bluuebunny/crossref_metadata_2025 huggingface dataset:
Marker chromosomes in A series of 10000 prenatal diagnoses. Cytogenetic and follow‐up studies
Authors: Sachs E. S. , Van Hemel J. O. , Den Hollander J. C. , Jahoda M. G. J.
Published: March 2007

In a series of 10 000 prenatal diagnoses 15 marker chromosomes were detected in our centre. Six of these were familial whilst nine had originated de novo. They were analysed with various staining methods. DA‐DAPI staining was positive in nine out of 12 pregnancies. Six pregnancies were continued. Five normal children were born, one ended in intrauterine fetal death of a normal fetus at 37 weeks. Nine pregnancies were terminated, showing six normal fetuses, one familial cat‐eye syndrome, one fetus with Down syndrome caused by additional trisomy 21 and one fetus with cystic kidneys resp. It is concluded that it seems safe to continue the pregnancy in cases of a familial marker, identical to that of one parent, whilst a de novo DA‐DAPI positive marker seems to present a low risk for fetal anomalies.
Lack of sampling site variation in chorion villus biopsy as assessed by DNA, enzymatic, morphological and cytogenetical analyses
Authors: Upadhyaya Meena , Jasani Bharat , Little Elizabeth , Harper Peter S. , Rees Derek , Roberts Adrian
Published: March 2007

A study of villus samples from eight random sites on five electively aborted chorion sacs was performed to determine any significant differences in yield, quality and composition of DNA, iduronate sulphate sulphatase activity and karyoptype status. The villi were also examined for their histological characteristics (e.g. stem, intermediate or terminal villi) and for HCG and BGP immuno‐reactivities. The overall findings indicated no significant site to site variations in any of the parameters studied. It is therefore proposed that any villus should be equally suitable for prenatal diagnosis.
Chorionic villus sampling: An analysis of the obstetric experience of 1000 cases
Authors: Brambati Bruno , Oldrini Angelo , Ferrazzi Enrico , Lanzani Alessandro
Published: March 2007

Chorionic villus sampling was performed between 7 and 12 weeks gestation in 1000 patients, 935 of whom intended to continue after fetal diagnosis. Transcervical and Transabdominal aspiration techniques were used providing a sampling success rate of 99 per cent. Anatomical and clinical contraindications to transcervical aspiration were pointed out, and the complementary role of the transabdominal approach evaluated.

In the 615 concluded pregnancies an overall abortion rate of 4.1 per cent was observed. A significant association between fetal loss and number of catheter insertions was demonstrated. Bacterial inoculation by catheter insertion and colonization of uterine cavity was suspected as the cause of chorionamnionitis diagnosed in two cases (0.2 per cent) after CVS. Bleeding was the most frequent early complication (12.0 per cent) following chorionic aspiration, but was not significantly related to pregnancy wastage. Late complications, i.e. premature rupture of membranes (0.8 per cent), preterm delivery (6.3 per cent), perinatal losses (1.2 per cent), placental disorders (1.6 per cent), and congenital defects (2.6 per cent) did not exceed the expected values. Normal intrauterine growth patterns were ultrasonically estimated by cross‐sectional and longitudinal studies, while the weight at birth was normally distributed in the range of the general population.
Prenatal diagnosis of β thalassaemia by reverse phase HPLC
Authors: Rouyer‐Fessard Ph. , Beuzard Y. , Vidaud M. , John P. , Mibashan R. S.
Published: March 2007

Reverse phase HPLC of radioactive globin chains has been compared to classical carboxy methyl cellulose chromatography for the prenatal diagnosis of β thalassaemia. The two methods correlated highly (r = 0.97 p < 0.0005) and provided an identical diagnosis for 40 fetal blood samples of fetuses homozygous or heterozygous for β thalassaemia. The HPLC procedure was much faster and required fewer biochemical steps (no globin preparation). It was at least as accurate and more sensitive than the classical chromatography. A single column can be used for 150 analyses and is always ready to be used. Last but not least it is much less expensive than CMC chromatography.
Prenatal diagnosis of the fragile X syndrome using fetal blood and amniotic fluid
Authors: Webb T. P. , Rodeck C. H. , Nicolaides K. H. , Gosden C. M.
Published: March 2007

Nineteen pregnancies at risk for the Martin–Bell syndrome have been monitored during the second trimester for the presence of the fragile Xq27. Of the 19 potential carrier mothers, 14 showed the presence of the fragile X in their lymphocytes at a level of 4 per cent or above. As one was a twin pregnancy, fetal blood was obtained at fetoscopy from 20 fetuses and amniotic fluid obtained simultaneously from 19 of them. Of the 20 fetuses, 18 were males (including both of the twins) and two were females. Of these 18 males, seven were found to carry the fragile Xq27 in lymphocytes and subsequently six of the seven were terminated. The diagnosis was confirmed in five of the six terminated fetuses (the sixth case was a patient whose pregnancy was terminated abroad) and also in a full‐term male baby. Five of the seven males without the marker X who came to term had their karyotypes confirmed post natally. Of the two female fetuses one was found to be a carrier of the fragile X and the other was not. Both babies had full‐term deliveries and both had their karyotypes confirmed post natally. In some cases the diagnosis made in fetal lymphocytes was confirmed later in amniocytes.
Parental decisions regarding termination of pregnancy following prenatal detection of sex chromosome abnormality
Authors: Holmes‐Siedle M. , Ryynanen M. , Lindenbaum R. H.
Published: March 2007

In the period of a retrospective study (1979–1984 inclusive) forty cases of sex chromosome aneuploidy were identified at amniocentesis in Oxford, England and in Kuopio, Finland; 25 of these pregnancies were subsequently terminated. A decision to continue was made more often for XYY and XXX karyotypes, by older mothers and older fathers, by couples with more previous children, and by couples living in England. A decision to terminate was made more often for XXY and non‐mosaic 45,X karyotypes, by younger mothers and younger fathers, by couples with few previous children, in all cases with abnormal ultrasound findings, when post‐amniocentesis counselling was given by an obstetrician, and by couples living in Finland. Previous miscarriages, or terminations of pregnancy, previous problems with infertility, marital status, or the type of counselling given before amniocentesis, appeared not to influence a couples' decision. Religious and ethical ideas were not studied systematically at the time and cannot be reported on.
Prenatal diagnosis of chronic granulomatous disease (CGD) in four high risk male fetuses
Authors: Huu Trung Pham , Dumez Yves , Marquetty Claude , Durandy Anne , Boue Joëlle , Hakim Jacques
Published: March 2007

Prenatal diagnosis of chronic granulomatous disease (CGD) was performed in four male high risk fetuses. The male sex was previously determined by an amniotic cell karyotype. Three kinds of test were performed on fetal blood obtained by umbilical venous puncture under fetoscopy at the 20th gestational week: nitroblue tetrazolium reduction (NBT) cytochemical test with phorbol myristate acetate (PMA) as activator; luminol enhanced chemiluminescence with activation by serum opsonized zymosan (STZ) or PMA; superoxide anion (0) production by measurement of the superoxide dismutase inhibitable reduction of cytochrome c with PMA as activator.

Results were compared to those obtained in six fetuses investigated for other inherited diseases. In one case, absence of granulocyte defects was confirmed at birth. In three other cases, the tests showed deficient metabolic oxidative granulocytes. The pregnancy was terminated and the CGD diagnosis was confirmed on the products of abortion. The use of three different techniques performed on whole blood for CGD prenatal diagnosis is recommended instead of a single isolated test to ensure a higher confidence in the diagnosis.
Revised estimates and projections of down syndrome births in the United States, and the effects of prenatal diagnosis utilization, 1970–2002
Authors: Goodwin Beth A. , Huether Carl A.
Published: March 2007

The objectives of this study were to: (1) calculate revised estimates and projections of United States annual Down syndrome (DS) births for 1970–2002, and (2) estimate the effects of amniocentesis on these baseline DS birth projections. Three models of amniocentesis utilization among 30–34 and ≧ 35‐year‐old women were considered. The recently revised Census Bureau birth projections, and new single year maternal age DS risk rates estimated from a 1970–1983 Ohio data set, were used. Data from all three Census Bureau projection series were analysed; series II was considered in depth since it is consistent with recent fertility levels.

Assuming no use of amniocentesis, total estimated DS births dropped from about 4770 in 1970 to 4120 in 1980 (a 14 per cent decline), but are projected to a plateau of about 5100 by the year 1990 (a 24 per cent increase). DS births to women ≧ 35 would increase dramatically from about 1050 in 1980 to 1900 in 2000 (an 81 per cent increase). Assuming 1983 Ohio prenatal diagnosis ratios for women aged 30–34 (1.7 per cent) and ≧ 35 (23.4 per cent) are used nationally, an annual reduction of about 7 per cent of DS births in 1986 and 9 per cent in 2002 would result. Fifty and 70 per cent utilization among women 30–34 and 235, respectively, would reduce DS births by about 33 per cent in 1986 and 38 per cent in 2002. Therefore, if the projected increase in DS births is to be averted, utilization of prenatal diagnosis by ≧ 30‐year‐old women must increase substantially.
Prenatal diagnosis of Fabry's disease by direct analysis of chorionic villi
Authors: Kleijer W. J. , Iiussaarts‐Odijk L. M. , Sachs E. S. , Jahoda M. G. J. , Niermeijer M. F.
Published: March 2007

Six pregnancies of three carriers for X‐linked Fabry's disease, were monitored by chromosome and enzyme analysis. Two affected male fetuses were detected by the demonstration of α‐galactosidase deficiency in amniotic fluid cells and chorionic villi respectively. The use of chorionic villi enabled a diagnosis within a few hours after sampling in the ninth week of pregnancy whereas the use of amniotic fluid cells in the earlier case required two weeks of culturing after amniocentesis in the 16th week.

Four female fetuses were found; heterozygosity was demonstrated in one by analysis of clones in the primary amniotic fluid cell culture.
First trimester studies of A fetus at risk for triose phosphate isomerase deficiency
Authors: Dallapiccola B. , Novelli G. , Cuoco C. , Porro E.
Published: March 2007

A first trimester prenatal diagnosis was offered to a mother whose child had died of haemolytic anaemia and multisystem disease caused by TPI deficiency. The deficiency state was characterized by greatly reduced TPI activity in both erythrocytes and peripheral lymphocytes. Specific activity of TPI in trophoblast homogenates from the index fetus was about 30 per cent less than in the controls, but the heat stability test showed overlap. These data were confirmed in uncultured and cultured amniotic cells, where glycolytic intermediate concentrations DHAP, GAP and FDP fell in the range of controls. These results suggested that the fetus was a TPI heterozygote. This prenatal prediction was confirmed by RBC and haematological studies at birth.
Prenatal diagnosis of thalidomide syndrome
Authors: Gollop T. R. , Eigier A. , Neto J. Guidugli
Published: March 2007

A case of thalidomide syndrome diagnosed by ultrasound in the 17th week of pregnancy is presented. The pregnant woman had leprosy and received adjuvant treatment with thalidomide. The affected fetus was exposed to the drug until the 35th day of pregnancy and presented absent external ears, upper limb phocomelia and absent tibiae and fibulae. No internal organ abnormalities were noticed at autopsy.
The amniotic band syndrome: A possible complication of amniocentesis
Authors: Kohn Gertrude
Published: March 2007

Malformations of the upper distal extremities were noted in an otherwise healthy infant whose mother underwent diagnostic amniocentesis. A causal relationship is postulated.
A simple technique for obtaining high quality chromosome preparations from chorionic villus samples using FdU synchronization
Authors: Gibas Longina M. , Grujic Slobodan , Barr Marie A. , Jackson Laird G.
Published: March 2007

A fluorordeoxyuridine (FdU) synchronization technique was applied to 30 chorionic villus samples (CVS) from patients undergoing first trimester fetal diagnosis. The villi were incubated for 15 h in the presence of FdU. The block in DNA synthesis was subsequently released using thymidine and after an additional 5 h of incubation the mitotic cells were arrested in metaphases using a high concentration of colcemid.

This method results in improved morphology of the chromosomes and a high mitotic index. A diagnostic chromosome analysis could be obtained in each clinical case using at least 15 well‐spread metaphases. G‐banded karyotypes were prepared of four metaphases in each case. The diagnostic procedure was completed within 48 h from the time of CVS. Use of this technique significantly improves the success rate of ‘direct’ chromosome analyses from CVS in a busy cytogenetic laboratory.
Chorionic villus sampling: Improved method for preparation of karyotypes after short‐term incubation
Authors: Terzoli G. L. , Lalatta F. , Gilbert F.
Published: March 2007

A method for the isolation and trypsin‐Giemsa banding of metaphases obtained after short‐term incubation (48 h) of cytotrophoblast cells from chorionic villus sample is described. A new slide‐making instrument, developed expressly to enhance the spreading of chromosomes from metaphases released from small tissue pieces, is responsible for the increase yield of analysable metaphases in this protocol.
Pseudomosaicism for trisomy 13: Three case reports
Authors: Malin Joanne , Singer Niecee , Warburtons Dorothy , Kardon Natalie , Kim Hyon J.
Published: March 2007

Pseudomosaicism is of particular concern in prenatal diagnosis when it involves mosaicism for a cytogenetic abnormality associated with a clinical syndrome which is compatible with postnatal life, such as trisomies for chromosomes 13, 18, and 21. The lack of data regarding the outcome of pregnancies involving these specific kinds of pseudomosaicism makes genetic counselling difficult. Three cases of prenatal diagnosis of pseudomosaicism for trisomy 13, each of which had a normal outcome, will be presented (Tables 1 and 2). The three main areas for consideration are: (1) the genetic counselling issues, (2) the additional prenatal diagnostic options available to evaluate the status of the fetus in an attempt to identify some of the clinical features of trisomy 13, and (3) the outcome of the pregnancies.
Very low versus undetectable maternal serum alpha‐fetoprotein values and fetal death
Authors: Haddow James E. , Hill Laura E. , Palomaki Glenn E. , Knight George J.
Published: March 2007

Very low maternal serum alpha‐fetoprotein (MSAFP) levels (<10 ng/mL) are known to be associated with non‐viable pregnancies, including conditions such as fetal death, molar pregnancies, and non‐pregnancies. There has not been agreement, however, as to whether very low MSAFP levels indicate already existing fetal deaths or are actually predictive. We analysed 230 pregnancies with MSAFP levels <10 ng/mL from among 15 807 women (1.5 per cent) screened consecutively during a three‐year period and identified 26 non‐viable pregnancies, 22 of which were diagnosed sonographically as part of the screening process (17 missed abortions, 3 blighted ova, 2 non‐pregnancies). Furthermore, 20 of these 22 pregnancies were associated with essentially undetectable MSAFP levels (<5 ng/mL). Our data indicate that pregnancies with MSAFP values <5 ng/mL are the group most strongly associated with fetal non‐viability and that very low MSAFP values are not strongly predictive for fetal death.
Prenatal diagnosis of chromosomal abnormalities from chorionic biopsy samples: Improved success rate using a modified direct method
Authors: Metaxotou C. , Antsaklis A. , Panagiotopoulou P. , Benetou M. , Mavrou A. , Matsaniotis N.
Published: March 2007

Several methods for fetal chromosome analysis using chorionic biopsy samples were compared. A modified direct method for culturing villi was considered to be the method of choice and details are presented of 186 pregnancies tested prenatally. The success rate in obtaining a fetal karyotype with the direct method was 93 per cent. The fetal loss rate in the prenatal series was 4.3 per cent and congenital abnormalities in the babies already born did not differ from the expected incidence.
Chromosome mosaicism and maternal cell contamination in chorionic villi
Authors: Cheung Sau W. , Crane James P. , Beaver Heidi A. , Burgess Ann C.
Published: March 2007

While chorionic villus sampling allows both early and rapid prenatal diagnosis of chromosome disorders, the accuracy of this technique has not been fully established. Maternal cell contamination and pseudomosaicism represent two major sources of diagnostic error. Combined use of both direct chromosome preparations and villus cultures is important in overcoming these problems. Direct preparations of villus tissue allow recognition of maternal cell contamination of villus cultures. Conversely, villus cultures yield higher resolution chromosomes and may be helpful in differentiating between true versus pseudomosaicism when two or more cell lines are identified in direct chromosome preparations. Preliminary data suggest that analysis of direct preparations from multiple individually processed villus fragments may also be of value in this regard. Until more experience is gained, mid‐trimester amniocentesis should be offered to CVS patients when mosaicism is encountered.
Fibrinopeptide a increases after Chorionic villus sampling
Authors: Al‐Gailani F. , Elias S. , Simpson J. L. , Green D.
Published: March 2007

Fibrinopeptide levels were measured in 20 women during transcervical chorionic villus sampling (CVS). Fibrinopeptide A, a sensitive indicator of fibrinogen cleavage by thrombin, significantly increased in five subjects, whereas there was no change in Bβ peptide, an indicator of fibrinolysis. The data suggest that modest fibrin formation, uncompensated by fibrinolysis, may be induced in some women by CVS.
First trimester diagnosis of adenosine deaminase deficiency
Authors: Dooley T. , Fairbanks L. D. , Simmonds H. A. , Rodeck C. H. , Nicolaides K. H. , Soothill P. W. , Stewart P. , Morgan G. , Levinsky R. J.
Published: March 2007

Adenosine deaminase deficiency has been detected in the first trimester by direct analysis of enzyme activity in chorionic villi in a pregnancy at risk. Data for purine nucleoside phosphorylase activity in chorionic villi from healthy controls in the first trimester are also presented and should allow equally rapid diagnosis of this disorder.
The value of chromosome analysis in cases of neural tube defects: A case of anencephaly associated with fetal DUP(2) (p24→pter)
Authors: Singer Niecee , Gersen Steven , Warburton Dorothy
Published: March 2007

A family is described in which two anencephalic fetuses were identified in two pregnancies. Autopsy revealed kidney anomalies in both fetuses. Chromosome analysis was performed only on the second fetus, which had a 46,XY,lOq+ karyotype. Parental chromosome analysis showed the maternal karyotype to be 46,XX,t(2;10) (p24;q26) thus demonstrating that the fetus was carrying a duplication 2(p24→pter).

Recurrence risks for anencephaly based on the cytogenetic abnormality were much higher than those which would be quoted for isolated anencephaly. This points out the necessity for complete diagnostic studies when a fetus with a neural tube defect is identified.

The literature in regard to the 2p duplication phenotype is reviewed. It is possible that the duplication of the distal segment of 2p results in a neural tube defect/kidney anomaly phenotype.
Trisomy 20 mosaicism in prenatal diagnosis–a review and update
Authors: Hsu Lillian Y. F. , Kaffe Sara , Perlis Theresa E.
Published: March 2007

A total of 66 cases with prenatal diagnosis of trisomy 20 mosaicism was reviewed. Since the majority of cases (85 per cent) was associated with grossly normal phenotype and the abnormalities noted in 15 per cent of cases were inconsistent and rather non‐specific, no causal relationship between trisomy 20 mosaicism and a specific malformation syndrome can be established. The possiblity of an association between an abnormal phenotype and a high percentage of trisomy 20 cells (> 60 per cent) must be considered preliminary and be viewed with caution. The fact that cells with trisomy 20 have not been recovered from blood cultures and were detected more frequently from specific fetal tissues, (such as kidney, rectum, oesophagus), and from placental tissues, suggests that trisomy 20 is more likely to be confined to certain fetal organs and to extra‐embryonic tissues. This review calls for the collection of more data on all cases of trisomy 20 mosaicism diagnosed prenatally, in order to provide more accurate information to the prospective parents.
Abnormal maternal serum chorionic gonadotropin levels in pregnancies with fetal chromosome abnormalities
Authors: Bogart Mark H. , Pandian M. R. , Jones O. W.
Published: March 2007

The alpha subunit of human chorionic gonadotropin (alpha‐hCG), human chorionic gonadotropin (hCG) and alpha fetoprotein (AFP) were measured in the serum of 25 women with chromosomally abnormal fetuses between 18 and 25 weeks of gestation and in 74 normal pregnancies. AFP levels less than 0.5 multiples of the median (MoM) or greater than 2.5 MoM were observed in 24 per cent of the abnormal pregnancies and in 6.76 per cent of the normal pregnancies. A low concentration of hCG (< 0.25 MoM) was observed in 8 per cent of abnormals and in 2.7 per cent of normals while an elevated concentration of hCG (>2.5 MoM) was observed in 56 per cent of abnormals and in 1.35 per cent of normals. Elevated hCG‐alpha (>2.5 MoM) was observed in 28 per cent of abnormals and in none of the normals. Determination of elevated levels of hCG‐alpha or hCG resulted in detection of 68 per cent of pregnancies with chromosomally abnormal fetuses with a false positive rate of 1.35 per cent. Determination of both elevated and depressed gonadotropin levels resulted in detection of 76 per cent of abnormal pregnancies with a false positive rate of 4.05 per cent. Measurement of hCG and hCG‐alpha in maternal serum samples can be used as a screening procedure for detecting pregnancies at risk for fetal chromosome abnormalities.
Prenatal diagnosis of a new syndrome: Holoprosencephaly with hypokinesia
Authors: Morse Richard P. , Rawnsley Eileen , Sargent Steven K. , Graham John M.
Published: March 2007

Markedly decreased fetal activity (akinesia/hypokinesia) is usually readily apparent to experienced mothers, and frequently this concern leads to attempts at prenatal diagnosis. We report prenatal diagnosis of two fetuses with congenital contractures, markedly decreased fetal movement, and microcephaly due to severe holoprosencephaly. Such familial recurrence to phenotypically normal parents suggests a newly recognized autosomal recessive or X‐linked syndrome that is readily detectable by prenatal ultrasonography.
Biamnial elevated alpha‐fetoprotein and positive acetylcholinesterase in twins, one with anencephaly
Authors: Holbrook R. Harold , Krovoza Ann M. , Schelley Susan , Ferguson James E.
Published: March 2007

Anencephaly in twin B was accompanied by elevated amniotic fluid alpha‐fetoprotein (AFP) and a positive acetylcholinesterase (AChE) band on gel electrophoresis in both twin sacs, although twin A was normal. AChE results did not help distinguish the false positive AFP in this set of twins, implying that AChE may diffuse transamniotically as has been previously postulated for AFP. In light of the low concordance rate for neural tube defects in twins, patient counselling in this situation must include the information that AFP and AChE may be falsely elevated in normal twin when the other twin has a neural tube defect.
Duration of vaginal bleeding and trisomy at prenatal diagnosis
Authors: Neugut R. H. , Lustenberger A. , Nicholas A. , Kline J. , Warburton D.
Published: March 2007

In the case‐control study of 118 women with autosomal trisomy identified at prenatal diagnosis and their 442 karyotypically normal matched controls, we found that there was no overall association between risk of trisomy and the presence of vaginal bleeding during pregnancy. However, a lengthy duration of bleeding appears to predict increased risk of trisorny.
Prenatal sonographic diagnosis of endocardial fibroelastosis secondary to aortic stenosis
Authors: Achiron Reuven , Malinger Gustavo , Zaidel Liliana , Zakut Haim
Published: March 2007

Endocardial fibroelastosis is characterized by a diffuse thickening of the left ventricular endocardium with or without other cardiac anomalies. This entity had been diagnosed prenatally previously (Bovicelli et al., 1984) at a gestational age of 36 weeks. A case of endocardial fibroelastosis due to aortic stenosis accompanied by pericardia! effusion, ascites, and hydramnion, diagnosed ultrasonographically and confirmed pathologically at 21 weeks of gestation, is presented.
Prenatal ultrasound diagnosis of macroglossia in the Wiedemann‐Beckwith syndrome
Authors: Cobellis G. , Iannoto P. , Stabile M. , Lonardo F. , Bruna M. Della , Caliendo E. , Ventruto V.
Published: March 2007

We report the ultrasound prenatal diagnosis at the 30th week of macroglossia in two sibs with the Wiedemann‐Beekwith syndrome; the syndrome was also present in their mother. A study of high resolution chromosomes did not show any anomaly.
Prenatal diagnosis of tetrasomy 47,XY, + i(12p) confirmed by in situ hybridization
Authors: Shivashankar L. , Whitney E. , Colmorgen G. , Young T. , Munshi G. , Wilmoth D. , Byrne K. , Reeves G. , Borgaonkar D. S. , Picciano S. R. , Marttn‐Deleon P. A.
Published: March 2007

A case of tetrasomy i(12p) detected prenatally is reported. The patient, a black, 33‐year‐old G3P2002 at 24 weeks' gestation with an unremarkable family history presented herself for prenatal care. Ultrasound examination showed a fetus with diminished femoral and humeral lengths, and hydramnios. A level II scan confirmed the presence of an omphalocele.

Amniocentesis at 31 weeks showed 47,XY, + i(12p) karyotype. An infant with multiple congenital anomalies was delivered at 34 weeks. The infant died after 5 h.

Genetic and ultrasonographic examinations in the third trimester were helpful in the investigation of this fetus with multiple congenital anomalies. The careful, complete team counselling afforded by this approach enabled the mother and family to be well adjusted to the strong possibility (and subsequent reality) of an abnormal infant.
Prenatal evaluation and outcome of fetal obstructive uropathies
Authors: Reuss A. , Wladimiroff J. W. , Scholtmeijer R. J. , Stewart P. A. , Sauer P. J. J. , Niermeijer M. F.
Published: March 2007

Between January 1982 and January 1986, 76 pregnant women between 15 and 40 weeks of gestation were referred because of suspected fetal obstructive urinary tract pathology. A total of 14 high‐level (ureter) and 17 low‐level (urethral) obstructions were diagnosed. High‐level obstructions were at the uretero‐pelvic level in 11 and at the uretero‐vesical level in 3 cases. Increased amniotic fluid volume was observed in 28 per cent. The survival rate was 86 per cent.

In the 17 cases of urethral obstruction, oligohydramnios was present in 70 per cent, associated structural defects in 30 per cent, and an abnormal karyotype in 6 per cent. Pregnancy was terminated because of progressive massive hydronephrosis in 41 per cent; intrauterine or neonatal death occurred in 47 per cent, resulting in a survival rate of only 12 per cent.
The BOR syndrome and renal agenesis‐prenatal diagnosis andfurther clinical delineation
Authors: Greenberg Cheryl R. , Trevenen Cynthia L. , Evans Jane A.
Published: March 2007

This is the first report of prenatal diagnosis of a fetus with brachio‐oto‐renal dysplasia (BOR) syndrome with right‐sided renal agenesis and severe left hypoplasia. The father of this fetus had malformed external ears, a left‐sided preauricular pit and branchial cyst, and bilateral mild to moderate deafness without a demonstrable renal anomaly. This family highlights the variable expressivity seen in the autosomal dominant BOR syndrome, the importance of genetic counselling for families with BOR syndrome, and the aetiologic heterogeneity of renal agenesis.
An embryogenic model to explain cytogenetic inconsistencies observed in chorionic villus versus fetal tissue
Authors: Crane James P. , Cheung Sau W.
Published: March 2007

While the fetus and placenta have a common ancestry, chorionic villus tissue does not always reflect fetal genotype. Data are presented from 15 CVS subjects in whom cytogenetic inconsistencies were observed when comparing (1) cultured chorionic villi, (2) direct chromosome preparations of intact villi, and (3) cultured fetal tissue. Embryogenic models are presented to explain these discrepancies. Mosaicism confined to direct chromosome preparations was the most commonly observed inconsistency. This can be explained by postzygotic non‐disjunction limited to cytotrophoblast. In all but one instance, the abnormal cell line was limited to the placenta, with the normal cell line reflecting fetal genotype. Analysis of direct chromosome preparations from multiple individually processed villus fragments may be helpful in recognizing mosaicism confined to the placenta. While both direct chromosome preparations and villus cultures can be misleading, the latter are more likely to reflect fetal genetic status since they are derived from the extraembryonic mesoderm.
HLA‐A,B,C,DR typing and 17‐OHP determination for second trimester prenatal diagnosis of 21‐hydroxylase deficient CAH
Authors: Grosse‐Wilde H. , Valentine‐Thon E. , Vögeler U. , Passarge E. , Lorenzen F. , Sippell W. G. , Bidlingmaier F. , Knorr D.
Published: March 2007

In 18 families at risk for the HLA‐linked, 21‐hydroxylase deficient form of autosomal recessive congenital adrenal hyperplasia (CAH), prenatal diagnosis (PD) was performed using two methods: (1) HLA‐A,B,C typing and in the latter 11 cases also DR typing of cultured amniotic fluid cells (AFC) using the standard microcytotoxicity assay, and (2) measurement of second trimester amniotic fluid 17‐hydroxyprogesterone (17‐OHP) concentration using gel chromatography and radioimmunoassay. The accuracy of the prenatal predictions was confirmed by postnatal HLA typing of umbilical cord blood lymphocytes and by clinical evaluation.

In 16/18 families, both HLA typing of AFC and 17‐OHP measurements proved informative for PD. The predictions of both methods were concordant in 14/16 families (88 per cent). In ten of these families, a normal fetus was predicted, and in four, an affected fetus; all pregnancies were carried to term and all predictions were confirmed postnatally. In 2/16 cases (12 per cent), however, the predictions were discordant: the prenatal HLA typing indicated an affected fetus, whereas the 17‐OHP values predicted a normal fetus. Both pregnancies were continued and two healthy boys were delivered. The discordance proved to be due to a ‘missed’ HLA antigen in one case and to serologically cross‐reactive HLA antigens in the second.

Finally, in 2/18 cases, prenatal assessment of fetal genotype had to rely on HLA typing alone as 17‐OHP measurement was not performed in one family and in the second family the 17‐OHP values obtained were not informative due to inadvertent continuation of hormone therapy to the date of amniocentesis. In both cases, the HLA typing data accurately predicted a normal fetus.

In conclusion, a combination of HLA typing of cultured AFC and 17‐OHP measurements of amniotic fluid permits accurate prenatal diagnosis of CAH in most cases (88 per cent). In addition, the supplementary use of HLA‐DR typing of AFC as presented here for the first time proved helpful in families with HLA‐A.B homozygosity due to parental sharing of antigens and can be informative for identifying HLA‐B/21‐OH recombinant haplotypes.
Prenatal diagnosis of the pterygium syndrome
Authors: Zeitune Móshe , Fejgin Moshe D. , Abramowicz Jacques , Aderet Noah Ben , Goodman Richard M.
Published: March 2007

We report two second trimester pregnancy terminations in the same woman following intrauterine ultrasonic findings of hydrops fetalis, polyhydramnios, lack of fetal movements, and short, fixed malformed limbs. One fetus also showed a cystic mass at the back of the head. Radiographic and anatomic studies of the fetuses demonstrated multiple pterygia, flexion contracture of multiple joints, abnormal facial appearance, cleft palate, pulmonary hypoplasia, and gracile bones. The cystic mass of the back of the head was found to be a cystic hygroma.

These findings are consistent with the lethal variant of multiple pterygium syndrome. Early prenatal diagnosis of this condition is possible using ultrasonography.
Prenatal diagnosis of galactosialidosis
Authors: Sewell A. C. , Pontz B. F.
Published: March 2007

The second prenatal diagnosis of galactosialidosis is reported. Neuraminidase and β‐galactosidase activities in cultured amniotic cells were deficient, this being confirmed by skin fibroblast enzyme assay on the affected fetus after interruption of the pregnancy. Cultured placental cells demonstrated the same enzyme deficiencies. Analysis of deproteinized amniotic fluid showed the presence of abnormal oligosaccharides specific for a‐neuraminidase deficiency.
Congenital pleural effusion: Prenatal ultrasonic diagnosis and therapeutic management
Authors: Bruno Margherita , Iskra Lilliana , Dolfin Giancarlo , Farina Daniele
Published: March 2007

A case of fetal pleural effusion detected by ultrasound at 33 weeks of gestation is described.
Interstitial deletion of chromosome 1 [del(1)(q25q32)] in an infant with prune belly sequence
Authors: Scarbrough Paula R. , Files Beatrice , Carroll Andrew J. , Quinlan R. William , Finley Sara C. , Finley Wayne H.
Published: March 2007

Relatively few cases of deletion 1q have been reported. These cases have been divided into three groups according to assigned breakpoints. They include proximal interstitial, intermediate interstitial, and terminal deletions. We present a male infant with an interstitial deletion of 1q with breakpoints determined by GTG banding as q25 and q32. Comparison with similar case reports suggests common physical features which include microcephaly, growth retardation, developmental delay, clinodactyly, and genital anomalies in affected males. However, no characteristic phenotypic appearance is definable.

The infant also presented with prune belly sequence (PBS) with Potter fades. Fetal ascites, as noted in this case on prenatal ultrasound, appears to be an early factor in the pathogenesis of PBS. Therefore, detection of fetal ascites should suggest the presence of the PBS association and the need for more extensive prenatal evaluation.
Amniotic fluid alpha‐fetoprotein levels and prenatal diagnosis of autosomal trisomies
Authors: Kaffe Sara , Perlis Theresa E. , Hsu Lillian Y. F.
Published: March 2007

Pregnancies with fetal trisomy 21 have been associated with low amniotic fluid alpha‐fetoprotein levels (AFAFP). This observation led to the suggestion that low AFAFP levels be used as a criterion for completion of a chromosomal analysis in patients who are not otherwise at increased risk for a fetal chromosome abnormality and in whom karyotyping might not have been completed for economic reasons. In order to assess the usefulness of such criteria, we reviewed the AFAFP levels of 90 cases of fetal trisomy 21, 23 cases of trisomy 18, and 10 cases of trisomy 13. These were compared with 2400 control samples with normal chromosome constitution. AFAFP levels were generally lower in pregnancies with trisomy 21, showing a median value of 0·72 MoM. However, 40 per cent of the trisomy 21 samples had AFAFP values greater than 0·8 MoM and 20 per cent were over 1·0 MoM. These data imply that over 50 per cent of Down syndrome cases might have been missed using a cut‐off level of 0·70 MoM for completion of chromosome analysis. Using a higher cut‐off level will leave only a small percentage of samples unkaryotyped. The distribution of AFP levels in trisomy 13 and 18 is no different from controls; we therefore believe that fetal karyotyping should be completed in every amniotic fluid sample obtained.
First trimester diagnosis of methylmalonic aciduria
Authors: Fowler B. , Giles L. , Sardharwalla I. B. , Donnai P. , Clayton J. K.
Published: March 2007

We have studied methylmalonyl CoA mutase activity in control chorionic villi to establish the potential use of assays performed directly on this tissue for prenatal diagnosis of methylmalonic aciduria. We report the detection of a fetus affected with the apo‐mutase deficient form of this condition at 9 weeks' gestation. Methylmalonyl CoA mutase was markedly deficient in chorionic villi, approximately 2–5 per cent of the mean control value. However, incorporation of label from [14C]‐propionate into protein was 10 and 40 per cent of the mean control value, respectively, in two portions of the same biopsy, highlighting potential problems in the use of this indirect assay. Normal results were obtained in chorionic villus samples from four other pregnancies ‘at risk’ for methylmalonic aciduria which were subsequently shown to be unaffected with this condition. The diagnosis in the affected pregnancy was confirmed by demonstration of a marked deficiency of methylmalonyl CoA mutase activity in villi obtained at termination and in cultured fetal fibroblasts. Reduced incorporation of [14C]‐propionate label into protein was also found in these tissues.
Termination of pregnancy by a dilatation‐evacuation technique to obtain placental tissue for DNA analysis
Authors: Ferrari M. , Cantù‐Rajnoldi A. , Pietri S. , Buscaglia M. , Nicolinl U.
Published: March 2007

In 57 patients, following prenatal diagnosis of a fetus affected by β‐thalassaemia major, we terminated the pregnancy by dilatation and evacuation. In 19, we have already performed DNA analysis to evaluate the feasibility of prenatal diagnosis in a subsequent pregnancy.
Trisomy 14 mosaicism leading to cytogenetic discrepancies in chorionic villi sampled at different times
Authors: Wegner R.‐D. , Hohle R. , Karkut G. , Sperling K.
Published: March 2007

Short‐ and long‐term cultures of chorionic villi obtained in the 11th week of pregnancy revealed trisomy 14. After induced abortion trisomy 14 mosaicism was established in fetal skin and umbilical cord tissue while a second long‐term culture of chorionic villi exhibited a normal karyotype. The results of the pathological investigations are discussed with respect to the cytogenetic findings.
OEIS complex (cloacal exstrophy): Prenatal diagnosis in the second trimester
Authors: Kutzner Deann K. , Wilson William G. , Hogge W. Allen
Published: March 2007

OEIS complex (exstrophy of the cloaca) is an association of fetal malformations that includes omphalocele, exstrophy of the bladder, imperforate anus, and spinal defects. Most cases should be prenatally detectable by maternal serum alpha‐fetoprotein screening, but an accurate diagnosis is essential for appropriate counselling of the family.
Amniotic fluid‐AFP in Down syndrome and other chromosome abnormalities
Authors: Crandall Barbara F. , Matsumoto Myles , Perdue Sondra
Published: March 2007

80·2 Per cent of 111 Down syndrome pregnancies had amniotic fluid (AF) alpha fetoprotein (AFP) levels on or below the median and 10·8 per cent at or below 0·5 MoM compared with 41·9 and 1·4 per cent of controls. These differences were even more striking when the gestational age was < 18 weeks compared with ⩾ 18 weeks. No such association was seen for other chromosome abnormalities including trisomy 18,45,X and mosaics, 47,XXY, 47,XXX, and other structural abnormalities and triploidy, even when high levels due to defects such as omphalocele and cystic hygroma were excluded. All cases of trisomy 13 and 80 per cent with 47,XYY had AF‐AFP levels above the median. Selection of cases for karyotyping by a low level of AF‐AFP would clearly fail to detect aneuploidies other than Down syndrome and is not recommended. A possible weak association between low maternal serum (MS) and AF‐AFPs in Down syndrome was most evident at < 18 weeks, suggesting that MS screening between 16 and 18 weeks may be the most informative time.
Trisomy 7 in chorionic villi: Follow‐up studies of pregnancy, normal child, and placental clonal anomalies
Authors: DeLozier‐Blanchet C. Dawn , Engel Eric , Extermann Philippe , Pastori Béatrice
Published: March 2007

Cytogenetic study of chorionic villi sampled because of advanced maternal age revealed, after overnight culture, an apparently non‐mosaic trisomy 7. Amniocentesis showed exclusively normal mitoses, and the pregnancy continued normally. One hundred mitoses from cord blood of the normal newborn revealed a non‐mosaic 46,XX complement. No cells with a proven trisomy 7 were found in cultures from either of two biopsies of the morphologically normal placenta, but the peripheral biopsy showed in multiple cultures an abnormal clone: 47,XX, + 20,‐2,‐21, + t(2;21)(p13;q22). To our knowledge, this is the first case of non‐mosaic trisomy 7 detected on CVS which has had follow‐up studies of amniotic fluid, cord blood, and term placenta.
Immunoblot detection of enzyme proteins of peroxisomal β‐oxidation in fibroblasts, amniocytes, and chorionic villous cells. Possible marker for prenatal diagnosis of Zellweger's syndrome
Authors: Shimozawa Nobuyuki , Suzuki Yasuyuki , Orii Tadao , Hashimoto Takashi
Published: March 2007

The amounts of enzyme proteins of peroxisomal β‐oxidation in fibroblasts and chorionic villous cells from infants with Zellweger syndrome and in fibroblasts, amniocytes, and chorionic villi from healthy controls were measured by immunoblot analysis. Immunoreactive proteins of peroxisomal acyl‐CoA oxidase and 3‐ketoacyl‐CoA thiolase were absent in fibroblasts and chorionic villous cells from the patients, yet these enzyme proteins were present in fibroblasts, cultured amniocytes, and chorionic villi from the normal controls. These results show that immunoblot analysis of peroxisomal β‐oxidation enzymes in amniocytes and chorionic villous cells is of potential value for the prenatal detection of Zellweger syndrome.
Prenatal diagnosis of a de novo unbalanced translocation (4p + ) following in vitro fertilization
Authors: Cannizzaro Linda A. , Hecht Barbara K. , Bixenman Helen A. , Pazdziorko Stephen , Tamis Robert , Hecht Frederick
Published: March 2007

We report herein a de novo unbalanced chromosome translocation in a fetus resulting from in vitro fertilization technology. Prenatal diagnostic analysis of an amniotic fluid revealed a 46,XX,4p+ karyotype. The origin of the extra material on the short arm of chromosome 4 could not be identified by a variety of banding techniques. However, examination of fetal parts did reveal some dysmorphic features.
Multiple sulphatase deficiency: Prenatal diagnosis using chorionic villi
Authors: Patrick A. D. , Young Elisabeth , Ellis Cheryl , Rodeck C. H.
Published: March 2007

Multiple sulphatase deficiency was diagnosed in the first trimester of pregnancy by demonstrating markedly reduced activities of arylsulphatases and heparin sulphamidase by direct assays on chorionic villi (CV). The diagnosis was confirmed by assays on cell cultures of villi and fetal skin fibroblasts. Two further pregnancies of this mother were monitored similarly and predicted to be unaffected; one produced a normal healthy infant, the other miscarried shortly after CV sampling.
Rapid karyotyping for prenatal diagnosis in the second and third trimesters of pregnancy
Authors: Basaran Seher , Miny Peter , Pawlowitzki Ivar‐Harry , Horst Jürgen , Holzgreve Wolfgang
Published: March 2007

Direct chromosome preparations were performed on placental villi obtained by ultrasoundguided needle aspiration between 18 and 37 weeks of pregnancy in 53 patients. The sampling yielded a sufficient amount of tissue with a maximum of two, and in most cases one, insertions. Placental biopsy is easily performed in cases of severe oligohydrammnios, where fetal blood sampling is usually more difficult. Direct karyotyping of placental villi is faster than chromosome analysis from fetal blood or application of the pipette method on amniotic fluid cells, and currently represents the most rapid approach to prenatal diagnosis of chromosomal abnormalities from the first to the third trimester of pregnancy.
Prenatal diagnosis of abdominal cystic hygroma
Authors: Kozlowski Karen J. , Frazier Cynthia N. , Quirk J. Gerald
Published: March 2007

We present a case of fetal abdominal cystic hygroma that presented at 19 weeks of gestation. Ultrasonographic evaluation of the fetus revealed soft tissue enlargement of the left leg and a retroperitoneal mass in the left pelvis and abdomen. This represents the first reported case of prenatal diagnosis of abdominal cystic hygroma.
First trimester prenatal diagnosis of haemophilia A: Two years' experience
Authors: Bröcker‐Vriends A. H. J. T. , Briët E. , Kanhai H. H. H. , Bakker E. , Dreesen J. C. F. M. , Leschot N. J. , van de Kamp J. J. P. , Pearson P. L.
Published: March 2007

We evaluated the feasibility, reliability, and acceptability of prenatal diagnosis of haemophilia A by DNA analysis of chorionic villi.

Twenty‐two women at risk to transmit the abnormal gene were referred for prenatal diagnosis, two of them twice. Two of the 22 women appeared to be non‐carriers by DNA analysis. In one of these women, the results were known only after chorionic villus sampling had been carried out.

Thirteen of the twenty carriers were heterozygous for an intragenic (Bell or Xbal) marker; six women were only heterozygous for the extragenic DXS52 (Stl4) locus. One of the women was homozygous for all the presently known DNA markers within or closely linked with the factor VIII locus.

Twelve of the 22 fetuses at risk were male, ten were female. Seven of the 12 male fetuses were shown to be affected and were subsequently aborted. Four male fetuses appeared to be not affected. In one case, the diagnosis was made by use of an extragenic marker. The woman rejected fetal blood sampling to confirm the diagnosis. After birth, a normal factor VIII level was found in three of the four cases. The fourth pregnancy is still continuing. In one of the 12 male fetuses, no diagnosis at the gene level was possible.

DNA analysis is expected to provide maximum certainty as to the phenotype of the fetus for approximately 60 per cent of the women; for another 37 per cent a rate of misdiagnosis of 4–5 per cent applies. In only 3 per cent of the cases will no diagnosis at the gene level be possible as yet.

The new possibility of a prenatal diagnosis in the first trimester of pregnancy enabled some of these women to have a family of their own and was appreciated in particular by the women who underwent fetoscopy in an earlier pregnancy.