bluuebunny/crossref_metadata_2025 huggingface dataset:
Birth prevalence of down's syndrome in England and Wales
Authors: Cuckle H. , Nanchahal K. , Wald N.
Published: March 2007

The natural birth prevalence of Down's syndrome for England and Wales in 1974–1987 (i.e., the birth prevalence in the absence of prenatal diagnosis and the induced abortion of affected pregnancies) was estimated by applying the maternal age‐specific birth prevalence derived from epidemiological studies to the number of births in single‐year age groups tabulated by the Office of Population Censuses and Surveys (OPCS). On average, the natural birth prevalence was 12.6 per 10 000 births and increased slightly from 12.2 to 13.2 per 10 000 births over the 14‐year period. Using data on induced abortions carried out on account of Down's syndrome reported to OPCS under the statutory abortion notification scheme, 14 per cent of affected births were avoided by the induced abortion of affected pregnancies, so that the actual birth prevalence of Down's syndrome was estimated at 10.8 per 10000 births. Using data on Down's syndrome births reported to OPCS under the voluntary congenital malformation notification scheme, the prevalence was 7.2 per 10000 births, so only 67 per cent of the estimated number of affected births were, in fact, notified to the scheme.
Cytogenetic studies of amniotic fluid taken before the 15th week of pregnancy for earlier prenatal diagnosis: A report of 114 consecutive cases
Authors: Rebello M. T. , Gray C. T. H. , Rooney D. E. , Smith J. H. , Hackett G. A. , Loeffler F. E. , Horwell D. H. , Beard R. W. , Coleman D. V.
Published: March 2007

One hundred and fourteen samples of amniotic fluid taken before 15 weeks of gestation were cultured for cytogenetic studies. The results of culturing these early amniotic fluid (EAF) samples were compared with the results of culturing 114 standard amniotic fluid (SAP) samples taken after 15 weeks of gestation matched for maternal age and received in the laboratory within the same week.

Cell culture was successful in all 114 of the EAF samples and in 111 SAP samples. There was no significant difference in the days to harvesting and days to reporting in the two groups. Three samples of SAP failed to grow and two EAF samples produced tetraploid karyotypes, so that in these five cases amniocentesis had to be repeated. These problems were attributed to toxicity of a fungicide used in the culture medium. Pseudomosaicism was noted in two EAF samples and one SAP sample; and maternal cell contamination was noted in one EAF and one SAP sample.

Thus, culturing and karyotyping cells harvested from EAF and SAP are similar, indicating that EAF samples from 12–14‐week pregnancies could be used for prenatal diagnosis.
Extraction of DNA from amniotic fluid cells for the early prenatal diagnosis of genetic disease
Authors: Rebello M. T. , Hackett G. , Smith J. , Loeffler F. E. , Robson S. , Maclachlan N. , Beard R. W. , Rodeck C. H. , Williamson R. , Coleman D. V. , Williams C.
Published: March 2007

Ten‐ml samples of amniotic fluid were taken from pregnancies being terminated at 8–14 weeks' gestation. DNA was extracted from the amniotic cells by sequential centrifugation and analysed using the polymerase chain reaction (PCR).

Fifteen samples were analysed for evidence of maternal contamination using Mfd5 oligo‐nucleotide primers for repeat polymorphisms. Ten amniotic fluid samples were tested for the Delta‐F508 deletion characteristic of cystic fibrosis to demonstrate a diagnostic application for the technique. In each case, DNA extracted from fetal tissue from the same pregnancy was included in the controls.

In 14 of the 15 cases tested with the Mfd5 primers, both the amniotic fluid DNA and the fetal DNA showed no evidence of contaminating DNA. In one case, neither the amniotic fluid cells nor the fetal cells yielded results. In nine of the ten cases tested with the Delta‐F508 primers, the amniotic fluid cell DNA provided accurate information about the genetic status of the fetus; in the tenth, the fetal DNA failed to amplify.

The results indicate that adequate DNA can be extracted from amniotic fluid from 8 weeks' gestation onward and these samples are suitable for prenatal diagnosis using PCR.
The impact of supportive intervention after second trimester termination of pregnancy for fetal abnormality
Authors: Elder S. H. , Laurence K. M.
Published: March 2007

The reactions of women who had had a termination of pregnancy for fetal abnormality in the second trimester have been studied retrospectively using a semi‐structured questionnaire. The severity of the grief reaction was measured and the outcome at 6months was compared with the findings from a previous study in South Wales which had led to the introduction of skilled support from genetic fieldworkers and formal genetic counselling after the termination. Of the 69 women interviewed, 55 (80 per cent) experienced an acute grief reaction and 17 (25 per cent) had not resolved their grief 6 months after the termination, compared with 37 (77 per cent) and 22 (46 per cent) out of 48 respectively in the previous study. Fifty‐seven (83 percent) women had found the fieldworker's intervention useful or very useful, some describing her support as essential. An association between poor resolution of the grief reaction with increasing maternal age and with poor perceived support from partners was noted. Improved follow‐up support and counselling have lessened the adverse emotional consequences and support should therefore be offered to all women undergoing termination for fetal malformation.
Chorionic villus sampling for fetal karyotyping in missed abortions
Authors: Appleman Z. , Rosensaft J. , Elchalal U. , Caspi B. , Chemke J.
Published: March 2007

Chorionic villus sampling (CVS) was performed in 12 pregnant women (9–25 gestational weeks) with ultrasonographic evidence of missed abortion. An ultrasonographically guided transabdominal (eight cases) or transcervical (four cases) approach was used. Fetal karyo‐typing was successful in all cases; in five, chromosomal aberrations were found and in seven, chromosome analyses revealed normal karyotypes. Tissue culture for fetal karyotyping was successful in only 72.5 per cent of 40 live pregnancies which were electively interrupted because of abnormal ultrasonographic findings or an abnormal fetal karyotype, and in 57 per cent of seven missed abortions. CVS is suggested as a feasible and effective method for fetal karyotyping in missed abortions and it seems to be superior to post‐abortion tissue culture.
Identification of duchenne muscular dystrophy genomic probe P20 constant Taq1 fragment corresponding to the EcoRV and Msp1 polymorphisms
Authors: Laing N. G. , Walker A. P. , Akkari P. A. , Chandler D. C. , Layton M. G. , Mears M. E. , Yamada T. , Bartlett R. J. , Pericak‐Vance M. A. , Hung W.‐Y. , Wapenaar M. C. , van Ommen G. , Roses A. D. , Kakulas B. A.
Published: March 2007

The majority of Duchenne and Becker muscular dystrophy cases are caused by deletions observable in Southern blots with cDNA probes for the gene. When the deletion includes polymorphic probes, they may be used to determine carrier status by deletion segregation analysis: non‐inheritance of parental alleles, or heterozygosity. The polymorphic genomic probe P20 is deleted in a large percentage of probands. P20 hybridizes with two constant fragments of 6.7 and 0.8 kb in Taql digests. In a number of probands, only the larger P20 Taq1 fragment is deleted. This study demonstrates that this fragment corresponds with the polymorphic EcoRV and Mspl fragments of P20. Families in which the upper Taql fragment is deleted may be screened for carrier status using non‐inheritance of parental alleles or heterozygosity of P20 in EcoRV or Mspl digests.
Fetal echocardiography using transvaginal and transabdominal probes during the first period of pregnancy: A comparative study
Authors: D'Amelio Renzo , Giorlandino Claudio , Masala Liana , Garofalo Massimo , Martinelli Monica , Anelli Giuseppe , Zichella Lucio
Published: March 2007

The authors compare the diagnostic possibilities of fetal transabdominal echocardiography versus transvaginal echocardiography. A larger diagnostic capacity is verified in different gestation ages with transvaginal probe between the 11th and 14th week of gestation. The results are emphasized by colour Doppler.
Congenital myotonic dystrophy: An often unsuspected cause of severe polyhydramnios
Authors: Levine Amy B. , Eddleman Keith A. , Chitkara Usha , Willner Judith P. , Vosatka Robert J. , Berkowitz Richard L.
Published: March 2007

Two cases of severe polyhydramnios are presented in which the unsuspected diagnosis of myotonic dystrophy was made in the patient and the fetus.
Detection of fetal cells in maternal blood
Authors: Yeoh S. C. , Sargent I. L. , Redman C. W. G. , Wordsworth B. P. , Thein S. L.
Published: March 2007

We report the detection of fetal cells in the maternal circulation by enzymatic amplification of a single copy gene sequence that was fetal‐specific. Fetal HLA‐A2‐positive cells were sorted from maternal HLA‐A2‐negative cells by flow cytometry and confirmed by demonstration of a fetal‐specific HLA‐DR4 sequence. However, this sequence could not be detected in unenriched maternal DNA prepared at 28 and 32 weeks' gestation. The sensitivity of detection was 1 HLA‐DR4‐positive cell in 105 HLA‐DR4‐negative cells. We conclude that prenatal diagnosis of paternally inherited autosomal‐dominant genetic defects may be possible by selective gene amplification of maternal peripheral blood. However, preliminary enrichment for fetal cells may be necessary.
HUMAN CHORIONIC GONADOTROPHIN AND ALPHA‐FETOPROTEIN LEVELS IN MATCHED SAMPLES OF AMNIOTIC FLUID, EXTRAEMBRYONIC COELOMIC FLUID, AND MATERNAL SERUM IN THE FIRST TRIMESTER OF PREGNANCY
Authors: Wathen N. C. , Cass P. L. , Kitau M. J. , Chard T.
Published: March 2007

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid obtained by high resolution transvaginal ultrasound‐guided amniocentesis from 32 women between 7 and 12 weeks of pregnancy were analysed for human chorionic gonadotrophin (hCG) and alpha‐fetoprotein (AFP). There was a highly significant difference between the hCG levels in amniotic fluid (median level 6.3 U/ml; range 1.6–310.0 U/ml) and those in extraembryonic coelomic fluid (median level 400.0U/ml; range 135.0–2250.0U/ml) (p<0.001; Mann‐Whitney U/–test). The levels of AFP were very similar in amniotic fluid (median 26.0 kU/ml; range 10.0–116.5 kU/ml) and extraembryonic coelomic fluid (median level 24.1 kU/ml; range 12.4–94.4 kU/ml).
Alteration in age‐specific risks for chromosomal trisomy by maternal serum alpha‐fetoprotein and human chorionic gonadotropin screening
Authors: Miller C. H. , O'Brien T. J. , Chatelain S. , Butler B. B. , Quirk J. G.
Published: March 2007

Maternal serum screening for alpha‐fetoprotein (AFP) and human chorionic gonadotropin (hCG) increases the detection rate of Down's syndrome (DS) pregnancies. To estimate the risk of a DS pregnancy for a particular woman, Wald et al. combine a trivariate function of AFP, hCG, and unconjugated oestriol with age‐specific risk. Calculation of independent likelihood ratios (LRs) for AFP and hCG has allowed us to examine the predictive value of each test alone and the combination. AFP and hCG were measured in stored serum samples from 672 normal, 8 trisomy 21 (DS), 9 trisomy 18, and 2 trisomy 13 pregnancies. AFP and hCG multiples of the median (MOM) were calculated for each sample. The LRs for AFP MOM and hCG MOM were calculated and combined with age‐specific risk. Of eight DS pregnancies, six had increased risk based on age and AFP. Addition of hCG detected two additional DS pregnancies. Of nine trisomy 18 pregnancies, four (44 per cent) had hCG MOM under 0–25. Three out of nine would have been classified as high risk by AFP, but none by combined AFP and hCG. Amniocentesis would have been recommended in 74 per cent of aneuploid pregnancies if both age and serum screening were used. Abandonment of amnio‐centesis based on age alone would have excluded two abnormal pregnancies from detection. Screening programmes should note that combined risk figures are specific for DS and do not include other trisomies. Detection of other trisomies requires inclusion of low hCG level as a discriminator and continuation of age‐based testing.
Further predictors of renal dysplasia in fetal obstructive uropathy: Bladder pressure and biochemistry of ‘fresh’ urine
Authors: Nicolini Umberto , Tannirandorn Yuen , Vaughan Janet , Fisk Nicholas M. , Nicolaidis Peter , Rodeck Charles H.
Published: March 2007

Urine was aspirated on two consecutive days from the dilated bladder of nine fetuses with lower urinary tract obstruction. Gestational age ranged from 17 to 35 weeks. Renal dysplasia was diagnosed histologically in four fetuses, whereas the other five had normal renal histology or only partial dysplasia.

Urinary sodium (Na+) and osmolality (Osm) decreased significantly in the second urine sample 1 day after bladder emptying (median decrease: Na+ = −11.3 per cent; Osm= −13.3 per cent). Although there were no significant differences between fetuses with or without renal dysplasia, normalization of an initially raised urine Na + concentration occurred at the second sample in a fetus with partially normal renal histology, thus correcting a false‐positive diagnosis of dysplasia.

Bladder pressure was measured at the time of the first urine sampling in seven fetuses and in a further eight with bladder outlet obstruction undergoing a single urine aspiration at 18–28 weeks. Bladder pressure was increased above the reference range in 8 of 15 fetuses with urinary obstruction, but there was no correlation between pressure and the degree of impairment of renal function.

Although no conclusive clinical guidelines can be drawn from this study for the evaluation of fetal renal function, these findings suggest that, in lower urinary tract obstruction, tubular reabsorption is impeded by the standing pressure in the urinary tract and that improvement of renal function may occur following relief of obstruction.
Prenatal diagnosis in autosomal dominant Beckwith‐Wiedemann syndrome
Authors: Viljoen D. L. , Jaquire Z. , Woods D. L.
Published: March 2007

A 20‐year‐old woman with Beckwith‐Wiedemann syndrome (BWS) was ultrasonographically appraised at intervals during her pregnancy. Unequivocal evidence for a diagnosis of BWS was obtained in the fetus and this was confirmed postnatally. Early ultrasound diagnosis enabled appropriate genetic counselling to be given; neonatal complications, such as hypoglycaemic episodes, were prevented.
Prenatal ultrasound diagnosis of Apert's syndrome
Authors: Narayan Harini , Scott Ian V.
Published: March 2007

A mother affected with Apert's syndrome was diagnosed by ultrasound scan at 16–17 weeks to have a fetus similarly affected. The typical features of acrocephaly and symmetrical syndactyly were seen. This is probably the first time that this condition has been diagnosed at such a gestation by ultrasound scan. The patient decided to continue the pregnancy, and intrauterine death occurred at 34 weeks. The diagnosis was confirmed by pathological examination.
Prenatal diagnostic procedure for leukocyte adhesion deficiency
Authors: Weening R. S. , Bredius R. G‐ M. , Wolf H. , van der Schoot C. E.
Published: March 2007

Leukocyte adhesion deficiency (LAD) is a rare autosomal recessive disorder which leads to recurrent severe infections due to impaired leukocyte functions. The disorder is caused by an absence or deficiency of leukocyte cell adhesion molecules (LeuCAMs) on the leukocyte membranes. The diagnosis is established with monoclonal antibodies against the LeuCAMs.

We have carried out a prenatal diagnostic procedure by means of cordocentesis in a mother who was 20 weeks pregnant and had previously given birth to a child with LAD. This previous child had the severe form of LAD with undetectable mRNA for the β chain, the common subunit of the LeuCAMs. We found that the fetal granulocytes expressed the LeuCAMs normally. At birth, the baby was physically normal and showed no signs of impaired leukocyte functions.
Consequences of prenatal diagnosis of cystic fibrosis on the reproductive attitudes of parents of affected children
Authors: Boué J. , Muller F. , Simon‐Bouy B. , Faure C. , Boué A.
Published: March 2007

Three hundred and twenty‐six French families with a cystic fibrosis‐affected child who were referred for prenatal diagnosis were analysed by sibship size: 74.2 per cent of the couples had no further pregnancies to term after the affected child, who was deceased in 34.6 per cent of cases. These couples were followed prospectively after prenatal diagnosis and 77 had two or more consecutive pregnancies with prenatal diagnosis. The aim of these couples was to succeed in constituting a family with two normal children.
Prenatal diagnosis of recurrent Larsen syndrome: Further definition of a lethal variant
Authors: Mostello Dorothea , Hoechstetter Leah , Bendon Robert W. , Dignan Peter St. J. , Oestreich Alan E. , Siddiqi Tariq A.
Published: March 2007

Larsen syndrome is characterized by multiple congenital joint dislocations and flattened facies. Some cases have been familial, with both autosomal dominant and recessive patterns of inheritance. Reports of a form of Larsen syndrome, lethal in the neonatal period, are reviewed. We present a family in which recurrence of the syndrome was diagnosed prenatally, but a lethal outcome again resulted despite preparation for anticipated perinatal complications. Because of the wide clinical variation and the lack of a known metabolic defect, delineation between the various forms of Larsen syndrome is difficult. While the lethal variant appears to be a combination of the Larsen phenotype and pulmonary hypoplasia, other features noted in the lethal cases, such as abnormal palmar creases and laryngotracheomalacia, are also seen in patients with Larsen syndrome who survive.
Progression of exencephaly to anencephaly in the human fetus—an ultrasound perspective
Authors: Wilkins‐Haug Louise , Freedman Walter
Published: March 2007

Exencephaly as a precursor of anencephaly is well delineated in animal studies. In humans, a similar though unproven embryologic sequence is postulated. In the case reported, serial ultrasound studies allowed us to identify a 16‐week human exencephalic fetus and observe the cephalic changes during its progression to a classic anencephalic appearance.
The normal fetus of an acardiac twin pregnancy: Perinatal management based on echocardiographic and sonographic evaluation
Authors: Donnenfeld Alan E. , van de Woestune Johanna , Craparo Frank , Smith Catherine S. , Ludomirsky Avi , Weiner Stuart
Published: March 2007

Experience with three prenatally diagnosed pregnancies complicated by an acardiac twin reveals that ultrasonography and echocardiography are helpful in detecting early signs of in‐utero congestive heart failure in the normal twin. The use of Doppler blood flow analysis to determine direction of blood flow, post‐mortem placental and fetal angiography, and umbilical cord blood gas determination provided proof that retrograde arterial perfusion occurs in the acardiac fetus. In a fourth pregnancy, an experimental approach to occlude the acardiac twin's umbilical cord was attempted, but was unsuccessful.
Screening for fetal Down's syndrome with maternal serum markers—an experience in italy
Authors: Mancini Giuliana , Perona Marco , Dalľamico Daniela , Bollati Carla , Albano Fulvia , Mazzone Raffaela , Rosso Maria , Carbonara Angelo Oscar
Published: March 2007

The effectiveness of maternal serum alpha‐fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin in screening for Down's syndrome (DS) was evaluated on 840 women who underwent amniocentesis for fetal karyotype on account of their age. The risk of a DS pregnancy was established using the method of Wald et al. (1988b), which combines the age‐specific risk with that indicated by the levels of the three serum markers. In women over 35, at cut‐off risk levels of 1:250 and 1:380, the false‐positive rate was 24 and 34 per cent, respectively. In all nine cases of DS, the estimated risk was higher than 1:250. The best screening strategy with the lowest false‐positive rate was obtained by combining the three serum markers. The results suggest that this kind of screening can be proposed during genetic counselling for women under 35 and older women wishing to avoid the risk of miscarriage induced by amniocentesis.
Prenatal diagnosis of inborn errors in peroxisomal β‐oxidation
Authors: Wanders R. J. A. , Schutgens R. B. H. , van den Bosch H. , Tager J. M. , Kleijer W. J.
Published: March 2007

In recent years, an increasing number of inherited diseases in man have been recognized in which there is an impairment in the peroxisomal β‐oxidation of very‐long‐chain fatty acids. In general, these disorders are associated with severe neurological and physical abnormalities and death within the first years of life. In this paper we describe our experience with regard to the prenatal diagnosis of a number of different inborn errors of peroxisomal β‐oxidation. Eleven pregnancies at risk were monitored by measuring very‐long‐chain fatty acid levels as well as very‐long‐chain fatty acid β‐oxidation in cultured chorionic villous fibroblasts and/or amniotic fluid cells. Five affected fetuses were identified. It is concluded that prenatal diagnosis in this group of diseases can be done reliably using cultured chorionic villous fibroblasts or amniotic fluid cells.
Prenatal diagnosis in multiple gestation: 20 Years' experience with amniocentesis
Authors: Anderson R. L. , Goldberg J. D. , Golbus M. S.
Published: March 2007

Three hundred and thirty‐nine cases of multiple gestation underwent prenatal diagnosis by amniocentesis. The spontaneous abortion rate (to 28 weeks) in this group was 3.57 per cent compared with our singleton abortion rate of 0.60 per cent. The perinatal mortality rate (PMR) and prematurity rate were not different from the singletons, and compared favourably with the PMR reported in the literature for multiple gestations which did not undergo any intervention during pregnancy. This increased abortion rate following amniocentesis may only represent the increased natural loss rate in multiple gestations, and not indicate any increased risk added by the procedure.
Pallister Killian‐mosaic tetrasomy 12 p syndrome. Another prenatally diagnosed case
Authors: Bresson J. L. , Arbez‐Gindre F. , Peltie J. , Gouget A.
Published: March 2007

A new case of mosaic tetrasomy 12 p (46, XY/47, XY, + i 12 p), diagnosed during pregnancy from ultrasonographic signs, is reported. We emphasize the peculiar position of the diaphragmatic hernia in this syndrome. Its presence or absence determines the vital prognosis and the age of diagnosis. The knowledge of its possible association with tetrasomy 12 p can contribute considerably to the neonatal diagnosis by directing the work of the cytogeneticist to tissue cultures which enable him to detect the presence of the tetrasomy.
Cu/Zn superoxide dismutase quantification from fetal erythrocytes—an efficient confirmatory test for Down's syndrome after maternal serum screening and sonographic investigations
Authors: Porstmann T. , Wietschke R. , Cobet G. , Stamminger G. , Bollmann R. , Rogalski V. , Pas P.
Published: March 2007

An enzyme immunoassay especially designed for the quantification of Cu/Zn superoxide dismutase (SOD) in erythrocytes has been applied to measure the SOD of outcomes with high risk for Down's syndrome. From 148 fetuses SOD was quantified from erythrocytes of umbilical vein blood and related to the number of cells, the content of haemoglobin (Hb), and to the haematocrit (Hc). Comparative studies between the SOD content of erythrocytes from the fetuses and their mothers resulted in similar SOD levels (14.09 ± 1.20 for fetal and 14.48 ± 1.63 for maternal cells) with a 1.84‐fold smaller variance for fetal cells. The best differentiation between normal fetuses and fetuses with Down's syndrome resulted from the SOD/cell ratio followed by the SOD/Hb ratio. Fixing a cut‐off value from the probability density functions that the method results in a specificity of 99.99 per cent, the sensitivity to detect cases of Down's syndrome was 99.71 per cent for the SOD/cell ratio, 70.92 per cent for the SOD/Hb ratio, and 60.21 per cent for the SOD/Hc ratio. Nine cases with Down's syndrome were correctly diagnosed by the SOD/cell ratio determination. Eight of these were confirmed as free trisomy 21 by karyotype analysis and one was found to be a triploidy. The latter was not detected by the SOD/Hb and SOD/Hc ratios because of the one‐third higher content of haemoglobin and the larger volume of the erythrocytes which resulted in ratios within the normal range.
Prenatal diagnosis of infantile hypophosphatasia
Authors: Kishi Fumio , Matsuura Shinya , Murano Ichiro , Akita Ayakazu , Kajii Tadashi
Published: March 2007

Prenatal diagnosis was attempted in a pregnant Japanese woman whose son had died of infantile hypophosphatasia, using chorionic villi sampled at 10 weeks of gestation. Southern blot analysis of restriction fragment length polymorphism was used as a guide, with cDNA for the human liver‐type alkaline phosphatase as a probe, and BclI as a restriction enzyme. The fetus was found to be a heterozygote; the pregnancy was allowed to continue; and the baby born was phenotypically normal.
Early amniocentesis at 11–14 weeks' gestation for the diagnosis of fetal chromosomal abnormality—a clinical evaluation
Authors: Hackett G. A. , Smith J. H. , Rebello M. T. , Gray C. T. H. , Rooney D. E. , Beard R. W. , Loeffler F. E. , Coleman D. V.
Published: March 2007

Early arnniocentesis between 11 and 14 weeks' gestation was offered to 110 women at risk of a chromosomally abnormal fetus due to maternal age. Four were found to be unsuitable for the procedure, and 106 early amniocenteses were performed. In 102 cases, clear amniotic fluid was obtained with a single tap. There were two dry taps and two bloodstained tapis; sampling was repeated in three of these cases before 15 weeks. In the fourth case, placental biopsy was performed at 16 weeks. Thus, we were able to obtain a satisfactory sample in all but three cases(2.8 percent).

Karyotyping of cells harvested from the early amniotic fluid samples was successful in all the 105 cases. Cell culture from the initial samples revealed a normal karyotype in 99 cases, two balanced translocations, two tetraploid karyotypes, and two cases of pseudomosaicism.

Of the 105 pregnancies successfully sampled, there have been two losses to date (1–8 per cent). Two further patients presented with premature rupture of membranes, both pregnancies having successful outcomes.

Sixty‐two babies have delivered to date, with four congenital anomalies. There were no respiratory problems. Twenty‐nine pregnancies are continuing without known complications, and details are not yet available on the remaining 12.

The results indicate that early arnniocentesis may replace the traditional test at 15–17 weeks.
Induction of fetal lung maturation with intra‐amniotic thyroxine in multiple pregnancy
Authors: Dan Uzi , Barkai Gad , Reichman Brian , Goldman Boleslow , Mashiach Shlomo
Published: March 2007

Two premature triplet pregnancies underwent repeated treatment aimed at acceleration of individual fetal lung maturity while administering intravenous tocolytic treatment. From the early third trimester, repeated amniocenteses were used for intra‐amniotic administration of thyroxine to each sac, while the individual fetal lung maturation rate was determined by surfactant microviscosity until lung maturity was achieved.
DNA‐based prenatal diagnosis of the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1)
Authors: Järvelä Irma , Rapola Juhani , Peltonen Leena , Puhakka Lea , Vesa Jouni , Ämmälä Pirkko , Salonen Riitta , Ryynänen Markku , Haring Pertti , Mustonen Aki , Santavuori Pirkko
Published: March 2007

Eleven fetuses at risk for the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1) were studied using DNA markers and the results were compared with the results of electron microscopy (EM) of chorionic villus specimens from pregnancies in the first or early second trimester of pregnancy. In four cases, the prenatal diagnosis was made independently with both methods, and in seven cases, the EM diagnosis was confirmed postnatally or from autopsy material using RFLP analysis. The two methods gave concordant results in all cases. The DNA analysis based on RFLP haplotypes also for the first time facilitates reliable carrier diagnostics. RFLP analysis based on polymorphic markers closely linked to the INCL locus is now available for prenatal diagnosis of this fatal brain disease, whose biochemical background is totally unknown and for which no treatment is available.
Prenatal paternity testing by dna analysis
Authors: Lobbiani A. , Nocco A. , Vedrietti P. , Brambati B. , Colucci G.
Published: March 2007

Prenatal paternity testing was evaluated by DNA analysis in chorionic villus biopsies obtained during the 7th‐22nd weeks of gestation. Using highly polymorphic variable number of tandem repeats (VNTR) probes, we analysed four cases consisting of mother/child/alleged father trios. In all cases, we were able to detect maternal and paternal alleles and could establish or exclude paternity. The application of DNA analysis represents a new important diagnostic aid for all cases that require a prenatal identification of paternity.
Prognosis of fetuses with a cystic hygroma
Authors: Bernstein Harold S. , Filly Roy A. , Goldberg James D. , Golbus Mitchell S.
Published: March 2007

This paper reports our experience with 55 fetuses identified in utero to have a cystic hygroma. The outcome of fetuses with an isolated cystic hygroma, cystic hygroma with non‐immune hydrops, and cystic hygroma with multiple anomalies was evaluated. Approximately two‐thirds of karyotypes were aneuploid, and a strong association of septation and aneuploidy existed. Only five cases, four of which had isolated hygromas, came to term and resulted in live births. Two of these involved small non‐septated lesions which resolved in utero.
Prenatal diagnosis and outcomes of five cases of mosaicism for an isochromosome of 20q
Authors: Richkind K. E. , Mahoney M. J. , Evans M. I. , Willner J. , Douglass R.
Published: March 2007

Five cases of mosaicism for an isochromosome of 20q have been detected from a total of 50 000 cases analysed for prenatal diagnosis by amniocentesis. Karyotypes were designated mos 46,X_/46,X_,i(20q). In all cases, the abnormal cell line was detected in more than one primary culture, thus fulfilling the criterion for true (level III) mosaicism. Indications for prenatal diagnosis were parental anxiety (two cases), low maternal serum alpha‐fetoprotein (AFP) (two cases), and high maternal serum AFP (one case). Level II ultrasounds on all five fetuses were normal, and the abnormal cell line was never detected in fetal blood and/or cord blood. All five pregnancies were continued and had normal outcomes, with birth weights ranging from 2.4 to 3.8 kg. The development of all five children has been normal, with the oldest child in the study now 4 years of age. We suggest that the abnormal cell line in each case was of extrafetal origin, and that this may be one of the more common examples of this phenomenon, occurring in approximately 1/10000 prenatal diagnoses. Mosaicism i(20q) may have been missed in the past because of the higher resolution necessary to detect this subtle change.
First‐trimester maternal serum unconjugated oestriol and alpha‐fetoprotein in fetal Down's syndrome
Authors: Crandall Barbara F. , Golbus Mitchell S. , Goldberg James D. , Matsumoto Myles
Published: March 2007

Maternal sera (MS) taken from 1396 women prior to chorionic villus sampling at 9–12 menstrual weeks were assayed for unconjugated oestriol (uE3) and alpha‐fetoprotein (AFP). Median levels increased by 41 and 26 per cent per week respectively in normal pregnancies. There were 32 pregnancies with a chromosome abnormality. The median MS uE3 and AFP were 0.73 and 0.75 multiples of the median (MoM) respectively in the ten cases of Down's syndrome (DS) but not decreased in the other abnormalities. These results suggest that both uE3 and AFP may be useful in identifying DS in the first trimester. Additional prospective studies are needed to confirm these findings.
Anxiety in women with low maternal serum alpha‐fetoprotein screening results
Authors: Abuelo Dianne N. , Hopmann Marita R. , Barsel‐Bowers Gail , Goldstein Amy
Published: March 2007

The purpose of this study was to measure anxiety in pregnant women who had low maternal serum alpha‐fetoprotein (MSAFP) screening test levels, received genetic counselling and chose to undergo amniocentesis for fetal chromosome analysis. Their anxiety levels were compared with the levels in women undergoing amniocentesis because of advanced maternal age. The results indicate a higher level of anxiety in women with low alpha‐fetoprotein (AFP) levels.
First‐trimester prenatal diagnosis of hypophosphatasia: Experience with 16 cases
Authors: Brock David J. H. , Barron Lilias
Published: March 2007

We have carried out first‐trimester prenatal diagnosis of hypophosphatasia in 1 6 pregnancies with a 1 in 4 risk of this condition. The liver/bone/kidney isoenzyme of alkaline phosphatase was measured in chorionic villus samples using a specific monoclonal antibody and an enzymatic amplification system. Fifteen of the 16 pregnancies were correctly predicted, while one has been lost to follow up. We suggest that this assay system is likely to be superior to DNA‐base methods for the first‐trimester prenatal diagnosis of hypophosphatasia.
Screening for Down's syndrome in older women based on maternal serum alpha‐fetoprotein levels and age: Preliminary results
Authors: Zeitune Moshe , Ben‐Tovim Talma , Fejgin Moshe , Amiel Aliza , Beyth Yoram
Published: March 2007

We report the results of screening for Down's syndrome (DS) in older women using published rate schedules based on maternal serum alpha‐fetoprotein (MSAFP) and age. Five hundred and seventeen patients aged 35 years and older, who were referred for a mid‐trimester genetic amniocentesis, were first tested for MSAFP and then underwent an amniocentesis. Individual risks for DS, combining MSAFP and age, were derived using three different published rate schedules. Theoretical selection for amniocentesis was made using the cut‐off level of the average collective risk for a 35‐year‐old woman (1:380 at live birth or 1:270 at amniocentesis). Six affected pregnancies (five with DS and one with trisomy 18), which were diagnosed prenatally, were all found to be at a higher risk than the specified cut‐off. These cases would have been diagnosed in any event, using any of the published rate schedules. According to these rate schedules, between 39 and 45 per cent of the patients would be in the lower risk group and therefore would have been counselled not to undergo amniocentesis. Further studies should be conducted in order to reach conclusive screening policies for DS in older women.
Mosaic trisomy 17 in amniotic fluid cells not confirmed in the newborn
Authors: Djalali M. , Barbi G. , Grab D.
Published: March 2007

A case of true fetal mosaicism 46,XY/47,XY, + 17 was diagnosed in amniotic fluid cells. After genetic counselling and unsuccessful periumbilical blood sampling the pregnancy continued to term, and a healthy male infant was born. Lymphocytes of the newborn had a normal karyotype. Follow‐up of the child at age 18 months showed normal physical and mental development indicating that the trisomic cell line was restricted most probably to the extra fetal tissue.
Is placental mosaicism associated with poor perinatal outcome?
Authors: Leschot Nico J. , Wolf Hans
Published: March 2007

In 37 pregnancies with placental mosaicism detected at first‐trimester chorionic villus sampling in 2000 pregnancies, two pregnancies (5.4 per cent) ended in a spontaneous abortion at 15 weeks (46,XX/47,XX, + 16) and in a perinatal loss in a term pregnancy (46,XY/ 47,XY, +10), respectively. The outcome of the other 35 pregnancies was normal. The total pregnancy loss rate before 28 weeks in the first 1000 pregnancies was previously reported to be 3.6 per cent.
Interstitial deletions without phenotypic effect: Prenatal diagnosis of a new family and brief review
Authors: Barber John C. K. , Mahl Harjit , Portch Janet , Crawfurd Martin D'A.
Published: March 2007

A 39‐year‐old woman (G4P1SAB2) was referred for amniocentesis for advanced maternal age. An interstitial deletion of the G‐dark band 11 pi 2 was found in the fetus. Blood from the mother and her previous son was cultured and the same deletion was found in both. The absence of phenotypic effect in this family further confirms that G‐dark euchromatic deletions are compatible with a normal phenotype, and underlines the importance of checking familial karyotypes even when apparently unbalanced structural rearrangements are found at prenatal diagnosis.
Isoelectric focusing pattern of human amniotic fluid α‐fetoprotein
Authors: Wiechen Kai , Plendl Hansjörg , Grote Werner
Published: March 2007

Isoelectric focusing (IEF) of amniotic fluid α‐fetoprotein (AFP) in thin‐layer polyacrylamide gels containing 8 M urea followed by immunoblotting reveals at least nine bands, band I lying next to the cathode. Compared with 298 amniotic fluid samples from normal pregnancies, we found that the density of band V was increased in seven cases of fetal death. In 16 amniotic fluid samples from pregnancies with open neural tube defects (ONTO), band V disappeared or was markedly decreased. In seven cases with elevated AFP and positive acetylcholines‐terase (AChE) due to contamination with fetal blood, no difference in pattern was observed compared with samples from normal pregnancies. It is suggested that IEF of AFP and subsequent immunoblotting are an apparently diagnostic test for ONTD and intrauterine fetal death (IUFD).
Prenatal diagnosis of harlequin ichthyosis by fetal skin biopsy; Report of two cases
Authors: Suzumori K. , Kanzaki T.
Published: March 2007

Two cases of harlequin ichthyosis were successfully diagnosed prenatally by fetal skin biopsy. The aborted fetuses were later confirmed to be afflicted with this very unusual skin disease. Both families had a previous history of harlequin ichthyosis. In performing the biopsy, it was found that amniotic fluid cytology can also be very helpful in the diagnosis of this kind of severe ichthyosis. With regard to these families, the disease may have been transmitted in an autosomal dominant fashion, and not in a recessive manner as is commonly believed.
Early transvaginal sonographic diagnosis of alobar holoprosencephaly
Authors: Bronshtein Moshe , Wiener Zeev
Published: March 2007

Holoprosencephaly is a cerebral anomaly resulting from incomplete cleavage of the primitive prosencephalon or forebrain. Early detection of this anomaly is very important since the most severe form is incompatible with life. The diagnosis also signals the need for a chromosomal determination since chromosomal abnormalities have been associated with this anomaly. An early diagnosis of alobar holoprosencephaly at 14 weeks' gestation, employing transvaginal sonography, is reported. Our findings are compared with prenatal transabdominal sonographic findings of holoprosencephaly which have been reported during the last decade in the literature.
Maternal serum human chorionic gonadotropin levels in twin pregnancies
Authors: Nebiolo Linda M. , Adams William B. , Miller Susan L. , Milunsky Aubrey
Published: March 2007

Introduction of combined screening with maternal serum alpha‐fetoprotein and human chorionic gonadotropin (MShCG) assays for fetal chromosome defects requires establishment of the normal range for twins. This report documents that the normal range for MShCG between 15 and 19 weeks in twin gestations was 1.84–2.41 multiples of the singleton median. Of the 192 twin pregnancies studied, 31.7 and 47.9 per cent had MShCG values ≥2.5 and ≥ 2.0 multiples of the singleton median, respectively.
Prenatal diagnosis for dystrophia myotonica using the polymerase chain reaction
Authors: Clark C. , Kelly K. F. , Smith N. , Fairweather N. , Brown T. , Johnston A. , Haites N. E.
Published: March 2007

The polymerase chain reaction has been used to detect an abundant class of short repeat DNA families of the form (dC‐dA)n.(dG‐dT)n, known as microsatellites. These units are found throughout the human genome and have been characterized for several loci including APOC2 on chromosome 19ql2‐ql3.2. The locus APOC2 is linked to the gene for dystrophia myotonica and a microsatellite within this locus was used to derive polymorphisms in a family to predict the inheritance of the disease. Chorionic villus sampling (CVS) was performed at 151/2 weeks' gestation. Following DNA extraction from the CVS material and parental blood samples, microsatellite analysis was carried out by the polymerase chain reaction.
Post‐mortem findings in a fetus with 48,XXY, + 21
Authors: Smith A. , Watson G. , Michas J. , Vtersbach R. , Ellwood D.
Published: March 2007

A fetus with 48,XXY, + 21 was detected on routine amniocentesis at 15 weeks for advanced maternal age. Fibroblast cultures from six different tissues were initiated after termination and each showed the same karyotype without any tissue limited mosaicism. The only pheno‐typic abnormality detected at post‐mortem examination was bilateral clinodactyly of the fifth finger which had been detected on ultrasound. The maternal serum alpha‐fetoprotein and the femur length were normal. Maternal age remains an essential criterion for prenatal diagnosis.
Preimplantation diagnosis: A patient perspective
Authors: Pergament E.
Published: March 2007

A new dimension in the prevention of birth defects will be achieved when genetic diseases can be routinely diagnosed in embryos prior to implantation. The impressions and attitudes towards preimplantation diagnosis were studied in prospective patients, women at high reproductive risk for a genetic disease. Their perspective highlighted not only the advantages and disadvantages of this new approach, but also those changes necessary in order for preimplantation diagnosis to become a useful and practical technique. The data presented are based on information obtained by a mailed questionnaire answered by 58 women. The main benefit of preimplantation diagnosis for these high‐risk women would be the ability to undertake a pregnancy without having to be subjected to the physical and/or emotional trauma of elective termination. Their major concerns related to possible damage to the embryo following biopsy, the cost of the procedure, and the low success rate of completed pregnancies. Other issues to be addressed before preimplantation diagnosis could begin to compare favourably with existing forms of prenatal testing were that the methods of obtaining oocytes or embryos should be simple, well tolerated, highly efficient, and low in maternal risk, and that the genetic analysis of embryonic or extraembryonic cells should be unequivocally accurate.
Chromosome analysis of multipronuclear human oocytes after in vitro fertilization
Authors: Martin‐Pont Brigitte , Selva Jacqueline , Bergere Marianne , Pillion Corinne , Hugues Jean Noel , Tamboise Agnès , Tamboise Edmond
Published: March 2007

Multipronuclear human eggs are frequent after in vitro fertilization. Their chromosome analysis can provide useful information. Before cleavage it can confirm the suspected poly‐ploidy. Among the cleaved multipronuclear eggs it provides an estimation of the incidence of the possible return to diploidy.

Ninety‐four multipronuclear eggs were fixed at the first, second, or third cleavage according to the air‐drying method of Tarkowski with or without colchicine exposure: 60 were successfully analysed. Twelve were stopped before cleavage (six without colchicine treatment and six with colchicine treatment). They were polyploid, confirming the cytological observation. Forty‐eight eggs cleaved and were stopped by colchicine treatment and karyotyped. Seventeen eggs (35 per cent) had produced diploid embryos. Mosaicism was frequent (15 cases, 31 per cent). Triploidy was not frequent (8 eggs, 17 per cent). Haploidy constituted the remaining cases (8 eggs, 17 per cent).

Our data indicate that the initial count of pronuclei is a reliable test. Multipronuclear one‐cell oocytes were confirmed to be polyploid. Furthermore, the developmental capacity of the multipronuclear oocytes is variable. Most of them cleaved. However, many multipronuclear oocytes led to diploid cleaving eggs.
β‐Glucuronidase activity in mouse oocytes, mouse preimplantation embryos, and human gametes
Authors: van Blerk M. , Lissens W. , Nijs M. , van der Linden M. , van Steirteghem A. C. , Liebaers I.
Published: March 2007

A microfluorimetric assay was designed to monitor β‐glucuronidase (β‐gluc) activity during the early development of mouse embryos and was also applied to measure β‐gluc activity in human sperm cells and single human oocytes. Mouse oocytes and preimplantation embryos at different stages of development, failed fertilized human oocytes, and human sperm cells were collected, and β‐gluc activity was analysed. In the mouse, β‐gluc activity could be measured starting from the morula stage on in a pooled sample of 15 embryos and at blasto‐cyst formation in one single embryo. β‐Gluc activity was low in human sperm cells. The enzyme could be readily demonstrated in 87 per cent of non‐fertilized human oocytes. Considerable variation in β‐gluc activity was noticed between individual oocytes.
Superovulation fails to increase human blastocyst yield after uterine lavage
Authors: Carson Sandra A. , Smith Albert L. , Scoggan Janet L. , Buster John E.
Published: March 2007

Uterine lavage affords the potential for non‐invasive human blastocyst recovery, with obvious potential for preimplantation genetic diagnosis. In an effort to duplicate in women the multiple blastocyst recovery per cycle that can be achieved in several other species, we initiated a programme in which fertile women underwent superovulation, followed by lavage and embryo collection.

We superovulated 15 fertile women, aged 21–40, in 29 cycles using one of four regimens. Insemination was by either intercourse or artificial intracervical donor insemination with cryopreserved sperm from men of proven fertility. In 28 of 29 cycles, the uterus was lavaged daily for 1, 2, or 3 days between 5 and 10 days after human chorionic gonadotropin (hCG) administration or luteinizing hormone (LH) surge. Almost total fluid volume was recovered in every lavage. There were no retained pregnancies and no complications. Surprisingly, only two morulae, one blastocyst, and four unfertilized ova were recovered. Thus, alterations in ovulation induction, insemination timing, or lavage techniques must be contemplated in order to increase the blastocyst yield and thus fulfil the potential of uterine lavage for preimplantation diagnosis.
Possible effect of gestational age on the detection of fetal nucleated erythrocytes in maternal blood
Authors: Bianchi Diana W. , Stewart Jane E. , Garber Mary Frances , Lucotte Gérard , Flint Alan F.
Published: March 2007

Maternal venous blood samples, obtained from six pregnant women, were used as a source of fetal nucleated erythrocytes (NRBC). Fetal cell enrichment was potentiated by flow sorting with the monoclonal antibodies Tf R, Leu‐4, and Leu‐M3. Single copy Y chromosomal DNA sequences were detected in samples obtained from two women at 11 and 12 weeks' gestation. Y DNA sequences were absent in a subsequent sample from one of these women at 19 weeks and in two other women at 16 and 20 weeks. All four women delivered males. Y DNA sequences were not detected in two women who delivered females. By combining these results with prior data on the detection of Y chromosomal DNA sequences in maternal blood from male‐bearing pregnancies, a relationship between gestational age and feta‐maternal transfer of NRBC is suggested.