionic villus sampling to women with singleton pregnancies and a PAPP‐A level below 0.3 MOM (approximately 6.5 per cent of this at‐risk group) would have detected all the Down syndrome fetuses at 10 weeks and 50 per cent at 11 weeks without selecting those cases destined to abort. This suggests that serum PAPP‐A should continue to be investigated as a potential first‐trimester screening test for Down syndrome.
Preaxial ray reduction defects as part of valproic acid embryofetopathy
Authors: Sharony Reuven , Garber Ann , Viskochil David , Schreck Rhona , Platt Lawrence D. , Ward Robert , Buehler Bruce A. , Graham John M.
Published: March 2007

It is well known that prenatal exposure of valproic acid (VPA) may be associated with the occurrence of neural tube defects (Robert and Gibaud, 1982). Additional adverse effects related to VPA exposure include craniofacial abnormalities, skeletal defects, brain defects, cardiovascular defects, and urogenital defects (DiLiberti et al, 1984; Winter et al, 1987; Huot et al, 1987; Jager‐Roman et al, 1986; Martinez‐Frias, 1990). Recently, radial ray reduction has been reported as a severe type of skeletal defect associated with VPA exposure (Jager‐Roman et al, 1986; Huot et al, 1987; Verloes et al, 1990). We report two additional cases of this severe limb reduction defect as part of a broader pattern of altered morphogenesis in fetuses exposed to VPA and to confirm an association between such severe specific skeletal defects and VPA exposure. We briefly review teratologic studies in experimental animals which document the biologic plausibility of this association, and suggest that fetuses exposed to VPA undergo detailed prenatal ultrasonographic evaluation of the limbs.
Randomized trial comparing first‐trimester transcervical chorionic villus sampling and second‐trimester amniocentesis
Authors: Ämmälä Pirkko , Hiilesmaa Vilho K. , Liukkonen Sirkka , Saisto Terhi , Teramo Kari , Koskull Harriet Von
Published: March 2007

A total of 800 patients were randomized at the 9th to 11th week of pregnancy either for transcervical chorionic villus sampling (CVS) on the day of trial entry or for amniocentesis (AC) at the 16th week. The indication for fetal karyotyping was maternal age in 94 per cent of the cases; the mean maternal age was 39.2 years. An adequate sample was obtained in 98.3 per cent of the cases in the CVS group and in all cases in the AC group. Retesting was indicated in 3.3 per cent of the CVS cases. An abnormal karyotype was found in 6.1 per cent of the CV samples and in 4.5 per cent of the amniotic fluid samples. There was one false‐positive chromosome result in both groups. Twelve (3.1 per cent) miscarriages occurred by the 22nd week of pregnancy in the CVS group in pregnancies intended to continue. No difference was seen between the groups for total fetal loss rates. The number of surviving infants in the CVS group was 92.2 per cent and in the AC group 91.7 per cent (rate difference 0.5 per cent (95 per cent confidence interval − 3.3 to 4.3)). In our study, both the diagnostic accuracy and the risk of fetal loss were equal in the CVS and AC groups.
Oral teratoma (epignathus) with intracranial extension: A report of two cases
Authors: Smith N. M. , Chambers S. E. , Billson V. R. , Laing I. , West C. P. , Bell J. E.
Published: March 2007

Epignathi are unusual congenital tumours presenting as oropharyngeal masses, often resulting in rapid asphyxia following birth. Occasionally, intracranial extension of the tumour is present, and two such cases are described. The presence of this complication, diagnosable by ultrasound examination, indicates that aggressive surgical treatment is inappropriate.
Cleft palate: Confirmation of prenatal diagnosis by colour Doppler ultrasound
Authors: Sherer David M. , Abramowicz Jacques S. , Jaffe Richard , Woods James R.
Published: March 2007

We present a case of a twin with trisomy 47,XX+i(9p) in whom the diagnosis of cleft palate was confirmed by colour Doppler imaging demonstrating abnormal fluid flow across the fetal pharyngeal bone defect. Application of this technique in cases predisposed for this congenital lesion may prove beneficial in the diagnosis of the more subtle types of isolated cleft palate.
Rapid prenatal diagnosis of Patau's syndrome in a fetus with an abdominal wall defect by 72 hour culture of cells from amniotic fluid
Authors: Roberts Selwyn H. , Little Elizabeth , Vaughan Merle , Creasy Michael R. , Jones Anthony , Powell Teyrnon G. , Dawson Andrew J.
Published: March 2007

A woman in the 32nd week of pregnancy was referred for investigation because of fetal abnormalities, including an abdominal wall defect, detected by ultrasonography. In view of the increased risk of chromosome abnormality, amniocentesis was performed to enable informed decisions about the management of the pregnancy and delivery to be taken. Cells from the liquor were inoculated into standard lymphocyte culture medium and incubated for 72 h. Slides with a high mitotic index and good quality metaphases, comparable to those from a blood culture, were obtained after harvesting. Cytogenetic analysis showed the karyotype to be 46,XY,—14,+t(13ql4q), which is consistent with Patau's syndrome. This technique appears to be an option for rapid karyotyping in cases of abdominal wall defect, where a chromosomal abnormality is suspected.
Prenatal diagnosis of a fetus with partial monosomy 7(q34→qter) and partial trisomy 18(q21→qter)
Authors: Pluchon E. , Giovangrandi Y. , Labbe F. , Le Bris M. J. , Collet M. , Brettes J. P. , Riviere D. , Riviere M. R.
Published: March 2007

Ultrasound examination of a 31‐year‐old woman at 27 weeks' gestation revealed fetal growth retardation, a bilateral cleft lip and palate, and the absence of median cerebral structures. Chromosome analysis after cordocentesis showed an abnormal karyotype with a structural abnormality of the long arm of chromosome 7: 46,XX,—7,+der(7), t(7;18) (q34;q21.3)mat. The pregnancy was terminated at week 29. The ultrasound findings were confirmed by post‐mortem examination, which also revealed a semilobar holoprosencephaly.
Doppler echocardiographic diagnosis of intrauterine closure of the ductus arteriosus
Authors: Chao Rong‐Chieh , Ho Esther Shih‐Chu , Hseeh Kai‐Sheng
Published: March 2007

A case of in utero closure of the ductus arteriosus was detected by Doppler echocardio‐graphy at 31 weeks of gestation. It presented as a non‐hydropic distressed fetus with ultrasound detection of tricuspid regurgitation. Pulsed Doppler ultrasound showed markedly decreased blood flow through the tricuspid and pulmonary valves and absent blood flow at the ductus arteriosus. These, as well as the resultant increased right‐to‐left shunting across the foramen ovale, were reaffirmed by colour flow mapping.
Prenatal diagnosis of anatomical connections in conjoined twins by use of contrast magnetic resonance imaging
Authors: Zoppini Cinzia , Vanzulli Angelo , Kustermann Alessandra , Rizzuti Tommaso , Selicorni Angelo , Nicolini Umberto
Published: March 2007

Omphalopagus conjoined twins were diagnosed by ultrasonography in a pregnant woman at 21 weeks' gestation. In order to clarify the anatomical connections, magnetic resonance imaging (MRI) was performed, having achieved fetal paralysis by intravascular injection of 100 mg of pancuronium into each twin. Prior to MRI, 2 ml of a 0.0001 mmol/ml solution of gadolinium DTPA was also injected into the stomach of one twin. The contrast agent opacified the bowel loops of both twins, indicating bowel to bowel anastomosis. Following pregnancy termination, autopsy confirmed the prenatal diagnosis.
Prenatal diagnosis of trisomy 9 mosaicism: Two new cases
Authors: Merino A. , De Perdigo A. , Nombalais F. , Yvinec M. , Le Roux M. G. , Bellec V.
Published: March 2007

We present two prenatal cases of trisomy 9 mosaicism, both of which presented intrauterine growth retardation (IUGR) and other abnormal ultrasound findings. In case A, mosaicism was found in amniotic fluid cell cultures, of which 65 per cent were trisomic cells, on average. In case B, trisomic cells were present in amniotic fluid cell cultures (12 per cent) but none were found in fetal cord blood. After autopsy, cytogenetic findings were confirmed in different tissue cultures. It is concluded that echographic indicators are a very useful tool for a correct prenatal diagnostic interpretation of trisomy 9. Suspected trisomy 9 mosaicism always requires further investigation and fetal cord blood cytogenetic analysis may not be considered as providing an accurate diagnosis of fetal trisomy 9.
Fetal akinesia/hypokinesia sequence: Prenatal diagnosis and intra‐familial variability
Authors: Bacino Carlos A. , Platt Lawrence D. , Garber Ann , Carlson Dru , Pepkowitz Samuel , Lachman Ralph S. , Sharony Reuven , Rimoin David L. , Graham John M.
Published: March 2007

Intrauterine fetal movement plays a key role in normal embryonic and fetal development (Moessinger, 1983). When movement is absent or decreased, abnormal development takes place which can be appreciated in newborns and/or fetuses with the fetal akinesia/ hypokinesia sequence. This sequence is caused by a number of heterogeneous entities which result in decreased fetal movements by the action of intrinsic or extrinsic factors. Prenatal diagnosis of the akinesia/hypokinesia sequence may be possible during the second trimester through the use of real‐time ultrasonographic evaluation of fetal movement. We report a family with three consecutive affected pregnancies in which the prenatal presentation of this sequence varied. Based on the phenotypic findings of the three affected fetuses, we believe that although they superficially resemble those features found in the New–Laxova syndrome, they are probably affected with a distinctly different lethal form of akinesia/ hypokinesia transmitted in an autosomal recessive fashion.
Prenatal diagnosis of congenital cytomegalovirus infection: False‐negative amniocentesis at 20 weeks' gestation
Authors: Catanzarite Val , Dankner Wayne M.
Published: March 2007

Cytomegalovirus (CMV) is the most common cause of congenital infection. Recent studies show amniocentesis to be a 100 per cent sensitive and 100 per cent specific predictor of congenital infection, and recommend that it be offered in the at‐risk pregnancy. However, these publications have focused on pregnancies at or beyond 22 weeks' gestation. Here, we report a case of maternal CMV hepatitis at 7–8 weeks' gestation, in which culture and polymerase chain reaction testing for CMV in amniotic fluid at 20 weeks' gestation were negative, but the infant had a positive CMV urine culture shortly after delivery. Implications for the prenatal diagnosis of CMV infection are discussed.
DNA confirmation of congenital myotonic dystrophy in non‐immune hydrops fetalis
Authors: Stratton Robert F. , Patterson Robert M.
Published: March 2007

We report on the prenatal diagnosis of congenital myotonic dystrophy in a case of nonimmune hydrops fetalis. DNA analysis of amniocytes revealed expansion of the trinucleotide (CTG) repeat within the myotonin PK gene, associated with myotonic dystrophy. The fetus was found to have approximately 1730 copies, while the normal population has between 5 and 27 copies, and minimally affected individuals have at least 50 copies.
Prenatal diagnosis of neonatal alloimmune thrombocytopenia using an allele‐specific oligonucleotide probe
Authors: Johnson Jo‐Ann M. , McFarland Janice G. , Blanchette Victor S. , Freedman John , Siegel‐Bartelt Jacqueline
Published: March 2007

The prediction of neonatal alloimmune thrombocytopenia (NAIT) in affected families is usually based on information about gene frequencies of the antigen systems involved, parental phenotyping, and fetal platelet counts. Recently the use of allele‐specific oligonucleotide probe typing for PlA (HPA‐1) antigens has been described to determine the risk of second or subsequent fetuses in families where one infant had the diagnosis of anti‐PlA1 (HPA‐1 a)‐mediated NAIT (McFarland et al, 1991a). This paper describes the first case in which the prenatal diagnosis of P1A (HPA‐1) antigen status was accomplished using this technology on genomic DNA derived from chorionic villus tissue in the first trimester, and presents the implications of these findings for the clinical management of this disorder.
Serum alpha‐fetoprotein and neural tube defects in the first trimester of pregnancy
Authors: Wald Nicholas J. , Hackshaw Allan , Stone Rossana
Published: March 2007

As part of the Medical Research Council randomized trial of vitamin supplementation in the prevention of neural tube defects (NTDs), maternal serum alpha‐fetoprotein (AFP) was available for 19 NTD pregnancies. Each of these was matched with four unaffected controls, by maternal age, participating centre, and duration of sample storage. The samples came from women whose gestational age ranged from 6 to 14 completed weeks. The median AFP level in the affected pregnancies was 1·2 multiples of the median value in unaffected pregnancies of the same gestational age (95 per cent confidence interval (CI) 0·83–1·59). This confirmed the view that serum AFP measurement is of no practical value in the detection of NTDs in the first trimester of pregnancy. The study also showed that folic acid supplementation, used as a method of preventing NTDs, had no effect on the concentrations of maternal serum AFP up to 14 weeks of pregnancy.
Transverse limb reduction defects after chorion villus sampling: A retrospective Cohort study
Authors: Mastroiacovo Pierpaolo , Tozzi Alberto Eugenio , Agosti Silvano , Bocchino Giancarlo , Bovicelli Luciano , Dalprà Leda , Carbone Laura Doria Laba , Lituania Mario , Luttichau Angelica , Mantegazza Franco , Nocera Gianfranco , Pachi Antonio , Passamonti Ubaldo , Piombo Giuseppe , Vasta Anna Franca
Published: March 2007

A retrospective cohort study was performed in five Italian obstetrical centres from 1984 to 1991 in order to verify the association between chorionic villus sampling (CVS) and transverse limb reduction defects (TLRDs). TLRD rates by period of gestation at CVS were calculated, and the study's results were compared with data from the general population. Of the 3430 pregnancies for which CVS was performed, 2759 had a known outcome. The overall rate for TLRDs was 1 in 1143 CVS pregnancies, four times higher than that of the general population in Italy (1 in 4458). The rate of TLRDs was 2·9/1000 for CVS performed at 9 weeks' gestation and 1·0/1000 for CVS at 10 weeks' gestation. A scalp defect was detected in a pregnancy in which CVS was performed at 10 weeks. A high proportion of pregnancies lost to follow‐up and the poor quality of the data may have affected the results. Nevertheless, our results suggest an association between CVS carried out at less than 10 weeks' gestation and TLRDs which is consistent with the findings of other studies. CVS should not be prepared at less than 10 weeks' gestation until additional evidence is obtained.
Prenatal confirmation of trisomy 12 mosaicism by fetal skin biopsy
Authors: Cartolano Rosa , Guerneri Silvana , Fogliani Roberto , Galimberti Andrea , Nicolini Umberto
Published: March 2007

Trisomy 12 mosaicism diagnosed at 16 weeks' amniocentesis in a 42‐year‐old woman was not confirmed at 18 weeks' gestational age in amniotic fluid or fetal blood. Fetal skin biopsy performed at the same time did, however, allow the detection of trisomy 12 in 1 of 14 fibroblasts analysed. Fetal skin biopsy can be included within the diagnostic procedures to be performed when a level III mosaicism is found in the amniotic fluid.
The association between ‘faint‐positive’ amniotic fluid acetylcholinesterase and fetal malformations
Authors: Sadovsky Yoel , Robbin Michelle L. , Crandall Barbara F. , Filly Roy A. , Golbus Mitchell S.
Published: March 2007

The finding of a ‘faint‐positive’ acetylcholinesterase band in amniotic fluid samples of women at 15 weeks' gestation or above is associated with an increased risk of fetal abnormalities, most commonly gastroschisis. This finding warrants a targeted sonographic evaluation, in order to rule out significant fetal malformations.