bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of prenatal detection of cardiac tumours in the diagnosis of tuberous sclerosis—report of two cases
Authors: Chitayat D. , McGillivray B. C. , Diamant S. , Wittmann B. K. , Sandor G. G. S.
Published: March 2007

Tuberous sclerosis is an autosomal dominant disease with variable expression. Little is known about the intrauterine course of the disease and the fetal age at which specific abnormalities may be detected. The role of prenatal detection of cardiac tumours in the diagnosis of two fetuses at 28 and 32 weeks' gestation based on fetal echocardiography is discussed. The prenatal and postnatal course of the disease is described.
Circulating ‘trophoblast’ cells in pregnancy have maternal genetic markers
Authors: Bertero M. T. , Camaschella C. , Serra A. , Bergui L. , Caligaris‐Cappio F.
Published: March 2007

A syncytiotrophoblast‐associated antigen identified by the monoclonal antibody (McAb) H315 is detectable on the surface of a low proportion of peripheral blood cells in pregnant women, raising the possibility of a new approach to prenatal diagnosis of genetic disorders. We aimed at verifying the trophoblastic origin of H315+ cells and their use for prenatal diagnosis of β‐thalassaemia. H315 + cells were separated from the peripheral blood of pregnant women: the DNA obtained from these cells in two selected cases was shown to have genetic markers indistinguishable from those of the mother and definitely different from the fetus. Our results suggest that H315 antigen is expressed by maternal cells and that prenatal diagnosis on peripheral blood of the mother using H315 McAb is not feasible.
Analysis of peripheral maternal blood samples for the presence of placenta‐derived cells using Y‐specific probes and McAb H315
Authors: Covone Angela E. , Kozma Robert , Johnson Peter M. , Latt Samuel A. , Adinolfi Matteo
Published: March 2007

Using flow cytometry, a small number of cellular elements expressing on their surface an antigen (H315) produced by placental trophoblast have been observed in the peripheral blood of pregnant women. This is in agreement with previous observations (Covone et al., 1984a,b) and recent results documenting the presence of a small number of H315‐positive cells in the peripheral circulation of pregnant women (Pool et al., 1987; Caligaris‐Cappio and Camaschella, personal communication).

When DNA extracts, prepared from H315‐positive cells sorted from maternal samples were tested by Southern transfer using Y‐specific probes (Y190 or Y411), a Y‐specific band could not be detected in any sample analysed, irrespective of the sex of the fetus. In control samples from healthy male donors, a Y‐specific band could be detected with as few as 800 46,XY cells without interference from contaminating 46,XX cells.

H315‐positive cellular elements, sorted by flow cytometry from the maternal peripheral blood, were also examined in interphase using Y‐specific probes (Y190 and Y431) and an in situ biotin‐avidin fluorescent hybridization technique. The great majority of the sorted H315‐positive cellular elements did not show a fluorescent Y body, even in samples from mothers who later delivered a male infant.

While previous investigations had failed to demonstrate the in vitro uptake of H315 antigen onto the surface of leucocytes from healthy males incubated in maternal sera, the present studies demonstrate that cells from male donors could adsorb this antigen following incubation in extracts prepared from retroplacental blood.

These findings thus suggest that the majority of H315‐positive nucleated cells previously detected by flow cytometry in the peripheral circulation of pregnant women are maternal cells which have adsorbed H315 antigen in vivo, either in soluble form or as small cell membrane fragments.
Prenatal diagnosis of cystic fibrosis using linked DNA probes
Authors: Schwartz M. , Super M. , Schmidtke J. , Buys C. , Farrall M. , Halley D. , Krawczak M. , Poncin J. E. , Loukopoulos D. , Devoto M.
Published: March 2007

This paper presents data collected in Europe on 107 prenatal diagnoses of cystic fibrosis (CF) using linked DNA markers. To date, 38 children have been born without CF, as predicted, demonstrating the present rapid move from research to clinical genetic service.
Pseudomosaic centric fission of chromosome 4 in amniotic cells
Authors: Nucaro A. , Falchi A. M. , Monni G. , Cao A.
Published: March 2007

This paper describes a case of pseudomosaic centric fission of chromosome 4 detected in amniotic fluid cell culture. The pregnancy went to term and the newborn had a normal chromosomal constitution.
Prolonged elevation of alphafetoprotein and detectable acetylcholinesterase after death of an anomalous twin fetus
Authors: Streit Judy A. , Penick George D. , Williamson Roger A. , Weiner Carl P. , Benda Jo Ann
Published: March 2007

Persistence of elevated alphafetoprotein (AFP) levels and the presence of an acetylcholinesterase (AChE) band in amniotic fluid have been reported to occur up to 11 weeks following intrauterine fetal demise (IUFD) of one twin (Bass et al., 1986). We now report a case where such prolongation of these findings was observed in a case of unrecognized monochorionic, monoamniotic twinning, in which case cord entanglement resulted in IUFD at an estimated 10–12 weeks and 25–26 weeks. The fetus suffering early demise (Fetus B) had multiple congenital anomalies, including a neural tube defect. The presence of this defect and/or fetal demise and bleeding into the amniotic sac is entertained as continuing sources of documented elevated AChE and AFP 9–11 weeks after the initial fetal death.

We re‐emphasize the possibility of unrecognized twinning as a cause of abnormal maternal serum and amniotic fluid study results in the face of one apparently normal fetus.
Prenatal diagnosis of haemoglobinopathies by ion exchange hplc of haemoglobins
Authors: Rouyer‐Fessard P. , Plassa F. , Blouquit Y. , Vidaud M. , Varnavides L. , Mibashan R. S. , Bellingham A. , Beuzard Y.
Published: March 2007

A new method, the cation exchange HPLC of haemoglobins, has been compared to the classical carboxymethyl cellulose (CMC) chromatography of globin chains for the prenatal diagnosis of beta thalassaemia and sickle cell disease. The two methods correlated highly. The HPLC procedure can use two independent and reliable means—optical density at 405 nm and radioactivity to determine the adult Hb/HbF + Fac ratio. The diagnosis is obtained in 15 mm by cation exchange HPLC.
Triploid fetus: An important consideration in the evaluation of very high maternal serum alpha‐fetoprotein
Authors: Kazazian Lillian C. , Baramki Theodore A. , Thomas Ronald L.
Published: March 2007

Two patients referred for evaluation of very high maternal serum alpha‐fetoprotein (10–20 multiples of the median) were carrying triploid fetuses with placentas showing features of partial hydatidiform mole. The diagnosis of fetal triploidy should be considered when there is a very high maternal serum alpha‐fetoprotein and no ultrasound evidence of open neural tube defect, ventral wall defect, or any other explanation. Therefore, chromosomal analysis of amniotic fluid cells in such cases is essential.
Prenatal diagnosis of a case of 46,XY, 18p — /46,XY, 18p + mosaicism
Authors: Stephen G. S. , Couzin D. A. , Watt J. L. , Rankin R.
Published: March 2007

A case of mosaicism involving structural abnormality of chromosome 18 found in cultured amniotic fluid is reported.
Fetal limb constriction: A possible complication of CVS
Authors: Christiaens G. C. M. L. , van Baarlen J. , Huber J. , Leschot N. J.
Published: March 2007

A case of fetal loss due to infection after first‐trimester chorionic villus sampling is described. The fetus was born at 18 3/7 weeks and showed an annular constriction of one of the arms as seen in the amniotic band sequence. Induction of congenital defects might be one of the complications of chorionic villus sampling.
Gelatin embedding and diagnostic ultrasound in the examination of the fetal and neonatal brain
Authors: Knowles S. , Parker S. , Weckert R. C. , Furness M. E.
Published: March 2007

We describe a new method for the post‐mortem examination of the fetal central nervous system. The brain is immobilized in gelatin prior to ultrasonic examination. Correlation with prenatal ultrasound is excellent and subsequent pathological examination is enhanced and facilitated.
Ethical problems in prenatal diagnosis: A cross‐cultural survey of medical geneticists in 18 nations
Authors: Wertz Dorothy C. , Fletcher John C.
Published: March 2007

In order to provide a basis for international discussion of ethics among geneticists, we surveyed the responses of medical geneticists to a questionnaire describing 14 hypothetical cases that posed ethical dilemmas. The cases were selected through discussions with leading geneticists in 12 nations, as representative of the most difficult problems of moral choice experienced in practice. Six cases involved indications for prenatal diagnosis or disclosure of information. All medical geneticists in each of 18 nations were included. Of 1053 asked to participate, 677 (64 per cent) responded. A large majority (83 per cent) would perform prenatal diagnosis for parents who oppose abortion but request the service. A smaller majority (63 per cent) would do so for maternal anxiety, and a minority (25 per cent) would perform for sex selection in the absence of X‐linked disease. Most would disclose conflicting controversial, or ambiguous test results, and two‐thirds would disclose colleagues' differences of opinion.
First‐trimester diagnosis of menkes disease: Intermediate copper values in chorionic villi from three affected male fetuses
Authors: Tønnesen T. , Gerdes A.‐M. , Damsgaard E. , Miny P. , Holzgreve W. , Søndergaard F. , Horn N.
Published: March 2007

Chorionic villus samples with copper contents of 1·91, 4·2, 5·6, and 6·3 ng/mg were observed in four cases with male karyotypes. These values were outside the range for unaffected males (0·30–0·85 ng/mg), and three of them were outside the control range (0·20–2·39 ng/mg). But these three values were below the values previously observed for affected Menkes fetuses (12·0–24·8 ng/mg).

Follow‐up by 64Cu uptake studies on the amniotic fluid cells was performed in three of these cases. A combination of 64Cu uptake and chase experiments on the amniotic fluid cells showed more convincingly than 64Cu uptake per se the direct copper values of 4·2 and 5·6 ng/mg to correspond to affected fetuses. Amniotic fluid cells from the male fetus with the CV copper value of 1·9 ng/mg showed normal results. The CV copper value of 6·3 ng/mg was considered pathognomonic for Menkes disease. The pregnancy was terminated, and the diagnosis was confirmed on fetal fibroblasts.

Maternal deciduum prepared from the placentae showed in one of the cases with an affected fetus copper values ranging from 1·5 to 5·7 ng/mg. In six additional diagnostic cases, the copper content was determined in both CV samples and maternal deciduum. In three of these cases with normal CV sample copper, maternal decidua values of 4·85–7·8 ng/mg copper were observed. These results show that maternal deciduum contamination of a CV sample could cause a false‐positive diagnosis.
Amniotic fluid acetylcholinesterase measurements: Comparing immunochemical and polyacrylamide gel techniques
Authors: Goldfine Christina , Knight George J. , Haddow James E. , Palomaki Glenn E.
Published: March 2007

In the present study, a recently reported immunochemical technique for measuring acetylcholinesterase (AChE) in amniotic fluid utilizing the 4F19 antibody was compared with the widely utilized polyacrylamide gel technique to determine whether the immunochemical assay provided an advantage in separating unaffected pregnancies from those associated with open spina bifida (OSB) and open ventral wall defects (OVWD). The study included (1) 73 amniotic fluid samples from unaffected pregnancies [alpha‐fetoprotein (AFP) < 2 MoM] with no visible gel AChE band, (2) nine bloodstained samples from unaffected pregnancies (AFP 2·2–4·0 MoM) with visible gel AChE bands, (3) 18 samples associated with OSB (AFP 2·2–7·0 MoM) with visible gel AChE bands, and (4) 20 samples associated with OVWD (AFP 3·2–53·5 MoM) with visible gel AChE bands. The immunochemical assay produced ranges of measurements in the four respective categories as follows: (1) 2–60 arbitrary units (AU): (2) 14–69 AU, (3) 61–593 AU, and (4)22–476 AU. Eight of the nine unaffected pregnancies with visible gel AChE bands had immunochemical measurements below the highest measurement for the samples with no visible AChE band (60 AU), as did five out of 20 OVWD pregnancies. Two of the OSB cases had values of 61 and 62 AU. These data indicate that the 4F19 specific monoclonal antibody to AChE is capable of distinguishing unaffected from affected pregnancies with reasonable reliability but that more work needs to be done to establish the extent of overlap between the unaffected and affected populations.
First‐trimester amniotic fluid acetylcholinesterase electrophoresis
Authors: Muller F. , Oury J. F. , Boue A.
Published: March 2007

Acetylcholinesterase (AChE) gel electrophoresis was performed on normal amniotic fluids obtained at 4–15 weeks of pregnancy. Until 8 weeks, all the fluids were AChE‐positive; the percentage of positive specimens decreased from 9 until 11 weeks and no positive specimen was found after 12 weeks. This method may allow early prenatal dignosis of neural tube defects after the 12th week.
In vitro amplification of the α1‐antitrypsin gene: Application to prenatal diagnosis
Authors: Hejtmancik J. F. , Holcomb J. D. , Howard J. , Vanderford M.
Published: March 2007

Discrimination of the M, Z, and S alleles of α1‐antritrypsin (AAT) has been carried out using in vitro gene amplification with the polymerase chain reaction (PCR). Amplification of 90 nucleotides surrounding the Z mutation site and 120 nucleotides surrounding the S mutation site dramatically improves the sensitivity and reliability of allele‐specific oligonucleotide (ASO) hybridization for direct detection of these alleles. Analysis is performed using Southern blots or dot blots hybridized with 19 base oligonucleotides and differentially washed for allele specificity. Amplification of the Z and S mutation sites can be combined in one PCR to allow detection of both mutations when analysed by gel electrophoresis and Southern transfer. This technique can be performed reliably using less than 0·1 μg of genomic DNA or less than 100 amniocytes or white blood cells. This technique has been used to perform prenatal diagnosis on a chorionic villus sample (CVS) in a fetus at risk for the ZZ Pi type form of AAT deficiency.
Visualization of fetal intra‐abdominal organs in second‐trimester severe oligohydramnios by intraperitoneal infusion
Authors: Nicolini Umberto , Santolaya Joaquin , Hubinont Corinne , Fisk Nicholas , Maxwell Darryl , Rodeck Charles
Published: March 2007

Fetal intraperitoneal infusion of saline was performed in two patients with severe oligohydramnios at 24 and 25 weeks' gestation in order to enhance visualization of intra‐abdominal organs. Renal agenesis was easily diagnosed. The technique can be considered as an alternative to artificial instillation of amniotic fluid in the differential diagnosis of conditions associated with severe oligohydramnios.
A prospective study of the incidence and significance of fetal choroid plexus cysts
Authors: Ostlere S. J. , Irving H. C. , Lilford R. J.
Published: March 2007

Cysts of the choroid plexus of the lateral ventricle can be detected in the fetus during routine scanning at 16–18 weeks' gestation with an approximate incident of one in every 120 pregnancies. It is likely that in a high percentage of cases cysts are bilateral and that their recent discovery is mainly due to improvements in imaging technology. Although the great majority of cases resolve and do not result in any morbidity, five cases of trisomy 18 and one case of trisomy 21 associated with fetal choroid plexus cysts have been reported. In this prospective study, choroid plexus cysts were detected in 42 fetuses, resulting in 40 normal infants and 2 cases of trisomy 18. It is concluded that there may be a relationship between fetal choroid plexus cysts and trisomy 18. In order to obtain a more precise and accurate result, a multi‐centre prospective study is being organized.
The significance of prenatal diagnosis of choroid plexus cysts
Authors: Khouzam M. N. , Hooker J. G.
Published: March 2007

A case is described of the prenatal diagnosis of choroid plexus cysts at 17 weeks' gestation which persisted beyond 36 weeks but could not be detected after delivery. At birth the child was found to have trisomy 18.
Chorionic villus sampling—short‐term versus long‐term culture in a subtle 2; 18 translocation
Authors: Smith A. , Cohen M. , den Dulk G. , Guirguis A.
Published: March 2007

Prenatal diagnosis on chorionic villous tissue was performed for a woman with the karyotype 46,XX,t(2;18)(q32;q12)—a subtle ‘difficult’ translocation. The case illustrates the necessity of good quality cytogenetics for accurate prenatal diagnosis. For chorionic villi this can be obtained only with long‐term culture.
The dilemma of chromosomal mosaicism in chorionic villus sampling—‘direct’ versus long‐term cultures
Authors: Nisani R. , Chemke J. , Voss R. , Appelman Z. , Caspi B. , Lewin A. , Dar H. , Reiter A.
Published: March 2007

Chromosomal mosaicism is one of several unanswered dilemmas in first‐trimester prenatal diagnosis. We report the course of a pregnancy in which a normal karyotype was detected on direct CVS preparation and fetal blood, 100 per cent trisomy 21 in one long‐term CVS culture, and low‐rate trisomy 21 mosaicism in a second long‐term CVS culture and amniocentesis. The phenotypically normal infant had a 6 per cent mosaicism of trisomy 21. It appears that a persistent low‐rate mosaicism in different tissues may be indicative of the true status of the fetus.
Intrauterine manometry: Technique and application to fetal pathology
Authors: Nicolini Umberto , Fisk Nicholas M. , Talbert David G. , Rodeck Charles H. , Kochenour Neil K. , Greco Pantaleo , Hubinont Corinne , Santolaya Joaquin
Published: March 2007

A technique is described for measuring pressure within the amniotic cavity and within fetal vessels and/or body compartments. Two saline‐filled catheters were connected at one end to needles inserted during indicated invasive procedures and at the other to silicon strain gauge transducers. In 36 pregnancies with normal liquor volume, stable intra‐amniotic pressure (IAP, range 1–14 mmHg) increased with gestation (r=0·48, p<0·01). In pregnancies complicated by severe oligohydramnios, IAP was ≤ 1 mm Hg and rose to normal levels with saline amnioinfusion. Raised IAP (range 17–26 mm Hg), found in pregnancies with gross polyhydramnios, fell with drainage of amniotic fluid. Subtraction manometry was used to determine supra‐amniotic pressure within the intervillus space, umbilical vein, umbilical artery, abdominal and thoracic cavities, and the urinary tract in normal and/or pathological fetuses. Low intravesical and intrapelvicalyceal pressures (median 6·5, range 2–10 mmHg) were noted in fetuses with obstructive uropathies. Intrauterine subtraction manometry appears to be a useful tool in the understanding of fetal pathophysiology and may be of clinical benefit in the therapeutic drainage and infusion of amniotic fluid and in the assessment of certain fetal disease states.
First‐trimester diagnosis of juvenile neuronal ceroid lipofuscinosis by demonstration of fingerprint inclusions in chorionic villi
Authors: Conradi N. G. , Uvebrant P. , Hökegård K.‐H. , Wahlström J. , Mellqvist L.
Published: March 2007

One of the most common hereditary, progressive encephalopathies in children—juvenile neuronal ceroid lipofuscinosis (NCL)—lacks methods for carrier detection and prenatal diagnosis. A transcervical chorionic villus biopsy was performed at 9 completed weeks in a fetus at high risk of this disease. The syncytiotrophoblast of the chorionic villi contained fingerprint inclusions similar to those observed in various cells from children with this disease. Together with previous reports of second‐trimester diagnosis in a case with late‐infantile NCL (MacLeod et al., 1984, 1985), the presence of typical inclusions in placental tissue sampled at term in the infantile NCL (Rapola et al., 1987) and the lack of pathological alterations in one fetus at high risk of juvenile NCL and without clinical and morphological signs of disease at the age of 15 months (Kohlschutter et al., 1989), our findings strongly indicate that an early prenatal diagnosis of (juvenile) NCL is possible.
Probable exclusion of juvenile neuronal ceroid lipofuscinosis in a fetus at risk: An interim report
Authors: Kohlschütter A. , Rauskolb R. , Goebel H. H. , Anton‐Lamprecht I. , Albrecht R. , Klein H.
Published: March 2007

In a family with two children affected by juvenile neuronal ceroid lipofuscinosis (JNCL) an attempt was made at the prenatal diagnosis of the disorder. The following tissues from the fetus at risk were investigated by electron microscopy and were found to be free of fingerprint profiles and curvilinear bodies, typical for JNCL: uncultivated amniotic fluid cells, lymphocytes isolated from fetal blood, and fetal skin biopsy specimens. The child was born at the 34th week of gestation and was clinically normal at the age of 15 months. Postnatally, lymphocytes (isolated at the age of 6 and 15 months) and skin tissue (taken at the age of 15 months) were found to be morphologically normal.

It is highly unlikely that the child is affected but definite proof of the absence of JNCL remains difficult at this age.
Chorionic villus culture for prenatal diagnosis of chromosome defects: Reduction of the long‐term cultivation time
Authors: Smidt‐Jensen Steen , Christensen Britta , Lind Anne‐Marie
Published: March 2007

We report in detail two series of chorionic villus cultivation for prenatal chromosomal diagnosis. Chorionic villi were sampled from both first‐ and second‐trimester pregnancies. One hundred cultures were treated with trypsin–EDTA for 2 h and collagenase overnight, (method A) and 100 were treated with trypsin–EDTA for 1 h and collagenase for 2 h (method B). Using short‐term enzymatic digestion, the cultivation time was reduced from 14 days to 6 days. Sufficient amounts of metaphases of good quality were present in 93 per cent of primary cultures harvested in situ, whereas enough metaphases of sufficiently good quality were in most cases present only after subcultivation of the cultures using method A. The decrease in cultivation time obtained is probably due to a higher yield of viable cells in monocellular suspension, an increased attachment efficiency, and a more rapid attachment of single cells (within 24 h).
Conceiving a fetus for bone marrow donation: An ethical problem in prenatal diagnosis
Authors: Clark Robin Dawn , Fletcher John , Petersen Gloria
Published: March 2007

We present a family who sought prenatal diagnosis in order to bear a healthy child to serve as an HLA–identical bone marrow donor for their son affected with Wiskott–Aldrich syndrome. They intended to abort HLA‐incompatible fetuses who would have been unsuitable bone marrow donors. This case led us to conclude that prenatal diagnosis should not be used to benefit a third party or facilitate the conception or abortion of a fetus for the purpose of generating an organ for transplantation. The limits of parental autonomy and physician responsibility are discussed.
Prenatal ascertainment of triploidy by maternal serum alpha‐fetoprotein screening
Authors: Freeman S. B. , Priest J. H. , Macmahon W. C. , Fernhoff P. M. , Elsas L. J.
Published: March 2007

We report our experience in ascertaining fetal triploidy during routine maternal serum alpha‐fetoprotein (MSAFP) screening. Three cases were identified after elevated MSAFP tests. Two of the three had normal amniotic fluid alpha‐fetoprotein (AFAFP). The third had amniocentesis too late for AFAFP interpretation. Three additional cases were detected by amniocentesis without prior MSAFP screening and none had an elevated AFAFP. A literature review revealed eight triploid fetuses detected as a result of an elevated MSAFP. Of the five with AFAFP quantitation, only one had an abnormal value and the elevation was minimal. In these 14 cases from our own and other reports, ultrasound findings of placental and fetal abnormalities were often noted, but a pattern diagnostic of triploidy was not present. We conclude that, for optimal prenatal detection of triploidy, fetal karyotyping should be included when an amniocentesis is performed for elevated MSAFP.
First‐trimester prenatal diagnosis of cystic fibrosis using the polymerase chain reaction: Report of eight cases
Authors: Gasparini Paolo , Novelli Giuseppe , Savoia Anna , Dallapiccola Bruno , Pignatti Pier Franco
Published: March 2007

Eight pregnancies at risk for cystic fibrosis have been monitored by first‐trimester prenatal diagnosis with DNA amplification analysis. The polymerase chain reaction (PCR) was used in all cases to amplify the region detected by KM 19. In two cases, the region detected by CS·7, another DNA probe tightly linked to the CF locus, was also examined. The results of the PCR determinations were confirmed using the Southern blotting procedure, by segregation analysis of restriction fragment length polymorphisms (RFLPs) relative to XV‐2c, J3·11, metH, metD, and KM19 probes.
Prenatal diagnosis of pelvic kidney
Authors: Colley N. , Hooker J. G.
Published: March 2007

A 30‐year‐old woman had serial ultrasound scans from 28 weeks' gestation which revealed the presence of a cystic area in the fetal pelvis. The ‘cyst’ remained unchanged until delivery at 41 weeks. Fetal growth and amniotic fluid volume were normal throughout. A pelvic kidney was confirmed at birth. The differential diagnosis and antenatal management of this ‘cyst’ are discussed.
Intrauterine mediastinal teratoma associated with non‐immune hydrops fetalis
Authors: Weinraub Z. , Gembruch U. , Födisch H. J. , Hansmann M.
Published: March 2007

We describe a rare case of non‐immune hydrops fetalis caused by mediastinal teratoma. The sonographic appearance was that of a mixed cystic and solid mass in the antero‐superior mediastinum. The teratoma, on post mortem, extended cranially to the upper part of the thyroid, exerting pressure and causing deviation of the trachea, oesophagus, and aortic arch. The pathogenesis of non‐immune hydrops fetalis suggests obstruction of venous return caused by this tumour.
Direct preparations from chorionic villi–relationship between villous morphology and mitotic index
Authors: Romagnano A. , Featherstone T. , Sun L. , Crane J. P. , Cheung S. W.
Published: March 2007

It has been postulated that chorionic villi with abundant sprouts have a higher mitotic index and are therefore preferable for obtaining direct chromosome preparations from chorionic villus samples. This theory was tested by correlating villous morphology with mitotic index. Surprisingly, no statistically significant relationship was found. Choice of culture medium, however, was found to be important, with serum‐free RPMI yielding a higher mitotic index than 40 per cent FCS in MEM. We conclude that villous morphology, as assessed in this study, is not a major factor in determining the success of direct chromosome preparations.
Prenatal screening and diagnosis of neural tube defects in England and Wales in 1985
Authors: Cuckle H. S. , Wald N. J. , Cuckle P. M.
Published: March 2007

A survey was carried out to determine the effect of prenatal screening and therapeutic abortion on births in 1985 with anencephaly and spina bifida in England and Wales. Maternal serum alpha‐fetoprotein tests were done on 399 288 women (60 per cent of pregnant women): 4 per cent were reported as being screen‐positive and 1 per cent had an amniocentesis. An estimated 534 pregnancies associated with anencephaly were terminated and an estimated 445 pregnancies associated with spina bifida (but without anencephaly) were terminated. Most (63 per cent) of the anencephalic pregnancies were first suspected from an ultrasound examination; 57 per cent of the spina bifida pregnancies were first suspected from a positive maternal serum alpha‐fetoprotein test, 35 per cent by ultrasound, and the remaining 8 per cent by other means. The birth prevalence of anencephaly declined by 94 per cent between 1964–1972 and 1985, but when the terminations of pregnancy on account of having a fetus with anencephaly are added to the births the decline in prevalence was only 50 per cent. The birth prevalence of spina bifida declined by 68 per cent over the same period but when the terminations were added to the births the decline in prevalence was only 32 per cent. Among births with anencephaly 66 per cent had had no screening or diagnostic tests in early pregnancy, but in those that did nearly all were positive–usually in twin pregnancies where one fetus was affected but not the other. Among births with spina bifida, 48 per cent had no tests and in those that did the results were mainly negative. We conclude that in order to monitor adequately the national screening programme for anencephaly and spina bifida a special neural tube defects register should be formed.
Prenatal diagnosis of purine nucleoside phosphorylase deficiency in the first and second trimesters of pregnancy
Authors: Kleijer W. J. , Hussaarts‐Odijk L. M. , Los F. J. , Pijpers L. , de Bree P. K. , Duran M.
Published: March 2007

Prenatal diagnosis was performed in two successive pregnancies of a mother with a previous child with purine nucleoside phosphorylase (PNP) deficiency. In one pregnancy, an affected fetus was diagnosed in the 18th week of gestation after the demonstration of PNP deficiency in cultured amniotic fluid cells. Also an abnormal purine nucleoside profile was found in the amniotic fluid. The diagnosis of an affected fetus was confirmed by the analysis of cultured fetal skin fibroblasts and placental villi. The complete deficiency of PNP activity in placental villi confirms that the prenatal diagnosis of this disorder is possible by the direct investigation of chorionic villi. In the subsequent pregnancy, a heterozygous fetus was predicted in the tenth week of pregnancy by using chorionic villi.
Prenatal diagnosis of phenylketonuria by haplotype analysis
Authors: Wulff K. , Wehnert M. , Schütz M. , Seidlitz G. , Herrmann F. H.
Published: March 2007

Prenatal diagnosis of classic phenylketonuria (PKU) was performed after chorionic villus sampling by means of linked restriction fragment length polymorphisms (RFLPs) using the cDNA probe ph PAH 247 (Kwok et al. (1985) Biochemistry, 24, 556–561). We report in this paper a PKU family who were only informative for RFLP analysis by a combination of two RFLPs on the basis of haplotype determination of the normal and mutant phenylalanine hydroxylase (PAH) alleles. The DNA analysis detected a PKU fetus homozygous for mutant PAH alleles and the mother opted for termination in the 12th week of gestation.
Trisomy 16 detected at chorion villus sampling
Authors: Hashish A. F. , Monk N. A. , Lovell‐Smith M. P. F. , Bardwell L. M. , Fiddes T. M. , Gardner R. J. M.
Published: March 2007

Trisomy 16 detected at chorion villus sampling (CVS) may reflect the placental but not the fetal karyotype. We describe a case in which the pregnancy continued until intrauterine death at 37 weeks. Cytogenetic study of two placental samples showed 47, +16 and 46,XX; the fetus was morphologically grossly normal, but fetal tissue culture was unsuccessful. Conservative management may be appropriate when trisomy 16 is detected at CVS and the pregnancy is normal ultransonographically.
Trisomy 12 mosaicism in amniocytes and dysmorphic child despite normal chromosomes in fetal blood sample
Authors: von Koskull Harriet , Ritvanen Annukka , Ämmälä Pirkko , Gahmberg Nina , Salonen Riitta
Published: March 2007

Trisomy 12 mosaicism (44 per cent) was detected prenatally in cultured amniocytes. A cordocentesis was performed to confirm the result. Only normal cells were found in the fetal blood sample. The fetus was estimated to be at a low risk of having a chromosomal abnormality and the pregnancy continued. Eight days after birth, a congenital heart defect was detected in the child. Several dysmorphic features were also evident. Further karyotyping of different tissues revealed normal blood and urinary cells but trisomic cells in the placenta (100 per cent) and in skin fibroblasts (25 per cent). The child died at 5 weeks of age. In this case, the fetal blood sample failed to reveal the real chromosome constitution of the fetus.
Resorbed co‐twin as an explanation for discrepant chorionic villus results: Non‐mosaic 47,XX, +16 in villi (direct and culture) with normal (46,XX) amniotic fluid and neonatal blood
Authors: Tharapel Avirachan T. , Elias Sherman , Shulman Lee P. , Seely Linda , Emerson Donald S. , Simpson Joe Leigh
Published: March 2007

Non‐mosaic trisomy 16 was observed in chorionic villus cytotrophoblasts (direct) as well as cultured mesenchymal core cells derived from the pregnancy of a 38‐year‐old woman. Chromosome preparations from amniotic fluid and neonatal cultures (cord blood) were 46,XX. Normal fetal growth as determined by serial ultrasound examinations occurred throughout the pregnancy, which resulted in a healthy 2724 g female. Multiple biopsies taken from the umbilical cord, placental cotyledons, and fetal membranes were 46,XX. However, a placental nodule and three of six cultures initiated from membranes (amnion and chorion) showed 46,XX/47,XX, + 16 mosaicism.

We propose that the trisomy 16 cells arose from residual villi derived from a trisomic cotwin that never developed. This case further demonstrates that normal fetal growth may presage normal outcome irrespective of cytogenetic findings in cytotrophoblasts (direct) and cultured mesenchymal core cells.
Prenatal diagnosis and psychological distress: Amniocentesis or chorionic villus biopsy?
Authors: Sjögren B. , Uddenberg N.
Published: March 2007

The psychological reactions of 211 women undergoing prenatal diagnosis (PND) with amniocentesis (group A, n = 122) or chorionic villus biopsy (group V, n = 90) were exmained by questionnaires and interviews. The distress experienced while waiting for the test, during the test procedure, and while waiting for the result was reported by the women, both in questionnaires and in interviews. In the questionnaires, no difference between the two diagnostic methods was observed. In the interviews, however, the women undergoing amniocentesis appeared significantly more distressed by the procedure. In group A 97 per cent and in group V 100 per cent wished a method which, like chorionic villus biopsy, could be used in the first weeks of pregnancy. The risk of miscarriage was, as described in other studies, regarded as a serious threat by the pregnant women.
Rapid sexing of human embryos by non‐radioactive in situ hybridization: Potential for preimplantation diagnosis of X‐linked disorders
Authors: Penketh R. J. A. , Delhanty J. D. A. , van den Berghe J. A. , Finklestone E. M. , Handyside A. H. , Malcolm S. , Winston R. M. L.
Published: March 2007

Sixty spare human embryos at various stages of preimplantation development were prepared for cytogenetic analysis. Fluorescent staining of those with metaphases allowed scoring for the presence of a Y chromosome. In situ hybridization was then performed using a biotinylated Y‐specific sequence, and the probe was detected by a standard streptavidinlinked alkaline phosphatase system. This enabled comparison of the chromosomal sex with that obtained after in situ hybridization in 28 embryos, and the sexing result obtained by the two methods was concordant in all cases. A further 21 embryos in which no metaphase chromosomes were obtained were sexed by biotinylated in situ hybridization only. Overall, 66 per cent of male interphase nuclei demonstrated a Y‐specific hybridization signal. Results were obtained in under 24 h, which may permit the sexing of an embryo biopsied during cleavage and the transfer of sexed embryos at the blastocyst stage to the mother's uterus in the same cycle as oocytes are collected for in vitro fertilization.
Trisomy 20 mosaicism confirmed in a phenotypically normal liveborn
Authors: Park Jonathan P. , Moeschler John B. , Rawnsley Eileen , Berg Susan Z. , Wurster‐Hill Doris H.
Published: March 2007

Prenatal diagnosis of trisomy 20 mosaicism in this case was based on cytogenetic analysis of cultured amniotic fluid cells (23/52 cells were trisomy 20 representing cells from each of four primary cultures). The pregnancy continued to term and the mosaicism was confirmed in the phenotypically normal male neonate by analysis of cultured foreskin fibroblasts (7/49 cells + 20) and placental cells 20/20 cells + 20) whereas the peripheral lymphocytes were cytogenetically normal (20/20 cells were 46,XY). This represents the first confirmation of trisomy 20 mosaicism in a phenotypically normal full‐term neonate.
Confirmation of a balanced chromosomal translocation using molecular techniques
Authors: Smart R. D. , Retief A. E. , Overhauser Joan
Published: March 2007

Investigation of a couple, who had produced three babies with cri du chat syndrome, showed initially that the mother had an apparent deletion of chromosome 5. It seemed likely that she had a balanced chromosomal translocation but it proved impossible to detect the second chromosome involved using routine cytogenetic methods.

Molecular techniques using quantitative hybridization dosage studies were performed and these showed that the mother had a double dose of DNA in the suspected delected area of chromosome 5.

Further studies, using in situ hybridization techniques, revealed that the missing segment of chromosome 5 had translocated onto the short arms of a C group chromosome and further analysis of prometaphase chromosomes showed the presence of a balanced translocation, 46,XY, t(5;9)(5qter → 5p14.1::9p22 → 9pter;9qter → p22::5p14.1 5pter).

As a result of these findings, it was possible to offer prenatal diagnosis to the patient in furture pregnancies, by detecting the presence of a balanced or unbalanced translocation in the fetus using molecular and cytogenetic techniques.
Cardiac and extra‐cardiac anomalies as indicators for trisomies 13 and 18: A prenatal ultrasound study
Authors: Wladimiroff J. W. , Stewart P. A. , Reuss A. , Sachs E. S.
Published: March 2007

The purpose of the present study was to establish sonographic markers for prenatal diagnosis of trisomies 13 and 18. Retrospective analysis of sonographic morphology was therefore carried out in seven fetuses with trisomy 13, and 16 fetuses with trisomy 18. Gestational age ranged between 17 and 39 weeks (median 28 weeks). Polyhydramnios and symmetrical growth retardation were present in 14 of 23 fetuses. A cardiac anomaly was diagnosed in all 23 fetuses, the majority representing a ventricular septal defect (n = 8) or double outlet right ventricle (n = 8). Extra‐cardiac anomalies were characterized by a high incidence of limb deformities (polydactyly, clenched hands, club feet; n = 15) and omphalocele (n = 7).

We conclude that the combined appearance of cardiac and extra‐cardiac anomalies should prompt fetal karyotyping. Cardiac anomalies in combination with fetal limb deformities and omphalocele are suspicious for trisomies 13 and 18.
Achondrogenesis type II (Langer–Saldino) in association with jugular lymphatic obstruction sequence
Authors: Wenstrom Katharine D. , Williamson Roger A. , Hoover William W. , Grant Stanley S.
Published: March 2007

The prenatal diagnosis of achondrogenesis in association with cystic hygroma is described. Ultrasound findings of severe short‐limbed dwarfism, decreased vertebral ossification, and normal ossification of the calvarium were all consistent with achondrogenesis type II. Although the unusual finding of associated cystic hygroma raised the suspicion of a concurrent chromosome abnormality, the karyotype of both fetal lymphocytes and fetal fibroblasts was normal. Autopsy confirmed dilated lymphatic channels in the basal endothelial layer of the skin, cystic hygroma, and coarctation of the aorta. Although previously unreported, we suggest that the features of this case of achondrogenesis indicate an association with lymphatic stasis and jugular lymphatic obstruction sequence in this syndrome.
Abnormal pregnancy sonogram and chromosomal anomalies: Four years' experience with rapid karyotyping
Authors: Hentemann M. , Rauskolb R. , Ulbrich R. , Bartels I.
Published: March 2007

Over a four‐year period, 140 pregnancies with different malformations detected by ultrasound were examined cytogenetically. Gestational age ranged from 13 to 36 weeks. Twenty‐six fetuses (18.6 per cent) had abnormal karyotypes, including trisomies, triploidy, monosomy X, and structural anomalies. Similar malformations were found in fetuses with different chromosomal anomalies, indicating that the types of malformations are not specific for particular chromosomal anomalies.

Chromosomal analysis was performed on amniotic fluid culture and by direct karyotyping of placental biopsies. Direct karyotyping is suggested to be the most rapid approach, especially if sonographic anomalies are detected close to the 24th week of gestation, shortly before delivery, and in cases of significant oligohydramnios.
Prenatal diagnosis of fetal glioblastoma multiforme
Authors: Geraghty A. V. , Knott P. D. , Hanna H. M.
Published: March 2007

Intracerebral tumours of the fetus are very rare conditions, most often presenting clinically as polyhydramnios and hydrocephalus. These conditions can be diagnosed with ultrasound and clearly differentiated from hydrocephalus and other intracranial lesions. The following report is of a case of an intracerebral tumour (glioblastoma multiforme) diagnosed at 33 weeks in utero using ultrasound. The prognosis for this condition is universally poor.
Prenatal diagnosis of β‐thalassaemia in Mediterranean populations by dot blot analysis with DNA amplification and allele specific oligonucleotide probes
Authors: Ristaldi M. S. , Pirastu M. , Rosatelli C. , Monni G. , Erlich H. , Saiki R. , Cao A.
Published: March 2007

In this study, we describe a simple strategy to detect β‐thalassaemia mutations in prospective parents and to make prenatal diagnosis in pregnancies at risk in the Mediterranean population. Screening of prospective parents is carried out by dot blot analysis on enzymatically amplified DNA with a set of oligonucleotide probes complementary to the most common mutations in this population. Prenatal diagnosis is accomplished by the same procedure on enzymatically amplified amniocyte or trophoblast DNA. The main advantages of this procedure are the simplicity, sensitivity (0.05 μg of DNA), and rapidity (12–24 h). Further simplification is obtained by amplification of the DNA from crude amniotic cell lysate. The very low amount of fetal material necessary for this analysis eliminates the need to culture amniotic fluid cells and may decrease the fetal loss rate associated with trophoblast sampling. The number of specific DNA sequences obtained by the amplification procedure allowed us to use non‐radioactive labelled oligonucleotide probes, which have several advantages compared to radioactive probes.
Schizencephaly: Prenatal diagnosis by computed sonography and magnetic resonance imaging
Authors: Lituania M. , Passamonti U. , Cordone M. S. , Magnano G. M. , Toma P.
Published: March 2007

Magnetic resonance (MR) imaging was performed at 29 weeks of pregnancy after ultrasonographic detection of an abnormal cleft in the fetal brain. Fetal neuromuscular blockade was induced by pancuronium bromide injected into the umbilical vein under continuous ultrasound (US) guidance. MR images supported the echotomographic diagnosis of schizencephaly improving the visualization of symmetrical broad clefts connecting the lateral ventricles with the subarachnoid space. Schizencephaly was finally confirmed by neonatal US, computed tomography, and MR.
Prenatal diagnosis of Lesch‐Nyhan syndrome: Experience with three fetuses at risk
Authors: Zoref‐Shani E. , Bromberg Y. , Goldman B. , Shaki R. , Barkai G. , Legum C. , Sperling O.
Published: March 2007

Our experience with the prenatal detection of the Lesch‐Nyhan syndrome (LNS; hypoxanthine‐guanine phosphoribosyltransferase (HGPRT) deficiency) in three fetuses at risk is reported. Enzyme activities were measured in cultured amniocytes in two pregnancies, and in tissues and cultures obtained from chorionic villus sampling (CVS) in a third pregnancy. In all tissues the specific activities of HGPRT and adenine phosphoribosyltransferase (APRT) were determined and APRT/HGPRT ratios were calculated. In addition to the enzyme assays, the rate of purine synthesis de novo was assessed in the two amniocyte cultures, and the rate of [14C]hypoxanthine incorporation into nucleotides and sensitivity to azaguanine were measured in one of the amniocyte cultures. We report the diagnosis of normal fetuses by study of amniocytes in two pregnancies and of LNS using CVS in one pregnancy. In all three cases the diagnosis was confirmed.
Unexpected ultrasonographic prenatal diagnosis of autosomal dominant polycystic kidney disease
Authors: Journel H. , Guyot C. , Barc R. M. , Belbeoch P. , Quemener A. , Jouan H.
Published: March 2007

The prenatal diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is now being reported with increasing frequency. We report three cases and review 12 cases of ADPKD diagnosed in the fetus by ultrasonographic findings. Increased echogenicity and renal enlargement are the main ultrasonographic signs of ADPKD. Renal cysts are uncommon. Diagnosis is easy in a family with a positive ADPKD history. Conversely, there may be no apparent family history, as in our three cases and three cases from the literature. We consider the problems of unexpected diagnosis, family investigation, and the prognosis of ADPKD in children with prenatally diagnosable forms.
Trisomic 22 placenta in a case of severe intrauterine growth retardation
Authors: Stioui S. , de Silvestris M. , Molinari A. , Stripparo L. , Ghisoni L. , Simoni G.
Published: March 2007

We describe a case in which a trisomic 22 placenta could be the cause of severe growth retardation in a chromosomally normal female fetus. At amniocentesis a mosaic 46,XX/ 47,XX, +22 was observed in amniotic fluid specimens sampled on two different occasions, while fetal blood from a diagnostic cordocentesis revealed a normal chromosome constitution. Postnatal studies showed the consistent presence of trisomic 22 cells in the placenta, while only normal metaphases were found in amnion, blood, and fibroblast cultures.
MATERNAL SERUM ALPHA‐FETOPROTEIN SCREENING FOR OPEN NEURAL TUBE DEFECTS IN TWIN PREGNANCIES
Authors: Cuckle H. , Wald N. , Stevenson J. D. , May H. M. , Ferguson‐Smith M. A. , Ward A. Milford , Barbour H. M. , Laurence K. M. , Norgaard‐Pedersen B.
Published: March 2007

Data on maternal serum alpha‐fetoprotein (AFP) levels at 13–24 weeks' gestation in 46 twin pregnancies with open neural tube defects (22 with anencephaly, 24 with open spina bifida) and 169 unaffected twins were used to estimate the detection and false‐positive rates associated with different cut‐off levels. Using the conventional cut‐off level of 2·5 multiples of the median (MoM) for unaffected singleton pregnancies of the same gestation and laboratory, the detection rate in twins was 99 per cent for anencephaly and 89 per cent for open spina bifida, with a false‐positive rate of 30 per cent. Using a 5·0 MoM cut‐off level to maintain a similar false‐positive rate to that found among singleton pregnancies at 16–18 weeks' gestation (about 3 per cent), the detection rate was 83 per cent for anencephaly and 39 per cent for open spina bifida. Estimates are provided of the odds of having an affected twin pregnancy given a positive AFP result as well as the odds for individual women with a raised AFP level.