bluuebunny/crossref_metadata_2025 huggingface dataset:
Second‐trimester diurnal variation of maternal serum alpha‐fetoprotein, human chorionic gonadotropin, and unconjugated oestriol: Is it present and does it affect the prediction of a patient's risk for fetal down syndrome?
Authors: Rose Nancy C. , Canick Jacob A. , Knight George J. , Pulkkinen Andrea , Tumber M. B. , Mennuti Michael T. , Palomaki Glenn E.
Published: March 2007

Both a cross‐sectional and a longitudinal study were performed to investigate whether or not the collection time should be taken into consideration when generating a patient's risk for fetal Down syndrome with multiple marker screening. Diurnal variations of third‐trimester alpha‐fetoprotein (AFP) levels and first‐trimester human chorionic gonadotropin (hCG) levels have been previously reported. In addition, large episodic fluctuations of conjugated and unconjugated oestriol (uE3) as well as a diurnal variation have also been reported in the third trimester. If the levels of these analytes routinely fluctuate during the day, they could affect a patient's risk calculation for fetal Down syndrome. The longitudinal study evaluated ten non‐diabetic women who underwent sequential sampling for AFP, hCG, and uE3. The cross‐sectional study evaluated 1953 patients for these three markers whose time of sampling was recorded between 8·00 a.m. and 5·59 p.m. Using either study design, no significant effect was seen in the median MOM levels of the screening analytes as a function of the time of day.
Urinary β‐core human chorionic gonadotrophin: A new approach to Down's syndrome screening
Authors: Cuckle H. S. , Iles R. K. , Chard T.
Published: March 2007

Human chorionic gonadotrophin (hCG) is the most discriminatory maternal serum marker of Down's syndrome. We have carried out a study to establish whether urinary β‐core‐hCG, a major metabolic product of hCG, might be an even better marker. Urine samples were available from seven singleton pregnancies with Down's syndrome, and one each of Edwards' syndrome, triploidy, and twins discordant for Down's syndrome. β‐Core‐hCG levels were corrected for creatinine and expressed as multiples of the normal gestation‐specific median (MOM) level derived from 67 singleton controls. There was a highly statistically significant elevation in level among the singleton Down's syndrome cases (P<0·0005; Wilcoxon rank sum test). All had levels exceeding 2 MOM with a median of 6·11 MOM (95 per cent confidence interval 3·7–10·0). The levels were extremely low in Edwards' syndrome (0·08 MOM) and triploidy (0·02 MOM), but the twin pregnancy discordant for Down's syndrome did not have a raised β‐core‐hCG level (0·64 MOM). The findings are sufficiently encouraging to investigate the possibility of urinalysis as a routine modality in the prenatal screening for Down's syndrome and other common serious aneuploidies.
Prenatal diagnosis by minisatellite analysis in italian families with phenylketonuria
Authors: Romano Valentino , Dianzani Irma , Ponzone Alberto , Zammarchi Enrico , Eisensmith Randi , Ceratto Nadia , Bosco Paolo , Indelicato Anna
Published: March 2007

A polymorphic short tandem repeat (STR) in intron 3 (Goltsov et al., 1993) and a variable number of tandem repeats (Hind III‐VNTR) flanked by two constant Hind III sites (Goltsov et al., 1992) have been recently identified in the human phenylalanine hydroxylase (PAH) gene. These polymorphisms are easily detected by the polymerase chain reaction (PCR) and gel electrophoresis. We report on the use of these two novel polymorphisms in three Italian families with pregnancies at risk for classical phenylketonuria (PKU). A carrier status for PKU was ascertained in two fetuses; the third family refused prenatal diagnosis, although informativeness was shown to be complete.
Hyperechoic fetal bowel: The perinatal consequences
Authors: Bahado‐Singh R. , Morotti R. , Copel I. A. , Mahoney M. J.
Published: March 2007

A number of publications have reported an association between the finding of hyperechoic fetal bowel on prenatal sonogram and disorders such as aneuploidy and cystic fibrosis. To define more precisely the significance of this finding, we systematically reviewed the published material on the subject. Based on a total of 357 reported cases, we documented a high prevalence of cystic fibrosis (25·6 per cent) and chromosome abnormality (12·4 per cent) associated with increased bowel echogenicity in the fetus. High rates of intrauterine growth retardation (14·9 per cent), fetal demise (9·0 per cent), and prematurity (15·3 per cent) were also found. The data were obtained from a population at high a priori risk for aneuploidy and included fetuses at 1 in 4 risk for cystic fibrosis reported in two studies. This increased the bias towards an adverse outcome. The rate of complications when a hyperechoic abdomen is noted in a low‐risk fetal population has so far not been delineated. Although the high frequency of complications found is of concern and warrants investigation, extrapolation of these risk figures to a fetal population at low a priori risk may not be appropriate.
Prenatal diagnosis of the Klippel‐Trenaunay‐Weber syndrome
Authors: Jorgenson Ronald J. , Darby Byron , Patterson Robert , Trimmer Kenneth J.
Published: March 2007

The Klippel‐Trenaunay‐Weber syndrome is a complex developmental disorder of the vascular and skeletal systems. While many features of the syndrome are congenital, it has not been diagnosed often before birth. This paper describes a case of Klippel‐Trenaunay‐Weber syndrome diagnosed at 19 weeks' gestation on the basis of sonographic findings and family history. The clinical variability of the syndrome is emphasized and the importance of family history in differential diagnosis is stressed.
Intrauterine intervention in a case of recurrent meconium peritonitis
Authors: Shyu Ming‐Kwang , Chen Chin‐Der , Hsieh Fon‐Jou , Yau Kuo‐Inn Tsou , Lin Ghi‐Jen , Lee Ming‐Liang
Published: March 2007

We present a case of recurrent meconium peritonitis detected in the second trimester and treated by intrauterine intervention. Antenatal ultrasound findings included fetal ascites and intra‐abdominal calcification. Aspiration of fetal ascites under ultrasound guidance and determination of the bilirubin concentration established the diagnosis of meconium peritonitis. Paracentesis was repeated to remove irritating intestinal contents and to decrease pressure on the fetal thorax. Although the exact cause of the meconium peritonitis remains unknown, the recurrence of the condition suggests a genetic basis. A possibility of cystic fibrosis was not considered because the clinical picture did not suggest it. Intrauterine intervention helped to establish the diagnosis of meconium peritonitis and may have contributed to the good outcome.
Prenatal diagnosis of bartter syndrome
Authors: Shalev H. , Ohaly M. , Meizner I. , Carmi R.
Published: March 2007

Bartter syndrome, an autosomal recessive disorder of hyperaldosteronism and increased plasma renin, was suspected in an at‐risk pregnancy due to the early occurrence of polyhydramnios. Further establishment of the diagnosis was accomplished by demonstrating increased levels of aldosterone in amniotic fluid and fetal cord blood. Electrolyte levels did not differ significantly from reported controls. It is thus suggested that polyhydramnios is the result of increased fetal urine output in Bartter syndrome and that amniotic fluid aldosterone is a reliable marker for the prenatal diagnosis of this condition.
Improvement of prenatal diagnosis of wilson disease using microsatellite markers
Authors: Loudianos G. , Figus A. L. , Loi A. , Angius A. , Dessì V. , Deiana M. , De Virgiliis S. , Monni G. , Cao A. , Pirastu M.
Published: March 2007

This paper describes a case of prenatal diagnosis for Wilson disease (WD) carried out in an at‐risk couple of Sardinian descent, following non‐directive genetic counselling. Diagnosis was obtained by using eight microsatellites located within or flanking the WD locus, six of which were 100 per cent and two 50 per cent informative. The use of several markers may limit the occurrence of misdiagnosis resulting from recombination or instability of repeats.
Successful outcome of pregnancy after treatment of maternal anti‐ro (SSA) antibodies with immunosuppressive therapy and plasmapheresis
Authors: Van Der Leij J. N. , Visser G. H. A. , Bink‐Boelkens M. Th. E. , Meilof J. F. , Kallenberg C. G. M.
Published: March 2007

In this short communication we describe a patient with anti‐SSA and anti‐SSB antibodies whose first child died of congenital complete heart block (CCHB). During her second pregnancy she was treated with prednisolone, azathioprine, and plasmapheresis, and levels of anti‐SSA and anti‐SSB antibodies fell significantly. The pregnancy evolved uneventfully and resulted in the birth of an unaffected male infant. This is the fourth reported case of a successful outcome of pregnancy after treatment with immunosuppressive drugs in a woman with a significant risk of recurrence of CCHB.
Exclusion of chromosomal mosaicism in amniotic fluid cultures: Determination of number of colonies needed for accurate analysis
Authors: Featherstone Terence , Cheung Sau W. , Spitznagel Edward , Peakman David
Published: March 2007

Most laboratories use the in situ or flask culture method and a two‐stage approach to mosaicism detection. Determination of the optimum number of metaphases to be counted depends largely on whether or not the colonies that grow from the cells in the amniotic fluid can be considered independent. Previous statistical analysis of data from mixed male and female amniocyte cultures indicated that for mosaicism detection these colonies can be considered independent (Cheung et al., 1990). This analysis was repeated with a set of mosaic cases from two independent prenatal diagnosis programmes. The same degree of colony independence was found with this set of data. This result was used to calculate the level of mosaicism that is excluded at a particular confidence level when set numbers of colonies are analysed at each stage. The tables generated apply directly to the in situ method and with modification they can be used with the flask method. The conclusions are (1) analysis of cells from multiple colonies enhances the likelihood of excluding true mosaicism; (2) analysis of more than one metaphase per colony offers little advantage in excluding mosaicism; and (3) the two‐stage approach is the most efficient. These conclusions should be used together with the expected clinical outcome of the actual cytogenetic abnormality, as discussed by Hsu et al. (1992).
Swedish survey on extra structurally abnormal chromosomes in 39 105 consecutive prenatal diagnoses: Prevalence and characterization by fluorescence in situ hybridization
Authors: Blennow Elisabeth , Bui The‐Hung , Kristoffersson Ulf , Vujic Mihailo , Annerén Göran , Holmberg Eva , Nordenskjöld Magnus
Published: March 2007

During 7 years (1985–1992), 39 105 consecutive prenatal diagnoses (34 908 amniocenteses and 4197 chorionic villus samples) were made at the five largest clinical genetic laboratories in Sweden. Thirty‐one cases of extra structurally abnormal chromosomes (ESACs) were found, giving a total prevalence of 0·8 per 1000. Twelve ESACs were inherited, 14 were de novo and in five the parental origin was unknown. This gives an estimated prevalence of 0·3–0·4 per 1000 for familial and 0·4–0·5 per 1000 for de novo ESACs. Retrospectively, the ESACs were characterized by fluorescence in situ hybridization (FISH). In nine cases, no material was available for this analysis. In 21 of the remaining 22 cases, the chromosomal origin could be identified by FISH. Seventeen of these (81 per cent) were derived from the acrocentric chromosomes, of which 13 originated from chromosome 15 (62 per cent). The most common ESAC was the inv dup(15) (57 per cent). Two cases were derived from chromosome 22, one from chromosome 14, and one from either chromosome 13 or chromosome 21. The four remaining cases consisted to two i(18p)s and two small ring chromosomes derived from chromosomes 4 and 19, respectively.
Prenatal ultrasonic diagnosis of obstructive bowel disease: A retrospective analysis
Authors: Heydanus R. , Spaargaren M. C. , Wladimiroff J. W.
Published: March 2007

Fetal obstructive bowel disease was diagnosed in 29 patients at 22–37 weeks (median 32 weeks) of gestation, seven (24 per cent) of whom also displayed other anomalies. Polyhydramnios was present in 20/29 cases (69 per cent). An abnormal karyotype existed in 7/29 cases (24 per cent), of which six were diagnosed prenatally (trisomy 21, n = 5; 69, XXX, n = 1) and one postnatally (trisomy 21). There was always an association with the ultrasonic ‘double bubble’ sign. Obstructive bowel disease was confirmed postnatally in 20/29 (69 per cent) cases, i.e., oesophageal atresia (n = 1), duodenal obstruction (n = 12), and small bowel obstruction (n = 7). Other anomalies existed in 6/29 (21 per cent) cases, i.e., multicystic kidney (n = 1) and multiple congenital anomalies (n = 5). The perinatal mortality rate was 35 per cent (7/20).
Rapid prenatal diagnosis of aneuploidy from uncultured amniotic fluid cells using five‐colour fluorescence in situ hybridization
Authors: Divane A. , Carter N. P. , Spathas D. H. , Ferguson‐Smith M. A.
Published: March 2007

In this paper we describe the use of five‐colour fluorescence in situ hybridization for prenatal diagnosis of aneuploidy using uncultured amniotic fluid cells. The analysis is based on ratio mixing of dual‐labelled probes and digital imaging for the detection and visualization of five different probes specific for the five target chromosomes, 13, 18, 21, X, and Y. A retrospective blind analysis of 30 coded uncultured amniotic fluid samples correctly detected fetal sex and five trisomy 21 cases. Multicolour fluorescence in situ hybridization used in this way allows rapid and simultaneous detection of the most frequent aneuploidies.
Prenatal activity of a fetus with early‐onset, severe spinal muscular atrophy
Authors: Kirkinen P. , Ryynänen M. , Haring P. , Torkkeli H. , Pääkkönen L. , Martikainen A.
Published: March 2007

A case of early‐onset, severe spinal muscular atrophy is reported. Normal fetal breathing movement patterns and heart rate accelerations were observed in spite of the severe hypotonia evident at birth.
MSAFP levels and oesophageal atresia
Authors: Chodirker B. N. , Chudley A. E. , Macdonald K. M. , Harman C. R. , Evans J. A.
Published: March 2007

This study was undertaken to evaluate the relationship between maternal serum alpha‐fetoprotein (MSAFP) levels and oesophageal atresia (OA). OA occurred in 16 fetuses of mothers who had an MSAFP test in the study interval. The multiple of the median (MOM) value for MSAFP averaged 1·54 ± 0·65 (range 0·5–2·9 MOM), which was significantly higher than the value seen in controls. The median MOM was 1·35. Using a cut‐off of 2·5 MOM, the sensitivity of MSAFP for detecting OA was 19 per cent. Although OA should be considered in the differential diagnosis of an elevated MSAFP level, MSAFP cannot be considered an appropriate screening test for OA given the low sensitivity.
Prenatal diagnosis of renal agenesis in a twin gestation
Authors: Kuller Jeffrey A. , Coulson Carol C. , McCoy M. Cathleen , Altman Georgia C. , Thorp John M. , Katz Vern L.
Published: March 2007

Bilateral renal agenesis is a lethal congenital anomaly. It appears to be transmitted in a polygenic pattern. The prenatal ultrasound findings consist of severe oligohydramnios, absence of the fetal bladder, and failure to identify fetal kidneys. Twin gestations with renal agenesis have been described in the paediatric literature. We detail a case of a patient with two prior affected pregnancies with bilateral renal agenesis. Her latest pregnancy was diagnosed prenatally, with one fetus with bilateral and the other fetus with unilateral renal agenesis. The ultrasound findings should be differentiated from the stuck twin phenomenon.
Does chorionic villus sampling compromise fetal umbilical blood flow?
Authors: Hibbard Judith U. , Loy Gary L. , Hibbard Mark C.
Published: March 2007

A possible association of limb reduction defects with chorionic villus sampling (CVS) may be related to compromised umbilical blood flow from the trauma of the procedure. We hypothesized that because CVS may disrupt or compromise umbilical blood flow to the fetus, either by vasoconstriction, bradycardia, or emboli, we would detect these changes using Doppler velocimetry. A cohort of 21 consecutive consenting patients undergoing first‐trimester elective CVS for prenatal diagnosis were entered into a prospective longitudinal study. Colour flow Doppler velocimetry was performed on fetal umbilical arterial blood flow immediately before and after CVS to measure the pulsatility index, fetal heart rate, per cent flow time, and maximum flow velocity. Measurements were obtained from three consecutive cardiac cycles in three different umbilical segments and averaged. Potentially confounding variables also recorded included gestational age, method of CVS, number of passes, number of aspirations, placental location, tissue sample size, and operator. Umbilical velocimetry values before and after CVS were compared using the paired t‐test and showed no statistically significant differences. No differences were found when data were analysed by gestational age, sample size, method, number of aspirations, placental location, or operator. We were unable to detect any significant change in fetal umbilical arterial blood flow velocimetry or heart rate after performing CVS. Umbilical blood flow does not appear to be routinely compromised by CVS.
A simple, rapid, and highly informative PCR‐based procedure for prenatal diagnosis and carrier screening of phenylketonuria
Authors: Eisensmith Randy C. , Goltsov Alexei A. , Woo Savio L. C.
Published: March 2007

The polymorphic information content (PIC) and the degree of heterozygosity of several polymorphic systems within the phenylalanine hydroxylase (PAH) gene were determined in 85 European Caucasian and 19 Chinese phenylketonuria (PKU) kindreds. The first system examined, a short tandem repeat (STR), had a PIC of 80 and 73 per cent in these Caucasian and Chinese samples, respectively. The degree of heterozygosity actually observed for this system was 81 and 64 per cent in the Caucasian and Chinese PKU families, respectively. Through the addition of a second polymorphism based on a variable number of tandem repeats (VNTR), the PIC was increased to 90 per cent in Caucasians, but only to 75 per cent in Chinese. The degree of heterozygosity observed for this combination was 94 per cent in European PKU families and 67 per cent in Chinese PKU families. The further addition of an Xmnl RFLP increased both the PIC and the level of heterozygosity in Caucasians to 95 per cent, but did not change either of these measures in Chinese. The combined use of these three polymorphisms significantly increases the informativity of prenatal diagnostic and carrier screening procedures in both Caucasian and Chinese PKU kindreds. Furthermore, since each of these polymorphisms can be studied by PCR‐based methods, these new tests can be performed more quickly and easily than previous Southern‐based procedures.
Fetal choroid plexus cysts and trisomy 18: Assessment of risk based on ultrasound findings and maternal age
Authors: Snijders Rosalinde J. M. , Shawa Luma , Nicolaides Kypros H.
Published: March 2007

This paper examines the association between fetal choroid plexus cysts (CPCs) and trisomy 18 and proposes a method by which risks can be derived taking into account both sonographic findings and maternal age. Data from our centre on the sonographic findings of 58 fetuses with trisomy 18 and 387 fetuses with CPCs as well as data from published series were used. It was calculated that the prevalence of CPCs in the general population is approximately 1 per cent and at mid‐gestation the incidence of CPCs in fetuses with trisomy 18 is approximately 50 per cent. In the 387 fetuses with CPCs, the incidence of trisomy 18 increased with maternal age and the likelihood ratio for trisomy 18 increased with the number of additional abnormalities, from 0·03 for those with isolated CPCs to 0·4 if there was one additional abnormality and 20·5 if there were two or more additional abnormalities. It was concluded that if the cysts are apparently isolated, the risk for trisomy 18 is only marginally increased and maternal age should be the main factor in deciding whether or not to offer fetal karyotyping. If one additional abnormality is found, the maternal age‐related risk is increased, so that even for a 20‐year‐old the risk for trisomy 18 is at least as high as the risk for trisomy 21 in a 35‐year‐old. In this respect, it may be considered desirable to offer such patients the option of karyotyping.
Flow cytometric method to measure urea‐resistant alkaline phosphatase from blood neutrophils for use in the prenatal screening of Down's syndrome
Authors: Agrawal Yash P. , Ylikangas Päivi , Parviainen Markku T. , Penttilä Ilkka M.
Published: March 2007

The histochemical measurement of urea‐resistant alkaline phosphatase from maternal blood neutrophils is known to have a high detection rate for the prenatal detection of Down's syndrome pregnancies. However, because the histochemical method is laborious and subjective to use, it has not gained widespread acceptance in prenatal screening programmes. We present a simple and objective method for the measurement of urea‐resistant alkaline phosphatase by flow cytometry. The method should allow the design of larger studies aimed at evaluating the role of neutrophil urea‐resistant alkaline phosphatase in the prenatal screening for Down's syndrome.
Chromosome preparations of both direct and long‐term cultures from the same fragment of chorionic villi
Authors: Dawson J. M. , Griffiths M. J.
Published: March 2007

A simplified method is described for processing both direct preparations and long‐term cultures from the same fragment of chorionic villi. Enzyme separation of the outer trophoblast layers (used for direct preparations) from the inner mesenchymal core (used to initiate long‐term cultures) facilitates the utilization of the same fragments for the two procedures, without jeopardizing the success of either method. This has proved useful in cases where the sample was so small that only one method of chromosome preparation may have been possible using other techniques.
Prenatal detection of congenital hypospadias in the wolf‐hirschhorn (4p —) syndrome
Authors: Viñals Fernando , Sepulveda Waldo , Selman Eliana
Published: March 2007

Hypospadias is one of the most prominent and characteristic midline defects in male infants with the Wolf‐Hirschhorn (4p —) syndrome. In this report we present a case in which hypospadias was identified prenatally at 29 weeks' gestation in association with intrauterine growth retardation. Cytogenetic evaluation after birth confirmed a 46, XY, del(4)(p14) karyotype. The prenatal identification of hypospadias in fetuses with intrauterine growth retardation and normal amniotic fluid should suggest a diagnosis of Wolf‐Hirschhorn syndrome.
Sonographic presentation of Hirschsprung's disease. A case of an entirely aganglionic colon and ileum
Authors: Eliyahu S. , Yanai N. , Blondheim O. , Reich D. , Siplovich L. , Shalev E.
Published: March 2007

Prenatal sonographic presentation of Hirschsprung's disease has been considered non‐specific and uncommon. This report presents a second‐trimester fetus with an aganglionic colon and ileum diagnosed by the sonographic presentation of dilated fetal bowel loops, increased abdominal circumference, and mild polyhydramnios. The prenatal sonographic diagnosis of Hirschsprung's disease helped to expedite early neonatal treatment.
Prenatal aneuploidy detection in interphase cells by fluorescence in situ hybridization (Fish)
Authors: Philip J. , Bryndorf T. , Christensen B.
Published: March 2007

FISH is a quick, inexpensive, accurate, sensitive and relatively specific method for aneuploidy detection in samples of uncultured chorionic villus cells and amniotic fluid cells. FISH allows detection of the autosomal trisomies 13, 18 and 21 and X and Y abnormalities and any other chromosome abnormality for which a specific probe is available. The detection rate of these abnormalities is high in informative samples which have a concordance of > 99.5% with cytogenetic results. A relatively high number of abnormal cases are found in uninformative samples. However, such samples should be regarded as samples to be investigated further. Clinical experience with the use of FISH for prenatal diagnosis is now beyond 10,000 cases; a number of clinical protocols and smaller trials have also been carried out, resulting in 90% of attempted analyses giving informative results with a high detection rate and extraordinarily low false‐positive and false‐negative rates Unsolved problems remain, such as occasional technical failures, admixtures of maternal blood and up to 20% uninformative scoring results, especially for abnormal specimens. FISH is at present used as an adjunct to classical cytogenetic analysis. However, this should not be interpreted as meaning that FISH could not be used as a methodology in its own right. If FISH were to be considered a Diagnostic test then this might be the case, due to the risk of false‐negative and false‐positive results and the fact that FISH does not allow a diagnosis of certain structural abnormalities. If, on the other hand, FISH is considered a screening test, which means that in all abnormal (or indeterminate) cases, classical cytogenetic analysis would follow the abnormal screening test, the accuracy which is potentially higher than for other screening methods, for example in cases of trisomy 21, justifies FISH as a prenatal screening test in its own right.
Preimplantation diagnosis
Authors: Delhanty J. D. A.
Published: March 2007

Research towards preimplantation diagnosis of genetic disease was initiated in the UK. in the mid 1980s with the aim of helping those couples who would prefer selection to occur at this stage rather than during pregnancy. Following in vitro fertilisation, (IVF), biopsy and removal of 1 or 2 of the totipotent cells from the cleavage stage 3 day old embryo provides the material for molecular genetic diagnosis without interfering with development. Earliest applications were in the avoidance of X‐linked disease by sexing embryos and selecting females for transfer to the mother. Initially, polymerase chain reaction (PCR) amplification of DNA from the biopsied blastomeres was performed using primers specific for sequences derived from the Y chromosome and this led to the birth of several normal girls. To reduce the risk of misdiagnosis due to amplification failure, PCR based methods for sexing the embryo now employ both X and Y specific sequences, but the preferred method is currently considered to be fluorescent in situ hybridisation (FISH) with fluorochrome labelled DNA probes to the embryonic nuclei that have been fixed and spread on slides. Dual FISH with probes from X and Y chromosomes allows unequivocal diagnosis of sex and determination of chromosome copy number, avoiding transfer of embryos with abnormal numbers of sex chromosomes, including those with only the maternal X that would be at 50% risk for the X‐linked disease. The application of FISH for preimplantation diagnosis has also led to the realisation that chromosomal mosaicism is common at the cleavage stage of development, a finding that has important implications for diagnosis of both dominant single gene disorders and trisomies, as well as for our understanding of early human development. Cloning and sequencing of the relevant genes has enabled the development of methods for the diagnosis of certain recessive single gene disorders in cleavage stage embryos. PCR based methods have to be developed for each condition, sometimes for each family if there is heterogeneity. Preimplantation diagnosis has been successful so far for cystic fibrosis, Tay Sachs disease, and Lesch‐Nyhan syndrome. Worldwide, 32 pregnancies have been established following all types of preimplantation diagnosis and with 29 babies born, there is no evidence for any adverse effect on development.
Carrier screening for cystic fibrosis
Authors: Brock D. J. H.
Published: March 2007

A number of different models of CF carrier screening have now been tested in pilot trials. Apart from opportunistic and cascade testing (which are strictly speaking not true forms of screening), the major programmes have been directed either to young adults in primary care or to pregnant women in antenatal clinics. Only in the latter form of screening has sufficient data been collected to allow conclusions to be reached on the optimum mode of delivery. It seems very probable that when CF carrier screening passes into routine service, it will be the antenatal couple model that is used.
Prenatal diagnosis in Canada — 1990: A review
Authors: Stranc L. C. , Evans J. A. , Hamerton J. L.
Published: March 2007

This paper presents the results of a detailed study of the genetic prenatal diagnostic services available in Canada in 1990. All 22 genetic centres offering prenatal diagnostic services as well as the 64 laboratories processing samples were surveyed. Data were collected from each to determine what testing was being done, how many women were being tested, for what conditions, and with what outcomes. Also, data on the 35 formal outreach sites were collected. The statistics presented are for the 1990 calendar year. This survey was conducted for the Canadian Royal Commission on New Reproductive Technologies.
Maternal urinary β‐core fragment of hCG/creatinine ratios and fetal chromosomal abnormalities in the second trimester of pregnancy
Authors: Hayashi Meicho , Kozu Hiromu
Published: March 2007

Our aim was to evaluate the potential value of the ratio of the maternal urinary beta‐core fragment of human chorionic gonadotropin (βC‐hCG) to creatinine (Cr) in discriminating between normal pregnancies and pregnancies associated with fetal chromosomal abnormalities. We hypothesized that pregnancies with fetal chromosomal abnormalities had abnormal quantities of βC‐hCG in the urine. The aims of the present study were to investigate retrospectively whether maternal urinary ratios of βC‐hCG/Cr are abnormal in women carrying fetuses with chromosome aberrations and to determine normative median values and a reference range for βC‐hCG/Cr between 14 and 19 weeks' gestation. Maternal urinary βC‐hCG and Cr concentrations were measured in 150 healthy women from 14 to 19 weeks and compared with ten cases of fetal chromosomal abnormalities matched for gestational age. The preliminary cut‐off points corresponded to 0·29 multiple of the normal median (MOM) and 2·83 MOM, which were equivalent to the tenth and 90th centiles of the normal range. Of ten cases of fetal chromosomal abnormalities, one out of one (100 per cent) case with trisomy 18 and three of four (75 per cent) cases of variant 9 chromosome had low βC‐hCG/Cr (≤0·29 MOM). One of five (20 per cent) cases with Down syndrome had elevated βC‐hCG/Cr (≤2·83 MOM). Urinary βC‐hCG/Cr ratios obtained in the second trimester may be useful for improved detection efficiency of Down syndrome, trisomy 18, and inversion of chromosome 9. Second‐trimester maternal urinary βC‐hCG/Cr should be investigated further as a potential marker for fetal chromosome anomalies.
Genetic amniocentesis in biamniotic twin pregnancies by a single transabdominal insertion of the needle
Authors: Buscaglia M. , Ghisoni L. , Bellotti M. , Marconi A. M. , Zamperini P. , Stripparo L. , Molinari A. , Grimoldi M. G. , Rossella F.
Published: March 2007

We present a technique to aspirate amniotic fluid from both sacs in biamniotic twin pregnancies using a single abdominal insertion with a spinal needle. It was successful in 48 out of 55 cases of biamniotic twin pregnancies referred to our perinatal unit between 1985 and 1994. The single insertion technique was used when the inter‐amniotic membrane was clearly evident and two separate free amniotic fluid pools could be reached by the operator with a single puncture. An adequate amount of amniotic fluid was sampled from both sacs to make a cytogenetic diagnosis in all cases. There were four fetuses with trisomy 21 in three twin pregnancies. In two cases, only one twin was affected whilst the co‐twin was normal, so that a selective feticide was performed. No miscarriages due to genetic amniocentesis were reported. After 1990, all genetic amniocenteses in biamniotic twin pregnancies (except for one case due to late booking) were performed between 14 and 15 weeks of gestation and with all cases except one, it was possible to sample both twins by a single puncture. We suggest that early amniocentesis (14–15 weeks) by a single abdominal puncture could be a reliable and safe alternative to first‐trimester chorionic villus sampling in twin pregnancies.
Prenatal ultrasound diagnosis of gastric outlet obstruction due to a pyloric web
Authors: Sharony Reuven , Sinow Robert , Asch Morris , Lachman Ralph
Published: March 2007

Gastrointestinal tract atresia has an incidence of 1 in 10 000 live‐births, while gastric outlet obstruction comprises only approximately 1 per cent of these malformations. A prenatally diagnosed case is described, followed by a discussion regarding the diagnosis and possible associated abnormalities.
Macroglossia: Prenatal ultrasonographic diagnosis and proposed management
Authors: Weissman Ariel , Mashiach Shlomo , Achiron Reuwen
Published: March 2007

A case in which macroglossia was the sole unusual prenatal sonographic finding in a fetus affected with trisomy 21 is presented. The differential diagnosis of fetal macroglossia is given, emphasizing its strong relationship to fetal aneuploidy, together with the principles for evaluation and management.
Exencephaly in autosomal dominant brachydactyly syndrome
Authors: Stagiannis Konstantinos D. , Sepulveda Waldo , Fusi Luca , Garrett Christine , Fisk Nicholas M.
Published: March 2007

Exencephaly was diagnosed at 17 weeks in a 27‐year‐old primigravida with abnormalities of the hands and a family history suggestive of autosomal dominant brachydactyly and clinodactyly. In this family there was also a history of ‘anencephaly’. To our knowledge, this is the first report on the association of exencephaly and autosomal dominant brachydactyly. As the relationship between hand and cranial anomalies is well established, we suggest that this association in our case could be due to a defect in the same gene.
Development of non‐invasive fetal DNA diagnosis from maternal blood
Authors: Takabayashi Haruo , Kuwabara Soryu , Ukita Toshihiko , Ikawa Kazumi , Yamafuji Kaoru , Igaras Tatsuhiro
Published: March 2007

Several attempts have been made to detect and retrieve fetal nucleated cells including nucleated erythrocytes (NRBCs), leukocytes, and trophoblasts in maternal blood. We have recently developed a new method for non‐invasive fetal DNA diagnosis from maternal blood. Peripheral blood granulocytes including NRBCs were isolated by a discontinuous density gradient method using Percoll (Pharmasia). NRBCs were found and retrieved at a single cell level using a micromanipulator under a microscope. To determine whether the origin of the NRBCs was maternal or fetal, the NRBCs were analysed by polymerase chain reaction (PCR) amplification to determine the presence of a Y‐chromosome‐specific repeat sequence in mothers carrying male fetuses. We were successful in predicting fetal sex accurately in 10 out of 11 samples taken from maternal blood. This new technique opens up fetal DNA diagnosis from maternal blood during the first trimester of pregnancy to the whole population because there is no risk to the fetus or the mother.
Mid‐trimester fetal sex determination from maternal peripheral blood by fluorescence in situ hybridization without enrichment of fetal cells
Authors: Hamada Hiromi , Arinami Tadao , Sohda Satoshi , Hamaguchi Hideo , Kubo Takeshi
Published: March 2007

To determine the fetal sex on 30 women who were 16–20 weeks pregnant, about 100 000 maternal blood nucleated cells were analysed by means of fluorescence in situ hybridization (FISH) with a Y‐chromosome‐specific DNA probe. Cells with the hybridization signal were detected in 12 of the 30 women. All the 12 mothers gave birth to a male child. Of the other 18 women who had no Y‐positive cells in the peripheral blood, 14 gave birth to a female child and four gave birth to a male child. These false‐negative results probably occurred because the number of cells examined was inadequate. The data obtained in this study suggest that fetal sex determination using maternal peripheral blood with FISH is possible and that this diagnostic method will be clinically useful when more cells are analysed.
An audit of trisomy 16 in man
Authors: Wolstenholme J.
Published: March 2007

Sufficient information is now available from the literature to produce an audit of trisomy 16, in a theoretical cohort of 100 000 recognized pregnancies, from gametogenesis to term and onwards. Recent reports of premature separation of chromosome 16 bivalents during maternal meiosis I provide a novel mechanism for generation of this aneuploidy. Most, if not all, errors resulting in recognized mosaic and non‐mosaic trisomy 16 pregnancies investigated using polymorphic DNA markers appear to originate at that stage. The incidence of this maternally derived trisomy 16 in the late first trimester is equivalent to 1500 cases in 100 000 recognized pregnancies, a figure which now corresponds very closely to the reinterpreted oogenesis data. Most trisomy 16 pregnancies are lost around 12 weeks' gestation, but of the order of 10 per cent (120–150 in this audit) undergo reduction to disomy, with 30 of these excluding aneuploidy from the fetal cell lineage (trisomic zygote rescue) and continuing into the second trimester. Maternal uniparental disomy (UPD) in one‐third of this latter group is associated with loss later in pregnancy or severe intrauterine growth retardation, but can be compatible with a viable pregnancy. Adverse pregnancy outcomes are not restricted to those with UPD. Analysis of reports of confined placental mosaicism for chromosome 16 without associated UPD indicates that the presence of high levels of trisomic cells in the placenta alone consistently produces a more variable inhibition of fetal growth, which may also, in cases, be associated with late pregnancy loss.
Prenatal diagnosis of neurofibromatosis type 1: From flanking rflps to intragenic microsatellite markers
Authors: Lazaro Conxi , Gaona Antonia , Ravella Anna , Volpini Victor , Estivill Xavier
Published: March 2007

Even though the neurofibromatosis type 1 (NF1) gene was cloned more than 3 years ago, the process of identifying mutations has not been fruitful, and genetic counselling is mainly based on the use of linked markers. Since 1990, we have analysed 130 NF1 families and have performed six prenatal diagnoses. In each case, genetic counselling has relied on linked markers and informativity was achieved in all of them. The use of intragenic microsatellite polymorphisms (IVS27AAAT2.1, IVS27AC28.4, IVS27AC33.1, and IVS38GT53.0) has increased the informativeness in our series of NF1 families to an average of 90 per cent, providing accurate diagnosis and confirmation of the disease status.
Rapid fetal karyotype from cystic hygroma and pleural effusions
Authors: Costa D. , Borrell A. , Margarit E. , Carrió A. , Soler A. , Balmes I. , Estivill X. , Fortuny A.
Published: March 2007

Fluid from pleural effusion (n=2) and cystic hygroma (n=7) was obtained from eight fetuses, between 13 and 32 weeks of pregnancy at the time when a conventional prenatal diagnosis procedure was carried out. As these fluids contain lymphocytes, they were processed like peripheral blood. A karyotype was obtained in 4 days in both cases of pleural effusion and in four out of seven samples of cystic hygroma. An abnormal karyotype was detected in three of the four samples of cystic hygroma: two trisomies 21 and a monosomy X. Different parameters were evaluated in order to predict the feasibility of obtaining a cytogenetic diagnosis. Our data showed that if the amount of fluid obtained was ⩾4 ml and the initial lymphocyte count (ILC) was >0.2 × 106 cells/ml, a cytogenetic diagnosis was possible from an initial concentration of cultured lymphocytes )ICCL) of >0.06 × 106 cells/ml.
Oligohydramnios with amnio‐chorionic separation at 15–16 weeks' gestation
Authors: Bronshtein Moshe , Zimmer Etan Z.
Published: March 2007

Nine patients with oligohydramnios and amnio‐chorionic separation were identified out of 7000 women who underwent a vaginal ultrasound examination at 15–16 weeks' gestation. Oligohydramnios was defined as a reduced amount of amniotic fluid, a distance of more than 1 cm between the chorion and amnion, and a good turgor of the amnion without floating membranes or intrauterine sheets. Fetal malformations were observed in all nine cases. In four of six fetuses where chromosomal analysis was available, an abnormal karyotype was found. It is concluded that oligohydramnios in the early second trimester is associated with fetal abnormality.
Early second‐trimester diagnosis of sirenomelia
Authors: Van Zalen‐Sprock M. M. , Van Vugt J. M. G. , Van Der Harten J. J. , Van Geijn H. P.
Published: March 2007

Two cases of sirenomelia are described, detected in the 14th and 16th weeks of gestation by transvaginal ultrasonography. A hypothesis for the aetiology of sirenomelia and its associated anomalies is discussed.
Echocardiographic diagnosis of fetal marfan syndrome at 34 weeks' gestation
Authors: Lopes Lilian M. , Cha Sang Choon , De Moraes Edécio Armbruster , Zugaib Marcelo
Published: March 2007

Fetal echocardiography was performed during the third trimester in a normal primigravida. The fetal heart was severely affected with the typical cardiac manifestations of Marfan syndrome. The medical history of the father was investigated and a mild form of the syndrome was diagnosed. The neonate died at 2 months of age of congestive heart failure.
Fetal cholecystomegaly: A prenatal marker of aneuploidy
Authors: Sepulveda Waldo , Nicolaidis Peter , Hollingsworth Jean , Fisk Nicholas M.
Published: March 2007

The fetal gall bladder can now be easily identified during the second and third trimesters using high‐resolution ultrasonography. In this report we present eight fetuses with an enlarged gall bladder detected on prenatal ultrasonography at a mean gestational age of 24.6 weeks (range 19–31 weeks). Additional ultrasonographic findings were present in four cases: fetal anomalies and intrauterine growth retardation in three and polyhydramnios in one. Of those cases associated with fetal anomalies, one woman underwent amniocentesis at 21 weeks revealing trisomy 18. The other two declined prenatal karyotyping; neonatal karyotyping revealed trisomy 13 in one and trisomy 18 in the other. Although an enlarged fetal gall bladder can be a normal variant in the second and third trimesters, the prenatal detection of cholecystomegaly should prompt a search for associated anomalies and other markers of aneuploidy. If found, prenatal karyotyping should be considered.
An increased incidence of haemangiomas in infants born following chorionic villus sampling (CVS)
Authors: Burton Barbara K. , Schulz Charlene J. , Angle Brad , Burd Laurence I.
Published: March 2007

The incidence of haemangiomas was ascertained by questionnaire in infants born to 578 consecutive CVS patients and 445 consecutive mid‐trimester amniocentesis patients seen at a single institution between 1 January 1989 and 31 May 1991. The incidence of 7·4 per cent reported in the amniocentesis group was comparable to previous estimates of the incidence of haemangiomas in the general population. In contrast, a 21·1 per cent incidence, three‐fold higher than that observed in the amniocentesis group, was observed among CVS‐exposed infants (P<0·001). This increased incidence was largely confined to patients undergoing a transcervical procedure. No correlation was observed between the incidence of haemangiomas and gestational age at sampling, sample size, number of sampling attempts, or a history of bleeding following the procedure.
Prenatal sonographic signs of possible fetal genital anomalies
Authors: Bronshtein Moshe , Riechler Avihai , Zimmer Etan Z.
Published: March 2007

The sonographic markers of female and male external genitalia have been documented in early and late gestation. The aim of the present study was to report our experience of possible sonographic markers of fetal genital anomalies. Sonography was performed with a vaginal probe in early gestation and an abdominal sector scanner in advanced gestation. The following genital anomalies were observed: hypospadias, epispadias, ambiguous genitalia, and testicular feminization or Smith‐Lemli‐Opitz syndrome. It is therefore concluded that prenatal diagnosis of some genital anomalies is now possible.
Genetic amniocentesis following multifetal pregnancy reduction to twins: Assessing the risk
Authors: Tabsh Khalil M. A. , Theroux Nancy L.
Published: March 2007

Fifty‐three patients who elected to reduce their pregnancies to a twin gestation in our centre are known to have subsequently undergone genetic amniocentesis. Five of these patients lost their entire pregnancy following the genetic amniocentesis procedure. This is equivalent to a 9·4 per cent pregnancy loss rate for reduced twin gestations in comparison with an expected loss rate of 2 per cent for non‐reduced twin gestations.
Serum lipid, apolipoprotein and lipoparticle levels in the human fetus
Authors: Legras B. , Durou M. R. , Ruelland A. , Gallou G. , Jezequel C. , Cloarec L.
Published: March 2007

Blood collected from 62 fetuses aged 20–38 weeks of gestation was studied. The values of ten lipid parameters were determined: cholesterol (TC), triglycerides (TGs), apolipoprotein Al (apo A1), apolipoprotein B (apo B), apolipoprotein E (apo E), total apolipoprotein CIII (apo CIII), apolipoprotein CIII present in particles containing apo B (apo CIII LpB) or not (apo CIII Lp non‐B), lipoparticles A1 (LpA1), and lipoprotein a (Lp(a)). The results show that, except for apo E, all the studied parameters were present in lower concentrations than in adults and newborns, and that Lp(a) is not detectable at that stage in life.
Prenatal sonographic diagnosis of intracranial haemorrhage: Report of a case with a sinusoidal fetal heart rate tracing, and review of the literature
Authors: Catanzarite Val A. , Schrimmer David B. , Maida Cynthia , Mendoza Art
Published: March 2007

The sinusoidal fetal heart rate pattern has been described in association with severe fetal anaemia, with fetal hypoxaemia, and with the administration of parenteral narcotics. Here, we report a case of decreased fetal movement in which a sinusoidal tracing was recorded. The sonographic diagnosis of a massive fetal intracranial haemorrhage was made. A non‐interventive approach was taken and the fetus died soon after in utero. We review 28 previous cases in which the prenatal sonographic diagnosis of fetal intracranial haemorrhage was made, including the underlying maternal and fetal factors and neonatal outcomes. We propose that the sinusoidal tracing in this case was due to the intracranial bleed and suggest that fetal intracranial haemorrhage be considered in the sonographic evaluation of the fetus with a sinusoidal pattern.